CEREBRAL CORTEX


TYPES OF CEREBRAL FIBERS: Cerebral Cortex has about 15 billion neurons, about as many glial cells, and a rich capillary network.

• COMMISSURAL FIBERS: Fibers that traverse from one cerebral hemisphere to the other.
  • Corpus Callosum carries most of this traffic.
  • Anterior Commissure carries some crossing traffic.
• ASSOCIATION FIBERS: Interconnect areas of the same cerebral hemisphere.
  • SHORT ASSOCIATION FIBERS: Join Neighboring regions.
  • LONG ASSOCIATION FIBERS: Join separate lobes (frontal to occipital, e.g.)
    • SUPERIOR LONGITUDINAL FASCICULUS: Is a long association fiber-bundle that interconnects the THALAMUS with the cerebral hemispheres.
    • ARCUATE FASCICULUS is a subset of the above. It connects Broca's Speech Area to Wernicke's Speech-Reception Area.
      • DISCONNECTION SYNDROME: Loss of the Arcuate Fasciculus, resulting in poor processing and formulation of speech.
• PROJECTION FIBERS: Afferent fibers coming into the Cerebral Cortex, and efferent fibers leaving the Cerebral Cortex.

FRONTAL LOBE:

• PRIMARY MOTOR CORTEX (Area 4):
  • Its fibers make up the Corticobulbar and Corticospinal Tracts.
  • SEGMENTOTOPIC ORGANIZATION (HOMUNCULUS):
    • Sacral is most medial. It is thus supplied by the Anterior Cerebral Artery.
    • Cervical / Head is most lateral, as you descend down the Pre-Frontal Gyrus. It is thus supplies by the Middle Cerebral Artery.
• PREMOTOR CORTEX (Area 6): Rostral to the Primary Frontal Cortex.
  • FNXN: Gross coordination of voluntary motor activity, such as adducting or abducting a limb.
• FRONTAL EYE-FIELD (Area 8): Rostral to the Primary Frontal Cortex.
  • FNXN: Voluntary conjugate movement of the eyes.
  • LOCATION: It close to the region responsible for movement of the eye.
  • REFLEX FOLLOWING CENTER in Parietal Lobe works with this lobe to allow eyes to follow an object in space.
  • LESION to this lobe will make eyes deviate toward the affected side.
• BROCA'S MOTOR SPEECH CORTEX (Area 44, 45): Inferior Frontal Gyrus.
  • LEFT SIDE ONLY: This area if responsible for formulation of Propositional Language, or meaningful language.
    • ASYMMETRY: The Left Side is usually (but not always) the dominant side for speech. It is significantly larger than the right side.
    • MOTOR APHASIA result from lesion to this area. Individual would have difficulty formulating meaningful language.
  • RIGHT SIDE ONLY: Formulation of emotional inflection and tone in speech.
• PREFRONTAL CORTEX: JUDGMENT, FORESIGHT, PERCEPTION

PARIETAL LOBE:

• PRIMARY SOMATOSENSORY CORTEX (Area 1, 2, 3): Post-Central Gyrus.
  • FNXN: Conscious perception of pain, temperature, proprioception, touch. The termination of third order sensory neurons from the VPL and VPM of Thalamus.
  • SEGMENTOTOPIC ORGANIZATION (HOMUNCULUS):
    • Sacral is most medial and thus supplied by Anterior Cerebral.
    • Cervical / Head is most lateral and thus supplied by Middle Cerebral.
• SOMATOSENSORY ASSOCIATION CORTEX (Area 5, 7): Ability to recognize sensations, recognize objects by touch, for example. They receive input from the Primary Cortex
  • LEFT SIDE ONLY:
    • AREA 5: Gross integration of somatic sensation.
    • AREA 7: Most posterior, and more sophisticated integration, interpretation of somatic sensation.
  • LESION = ASTEREOGNOSIS: Inability to recognize an object, such as a quarter, with eyes closed, by touch.
  • RIGHT SIDE ONLY: Areas 5 and 7 give us spatial control related to the visual system (such as ability to move with eyes closed).
• NEGLECT SYNDROME: A lesion to the posterior Parietal Lobe of the Non-Dominant Hemisphere.
  • It is posterior because more sophisticated sensory association fibers tend to converge on the Parieto-Occipital Junction, from three areas:
    • Higher Somatic Sensation (from Parietal Lobe)
    • Higher Visual Sensation (from Occipital Lobe)
    • Higher Auditory Sensation (from Temporal Lobe)
  • SYMPTOMS: The person doesn't recognize half of his body as being his own. Only able to dress one half of his body, etc. Strange...

TEMPORAL LOBE:

• PRIMARY AUDITORY CORTEX (Area 41, 42): Concealed within the lateral fissure, on the Transverse Temporal Gyri.
  • FNXN Hearing. It is the end of the pathway that started with Lateral Lemniscus ------> Inferior Colliculus ------> Medial Geniculate Body ------> Primary Auditory Cortex
• AUDITORY ASSOCIATION CORTEX (Area 22): One of the Superior Temporal Gyri.
  • GENERAL FUNCTION: Association and integration of auditory information.
  • WERNICKE'S RECEPTIVE SPEECH (Area 22): The Caudal part of the Auditory Association Cortex on the dominant
    • LEFT SIDE ONLY, FNXN: The interpretation of propositional (i.e. meaningful) language.
    • RIGHT SIDE ONLY, FNXN: The interpretation of emotional inflection in speech. Interpretation of tone in speech.
• ANGULAR GYRUS: Posterior Temporal Lobe, surrounding the Superior Temporal Sulcus.
  • FNXN: It is responsible for interpretation of written language (i.e. reading).
• SUPRAMARGINAL GYRUS: Wraps around the end of the Lateral Fissure, contiguous with Wernicke's Area.
  • FNXN: It is responsible for the ability to write meaningful language (i.e. write cursive).

OCCIPITAL LOBE:

• PRIMARY VISUAL CORTEX (Area 17): It surrounds the Calcarine Fissure
  • FNXN: Each side of Area 17 receives visual info from the contralateral field of vision.
  • LESION: Hemianopia, blindness to the contralateral field of vision.
• VISUAL ASSOCIATION CORTEX (Area 18, 19): Extending outward from calcarine sulcus, on medial and lateral occipital lobe.
  • FNXN: Recognition of visual images; relate present to past visual experiences.

LESION TO THE LATERAL LEFT FRONTAL LOBE: Occlusion in the distribution of Middle Cerebral Artery

• AREA 44&45: Lost motor speech.
• AREA 8: Loss of contralateral (right) visual eye field.
• AREA 4: Lose the lateral part of area 4
  • Contralateral lower facial paralysis (Central Lesion of VII -- the most important marker).
  • Also paralysis of upper extremity.

LESION TO LEFT TEMPORAL AND POSTERIOR PARIETAL LOBE: Occlusion in the distribution of Middle Cerebral Artery.

• ANGULAR GYRUS: Loss of ability to read.
• SUPRAMARGINAL GYRUS: Loss of ability to write.
• WERNICKE'S AREA: Loss of ability to understand spoken language.
• NEUROEMBRYOLOGY
  
  
  Development of Neural Tube:
  • Neural Plate: thickening of embryonic ectoderm, Day 18.
  • Notochord: Just ventral to the neural plate. It induces formation of the Neural Tube.
  • Neural Folds are formed on the Neural Plate next, they begin to move toward each other, forming a Neural Groove.
  • NEURAL TUBE: Is formed from the primitive Neural Groove. This occurs first in the midsection of the embryo and then proceeds rostrally and caudally.
    • Rostral Neuropore and Caudal Neuropore are the open ends of the Neural Tube.
  • NEURAL TUBE DEFECTS:
    • SPINA BIFIDA: Failed closure of the Caudal part of the Neural Tube. But, the nervous system continues to develop normally.
    • Meningoceles (outpocketings of meninges) and Meningomyeloceles (outpocketings of meninges + nervous tissue) will result.
    • ANENCEPHALY: Failure of rostral closure of neural tube and subsequent differentiation.
  NEURAL CREST CELLS: Lie on either side of the Neural Groove and are pinched off by closure of the Neural Tube. They form a number of important structures.
  • Dorsal Root Ganglia and portions of sensory ganglia that are like the Dorsal Root (V, VII, VIII, IX, X)
  • Sympathetic Ganglia
  • Parasympathetic (Enteric) Ganglia
  • Pia and Arachnoid Mater
  • Schwann Cells
  • Melanocytes
  Proliferation in Neural Tube:
  • Cells start connected both to the internal and external limiting membranes of the neural tube, but ultimately remain connected only to the internal limiting membrane.
  • NEURAL BIRTHDAY: Occurs when a cell-line has had its last division and remains in the same structure terminally thereafter. Neurons from the same structure tend to have the same Neural Birthdays.
  • THREE LAYERS of Proliferating Tube:
    • Ventricular Layer: Contains dividing cells.
    • Mantle Layer: Postmitotic neuronal cells bodies (after their birthday)
    • Marginal Layer: Axoplasmic extensions of the mantle layer.
  • NEURAL VESICLES: At 3 weeks, three distinct outpocketings can be made out. These are the classical three vesicles out of which entire nervous system grows:
    • Rhombencephalon (Hindbrain)
      • Myelencephalon ------> Medulla Oblongata
      • Metencephalon ------>Pons, Cerebellum
    • Mesencephalon (Midbrain) ------> Midbrain
    • Prosencephalon (Forebrain) ------> Diencephalon + Telencephalon
      • Diencephalon
        • Thalamus
        • Epithalamus
        • Hypothalamus
        • Subthalamus
      • Telencephalon ------> Cerebral Hemispheres
  • VENTRICLES will arise from the Central Canal of the Neural Tube.
  • FLEXURES: Characteristic flexures create the shape of the CNS
    • 26 Days: Mesencephalic and Cervical Flexures.
    • 35-50 Days: Pontine Flexure brings the Cerebellum to lie dorsal to the Pons.
  SPINAL CORD DEVELOPMENT:
  • Sulcus Limitans: It appear along the Neural Tube, and separates dorsal and ventral regions of the spinal cord.
    • ALAR (DORSAL) PLATE: Neurons become specialized for sensory.
    • BASAL (VENTRAL) PLATE: Neurons become specialized for motor.
  BRAINSTEM / CEREBELLUM DEVELOPMENT:
  • MEDULLA
    • CN NUCLEI are arranged in Columns in the medulla.
    • CLOSED MEDULLA:
      • ALAR PLATE Derivatives: Nuclei Cuneatus and Gracilis.
      • BASAL PLATE Derivatives: Corticospinal fibers
    • OPEN MEDULLA: The Alar Plate is displaced laterally. So, sensory stuff is now lateral to motor stuff, which tends to be more medial.
  • PONS: It maintains the alar / basal plate distinction between sensory / motor.
  • CEREBELLUM: Formed from the Rhombic Lips of the Alar Plate of the Pons.
    • These lips fold medially to cover the Pons, so that Pons is ventral to Cerebellum.
    • There are two proliferative zones present during development:
      • FIRST: VENTRICULAR ZONE produces deep neurons and an external granule layer, which is present only in the developing cerebellum.
      • SECOND ZONE: It is established in the external granule layer.
  TELENCEPHALON: The neurons develop in an "inside-out" fashion. The earliest neuronal birthdays occur closest to the medullary center, then neurons migrate beyond that.
  Cellular Events in Development:
  • Making Neuronal Connections:
    • Sometimes a neuron will reel out its axon as it grows.
    • At other times, a neuron will use physical or chemical (chemotaxis) cues to grow toward a target.
  • Synaptic Plasticity: Modifications to neuronal connections made after development is complete.
    • They can be made as an alternative pathway following damage to a connection.
    • They can be made in the process of "learning."
  • Programmed Cell Death: More neurons than are needed are made during development.
    • Neurons that are unsuccessful at making their connections are then lost (killed, DEAD) by a pre-programmed neuronal cell death.

ACTION POTENTIAL MEASUREMENT, NERVE-TRUNK PROPERTIES
EXTRACELLULAR RECORDING: Non-invasive recording of action potentials by placing electrodes outside the neuron, on the skin.

• MONOPHASIC RECORDING: Utilizes one electrode plus a ground electrode. The electrical potential outside the neuron is then recorded as action potentials pass through.
  • DEPOLARIZATION is represented as an upward peak on the graph, where up is more negative and down is more positive. As the action potential passes the electrode, the outside of the neuron becomes more negative, as Na+ flux in.
• BIPHASIC RECORDING: Utilizes two electrodes and measures the potential difference between them.
  • Depolarization passes the first electrode: The first electrode becomes negative with respect to the second electrode.
    • Negative (upward) deflection on graph.
  • Depolarization passes the second electrode: The two electrodes are now both depolarized and therefore have the same volt-potential.
    • Graph returns to zero-line.
  • Depolarization then reaches second electrode while first depolarizes.
    • Positive (downward) deflection on graph.
• THRESHOLD POTENTIAL: With external stimulation, large axons are excited more easily (have a lower threshold potential) than small axons because they have a lower internal resistance.

AXON DIAMETER: Many properties of nerves vary according to axon diameter:

• CONDUCTION VELOCITY: There is a linear relationship between axon diameter and conduction velocity:
  • Myelinated Axons: CONDUCTION VELOCITY (m / sec) = 6 x Diameter (micron)
  • Unmyelinated Axons: CONDUCTION VELOCITY (m / sec) = 1.7 x Diameter (micron)
• EXTRACELLULAR EFFECTS:
  • The amplitude of the extracellular action potential varies directly with cell diameter.
  • The threshold for extracellular stimulation varies inversely with axon diameter. The larger the axon, the lower the stimulus threshold.
• LOCAL ANESTHETICS: Small axons are blocked before large axons.
• LARGE AXONS are more sensitive to (blocked first by):
  • Temperature change
  • Pressure change
  • Extracellular positive stimulation
  • Asphyxia, anoxia

COMPOUND ACTION POTENTIAL: An extracellularly stimulated action potential that has graded stimulus intensity. It only occurs with artificial stimulation.

• SUMMATION: The potential shows summation of the individual axons contained within the nerve being stimulated.
  • At low stimulus intensity, only the largest axons will be stimulated.
  • At higher intensity, more axons will be stimulated, and a higher resultant stimulus intensity will be recorded.

CLASSIFICATION OF NERVE TRUNKS:

• ELECTROPHYSIOLOGICAL CLASSIFICATION: Use capital letters. Based on conduction velocities.
  • This scheme is used for all nerves but muscle spindle afferents.
  • Cutaneous Afferents use this designation.
  • CATEGORIES:
    • A-alpha = fastest nerves, 120 m / sec: Alpha Motor neurons innervating extrafusal muscles
    • A-beta
    • A-gamma = Gamma motor neurons innervating intrafusal muscle.
    • B
    • C
• ANATOMICAL CLASSIFICATION: Use roman numerals. Based on axon diameter.
  • Only Muscle Spindle Afferents use this designation.
  • CATEGORIES:
    • I (largest nerves) = Primary muscle spindle and Golgi Tendon afferents
    • II = Secondary muscle afferents; skin, touch, and pressure afferents
    • III = Skin, temperature, fast pain; Autonomic
    • IV = slow (dull) pain fibers; Autonomic

BELL-MAGENDIE LAW: Afferent nerves enter over the dorsal Root, and efferent nerves leave through the Ventral Root.

• EXCEPTION: Some Pelvic Viscera pain and temperature axons enter the spinal cord through the Ventral Root.
  • The Dorsal Root Ganglion is still in dorsal root, but the post-ganglionic axons bends around the Rami Communicans and actually enters the spinal cord through the Ventral Root.
  • CLINICAL: Thus, sectioning of dorsal roots will not completely alleviate pelvic pain.

MEASURING CONDUCTION VELOCITY: Conduction velocity of a motor axon cannot be measured directly, because it would include the time for the potential to cross neuromuscular junction and to conduct through the muscle membrane. If you want to just measure conduction through the nerve itself:

• • PROCEDURE:
    • Place two electrodes on the forearm, on two different parts of the Median Nerve.
    • Stimulate the Abductor Pollicis muscle.
    • On the graph, record the different in time (latency period) between stimulation and muscle flexion.
    • Use equation above to get conduction velocity, m / sec
• PAIN FIBERS: In measuring sensory nerves, sharp pain fibers (pin prick) travel faster than temperature fibers. So, a withdrawal reflex from sharp pain occurs faster than a withdrawal reflex from a hot stove.
• LOCATING AXIAL NEUROPATHIES: We can't directly, non-invasively stimulate nerves that aren't in the extremities, but we can determine conduction problems by using a REFLEX ARC.
  • SEGMENTALLY stimulate a sensory nerve going up the arm, and induce a reflex. If a local stimulation shows normal velocity, but the reflex took too long of a time, then you can deduce that their must be a conduction problem in the proximal part of the reflex.
• ELECTROMYOGRAM (EMG): Test to measure muscle contractility and stimulation of motor nerves.
  • The amplitude of the muscle response tends to drop off as you go from distal to proximal, by about 15%
  • REPEATED STIMULATIONS: The normal response should show the same magnitude for each stimulation with repeated stimulations of low frequency. With higher frequency (i.e. tetanic stimulation), normal response should be a tetanic graph (increasing tension with decreasing magnitude on each successive stimulus).
    • MYASTHENIA GRAVIS: On an EMG it will show a Decrescendo (decreasing magnitude) graph with repeated stimulations.
      • Low frequency stimulations (non-tetanic) are used to diagnose MG.
      • MG is an auto-immune disorder against the post-synaptic neuron (nerve terminal)
    • MYASTHENIC (EATON-LAMBERT) SYNDROME: On an EMG it will show a Crescendo (increasing magnitude) graph with repeated stimulations.
      • High frequency stimulations (Tetanic Stimulation), which hurts a lot, are used to diagnose Myasthenic Syndrome.
      • This syndrome is an auto-immune disorder against the pre-synaptic neuron.
      • SPINAL CORD, SPINAL CORD REFLEXES
        
        
        MOTOR UNIT: An alpha-Motor Neuron, plus all of the muscle cells it innervates.
        • alpha-Motor Neurons innervate extrafusal muscles.
        • Final Common Pathway
        • Any given muscle cell is innervated by only one alpha-Motor Neuron.
        • INNERVATION RATIO: The number of alpha-neurons innervating a whole muscle (innervation density) depends on the amount of control over the muscle we need.
          • Extraocular Muscles = 9 : 1 (9 muscle cells to 1 neuron) ratio, high innervation density.
          • Postural Muscles = 2000 : 1 (2000 muscle cells to 1 neuron) ratio, low innervation density.
        • OBLIGATORY, NON-GRADED STIMULATION: Every time an alpha-neuron is fired, it will cause an action potential in every muscle cell it innervates. There are no graded or partial potentials.
          • MYASTHENIA GRAVIS and other pathologies may prevent an action potential from happening with every neuron firing -- but this is pathological and not the normal circumstance.
        • MOTOR NEURON POOL: All of the motor neurons that innervate a single muscle. They are arranged close to each other in the ventral horn, according to somatotopic organization:
          • SPINAL CORD ORIENTATION: The more dorsolateral you go, the more you go distally away from the midline:
            • DORSOLATERAL Part of Ventral Horn: Innervates Extremities Muscles
            • VENTROMEDIAL Part of Ventral Horn: Innervates Axial Muscles
          • FLEXORS: Nerves going to flexors tend to lie dorsally.
          • EXTENSORS: Nerves going to extensors tend to lies ventrally.
        FORCE TRANSDUCTION: Twitch Tension in a muscle is increased by increasing the frequency with which alpha-motor neurons are fired.
        • With high frequency firing, the muscle doesn't get a chance to completely relax before the next action potential.
          • Tetanus is maximal twitch tension.
        • PRINCIPLE OF ORDERLY RECRUITMENT ACCORDING TO SIZE: INTRACELLULAR, physiological stimulation of nerves, the smallest axons are stimulated first (have the lowest threshold), and largest axons are stimulated last.
        • • This is another way to increase the force with which a muscle contracts: "Recruit" more alpha-neurons to fire on the muscle. In this case, again, the smallest neurons will fire first (small twitch tension), and larger neurons will fire later (larger twitch tension).
          • V = IR: Small neurons have a higher resistance, which means they will show a stronger depolarization (V) for the same current (I).
            • That's why they fire first. This is the opposite of external stimulation, where smaller neurons are stimulated last.
          • In physiological stimulation, smaller neurons have a smaller threshold potential than larger neurons.
        SLOW -vs- FAST TWITCH MUSCLE SLOW TWITCHFAST TWITCHalpha-Motor Neuron DiameterSmallLargeConduction VelocityFastSlowMuscle Cells innervated (motor unit size)Fewer cells innervated, and with a smaller diameterMore cells innervated, with a larger diameterTwitch TensionSmall tensionLarge tensionContraction SpeedSlow speed of contractionRapid contractionExtracellular spike size (magnitude)SmallLargeMetabolismOxidative (lots of mitochondria)Glycolytic (few mitochondria)Capillary SupplyHighLowResistance to fatigueHigh resistance to fatigueEasily fatiguedMuscle ColorRed (from mitochondria)WhiteFunctional AdaptationGenerate small forces over a long period of time -- EnduranceGenerate large forces for a brief time -- Sprint
        MUSCLE SPINDLE: Intrafusal muscle fibers are innervated by afferent nerves that send signals back to the CNS about the muscle's contractility. The muscle spindle is arranged in parallel with extrafusal muscle.
        • Two different types of muscle fibers: They run parallel to each other in the muscle spindle. They both have respective equatorial and polar regions.
          • BAG FIBERS: The velocity component of the muscle spindle. These fibers convey how quickly the muscle spindle is changing length.
            • EFFERENT INNERVATION is by Dynamic Gamma Efferents, which serves to increase the sensitivity of the velocity component.
            • AFFERENT INNERVATION is by IA Afferents only, which form Annulospiral Endings
          • CHAIN FIBERS: The length component of the muscle spindle. These fibers convey the spindle length at any instant in time.
            • EFFERENT INNERVATION is by Static Gamma Efferents, which serves to increase the sensitivity of the length component.
            • AFFERENT INNERVATION is by both IA (Annulospiral) and IIA Afferents (Flower Spray)
        • Two different regions of the muscle spindle:
          • EQUATORIAL REGION: Contains muscle cell nuclei, and no actin or myosin. It behaves like a spring.
            • AFFERENT INNERVATION is by Muscle Spindle Ia Afferents. When the spindle is stretched, these afferents fire.
              • Stretch Muscle ------> Increase Ia and IIa firing rate
              • Contract Muscle ------> Decrease Ia and IIa firing rate
          • POLAR REGION: Contains striated muscle, actin, and myosin.
            • EFFERENT INNERVATION is by Static Gamma Efferents
              • Gamma Firing ------> Contract polar region ------> Stretch whole spindle ------> Increase Ia Afferent firing rate
        • IA AFFERENT NERVES: They synapse with alpha-Motor Neurons that go back to the same muscle.
          • "Local Sign": The response is confined exclusively to the muscle cell from which the signal originated.
          • RAMP AND HOLD EXPT: Stretch a muscle and keep it stretched, and IA afferents will detect both the velocity and length of the muscle.
            • They show a marked increase in activity while the muscle is being stretched, then they drop back down once stretching ceases, although they drop down to a higher basal level than before.
          • ANNULOSPIRAL ENDINGS: They form annulospiral endings, on both bag and chain fibers, on the equatorial region of the spindle.
        • IIA AFFERENT NERVES: Their pathway is more complex. The connection is not monosynaptic but rather involves interneurons.
          • RAMP AND HOLD EXPT: Stretch a muscle and keep it stretched, and IIA Afferents will detect only length of muscle spindle.
            • They show an increase in firing-rate as muscle is being stretched, and they maintain the new firing frequency once the muscle is being held at the new length.
          • FLOWER SPRAY ENDINGS: They form "flower spray" endings on the polar regions of the spindle, which help them detect the current muscle length.
        • STATIC GAMMA EFFERENT NERVES: They increase the length sensitivityof the muscle spindle.
          • They innervate Chain fibers in the polar regions of muscle spindles.
          • They bring about strong contraction in the poles of the spindle.
          • FNXNS in the Muscle Spindle:
            • Static Gammas increase the sensitivity of IA afferents and IIA afferents to change in spindle length. IA and IIA fibers will fire with higher frequency, in response to less change in length.
            • Static Gammas prevent unloading (temporary pause) of spindle afferents, which occurs with spindle shortening.
        • DYNAMIC GAMMA EFFERENT NERVES: They increase the velocity sensitivityof the muscle spindle. That is, under the influence of Dynamic Gammas, the spindle will respond more quickly to a faster rate of change of spindle length.
          • They innervate Bag fibers.
          • They increase muscle tension but there is no contraction -- i.e. spindle length doesn't change.
          • FNXN: They produce a large increase in the velocity sensitivity of muscle spindle IA afferents. Dynamic Gammas do not affect IIA afferents.
        GOLGI TENDON ORGAN: The muscle receptor responsible for the Inverse Stretch Reflex.
        • STRUCTURE: It is a capsule of elastic fibers, in series with (i.e. attached to the end of) 1% of all extrafusal muscle fibers.
          • 99% of extrafusal fibers do not connect to the Golgi Tendon Organ.
        • FNXN: When Golgi Tendon stretches, it will decrease alpha-Motor Neuron activity back to the same muscle, preventing further contraction and reducing muscle tension.
          • Also it will send muscle information back to cerebellum.
          • The GTO increases muscle compliance, as in muscles needing to "give" a little (by lengthening to absorb shock) when jumping off a roof and landing on feet.
          • Compensation for fatigue.
        • 1B AFFERENT NERVES: They innervate the Golgi Tendon Organ. Stretching of the Golgi Tendon fire these nerves.
          • They goto spinal cord ------> SYNAPSE with INHIBITORY INTERNEURON ------> Inhibit alpha-Motor Neuron activvity back to same muscle.
        STRETCH REFLEX: Contraction of a muscle elicited by stretch of the muscle, such as the patellar tendon reflex.
        • AFFERENT LIMB: Muscle spindle IA Afferents.
        • EFFERENT LIMB: alpha-Motor Neurons.
        • PATHWAY: Monosynaptic. Stretch Muscle ------> Increase firing rate of IA Afferents ------> Fire alpha-Motor Neurons back too same muscle ------> increase muscle tension.
        • EXPT: Decerebrated Cat soleus muscle
          • Experimenter did a Ramp-and-Hold experiment, stretching the muscle. Muscle tension increased as he stretched the muscle, due to the Stretch Reflex. After a certain point the muscle tension stopped increasing.
          • CUT DORSAL ROOTS and the tension was even greater, due to lost inhibition by the Vestibulospinal Tract.
        INVERSE STRETCH REFLEX: Once you stretch a muscle past a certain threshold, the rigidity will "melt away" and the muscle will stretch easily. Past the threshold, the muscle is undergoing the inverse stretch reflex.
        • AFFERENT LIMB: Golgi Tendon Organ, IB Afferents
        • EFFERENT LIMB: alpha-Motor-Neuron disynaptic inhibition
        • PATHWAY: The reflex is disynaptic. Stretch Muscle past threshold ------> Golgi Tendon Organ stretches ------> IB Afferents fire ------> SYNAPSE with INHIBITORY interneuron in spinal cord ------> DECREASE alpha-Motor Neuron Activity back to same muscle ------> Decrease muscle tension ------> muscle lengthens easily
        WITHDRAWAL (FLEXION) REFLEX: Remove hand from a burning stove, for example.
        • Paraplegia / Quadriplegia: It causes an increased Withdrawal Reflex, and it may also result in unintended autonomic responses such as defecation, urination.
        • C FIBERS: Pain fibers initiate the reflex.
        • PATHWAY: C-Fiber activation ------> Dorsal Root ------>Excitatory synapses to alpha-neuron and gamma-neuron ------> contraction of same muscle.
          • Activation of the gamma neuron will cause activation of IA Afferents, which will then initiate the stretch reflex ------> more alpha-activation.
          • The net result of this is that you get a large, long lasting reflex. The reflex itself can easily outlast the original pain stimulus.
          • There is also a recurring excitatory circuit, some excitatory interneurons will send fibers back to other excitatory interneurons, which potentiates the original signal in the spinal cord.
        RECIPROCAL INNERVATION: IA Afferents from an extensor muscle will synapse with an interneuron that inhibits the opposing (i.e. flexor) muscle.
        • IA AFFERENTS therefore have two monosynapses in the spinal cord:
          • Excitatory (EPSP) to the alpha-Motor Neuron of the same muscle
          • Excitatory interneuron ------> Inhibitory (IPSP) to the alpha-Motor Neuron of the opposing muscle.
        • The inhibitory arm of the reflex is disynaptic, while the excitatory arm is monosynaptic.
        CROSSED EXTENSOR REFLEX: The contralateral reflex for the withdrawal reflex. Step on a tack, and you withdraw one foot while extending the other.
        • PATHWAY: Pain fibers synapse with two interneurons in spinal cord -- one to ipsilateral side and one goes across ventral white commissure to contralateral side.
          • IPSILATERAL will then make two synapses, to cause FLEXION of the ipsilateral limb.
            • EXCITATORY to ipsilateral flexor muscle.
            • INHIBITORY to ipsilateral extensor muscle.
          • CONTRALATERAL will then make two synapses, to cause EXTENSION of the contralateral limb.
            • EXCITATORY to contralateral extensor muscle.
            • INHIBITORY to contralateral flexor muscle.
        MUSCLE TONE DISORDERS: Hypotonia and Hypertonia arise from disorders in the sensitivity of alpha-Motor Neurons.
        • HYPOTONIA: Decreased alpha and gamma neuron excitability. Diminished reflexes and flaccid paralysis.
          • Examples: Early phase of spinal cord transection
        • HYPERTONIA: Increase tonic stretch reflex, i.e. the response to muscle length when the muscle is not moving. Sustained contraction at rest, increased tonic stretch reflex, increased muscle stiffness
          • Examples: Decerebrate Rigidity (UMN Paralysis), Parkinson's Disease
        • SPASTICITY: Increased phasic stretch reflex, i.e. the response to muscle velocity when it is stretching. The faster the stretch, the worse is the resistance to the stretch.
          • Examples: Late phase of spinal cord transection, Motor Cortex / SMA lesions.
          • Factors that contribute to Spasticity:
            • Increased synaptic efficacy, i.e. strength of response at a synapse
            • Collateral Sprouting of axon terminals, to replace lesioned axons. In the end this can result in higher sensitivity than originally.
            • Loss of presynaptic inhibition ------> alpha-Motor Neurons fire more frequently and/or more readily.
            • (Minor Contributor): Gamma Efferent hyperactivity.
          • CLONUS: Rhythmic series of contractions brought about by quick stretch of a spastic muscle. Clonus can occur with spastic muscles.
            • It is a self-sustaining Cycle: Spastic muscle stretch ------> IA fire outburst ------> alpha-Motor strong activation -------> Reflex contraction and muscle shortening ------> ------> Rebound lengthening ------> ------> cycle repeats
        SPINAL MUSCULAR ATROPHY (SMA):
        • Types of Spinal Muscular Atrophy:
          • ACUTE SMA 1: Onset at birth and death before age 2
            • SYMPTOMS: Death ultimately from failure of respiratory muscles and respiratory infection.
          • INTERMEDIATE (Werdnig-Hoffman) SMA 2: Survival beyond 4 years.
            • SYMPTOMS: Diminished reflexes and general muscle weakness. Absent reflexes by age 2.
              • Scoliosis.
              • Death ultimately by respiratory complications.
          • CHRONIC (Kugelberg-Welander) SMA 3
            • SYMPTOMS: First presentation is weakness in the proximal lower limbs, then upper extremities later (this pattern holds for all types of SMA).
        • GENETIC BASIS:
          • SURVIVAL MOTOR NEURON (SMN): The SMN gene is defective (duplication mutation) in virtually all cases of SMA.
            • The SMN gene is located on Chromosome 5
            • FNXN: The protein product is a membrane receptor. They think that it may be a receptor for a muscle-derived trophic substance. Details are unknown.
          • NEURONAL APOPTOSIS INHIBITORY PROTEIN (NAIP): The NAIP gene is defective (duplication mutation) in many SMA cases, however this defect is not required for SMA.
            • The NAIP gene is located on Chromosome 5
            • The presence and severity of the NAIP defect correlates with how severe the SMA case is.
            • FNXN: The NAIP protein product is thought to prevent apoptosis (programmed cell death) during development. Thus in the absence of NAIP, some neurons that were supposed to survive actually die instead.

CENTRAL MOTOR SYSTEMS


Categories of Descending Systems:

• Traditional Categories: Pyramidal and Extrapyramidal. There are problems with this categorization:
  • It grossly overemphasizes the importance of the Pyramidal system. You can lesion the pyramidal tract without intractable motor deficits.
  • It artificially groups together systems that are functionally unrelated.
• DORSOLATERAL: Tracts located in the dorsolateral fasciculus of the spinal cord. They control distal muscles and are largely crossed. They run close to the distal alpha-motoneuron which also like laterally.
  • CORTICOSPINAL TRACT: The traditional pyramidal system. 90% crossed (Lateral CST) and 10% uncrossed (Anterior CST)
    • ORIGIN: Motor Cortex
    • Somatotopic Organization.
    • FNXN: On average, it excites both flexors and extensors, and often shows reciprocal inhibition of the opposing muscle.
    • LESIONS:
      • CORTICOSPINAL TRACT: Produces loss of independent finger movement and distal weakness. Mild deficits, especially if the red nucleus is intact.
      • MOTOR CORTEX LESION: Highly incapacitating. Severe paralysis of contralateral muscles.
        • INITIALLY: Flaccid Paralysis
        • LATER: Spastic (UMN) Paralysis kicks in as spinal reflexes become hypersensitive.
    • PHYLOGENY: New (only mammals)
  • RUBROSPINAL TRACT:
    • ORIGIN: Red Nucleus.
    • Somatotopic Organization.
    • LESION of the Rubrospinal System produces little or no deficit if the Corticospinal tract is intact.
      • RED NUCLEUS LESION (as opposed to the tract) will cause cerebellar-type disturbances.
    • FNXN: Receives influences from both motor cortex and cerebellum, and mediates influence on alpha-motoneurons as a result.
    • PHYLOGENY: Relatively new (reptiles)
• VENTROMEDIAL: Tracts located in the ventromedial fasciculus of the spinal cord. The control proximal (axial) muscles and are largely uncrossed. They run close to the proximal alpha-motoneurons which also lie medially.
  • LESIONS: Lesions of this system are very incapacitating. Inability to maintain upright posture.
  • RETICULOSPINAL TRACT:
    • ORIGIN: Reticular Formation
    • It is the only descending system that does not show somatotopic organization.
    • FNXN: On average, it excites flexors and inhibits extensors.
      • These neurons are involved with coordination of limb movement.
      • CENTRAL PATTERN GENERATOR (CPG): In the brain stem (Reticular Formation), it mediates the signals that are necessary for locomotion (walking and running). These signals are carried through Reticulospinal Tract.
    • PHYLOGENY: Old
  • VESTIBULOSPINAL TRACT:
    • ORIGIN: Lateral Vestibular Nucleus
    • Somatotopic Organization.
    • FNXNS: On average, it excites extensors and inhibits flexors.
      • These neurons are important for maintaining an upright posture.
    • PHYLOGENY: Old
• Interstitial Spinal and Tectospinal Tracts: They are involved in control of head and neck muscles. Other than that don't worry about them.

General Properties of Descending Systems:

• ALPHA-GAMMA CO-ACTIVATION: Descending systems will send excitatory branches to both alpha and gamma neurons at the same time. Since gamma neurons ultimately increase alpha activity, this helps to amplify the excitatory signal.
• AUTOMATIC LOAD COMPENSATION: Muscles will automatically adjust their tension to accommodate the "load" on the muscle.
  • INCREASED LOAD will stretch a muscle that is contracting.
  • This stretching will trigger Ia Spindle Afferents ------> Increase alpha-activity even further ------> increase muscle tension ------> overcome the increased load.
  • Gamma co-activation (which is unaffected by Spindle Afferents) also occurs. This further helps to modulate automatic load compensation.
• HIGHER INFLUENCE on SPINAL REFLEXES:

• • INVERSE STRETCH REFLEX: We have higher control over sensitivity of the Inverse Stretch Reflex.
    • Under conditions where muscle needs to have higher compliance, the higher systems can fire Inhibitory Ib Interneurons ------> inhibit alpha-neuron activity.
    • In effect, this makes the Inverse Stretch Reflex kick in earlier, i.e. at a lower threshold tension.

• "PYRAMIDAL SENSORY" SYSTEM: The Corticospinal system does have "sensory" neurons that serve to screen out routine stimuli, by putting inhibition on sensory nuclei in the brainstem and spinal cord.
  • PATHWAY: Descending fibers originate from Primary Somatosensory Cortex ------> Dorsal Column Nuclei and Dorrsal Horn ------> excite or inhibit the dorsal column nuclei.
    • These fibers travel in the opposite direction as most neurons in the Somatosensory Cortex.
    • These fibers travel through the pyramidal tract.

THE BABINSKI REFLEX: Test for UMN Lesions.

• TEST: Stroke the ventrolateral aspect of the foot (the sole of the foot).
  • Normal Response: Toes should point down; Plantarflexion.
  • Pathological Response: Toes point upward and fan out; Dorsiflexion. This indicates a problem with the Corticospinal Tract in adults.
• INFANTS normally show a positive Babinski until two years of age.

THE MOTOR (PRE-CENTRAL) CORTEX: BRODMANN'S AREA 4

• SOMATOTOPIC ORGANIZATION:
  • MEDIAL: Nearest the top of the cortex. Contains upper neurons for the FOOT
  • LATERAL: Nearest the temporal lobe. Contains upper neurons for the HEAD and NECK
• Muscle Groups capable of the most skilled movements (Ocular muscles, facial muscles, and hands) have the largest representation of neurons in the Motor Cortex.
• FORCE TRANSDUCTION: There is a linear relationship between the force of muscle contraction and the firing rate of Upper Motor Neurons
  • There is a 70 - 100 msec time difference between the initiation of the UMN signal and contraction of the target muscle.
• LESION: A motor cortex is much more severe than pyramidal tract lesions. In pyramidal tract lesions, the motor cortex is still intact and can still influence the extrapyramidal systems to maintain some motor control.
  • INITIALLY: Motor Cortex lesions produce a Flaccid Paralysis, as there is a huge loss of excitatory input on alpha-neurons ------> hyperpolarization.
  • LATER (after ~2 months): Spastic Paralysis and Hyperreflexia, as the alpha-neurons compensate for the lost excitatory input by becoming more sensitive and firing spontaneously.

Secondary Cortical Motor Areas:

• SUPPLEMENTARY MOTOR AREA (SMA): BRODMANN'S 6 (Pre-Motor Cortex), most medially.
  • FNXN: Involved with executing pre-programmed or planned motor movements (such as playing the piano or typing).
  • EXPT: MEASURE CEREBRAL BLOOD FLOW (which indicates neuron activity) in human patients performing motor tasks.
    • Simple Finger Flexion Test: Touching index finger to thumb repeatedly.
      • MOTOR CORTEX lit up because of movement of fingers
      • SOMATOSENSORY CORTEX lit up because of touching the fingers.
    • Complex Sequence Test: Touch different fingers to the thumb in a pre-determined, complicated sequence.
      • MOTOR and SOMATOSENSORY CORTICES lit up as before.
      • SMA also lit up: CONCLUSION = this suggests that the SMA is involved in executing the complex sequences.
    • Internal Programming Test: Subject had to rehearse the complex movement of the fingers in his head, without making any actual movements.
      • SMA was heavily activated while the MOTOR CORTEX and SOMATOSENSORY CORTEX were not, because the fingers weren't actually moving.
• PREMOTOR CORTEX: BRODMANN'S 6 (Pre-Motor Cortex), most laterally.
  • FNXN: Involved with assembly of new motor programs and "learning" of repeated motor sequences.

• PARIETAL AREAS 5 and 7: Selective Attention to areas in EXTRA PERSONAL SPACE. Extra personal space is the space external to our bodies, but within reach.
  • PARIETAL AREA 5: It helps control movement of the limbs in response to extra personal space.
    • It will send selective attention neurons to influence the Motor Cortex.
  • PARIETAL AREA 7: It helps control movement of the eyes in response to extra personal space.
    • Three categories of these neurons, each one influencing the respective area of the motor cortex (see Eye-Movement section for details)
      • Saccade Related
      • Fixation Related
      • Smooth Pursuit Related
  • NEGLECT SYNDROME: Unilateral lesions of Parietal Cortex, especially to the non-dominant hemisphere.
    • SYMPTOMS: Patients ignores the contralateral side of his or her body. Patient will not recognize, dress, take care of, or understand one half of the body.
      • There may also be contralateral hemiparalysis.
      • Apraxia: Difficulty drawing objects in 3D, such as drawing a clock that is completely round.
      • Astereognosis: Failure to recognize objects placed in contralateral hand.
      • Anosognosia: Denial of symptoms
      • EYE MOVEMENTS AND VESTIBULAR SYSTEM
        
        
        SACCADES: Extremely rapid movement of eyes, creating an instantaneous change in gaze, from one location in space to a different location.
        • It is not possible to voluntarily move the eyes in a continuous, smooth path across space, from one side of the room to the other.
        • VISUAL FIELD: There is no blur of the visual field with saccades, i.e. you can't see the field move as you move your eyes. This is because:
          • The movement is too rapid for the visual apparatus to process.
          • COROLLARY DISCHARGE: The same signal that produces the saccade also inhibits the Lateral Geniculate Nucleus from processing visual stimuli during the eye movement.
        • VOLUNTARY SACCADE: The signal originates in the Frontal Eye Field (Area 8).
          • PATHWAY: Frontal Eye Field (Area 8) ------> Superior Colliculus ------> Reticular Formation ------> Oculomotor Neurons ------> Saccade movement.
        • REFLEX SACCADE: Involuntary saccades made to a novel stimulus, such as an unexpected flash of light, that appears in the visual field.
          • The reflex involves the SUPERIOR COLLICULUS directly and does not utilize input from the Frontal Eye Field.
          • PATHWAY: Novel Stimulus ------> Retinal Ganglion Cells ------> Superior Colliculus ------> Reticular Formation ------> Oculomotor Neurons ------> Saccade response to stimulus
          • SOMATOTOPIC ORGANIZATION: Superior Colliculus has somatotopic organization across two layers:
            • Superficial Layers of Superior Colliculus contain specific sensory neurons from the visual field.
            • Deep Layers of Superior Colliculus contain neurons that effect eye-movements. These neurons have a 1:1 correspondence with the sensory neurons, i.e. the eye movements will move to the same spot from which the sensory neuron originated.
        SMOOTH PURSUIT: Eye movements involved in maintaining fixation on a moving target while the head is stationery.
        • VELOCITY of movement is less than that for saccades: 30 / sec maximum. You can't keep up with a really fast moving object and hence it will appear as a blur.
        • INVOLUNTARY: These actions are an involuntary reflex. You cannot prevent smooth pursuit movements (such as following your finger with your eyes) without shifting your gaze elsewhere.
        • PATHWAY: Retinal stimulus (indicating slip of focus) ------> Retinal Ganglion Cells ------> Lateral Geniculate Nucleeus ------> Visual Cortex ------> Reticular Formation ------> Oculomotor Neurons ------> Smooth Pursuit movement.
        VESTIBULO-OCULAR REFLEX (VOR): Maintaining gaze on a fixed object while moving your head. The direction of eye movement will be equal and opposite to that of the head, i.e. the eyes will turn medially.
        • PATHWAY: DISYNAPTIC. Vestibular Hair Cell Deflection ------> VIIIth nerve ------> Ipsilateral Medial Vestibular Nucleus increases firing rate ------> it SYNAPSES with two different nerves
          • EXCITATORY SYNAPSE to ipsilateral Oculomotor Nucleus ------> ipsilateral eye turns medially, in opposite direction as original head movement.
          • INHIBITORY SYNAPSE to ipsilateral Abducens Nucleus ------> prevent eyes turning laterally
        • CONTRALATERAL SIDE: The exact converse will be going on: Contralateral Medial Vestibular Nucleus is INHIBITED ------> decrease Oculomotor firing and increase Abducens firing ------> contralateral eye turns laterally, in the opposite direction as original head movement.
        • MEDIAL LONGITUDINAL FASCICULUS (MLF) also helps to coordinate the gaze between the two eyes. It works in synergy with the VOR reflex.
        SEMICIRCULAR CANALS: Detect head turns and keep them in balance; detect angular acceleration.
        • FUNCTIONAL PAIRS: Semicircular Canals are divided in PAIRS of canals that counter each other in terms of their response to head turns (one will be stimulated while the other will be inhibited to the same degree).
          • Left Horizontal Canal <====> Right Horizontal Canal
            • The horizontal canals are actually at an angle 30 above the horizontal. Tilt the head forward to make these canals truly horizontal.
          • Left Anterior Canal <====> Right Posterior Canal
          • Left Posterior Canal <====> Right Anterior Canal
        • ANATOMY:
          • The Semicircular Canals are attached to the Utricle.
          • They contain Endolymph to make the hair cells move. Endolymph is continuous throughout the Utricle and Semicircular Canals.
          • AMPULLA: The enlargement at one end of each canal, where the hair cell receptors are located.
          • CUPULA: In the Ampulla, the gelatinous mass into which the hair cells insert.
        • HAIR CELLS: Scarpa's Ganglion contains the cell bodies of the hair cells, which form the VIIIth (Vestibular) nerve.
          • STEREOCILIA insert into the Cupula and move in response to head movements.
          • KINOCILIUM is the end cilium, larger than the other cilia.
          • VIIIth NERVE STIMULATION:
            • When the stereocilia bend toward the Kinocilium ------> depolarization of VIIIth fibers occurs.
            • When the stereocilia bend away from the Kinocilium ------> hyperpolarization of VIIIth fibers occurs.
          • ORIENTATION OF KINOCILIUM:
            • HORIZONTAL CANALS: The Kinocilium is located closest to the Utricle (i.e. most medially)
            • ANTERIOR, POSTERIOR CANALS: The Kinocilium is located furthest from the Utricle, i.e. most laterally.
        • EXAMPLE: TURN HEAD RIGHT, The endolymph fluid will move left initially (due to inertia). Hair cells in the Horizontal Canals will deflect to the left.
          • RIGHT HORIZONTAL CANAL: Stereocilia move toward Kinocilium ------> activate VIIIth nerve afferents.
          • LEFT HORIZONTAL CANAL: Stereocilia move away from Kinocilium ------> inhibit VIIIth nerve afferents.
        OTOLITH ORGANS:
        • UTRICLE
        • SACCULE
        VESTIBULO-POSTURAL REFLEX: Compensation for turning the body to the right or the left. Example: TURN BODY RIGHT, and two responses happen
        • RIGHT SEMICIRCULAR CANALS ACTIVATE ------> Activate Right VIIIth nerve afferents ------> activate right Vestibulospinal Tract ------> excite extensors on the right ------> net extension on right side.
        • LEFT SEMICIRCULAR CANALS DEACTIVATE ------> Inhibit Left VIIIth nerve afferents ------> inhibit left Vestibulospinal Tract ------> inhibit extensors on the left ------> net flexion on left side.
        • RESULT: Turn the body right, and the body attempts to fall (flex) toward the left for compensation.
        NYSTAGMUS REFLEX: The reflexive response of eye movements to continual rotation in one direction. SPIN BODY TO THE RIGHT, and the eyes will do the following:
        • Vestibulo-Ocular Reflex (VOR): Initially there will be slow rotation to the left. However, as rotation continues, the eyes will no longer be able to turn left, so there must be a resetting of gaze.
        • Involuntary Saccade: The eyes will instantaneously reset the gaze toward the right, i.e. in the same direction as rotation. This reflex is not VOR but rather is an involuntary saccade.
        • NYSTAGMUS is the combination of the two reflexes above, in alternating order with each other (A, then B, then A, then B). This is the eye's response to continual rotational movement.
        • The direction of nystagmus, by convention, is the direction of the reflexive saccade. Thus: Spinning the head right results in a "rightward" nystagmus reflex.
        BARANY CHAIR TEST: Rotate a person in a chair really fast to the right for about 30 sec; stop the chair, and then test for leftward acceleration reflexes of the eyes.
        • Post-rotational Component: After stopping the chair, you will be testing for deceleration to the right, which is the same as testing reflexes for leftward acceleration.
          • What the semicircular canals detect is the rate of change of velocity of the fluid (angular acceleration), not the movement of the fluid itself (angular velocity). Net angular acceleration will be to the left in this case.
        • EXPECTED RESULTS: You would thus expect a leftward Nystagmus once the chair is stopped.
          • So, you look for the patient rotating his eyes toward the right (VOR reflex), and then instantaneously shifting them left (reflex saccade), then rotating eyes rightward again, etc.
        INNER NUCLEAR OPHTHALMOPLEGIA: Lesion in the MLF, as often occurs with Multiple Sclerosis.
        • SYMPTOM: You lose coordinated gaze of the medial rectus (CN III).
        • RIGHTWARD ROTATION VOR: Your right eye would be able to move laterally just fine, but your left eye would not move medially.
        • So with this condition, lateral movements are fine but medial movements in the VOR reflex are impaired.
        UNILATERAL LABYRINTHECTOMY: Unilateral lesion of VIIIth Nerve.
        • VIIIth nerve on both sides has a high basal level of activity.
        • LESION the RIGHT VIIIth NERVE: It will produce an effect similar to LEFTWARD ROTATION, i.e. net stimulus of the Left VIIIth nerve:
          • SYMPTOM: Leftward Nystagmus
        CALORIC STIMULATION: Clinical test for functionality of semicircular canals.
        • Tilt head back 60 so that the horizontal canals are oriented vertically.
        • Irrigate inner ear with water of different temperature, then, NORMAL RESPONSES:
          • Warm Water: Nystagmus toward the ear being irrigated.
          • Cold Water: Nystagmus toward the opposite ear (cold water will inhibit the vestibular receptors)

THE CEREBELLUM AND BASAL GANGLIA


CEREBELLAR FIBERS AND CELL TYPES:

• AFFERENT FIBERS:
  • MOSSY FIBERS: They make excitatory synapses with Granule Cells. They will ultimately influence a large number of Purkinje Cells via the Granule Cell output.
    • They receive input from all incoming sources except the Inferior Olive:
      • Spinocerebellar Tract (motor info about the extremities)
      • Pontine Nuclei (motor info about the head and neck)
    • They will send collaterals to the Deep Cerebellar Nuclei, as well as to the Granule Cells
  • CLIMBING FIBERS: They make powerful, obligatory excitatory synapses on a very SMALL NUMBER of Purkinje Cells
    • They all originate from the Inferior Olivary Nucleus
    • They all will send collaterals to the Deep Cerebellar Nuclei directly, as well as to the Purkinje Cells.
• GRANULE CELLS, also called PARALLEL FIBERS, are strictly within the cerebellum, in the folia. They are interneurons in the cerebellar circuit.
  • They make excitatory synapses with a LARGE NUMBER of Purkinje Cells
  • They are called parallel fibers because their fibers run parallel to the folia (folds) of the cerebellar hemispheres.
  • Granule cells will also send excitatory signals to the following inhibitory interneurons:
    • Basket Cells: They will in turn inhibit Purkinje Cells
    • Stellate Cells: They will in turn inhibit Purkinje Cells
    • Golgi Cells: They will provide negative feedback and inhibit the Granule Cells
• PURKINJE CELLS: EFFERENT FIBERS
  • They are the only "efferent" fibers in the cerebellar cortex. They will make synapses on the Deep Cerebellar Nuclei ------> transmit info to the rest of the CNS.
  • Purkinje cell input onto the Deep Cerebellar Nuclei is always inhibitory, using neurotransmitter GABA.
• DEEP CEREBELLAR NUCLEI: They will project to Thalamus ------> excitatory connection to Motor Cortex ------> excitatory influence on descending systems.
  • FNXNS:
    • Receives excitatory collateral branches from Mossy fibers and Climbing Fibers.
    • Receives inhibitory tonal input from Purkinje Cells.
    • Deep Cerebellar Nuclei have a high background firing rate, thus Purkinje Cell inhibitory input is modulated.
  • NUCLEI:
    • FASTIGIAL NUCLEUS: Medial-most
    • INTERPOSITUS NUCLEUS: Middle o' the road
    • DENTATE NUCLEUS: Lateral-most

VESTIBULOCEREBELLUM: Archicerebellum.

• STRUCTURE: FLOCCULONODULAR LOBE is the small lobe on the posterior inferior aspect of cerebellum. It modulates VOR and Postural Reflexes.
• FNXNS:
  • MODULATE VESTIBULO-POSTURAL REFLEX: Cerebellum does fine tuning of postural reflexes, adjusting the magnitude, strength, and range of movement.
    • PATHWAY: VIII Nerve Afferents--> Mossy Fibers to the Cerebellum ------> Fastigial Deep Nucleus ++ Vestibular Nucleus ------> Reticulospinal + Vestibulospinal Tracts ------> influence alpha-motor neurons.
      • Excitatory signals to Vestibulospinal will excite (modulate) the extensors.
      • Excitatory signals to Reticulospinal will excite (modulate) the flexors.
      • Fastigial Nucleus does the calculations for these adjustments, although some fibers also go directly to the descending tracts without going through fastigial nucleus.
  • SUPPRESS VOR REFLEX: If you want to follow a moving an object while moving your head too, then you don't want the VOR reflex to move your eyes. Under these circumstances the vestibulocerebellum will supress that reflex.
    • PATHWAY: VIIIth Nerve collateral afferents enter cerebellum as Mossy Fibers ------> Excite Granule Cells in cerebellum ------> Excite Purkinje Cells ------> Inhibition of Vestibular Nucleus ------> Cancel or modulate excitatory input from VIIIth afferents.
    • Note that the VIIIth nerve is still firing to activate the VOR reflex. The only difference is that now the end-signal is being canceled (or lessened) by the cerebellar input.
  • ADJUST REFLEX GAIN: If you put on reversing prisms (which reverse the movement of the visual field), your VOR reflex will compensate for the new visual input within a few days. This change in the VOR reflex is dependent on the Cerebellum and Inferior Olive.
• LESIONS: Can be caused by a medulloblastoma in children, or by chronic alcoholism. It will produce two defects:
  • Nystagmus is produced from unmodulated VOR reflex.
  • Disequilibrium, an inability to maintain posture, from unmodulated postural reflexes.
• REPAIR SHOP THEORY: Based on reversing prisms experiments and others, this theory says that the cerebellum is responsible for continually responding to the changing behavior of neurons with regard to voluntary movements and reflexes.

SPINOCEREBELLUM: Paleocerebellum

• STRUCTURES
  • VERMIS: Midline structure, receives input from Vestibular Nuclei and Spinocerebellar Tract.
  • PARAVERMIS: On either side, receives input only from Spinocerebellar Tract.
• FNXN: Continual correction of movements, comparing actual motor movement with motor cortex "intentions" of movement.
  • INPUT: Spinocerebellum receives input from motor cortex and spinocerebellar tract.
    • It then reconciles those signals with each other (actual action reconciled with intended action), and issues a correction factor.
  • OUTPUT:
    • Vermis ------> Fastigial Nucleus + Vestibular Nucleus ------> Descending Extrapyramidal Tracts
    • Paravermis ------> Fastigial Nucleus + Interpositus Nucleus ------> Descending Extrapyramidal Tracts
• SOMATOTOPIC ORGANIZATION: The spinocerebellum has somatotopic organization with regard to the regions of the body it is "comparing." Head and neck is generally nearest the center, with extremities in the periphery.

CEREBROCEREBELLUM: Neocerebellum

• STRUCTURE: The large lateral hemispheres that make up most of the cerebellum.
• FNXN: Programming of repeated movements. Calculating the "metrics" of movements, such as reaching for an object in space. We don't consciously think about these details of conscious movement.
  • INPUT: Pontine Nuclei from Cerebral Cortex.
  • OUTPUT: Dentate Nucleus ------> Thalamus ------> Motor Cortex
• PATHWAY of MODULATION: Limbic System initiates the drive or desire to move
  • Limbic System ------> Frontal Cortex (conscious or subconscious judgment and intention) ------> Pontine Nuclei ------> Cerebellum ------> Dentate Nucleus ------> Thalamus ------> Motor Cortexx ------> movement is executed
• LESION: CEREBELLAR SYNDROME. This is a lesion of both Spinocerebellum and Cerebrocerebellum, as there is rarely (i.e. never) a lesion of only one or the other.
  • Hypotonia: From reduced gamma neuron activity, due to loss of extrapyramidal excitatory input.
  • Ataxia, Asynergia: Lack of coordinated movement. Most important, errors in METRICS of movement (reaching arm too far or too close to target)
  • INTENTION TREMOR, Dysmetria: A problem terminating movements, or a tremor that only present when moving. This is different than Resting Tremor which occurs with Parkinson's.
  • Adiadochokinesis: Inability to make rapid alternating movements, such as pronation and supination of hand.
• LESION: IPSILATERAL DEFICIT. All lesions of the cerebellum produce ipsilateral deficit because the system is double-crossed.
  • Deep Nuclei cross the midline to opposite motor cortex.
  • Upper motor neurons cross again through pyramidal decussation.

BASAL GANGLIA: Components

• STRIATUM: Uses GABA as inhibitory transmitter; it projects to ------> Globus Pallidus to have inhibitory influence.
  • PUTAMEN
  • CAUDATE NUCLEUS
• GLOBUS PALLIDUS:
  • It receives inhibitory input from the Corpus Striatum.
    • Some of these inhibitory fibers carry GABA and Substance P as transmitters. These act on the GPi and are inhibitory.
    • Other inhibitory fibers carry GABA and Enkephalins as transmitters. The pathway of these signals:
      • Corpus Striatum ------> GPe ------> Subthalamic Nucleus ------> GPi
  • FNXN: It projects inhibitory neurons to the thalamus to modulate motor function.
    • Loss of this inhibition will result in Hemiballismus.
  • INTERNAL SEGMENT (GPi): It is functionally continuous with the Substantia Nigra, Pars Reticularis (SNr)
    • FNXN: Along with the SNr, it is the OUTPUT NUCLEUS of the Basal Ganglia. The GPi normally inhibits the Thalamus (via GABA).
      • In Parkinson's Disease, it is overactive.
    • SOMATOTOPIC ORGANIZATION: Continuous with the SNr, its output goes to the limbs.
  • EXTERNAL SEGMENT (GPe)
• SUBTHALAMIC NUCLEUS: The subthalamic nucleus normally stimulates the GPi.
  • In Parkinson's Disease, it is overactive.
  • In Huntington's and Hemiballismus, it is underactive.
• SUBSTANTIA NIGRA
  • PARS RETICULARE (SNr): Ventral part of the Substantia Nigra. It is functionally continuous with the Internal Globus Pallidus (GPi)
    • FNXN: Along with the SNr, it is the OUTPUT NUCLEUS of the Basal Ganglia.
    • SOMATOTOPIC ORGANIZATION: Continuous with the GPi, its output goes to the head and neck.
  • PARS COMPACTA (SNc): Dopamine-containing neurons.
    • NIGROSTRIATAL TRACT: Substantia Nigra, Pars Compacta releases Dopamine. Dopamine acts on the Corpus Striatum and has both inhibitory and excitatory effects, depending on the connection.
      • CIRCUIT: SNc ------> excitatory on Striatum ------> (Substance P) Inhibitory on GPi ------> result is inhibition of Thalamic projections ------> Cerebral cortex doesn't receive the Thalamic projections.
      • CIRCUIT: SNc ------> inhibitory on Striatum ------> (Enkephalins) inhibitory on GPe ------> inhibitory to Subthalamic Nucleus ------> GPi ------> result is inhibition of Thalamic projections ------> Cerebral Cortex doesn't receive the Thalamic projections.
• BASAL GANGLIA Basic Circuitry: Cerebral Cortex ------> Striatum ------> GPi + SNr ------> Thalamus ------> Motor cortical output

PARKINSON'S DISEASE: A lesion of the Dopamine-containing Nigrostriatal Tract, producing a dopamine deficit.

• SYMPTOMS: Parkinson's Disease is a hypokinetic disorder.
  • Lead Pipe Rigidity: Resistance to movement.
  • RESTING TREMOR: To be distinguished from an intention tremor (as in Cerebellar Syndrome). This is a tremor when there is no movement.
    • This tremor is of a lower frequency than corresponding Intention tremor.
    • The tremor is better when in motion, so it is less debilitating than a moving tremor.
  • Akinesia / Bradykinesia: Inability to initiate movement, or slow initiation of movement.
    • This symptom responds well to treatment.
  • Postural Instability
  • Cognitive Problems
• ETIOLOGY: Deficiency of dopamine exerts its effects through two pathways. Both pathways ultimately result in over activity of the Globus Pallidus Interna ------> Over suppression of Thalamus ------> fewer thalamic projections to the Motor Cortex.
  • In Parkinson's Disease, the subthalamic nucleus is overactive.
  • Dopamine can get to 20% below normal before Parkinsonian symptoms will occur.
• PROGRESSION OF DISEASE: Cognitive loss and eventual death from respiratory failure.
• TREATMENT:
  • L-DOPA is drug of choice.
    • CONVERSION: L-DOPA is a Dopamine precursor that can get through the blood-brain barrier. It is converted to Dopamine by DOPA-Decarboxylase once in the brain.
    • CARBIDOPA: This is always given with L-DOPA. It is a DOPA-Decarboxylase Inhibitor which blocks conversion of L-DOPA ------> Dopamine in the periphery.
    • SIDE-EFFECTS:
      • ON-OFF Phenomenon: Suddenly therapy is ineffective, periodically.
      • Freezing Phenomenon: All of the sudden become rigid and stop, unable to initiate movement.
      • The drug becomes less effective with long-term use.
      • Dyskinesias: Involuntary movements (another form of tremors, hyperkinetic) result from the excessive dopamine.
  • THALAMOTOMY: Surgical lesion of Ventral Lateral Thalamus, for the treatment of tremors. this surgery does not alleviate the original problem, so it is only symptomatic treatment.
    • CANDIDATES: People who don't respond well to L-DOPA (~10%), have terrible side-effects with L-DOPA, or who have debilitating tremors.
      • Must have no cognitive deficiencies and be able to respond well to surgery.
    • ELECTRO-STIMULATION OF THALAMUS: Surgically implant an electrode on the Thalamus and another in the chest. Then use a magnet to stimulate thalamus periodically and INHIBIT it.
      • This is a surgical alternative to outright Thalamotomy, leaving the VL Thalamus intact and only inhibiting it as necessary.
  • PALLIDOTOMY: Surgical lesion of Globus Pallidus Interna. This surgery has been shown to be the most effective.
    • CANDIDATES: Pretty much the same as for thalamotomy.
    • RISKS: Loss of visual field, because the GPi is very close to Optic Tract.
    • ELECTROSTIMULATION is on the horizon, and currently experimental at KUMC.
• HISTORICAL STUFF:
  • Stereotactic Surgery: Early attempts to place a brain lesion in specific place, using a pineal calcification (on a skull film) as a reference point.

HUNTINGTON'S CHOREA: Lesion of the Corpus Striatum, involving GABA and Enkephalin neurons

• ETIOLOGY: Loss of Corpus Striatum GABA/Enk neurons ------> Disinhibition of the Globus Pallidus Externa ------> Excessive inhibition of the Subthalamic Nucleus.
  • The subthalamic nucleus is deficient
• SYMPTOMS: Huntington's is a hyperkinetic disorder.
  • The result is a lesion similar to the effects of a Subthalamic Nucleus lesion (i.e. Hemi-ballismus).

HEMIBALLISMUS: Lesion of Subthalamic Nucleus, ruins the GPi inhibitory neurons that project to the thalamus ------> over excitation.

• SYMPTOM: Violent, involuntary movement of contralateral limb.
• ETIOLOGY: Usually created be a vascular lesion (stroke) specific to the Subthalamic Nucleus.
  • The subthalamic nucleus is deficient
  • SOMATIC SENSATION
    
    
    TRANSDUCTION: The process by which a physical stimulus is converted into a neural signal and sent to the CNS.
    • Trigger Zone: The threshold of stimulus, in the sensory receptor, at which an action potential is generated. Some sensory receptors are more sensitive than others.
    • MODALITY SPECIFICITY: Any particular sensory unit is most sensitive to only one modality.
      • There are four broad classes of somatic stimuli:
        • Tactile Sensation (Pressure, Cold)
        • Proprioception (body position and movement)
        • Thermosensation
        • Pain
      • The modality to which a receptor it is sensitive is called the adequate stimulus for the receptor.
      • The specific modality is the one that triggers the receptor at the lowest threshold potential. Other modalities may also trigger the receptor, but at much high potentials.
    • Paradoxical Cold is an exception to the Modality Specificity rule.
      • Sometimes heat may be perceived as cold, because it triggers cold fibers rather than warm fibers.
      • Normally warm fibers are triggered by an increase in temperature, and cold fibers by a decrease in temperature.
    FIBER DIAMETER AND MODALITY SPECIFICITY:
    • Class II (A-beta) Fibers: Cutaneous Sensation
      • Fibers terminate in specialized nerve endings such as Merckel's Disks and Pacinian Corpuscles.
      • ASPHYXIA: These fibers are most sensitive to asphyxia and to physical insult, because they are the largest of the sensory fibers.
      • Anesthesia: These fibers are the last to be blocked by anesthesia -- they are the largest fibers.
    • Class III (A-delta) Fibers: Fast Pain, crude touch, temperature sensation.
      • Fibers terminate in free nerve endings.
      • FAST PAIN: Pin-prick pain; it is the first pain you will feel when pricking your finger.
        • These fibers are sensitive to intense mechanical stimulation (such as a puncture) and temperature.
        • Purpose = these fibers cause us to quickly withdraw away from a dangerous stimulus.
    • Class IV (C) Fibers: Slow Pain, crude touch, temperature sensation.
      • Fibers terminate in free nerve endings.
      • SLOW PAIN: Throbbing pain, which evokes the troublesome affective experience of pain.
        • These fibers are respond to visceral noxious stimuli -- either mechanical, heat, or chemical.
        • Purpose = these fibers cause us to immobilize the body part so it can heal.
      • ANESTHESIA: Slow pain fibers are the most sensitive to local anesthesia. Anesthesia blocks small-diameter fibers before large-diameter.
      • Asphyxia: These fibers are the last to be blocked by asphyxia, as they are the smallest fibers.
    CLASSDIAMETER VELOCITY
    ELECTRICAL STIMULATION
    SENSATIONII (A-beta)Relatively large diameter Fast conduction velocity
    Lowest
    threshold i.e. first to be stimulated
    Cutaneous Sensation III (A-delta)Small diameter Slow conduction velocity
    Medium threshold
    Fast Pain
    Crude Touch Some temperature
    IV (C)Smallest diameter Slowest conduction velocity
    Highest
    threshold i.e. last to be stimulated
    Slow Pain
    Crude Touch Some temperature
    
    FREE NERVE ENDINGS: Pain and temperature both end in free nerve-endings in the skin.
    SPECIALIZED NERVE ENDINGS: They mediate tactile sensation: flutter, vibrations, and pressure.
    • MEISSNER'S CORPUSCLES: They mediate the sensation of flutter -- localized, slow vibrations.
      • Rapidly-Adapting, Phasic response: The receptor shows Adaptation in that it stops firing after the same stimulus has been present for a while. It "blocks" out the stimulus once the stimulus becomes old news.
      • Anatomical Distribution: Found in Glabrous (non-hairy) skin, as in palm of hands.
        • The nerve fiber loses its myelin sheath before entering the corpuscle.
        • Serves the same purpose that hair follicles serve in hairy skin, i.e. sensation of flutter.
    • PACINIAN CORPUSCLES: They mediate the sensation of vibration.
      • Rapidly-Adapting, Phasic response: The receptor stops firing after the stimulus has been present for a while.
      • STRUCTURE: It is like an onion.
        • If you remove the layers of the onion, then the receptor becomes slowly-adapting. The onion-layers thus serve the purpose of adaptation -- they make it so the underlying nerve fiber is only discharged temporarily.
        • The onion layers also filter out the low-frequency stimuli, such that Pacinian Corpuscle has frequency specificity for high frequency vibrations.
    • MECKEL'S DISKS: Mediate sensitivity to pressure.
      • Slowly-adapting, Tonic response. The nerve continues to discharge as long as the stimulus remains. So, you continue to feel pressure as long as the pressure is still there.
    ADAPTATION: "A decrease in neural response to sustained stimulation." Meissner's and Pacinian corpuscles both show adaptation.
    • PHASIC RESPONSE refers to the fact that the receptor will fire only when there is a change in stimulation.
    • TONIC RESPONSE: Refers to continual firing of the receptor when a continual stimulus is present. No change in stimulus is necessary to maintain firing.
    DORSAL-COLUMN MEDIAL-LEMNISCAL PATHWAY: Proprioception and Discriminative Touch run parallel with each other but actually have separately named paths.
    • PATHWAYS: For spinal components (not trigeminal). These fibers enter through the medial branches of the Dorsal Horn.
      • DISCRIMINATIVE TOUCH: Discriminative Touch fibers are Group II (A-beta) fibers.
        • First-Order: Nucleus Gracilis (medial, S4-T5) and Cuneatus (Lateral, C1-T4) carry first-order neurons.
        • Thalamic Relay: VPL, Ventral Posterolateral Nucleus of Thalamus.
        • Somatosensory Cortex: Area 3b
          • So, Area 3B receives 3rd-order neurons originating from specialized receptors (Meckel's Disks), via Group II fibers
      • PROPRIOCEPTION: Conscious Proprioception receptors are 1A-SPINDLE FIBERS
    • • • Evidence: Joint position and movement can still be perceived following anesthesia to the joint capsule or following replacement with a prosthetic joint. Thus, the proprioception fibers don't lie within the joint.
        • First-Order: Nucleus Z (S4-T5) and External Cuneate Nucleus (C1-T4)
        • Thalamic Relay: VPS, VENTRAL POSTERIOR SUPERIOR Nucleus of Thalamus.
        • Somatosensory Cortex: Area 3a
          • So, Area 3A receives IIA Spindle Afferents for proprioception signal.
    • SOMATOTOPIC ORGANIZATION
      • Spinal Cord: Sacral is most medial and Cervical is most lateral. As you move up the cord, sacral segments enter the cord first, and higher up segments enter right "on top of," i.e. lateral to, the sacral segments.
      • THALAMUS: Somatotopic Organization is essential reversed.
        • VPM: Trigeminal, i.e. head, is most medial in medial nucleus.
        • VPL: Spinal is more lateral.
        • VPS: The VPS lies above both of the other nuclei, and it maintains the organization of head = medial, and sacral = lateral
      • SOMATOSENSORY CORTEX: There are four relatively complete maps of the body: 3a, 3b, 1, and 2.
        • Sacral (lower body) is most medial, at the top of the somatosensory cortex.
        • Cervical (upper body) is most lateral, at the temporal pole of the somatosensory cortex.
      • DISTORTED REPRESENTATION: Finger tips, lips, and tongue get a disproportionate amount of cortex, because they are the most sensitive sensory organs.
    • DESCENDING SENSORY Connection: Descending Sensory fibers go from Sensory Cortex ------> Thalamus ------> Dorsal Column Nuclei. They may serve a role in adaptation or filtering repetitive stimuli, but function is unsure.
    • LESIONS:
      • Tabes Dorsalis: Secondary to Syphilis; lesion of dorsal columns. Patients show deficits in proprioception and discriminative touch, but not pain and temp.
      • Transection of Dorsal Columns: Results in large increase in two-point discrimination.
      • Destruction of S1 (Somatosensory Cortex): Expected sensory deficits result.
    Labelled Line Theory: There are separate pathways for each modality of sensation, and these all run into the CNS in a parallel fashion.
    • CORTICAL COLUMNS: Each column contains layers that represent different modalities, but they all came from the same region of the body.
      • So, neurons in the same "layer" or lamina of the cortex will exhibit the same modality specificity.
    RECEPTIVE FIELDS: The area of skin which, when appropriately stimulated, causes a neuron to discharge.
    • The smaller the receptive field, the more sensitive is the sensory ability. Smaller receptive fields mean higher acuity.
    • Proprioceptive and Discriminative Touch (DC-ML) fibers have smaller receptive fields than pain and temp (anterolateral) fibers.
    • TWO-POINT THRESHOLD: The minimum distance, on the skin, at which two pin-points can be distinguished. The smaller the two-point threshold, the higher the tactile acuity.
      • Fingertips and lips have smallest two-point-thresholds (~2 mm), while trunk has much larger threshold (~60 mm)
    • Small receptive fields correspond to high innervation density and a disproportionately large amount of somatosensory tissue in the CNS.
    PHANTOM LIMB SYNDROME: People who have had a severed limb still retain sensation that the limb is there (proprioception) when other parts of the body are stimulated, such as the face.
    • This is due to plasticity of neurons in the CNS. The CNS neurons that used to supply the missing limb are near the face, so they can get stimulated when face is stimulated.
    HIERARCHICAL PROCESSING: As one ascends through the CNS, more complex types of sensations are processed.
    • Area 3a and 3b (aka S1) are the first recipients of sensory information.
    • Area 1 and 2 (aka S2 (?)) receive input from Areas 3a and 3b. Thus 1 and 2 are higher up in the processing of somatic sensation.
      • For example, Areas 1 and 2 can discriminate selectivity of movement of a finger across the skin, whereas area 3 cannot.
    • AREA 2: It is unique in that it receives a convergence of multiple modalities. Both Proprioceptive and Tactile input can arrive at the same fibers.
      • This convergence of function allows for Area 2 to perform Stereognosis (identifying objects by touch). Area 2 lesion results in severe deficit in this specific ability.
    NEGLECT SYNDROME: Lesion of posterior Tempero-parietal area. Extinction occurs in the Neglect Syndrome. Extinction is failure to recognize a specific stimulus (either visual, somatic, and/or auditory) on one side of the body, contralateral to the lesion.
    PAIN:
    • Terms:
      • Nociceptive Stimuli: Stimuli that produce pain.
      • Analgesia: A condition in which nociceptive stimuli are not perceived as painful.
    • Two components of Pain: The two components of pain are separable by drugs.
      • The sensation of pain itself.
      • The affective component of pain in which it is perceived to be painful or unpleasant.
      • Morphine separates these two components such that patients still feel the pain but they do not find it to be unpleasant or "painful."
    • PAIN-PRODUCING STIMULI (PPS): Chemicals that are involved in transduction of slow-pain fibers.
      • POTASSIUM: High extracellular K+ is indicative of tissue damage and is therefore painful.
      • BRADYKININS: Tissue injury ------> proteolytic enzymes into the extracellular fluid ------> react with gamma globulins to create Bradykinins.
        • Bradykinin is one of the most painful substances known. It activates C-Fiber terminals.
        • Bradykinins causes vasodilation.
        • Bradykinins causes the production of Prostaglandin E2 (PGE2), which serves to enhance the sensitivity of painful C-Fibers.
          • Aspirin will block this prostaglandin synthesis, wouldn't ya know??
      • HISTAMINE: Substance-P, released by C-fibers, causes Mast Cells to release Histamine.
        • Histamine can also activate C-fiber terminals.
    • Neurotransmitters used in Anterolateral System:
      • GROUP III (A-delta) NEUROTRANSMITTER: Glutamate
      • GROUP IV (C-FIBER) NEUROTRANSMITTERS: C-Fibers have two neurotransmitters which cause vasodilation when released on vessels.
        • Substance-P: Increases capillary permeability, perhaps via NO.
        • Calcium Gene-Related Peptide (CGRP): It enhances the vasodilatory effects of Substance-P.
    • ANTEROLATERAL SYSTEM PATH:: Group-III (Fast Pain) and IV (slow-Pain) fibers enter the spinal cord through the lateral portion of the Dorsal Root over the Tract of Lissauer ------> Ascend one or two segments ------> Synapse in Substantia Gelatinosa ------> CROSS ------> Ascend in Anterolateral tract.
      • NEOSPINOTHALAMIC PATHWAY: Fast pain (III) and temperature sensation.
        • Second order neurons terminate in the VPL of Thalamus.
        • These neurons are modality specific, have high thresholds of stimulation, and have small receptive fields -- all things expected for fast, sharp, localized pain.
        • MARGINAL ZONE: Lamina I and Vof the Dorsal Horn. This is the outermost and innermost layers of the Anterolateral System.
          • Fast Pain only goes through the Marginal Zone.
          • The fibers split into layers in the Tract of Lissauer.
      • PALEOSPINOTHALAMIC PATHWAY: Receives Slow-Pain (IV) fibers, plus some Fast-Pain.
        • Second order neurons terminate in Intralaminar Nuclei of Thalamus.
          • Lesion of the Intralaminar Nuclei will relieve chronic pain.
        • These fibers mediate, chronic deep pain, but not cutaneous pain.
        • Lamina II and III carry the Slow Pain fibers -- the middle two layers of Anterolateral System.
    • Anterolateral Cordotomy: Sectioning the anterolateral cord on the contralateral side in order to relieve intractable pain.
    • Targets of Anterolateral Pathway:
      • Spinoreticular Pathway: Also for modulation of pain (see below)
      • Spinotectal Pathway: Also involved in pain control; orientates our response to painful stimuli.
      • Spinothalamic Pathway: The primary pathway for pain transmission to Thalamus.
    TRIPLE RESPONSE OF ***** (AXON REFLEX):
    • Wheal: Localized raised area resulting from vasodilation from local irritants.
    • Flare: Reddened area surrounding the wheal.
      • It is a axon-axon reflex that does not go through the CNS. Local Nociceptive fibers are stimulated, and they send messages to neighboring fibers to cause a "flare" of vasodilation around the original wheal.
    • Capsaicin is a peppery substance that causes the wheal-and-flare response locally. Applied continually, it will desensitize the C-Fibers to local allergens and can thus be used as a topical analgesic.
    • HYPERALGESIA: Enhanced sensitivity to pain occurs in the region following the Wheal and Flare response.
    THALAMIC (CENTRAL PAIN) SYNDROME: Spontaneous pain, and exaggerated responses to pain stimuli, resulting from a vascular lesion in the Thalamus.
    • Triad of related symptoms:
      • Spontaneous Pain
      • Non-Injurious stimuli (light touch, movement) are perceived as painful.
      • Hyperalgesia: aggravated pain response.
    • Originally, it was thought that only the Thalamus produced these symptoms, but it is now known that a lesion anywhere along the pain pathway (such as anterolateral cordotomy) can produce the symptoms.
    Mechanisms of ANALGESIA:
    • GATE CONTROL THEORY: Transmission of pain information can be modified by descending CNS large-fibers. Endogenous activity in large-fiber pathways can block pain.
      • After you bump your head, rubbing it can help it. When you rub your head you are stimulating large fiber pathways.
      • Spinotectal and Spinoreticular Pathways: These are ascending pathways that in turn lead to inhibition of pain transmission in the dorsal horn. These pathways are an endogenous way of modulating pain.
        • Alternative pathway for pain fibers: Nociceptive stimuli ------> Periaqueductal Gray of Midbrain and Periventricular Gray of Thalamus ------> Nucleus Raphe Magnus of the Reticular Formation.
        • Serotonergic Pathway:From Nucleus Raphe Magnus the signal goes back down to Dorsal Horn of Spinal Cord ------> synapse with interneuron in Substantia Gelatinosa at all levels ------> inhibit the pain signal at the point of entry into the spinal cord.
        • Noradrenergic Pathway: There is also a Noradrenergic pathway that has a modulatory effect on pain.
      • Stimulus0Produced Analgesia can occur from electrical stimulation of the periaqueductal gray. Again, this analgesia has its effect by inhibiting pain transmission in Dorsal Horn.
    • OPIOIDS:
      • Inject very small amount of Morphine into one of two CNS regions to cause profound Analgesia:
        • Periaqueductal Gray
        • Dorsal Horn
      • Opioid Receptors: Enkephalins and Endorphins are the endogenous ligands for these receptors. Opiates also bind to them but with higher potency.
        • Opioid -Receptors are found in Periaqueductal Gray.
          • Naloxone is an antagonist to this receptor.
    • STRESS-INDUCED ANALGESIA: Extreme stress (Epinephrine) can induce analgesia so that a person can perform actions that would normally be painful. The action is not perceived as painful until after the stressful event is over.
    RADICULAR PAIN: Pain localized to the dermatome of a dorsal root.
    • Injury to a single Dorsal Root will not usually produce Anesthesia, because there is overlap between dermatomes.
    • Paresthesia (tingling, etc.) is common however, and Radicular Pain often occurs with Paresthesia.
    REFERRED PAIN: Visceral injury will send afferent pain information on the same nerves that also serve a cutaneous region. Because the brain is more used to getting sensory input from the cutaneous region of the nerve, the CNS will interpret the pain as originating from the cutaneous region.

VISION


CONVEX LENS: Converging rays. They shorten the focal length and can be used to correct for farsightedness.

• Positive Focal Length -- focal point is in front of the lens.

CONCAVE LENS: Diverging rays. They lengthen the focal lengthy and can be used to correct for nearsightedness.

• Negative focal length -- focal point is behind the lens.

LENS POWER: It indicates how much the lens can converge or diverge the light rays. The stronger the power, the shorter the focal length. A short focal length means the light is being bent a lot.

EMMETROPIC EYE: Normal vision, in which the light rays form an image on the retina.

• The natural eye has two convex lenses which serve to focus the light on the retina.
  • Cornea
  • Crystalline Lens
• The image on the retina is a "real" image -- upside down and inverted.
• ACCOMMODATION: A relaxed lens is relatively flattened and lets you focus at a distance. Accommodation increases the curvature of the lens to focus for near vision.
  • Relaxed lens lets you focus at 63 mm from the surface of eye.
  • Cycloplegics are topical drugs you can put on the eye to inhibit the accommodation reflex and cause the lens to relax.
  • PRESBYOPIA: The loss of accommodation ability occurs with age. Children have up to 14 diopters of power to accommodate, while old adults may have only 1 or 2 diopters, or none.

MYOPIA, NEARSIGHTEDNESS: You can see things up close just fine but have difficulty seeing into the distance.

• The image forms in front of (anterior to) the retina.
• Corrective Lens: Diverging (Concave) Lens, to lengthen the focal length and move the image back a little so it forms on the retina.
• Other corrective procedures:
  • Radio Keratotomy (RK): Use fine diamond scalpel is used to make radial incisions in cornea, in order to flatten the cornea itself.
  • Photorefractive Radio Keratotomy (PRK): UV laser is used to blow off pieces of the cornea, a bit at a time.

HYPEROPIA, FARSIGHTEDNESS: You can see things far away just fine but have difficulty seeing things up close.

• The image forms behind (posterior to) the retina.
• Corrective Lens: Converging (Convex) Lens, the shorten the focal length and move the image forward a little so it forms on the retina.
• Other corrective procedures:
  • Laser Keratothermoplasty: Surgery that increases the curvature of lens.

ASTIGMATISM: A problem in which the cornea has two different radii of curvature (one horizontal and one vertical) and two different focal points. Essentially, the cornea is deformed such that the horizontal and vertical focal lengths don't match up with each other.

• Torus is donut-shaped thingie that has two radii of curvature: R1 is the radius of the donut itself, and R2 is the cross-sectional radius of the donut.
• Corrective Lens: CYLINDRICAL LENS. The cylindrical lens is curved only in the horizontal plane -- not in the vertical plane.
  • There is no power in the vertical direction.
  • Regular lenses can't be used because the lens would correct for the problem in one direction, only to cause a distortion in the other direction.
  • After correction, the patient may still be highly myopic. This can be further corrected with a normal spherical lens.

VISUAL ACUITY: The minimal angular resolution of the eye.

• beta = the minimum angle of resolution of two dots. The minimum subtended angle at which a patient can perceive two dots as distinct.
  • Minutes of arc are used to measure this angle, where 60 minutes = 1 degree. Degrees are too course of a measurement.
• Limit to Visual Acuity: The ultimate (theoretical) limit to visual acuity are the photo-receptors of the eye.
  • In the fovea (finest visual acuity), photoreceptors are separated by about 3 microns, which corresponds to a theoretical minimum subtended angle of 0.6 minutes. This theoretical minimum is never attained due to some diffraction of light in the eye.
• Factors that affect Acuity:
  • Pupil size. Small pupils result in better visual acuity.
• SNELLEN EYE CHART: Made of strokes and gaps, which in standard form should be separated by 5 units from each other.
• 20 / 20 (x / y) vision:
  • NUMERATOR: The distance at which the patient stands from the chart. It is basically always 20!
  • DENOMINATOR: The distance at which the letter would subtend 1 minute of arc for this patient. This is equivalent to the distance at which an emmetropic eye could view the letter.
  • Due to the above, the relationship between minutes of arc and the Snellen Eye Chart is that the distance = (20)(minutes of arc).
    • So, if you had 20 / 300 vision, then your minimum visual acuity would be 15 minutes of arc.

OPTICAL AXIS: Straight through the lens. It is slightly medial to the Visual Axis, which is where the fovea is located.
THE RETINA: From the back of the eye (outer limit of eye) to the inner most layer...

• RETINAL EPITHELIUM: Not officially part of the retina.
  • Choroid -- Not officially part of the retina. It is the blood supply to the retina.
  • Retinal Pigmented Epithelium -- Not officially part of the retina, support and recycling of rhodopsin disk-membranes.
• PHOTORECEPTOR LAYER
  • OUTER SEGMENT: Photoreceptor Cells, containing the photosensitive elements.
  • INNER SEGMENT LAYER: Continuation of Photoreceptor Cells, containing the mitochondria and other support organelles.
• OUTER LIMITING MEMBRANE really isn't a membrane, but consists of tight junctions between the cytoplasmic extensions of Muller Cells. It contains MULLER CELLS which are Retinal Glial cells.
  • Muller cells have their end-feet on both the outer and inner limiting membranes.
  • They regulate the extracellular K+ concentration in the environment.
  • They contain Glutamine Synthetase, necessary for metabolism of Glutamate, which is the main excitatory neurotransmitter in the visual system.
• OUTER NUCLEAR LAYER: Contains the cell-bodies of the photoreceptors.
• OUTER PLEXIFORM LAYER: Contains synaptic connections between the photoreceptor-cells and the integrating neurons (amacrine and horizontal cells).
• INNER NUCLEAR LAYER: Contains the cell-bodies of the integrating cells. There are three integrating cell types:
  • Amacrine Cells
  • Horizontal Cells: Process lateral information.
  • Bipolar Cells: This is the basic second-order neuron. The "Standard Synapse" is photoreceptor cell ------> bipolar cell ------> ganglion cell.
  • Muller Cells: This cell extends almost the entire length of the retina.
    • Their tight junctions form the external limiting membrane on the outer surface of retina.
    • They extend all the way through retina, and parts actually lie on the internal limiting membrane.
• INNER PLEXIFORM LAYER: Contains synaptic connections between the integrating cells and the Ganglion Cells.
• GANGLION CELL LAYER: Contains the cell-bodies of the Ganglion Cells. They're afferent fibers make up the optic tract.
• NERVE FIBER LAYER: Unmyelinated axons of Ganglion cells.
• INTERNAL LIMITING MEMBRANE: Separates the neural retina from the Vitreous Body.

OPTIC DISK: Region of retina where the optic nerve and blood vessels enter. The optic disc is a blind-spot, but it is in a different part of the visual field for each eye so normally (with both eyes open) the blind-sport is not evident.

• You can see the Optic Disc through the Ophthalmoscope, and this is where you go to test for vascular problems or CNS problems, such as Papilledema which indicates CSF buildup.

FOVEA: Contains no vessels, no inner-nuclear layer, no ganglion cell layer, and no rods. Just a high concentration of cone-photoreceptors.
PRIMARY PHOTO TRANSDUCTION:

• THE ROD CELL: Specialized for low-acuity vision in the dark.
  • Rod cells are sensitive to blues and purples in the spectrum.
• THE CONE CELL: Specialized for high-acuity vision in the light.
  • Red Cone Cell:
    • Protanomalous means deficiency of red pigment.
    • Protanopia means total red color blindness.
  • Green Cone Cell:
    • Deuteranomalous means deficiency of green pigment
    • Deuteranomopia means total green color blindness
  • Blue Cone Cell:
    • Tritanomalous means deficiency of blue pigment (rare)
    • Traitanomopia means total blue color blindness (rare)
• OPSINS: Rod cells contain Rhodopsin and Cone-cells contain Cone-Opsins.
  • Photon of Light CHANGES THE CONFIGURATION of RETINAL from 11-cis-Retinal ------> all-trans-Retinal. This is the chemical basis for photo transduction.
  • The trans-Retinal then escapes the cone cells and goes back to the epithelium where it will get recycled.
• IN THE DARK: The rod-cell is depolarized.
  • High levels of cGMP are in the rod-cells.
  • Na+-Ca+2-Channels are open. The channel accommodates both Na+ and Ca+2, although Na+ is the major ion to come in.
  • The cell is depolarized as Na+ continually comes in, and is pumped back out via Na+/K+-ATPase located in the inner segment.
  • The cell is releasing excitatory neurotransmitter (glutamate, aspartate) onto the secondary neurons.
• IN THE LIGHT: The rod-cell becomes hyperpolarized.
  • cGMP gets cleaved to GMP by phosphodiesterase.
  • The Na+-Channels close.
  • Na/K-ATPase quickly restores the cell to what we normally think of as resting potential -- cell is hyperpolarized.
  • The cell stops releasing neurotransmitter.

SECONDARY CELLS: They receive signals from the photoreceptors.

• Bipolar Cells:
  • ON BIPOLAR CELLS: The CENTER of the cell depolarizes in the light.
    • This requires a sign-reversal of the membrane potential, since they receive a hyperpolarizing signal from the photoreceptors.
    • It will detect a light spot with a dark background.
  • OFF BIPOLAR CELLS: The CENTER of the cell hyperpolarizes in the light.
    • This does not require a sign-reversal. The membrane potential remains the same.
    • It will detect a dark spot with a light background.
• CENTER-SURROUND INHIBITION: The region immediately surrounding the center of the cell provides contrast, which makes it easier for the brain to interpret the visual stimuli.
  • When the center is stimulated, the SURROUND is inhibited by horizontal cells
  • When the SURROUND is stimulated, this indicates that light is nearby but not directly on the center. Thus the center is inhibited by horizontal cells.
  • HORIZONTAL CELLS are inhibitory interneurons that provide lateral inhibition to surrounding regions: Photoreceptor ------> Excitatory to Horizontal Cell ------> Inhibitory to the neighboring photoreceptor and bipolar regions (i.e. the "surround" area of visual field).
• GANGLION CELLS: Each Ganglion Cell has a Receptive Field Center which corresponds to specific Bipolar Cells, which in turn corresponds to specific photoreceptor cells.
  • ON GANGLION CELLS: They are stimulated by the light, i.e. by On Bipolar Cells.
  • OFF GANGLION CELLS: They are stimulated by the dark, i.e. by Off Bipolar Cells.
  • CENTER-SURROUND ORG:
    • If you shine a light in the center of an ON-GANGLION's receptive field, then it will be completely turned.
    • If you shine a light neatly around the periphery of an ON-GANGLION's receptive field, then it will be completely turned off.
    • The converse, of course, hold for the Off-Ganglion cells.
• X and Y SYSTEM is another way to divide up all the cells in the retina, according to their visual function.
  • X-SYSTEM (P) is specialized for high visual acuity and color information.
    • P stands for Parvocellular Layer of the Lateral Geniculate Nucleus.
  • Y-SYSTEM (M) is specialized for quick detection of motion, such as turning your head to glance at motion in the periphery.
    • M stands for Magnocellular Layer of the Lateral Geniculate Nucleus.
    • This system utilizes the Amacrine Cells which turn on with sudden changes in visual field, i.e. motion.

VISUAL FIELDS:

• Visual Field Organization with Retina:
  • NASAL HALF: The axons of the nasal (medial) half of the retina cross at the optic chiasm and go into the CNS via the contralateral optic tract.
  • TEMPORAL HALF: The axons on the temporal (lateral) half of the retina do not cross at the optic chiasm and go into the CNS on the ipsilateral optic tract.
  • LEFT VISUAL FIELD: Corresponds to the nasal half of your left retina and the temporal half of your right retina.
    • All information in the left visual field winds up in the right hemicortex.
  • RIGHT VISUAL FIELD: Corresponds to the nasal half of your right retina and the temporal half of your left retina.
    • All information in the right visual field winds up in the left hemicortex.
• VISUAL FIELD DEFICITS:
  • Terms:
    • Homonymous: The same half of each visual field is affected when either eye is tested.
      • This generally happens with central lesions, such as in the Occipital Lobe, or a complete loss of the Lateral Geniculate Nucleus.
    • Heteronymous: Opposite visual fields are affected when either eye is tested.
      • This happens with Pituitary Tumor.
    • Hemianopia: Loss of vision in one half of the visual field.
    • Quadrantanopia: Loss of vision in one quarter of the visual field.
  • TUNNEL VISION: No vision in the periphery, or in the temporal visual fields.
    • A pituitary tumor cam impinge on the medial fibers of the optic chiasm -- the fibers that cross. That would be the nasal halves of each retina, corresponding to the temporal visual fields. Thus pituitary tumor can result in tunnel vision.
    • This lesion would be called a BITEMPORAL HETERONYMOUS HEMIANOPIA.
    • You can see tunnel vision happen with infertility because of the pituitary tumor.
  • SUPERIOR QUADRANTANOPIA: MEYER'S LOOP Unilateral damage to the ventral aspect of the Lateral Geniculate Nucleus, which contains a representation of the superior visual field, headed toward the inferior bank of the Calcarine Sulcus.
    • Meyer's Loop is the visual track going from LGN to the Visual Cortex. It travels around lateral edges of the lateral ventricles.
  • HOMONYMOUS HEMIANOPIA WITH MACULAR SPARING: Lesion to the Optic Radiations or Visual Cortex on one side.
    • Macular Sparing means that central (macular) vision still remains, but the rest of the vision is gone. Why this occurs is unknown.

LATERAL GENICULATE NUCLEUS:

• MAGNOCELLULAR LAYER: Layers 1-2. These layers process Y-Cell information from the retina -- sudden motion detection.
  • This is the Where System, telling you where things are in space. These neurons will ultimately project to the Parietal Lobe to help you orient "where" you are in your visual world.
• PARVOCELLULAR LAYER: Layers 3-6. These layers process X-Cell information from the retina -- visual acuity and color.
  • This is the What System. These neurons will ultimately send projections to Temporal Lobe (Wernicke's area, perhaps?) to help you identify what things are.
• Orientation: Different LGN layers process information from different eyes. All of the information from the retina is kept in separate layers in the LGN, so it can be sent to distinct parts of visual cortex.
  • Layers 1, 4, 6 process the contralateral eye.
  • Layers 2, 3, 5 process the ipsilateral eye.
  • Horizontal Orientation: Generally, information in each visual field is represented in contralateral LGN. As you move more laterally in the visual field, its representation moves more laterally in the contralateral LGN.

PRIMARY VISUAL (STRIATE) CORTEX: Area 17.

• Visual Field Organization: Each occipital love processes the contralateral visual field.
  • UPPER QUADRANT of each visual field is on the lower bank of the Calcarine Sulcus.
  • LOWER QUADRANT of each visual field is on the upper bank of the Calcarine Sulcus.
  • Fovea: The region of highest visual acuity is represented by the most posterior (caudal) part of the Visual Cortex, and it has the largest (disproportionate) representation of neural tissue.
• MEYER'S LOOP: Optic Radiations are the visual track going from LGN to the Visual Cortex. They form Meyer's Loop as they travel around the lateral aspect of the lateral ventricles.
  • Again, Meyer's Loop lesion leads to visual-field deficit of the contralateral quadrant.
  • Because of its anatomical arrangement, damage to the temporal lobe can cause superior homonymous quadrantanopia.
  • For similar reasons, damage to the parietal lobe can cause inferior homonymous quadrantanopia.
• CORTICAL COLUMNS: Layers of the Striate Cortex, from Pia to White Matter, are arranged into columns. All visual neurons enter the Visual Cortex through Layer IV of the cortex.
  • ORIENTATION COLUMNS: All neurons in the same column will process will same visual-orientation information.
    • For example, in the same column, all neurons may process vertically oriented lines or horizontally oriented lines, but not both.
  • EYE-DOMINANCE COLUMNS: Any particular column will contain exclusively information from the left eye or the right eye.
    • Left and Right-Eye Columns alternate with each other, so that a left eye-column of one orientation is right next to the right eye column for the same orientation.
  • HYPER COLUMNS: The combination of the Left-Eye Column, Right-Eye Column, plus all possible Orientation-Columns for a single part of the visual field.
    • Each hyper column contains a complete visual representation for a particular part of the visual field.
• CYTOCHROME BLOBS: Color processing. These blobs are present in each of the hyper columns, too.

EXTRA STRIATE CORTEX: Visual Association cortices.

• Area V2: The primary extra striate cortex; it receives lots of info from VI, the Striate Cortex. It processes depth information.
• Area V5: Processes information about motion.
• Area V4: Involved in color processing. It receives color information from V2.
• Area IT: Part of the temporal lobe involved with recognition of faces.
  • Lesion in this area results in Prosopagnosia, failure to recognize familiar faces.

Other Retinal Projections: Retinal projection that go somewhere other than the LGN.

• Accessory Optic Nuclei: Sensitive to movement of large visual fields and involved with the nystagmus reflex.
• Suprachiasmatic Nuclei: Part of Hypothalamus; it receives light information in order to influence circadian rhythms.
• Superior Colliculus: Involved with movement of eyes relative to visual stimuli and foveation, focusing, on a moving object.
  • There is a sensory map in the superficial layer that has 1:1 correspondence with a motor map in the deep layer. So, when one part of visual field is stimulated, the corresponding motor part directs the eyes to the visual stimulus.
• Pretectum: Direct and consensual pupillary light reflexes. It receives bilateral information from the eyes, and projects bilaterally to the Edinger Westphal (CN III) nucleus.

HEARING


Measuring Frequency and Volume:

• SOUND-PRESSURE LEVEL (SPL): A measure of the intensity (volume) of sound in Watts / m2. It is related to decibels logarithmically: a tenfold change in SPL corresponds to a linear increase of 20 decibels.
  • If the SPL is one million times (106) stronger, then the number of decibels is 6 x 20 = 120 decibel increase.
• Threshold: The least amount of stimulus energy (SPL) required for the ear to register a sound.
  • Threshold is frequency dependent. Some frequencies have a lower threshold (are more easily heard) than other frequencies.
  • Lowest threshold occurs at 1 - 3 kHz frequency, which is the optimal pitch at which humans hear.
  • Frequency Threshold Curve shows the threshold SPL at different frequencies. The thresholds get higher (i.e. more difficult to hear) at high frequencies.
    • Because of this arrangement, Sensorineural hearing loss will show a hearing-deficit at high frequencies before it will show it at low frequencies.
• DYNAMIC RANGE OF HEARING: The range of volume that the human ear can detect without incurring damage. The range at 3 kHz is 0 - 120 dB
• AUDIOGRAM: A frequency-threshold curve, in which the deficit from normal is graphed at each frequency range.

EXTERNAL EAR, Pinna:

• It resonates to increase the SPL of the sound between 1 and 3 kHz.
• It plays a role in sound localization -- its shape aids us in determining where a sound is coming from.

MIDDLE EAR: Air-filled cavity. Malleus ------> Incus ------> Stapes

• Impedance Mismatching: The middle ear bones amplify the sound vibrations from the tympanic membrane to the oval window.
• This amplification of sound gives us a 15 dB advantage. Removal of middle-ear ossicles does not result in deafness, but rather results in a 15dB hearing loss.
• Tensor Tympani and Stapedius contract reflexively in response to high intensity sound.
• Middle Ear Pathologies:
  • Otitis Media: Watch it with children. It will severely impair their language acquisition if they are chronically hard of hearing during those formative years.
  • Otosclerosis: Conductive Hearing Loss. Stapes no longer vibrates properly against oval window due to abnormal bone growth.

COCHLEA:

• MODIOLUS: The central "shaft" of the Cochlea, around which it screws.
  • The modiolus contains the Cochlear Nerve (VIII)
  • SPIRAL GANGLION: The starting point of the VIIIth nerve, it is in the Modiolus at the base of the Spiral Lamina.
• SCALA MEDIA:Endolymph fluid similar in composition to intracellular fluid (high in K+ and low in Na+). The Scala Media contains the sensory hair cells and the Organ of Corti
  • TECTORIAL MEMBRANE is inside the scala media, right on top of the hair cells.
    • FNXN: Shearing Force is created by movement of the Tectorial Membrane across the hair cells. Sound waves cause the tectorial membrane to move.
      • The Tectorial Membrane tends to move in an opposite direction as Basilar Membrane. This aids in the shearing force.
      • SOUND TRANSDUCTION: This shearing force transduces the mechanical sound wave into an electrical stimulus.
  • STRIA VASCULARIS: Highly vascular epithelium forming one wall of the Scala Media. It secretes endolymph into the Scala Media.
• SCALA TYMPANI: Perilymph fluid. In cross section, it is the section below each Scala Media, below the Basilar Membrane.
  • BASILAR MEMBRANE: It separates the Scala Media from the Scala Tympani. It forms the base of the Scala Media.
    • The Organ of Corti, containing sensory hair cells, lies on the basilar membrane.
    • SOUND TRANSDUCTION: The Basilar Membrane moves upward, toward the Scala Vestibuli, to initiate the shearing of the Tectorial Membrane.
• SCALA VESTIBULI: Perilymph fluid. In cross section, it is the section above each Scala Media, above the Vestibular Membrane.
  • VESTIBULAR (REISSNER'S) MEMBRANE: Very delicate membrane separating the Scala Media from the Scala Vestibuli.
  • The Scala Vestibuli is continuous with the Oval Window. It therefore conducts sound waves, through perilymph, toward the apex of the Cochlea.
  • HELICOTREMA: A hole at the apex of the cochlea. It connects the Scala Vestibuli to the Scala Tympani
    • It allows the Basilar Membrane to resting position in the event of constant pressure on the membrane.

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ORGAN OF CORTI: It is located in the Scala Media, a top the Basilar Membrane.

• INNER HAIR CELLS: They are closer to the Modiolus. They are very tightly held into place.
  • STRUCTURE:
    • There is usually only one single row of inner hair cells. They have stereocilia that brush up against the Tectorial Membrane.
    • They are situated such that the stereocilia are in endolymph while the rest of the hair cell is in perilymph.
  • FNXN: These cells are the primary sound receptors. They respond to shearing movements of the Tectorial Membrane.
  • Inner Hair Cells send primary VIIIth Afferents into the CNS, via the Spiral Ganglion.
• OUTER HAIR CELLS: There are more of them, located laterally, away from the tectorial membrane.
  • STRUCTURE: They have more room to breathe -- there is open space laterally.
    • They are in multiple rows.
    • Apex of the cells is embedded in Reticular Lamina. This layer forms the ionic border between endolymph and perilymph.
  • FNXN: These cells can move the basilar membrane and can "tune" the frequencies of the basilar membrane.
    • They receive OLIVOCOCHLEAR BUNDLE (OCB) FIBERS from the Superior Olivary Nucleus. This is efferent innervation that provides both positive and negative feedback to the hair-cell apparatus. It will affect how sensitive the tectorial membrane is to mechanical transduction.
      • POSITIVE FEEDBACK: The OHC's serve to amplify quiet sounds by making the Tectorial Membrane more sensitive to shearing.
      • NEGATIVE FEEDBACK: The OHC's serve to dampen loud sounds by making the Tectorial Membrane less sensitive to shearing.
    • The Outer Hair Cells also help in frequency selectivity. Loss of OHC's results in a flattened tuning curve -- VIIIth nerve afferents become less frequency-selective in the tones they carry.
  • DISEASE: Outer Hair Cells are subject to disease a lot. Commonly, the OHC's will be missing in a person but the inner hair cells will still be intact. Sensorineural hearing loss, but not total deafness, results.
    • Disease ------> Less Frequency Selectivity
    • Disease ------> The patient is more sensitive to loud sounds.
• OTOACOUSTIC EMISSION: Energy emitted by the Outer Hair Cells, which is a real sound and can be detected by the Cochlea. When such emissions are detected, Objective Tinnitus results.
  • Objective Tinnitus: Ringing in ear when a sound wave is actually present, being generated internally.
  • Subjective Tinnitus: Ringing in ear when no sound wave is present.

FREQUENCY SELECTIVITY: Sound is mapped to different parts of the Cochlea according to frequency. Each part of the cochlea is most sensitive to a small range of frequencies, i.e. it has the lowest threshold.

• BASE: Outer part of Cochlea transduces high frequency waves.
  • It is stiff and narrow, helping it to detect high frequencies.
• APEX: Inner part of Cochlea transduces low frequency waves.
  • Flaccid and broad, helping it to detect low frequencies.
• Both systems are also energy dependent. Frequency Selectivity still occurs with anoxia, but it isn't as well tuned.
• Tuning Curve: If you were to plot the frequency of sounds traveling on any particular VIIIth fiber, you would find that individual VIIIth afferents are also frequency selective, according to which hair cells they innervate.

ENDOLYMPHATIC POTENTIAL: +80mV Potential. The Scala Media is positive with respect to the hair cells, and with respect to the perilymphatic compartments.

• DEPOLARIZATION: Inner Hair Cell Stereocilia move toward Kinocilium ------> Open K+-Channels ------> K+ enters the hair cells from the scala media ------> depolarization and nerve firing result.
• POTASSIUM: It is unusual for this flow of K+ to result in depolarization. There is a large (+140mV) driving force for K+ to enter the cell, however.
• Glutamate: The IHC's probably use glutamate as an excitatory neurotransmitter to excite VIIIth afferents headed into the CNS.

HEARING LOSS:

• Acoustic Neuroma: The most common type of CNS hearing loss, i.e. damage to the VIIIth nerve itself.
  • Bell's Palsy is common secondary symptom, as VIIIth nerve neuroma can also compress the VIIth nerve in the inner ear.
• Conduction Hearing Loss: Otosclerosis or Otitis Media.
  • WEBER'S TEST can be used to distinguish conductive hearing loss from sensory hearing loss. Apply a vibrating tuning fork to the skull of a patient who has hearing loss in one ear.
    • If Conductive Hearing Loss: The sound will be louder to the patient in the deficient ear. Conduction through skull bypasses the conductive hearing loss problem./
    • If Sensorineural Hearing Loss: The sound will seem louder in the other ear -- the ear that doesn't have the sensorineural loss.
• Sensorineural Hearing Loss: The most common type of hearing loss. Usually the problem is the hair cells, and the VIIIth nerve fibers are left intact.
  • CAUSES:
    • Genetic, perinatal
    • High intensity sounds ------> IHC + OHC damage
    • Ototoxic Drugs: Aminoglycoside antibiotics, loop diuretics, some chemotherapeutic agents.
• Presbyacusia: Loss of hearing with age.

COCHLEAR IMPLANTS: Put in an implant that can provide direct stimulation to VIIIth-Nerve afferents. This can be done even if there is hair-cell deafness.

• This can restore some hearing but not usually speech perception. Best case scenario is speech perception is restored with practice.

MENIERE'S DISEASE:

• TRIAD OF SYMPTOMS: Patient will get ringing in ear, then a "fullness" in ear, then hearing loss will drop off, then vertigo.
  • Tinnitus (ringing in ear)
  • Fluctuating Hearing Loss
  • Episodic Vertigo
• ETIOLOGY: Idiopathic, Traumatic, Post-Syphilis, Viral
• PATHOPHYSIOLOGY:
  • TRAUMA: Damage to the Endolymphatic Sac; you can't absorb endolymph fluid ------> fluid overload.
  • Vestibular Membrane ruptures from buildup of inner fluid and pressure.
  • Hair Cell Toxicity then occurs from mixing of endolymph and perilymph fluids. Some cell death. They think the membrane can heal itself, hence resultant hearing loss is only temporary.
• TREATMENT: Most common treatment is medicine designed to decrease the amount of inner ear fluid.
  • Salt balance / diuretics play a big role in treatment.
  • Meclizine-Antivert, Valium, and Compazine can all be used as Vestibular suppressants.
  • SURGICAL: Only if they don't respond well to medicine.
    • Endolymphatic Shunt:: A surgical method that enhances the fluid-resorption of endolymphatic fluid.
    • Vestibular Nerve Section (not preferred) in the case of severe Vertigo. The problem is that this treatment is only symptomatic.
    • Labyrinthectomy: Removal of semicircular canals, resulting in complete destruction of all of VIII -- both Vestibular and Cochlear.
      • Oscillopsia is a terrible visual side-effect where people bounce up and down.
• PROGNOSIS: Progressive, untreated Meniere's disease leads to irreversible hearing loss. Early treatment is therefore essential.

CENTRAL AUDITORY PATHWAYS:

• Primary Sound Transmission: VIIIth Nerve ------> Cochlear Nucleus ------> Ventral and Dorsal Cochlear Nuclei ------> Inferior Colliculus where it SYNAPSES
• Secondary Sound Transmission: Inferior Colliculus ------> Brachium of the Inferior Colliculus ------> Medial Geniculate Body ------> Primary Auditory Cortex (Area 41).
• SOUND LOCALIZATION: The process of figuring out where in space a sound is originating from.
  • SUPERIOR OLIVARY COMPLEX receives binaural (both ears) input, processes it, and sends a modifying signal to the Inferior Colliculus indicating the source of sound.
    • Lateral Superior Olive: Sensitive to intensity differences between the two ears.
    • Medial Superior Olive: Sensitive to temporal (time) differences of signals coming in between the two ears.
  • DUPLEX THEORY OF SOUND LOCALIZATION: States that sound localization occurs by two different mechanisms, according to the frequency of the sound.
    • HIGH FREQ (greater than 3 kHz): The head casts a shadow on the sound wave, causing it to have a different intensity in each ear, which enables the auditory system to localize the source of the sound.
    • LOW FREQ (less than 3 KhZ): The sound waves are traveling slow enough that they reach each ear at different times, enabling the Auditory System to localize the source of the sound.
• Superior Colliculus (not Inferior): Plays a role in sound processing, in paying attention to peripheral space (same role as in visual processing). The auditory information and visual information are parallel to each other and occupy different layers in the same cortical columns within the Superior Colliculus.

AUDITORY EVOKED POTENTIALS: Place electrodes on head to measure the actual electrical activity generated by signals in the Auditory pathway.

• It is used as a substitute for normal hearing tests when a hearing test isn't possible: examples = infants, invalids, malingerers who behave like they are deaf when in fact they can hear.
• Can be used to diagnose some demyelinating diseases, such as Multiple Sclerosis, by studying the waveforms that are evoked in the auditory pathway.

TASTE AND SMELL


TASTE BUDS:

• Papillae:
  • Circumvallate Papillae: Located on the border between anterior 2/3 and posterior 1/3 of tongue. They contain the highest concentration of taste receptors.
    • INNERVATION: The Glossopharyngeal Nerve (CN IX) which goes back to the Petrosal Ganglion
  • Foliate Papillae: Located on the sides of the tongue and toward the back. Sparsely populated with taste buds.
    • INNERVATION: Facial Nerve (Chorda Tympani) which goes back to the Geniculate Ganglion.
  • Fungiform Papillae: Most abundant. Located on Anterior 2/3 of tongue.
• Taste Bud Structure: Regeneration of Gustatory cells occurs, so if you burn your tongue the sensation of taste will return!
  • Receptor Cells have microvilli and are connected by tight junctions.
  • Supporting Cells are immature receptor cells.
  • Basal Cells are stem cells that produce new supporting cells, then new receptor cells.
    • Basal Cells ------> Supporting Cells ------> Receptor Cells
• INNERVATION:
  • Anterior 2/3: Facial Nerve (VII) ------> Geniculate Ganglion
  • Posterior 1/3: Glossopharyngeal (IX) ------> Petrosal Ganglion
  • Gustatory fibers on the Epiglottis are innervated by the Vagus (X) ------> Nodose Ganglion
  • SOLITARY NUCLEUS in ipsilateral brain steam receives afferents from all of the above.
• DEFICITS:
  • Conductive Taste Loss occurs with lack of saliva. Saliva, dissolving the chemicals in food, is required for taste.
  • Neural Taste Loss can occur, but it is rare because there are so many taste fibers.

ENSEMBLE ENCODING: Taste is perceived as a combination of the four basic tastes.

• Bitter: Back of the tongue
  • Uses IP3 ------> Ca+2 as a second messenger.
• Sour: Posterior sides of the tongue.
  • Uses H+ to block K+ efflux ------> direct depolarization
• Sweet: Tip of the tongue
  • Uses cAMP as a second messenger
• Salty: Anterior sides of the tongue
  • Opens Na+-Channels ------> direct depolarization

OLFACTION:

• Olfactory Cells: They are actually, themselves, neurons. They are original in that regard.
  • Basal Cells: They differentiate directly into Olfactory Receptor cells, without the supporting cell intermediate.
  • Olfactory Neurons Regenerate. Every time a new neuron is born, it must find its way through the Cribriform Plate and into the CNS.
• ENSEMBLE ENCODING: The system is even less organized than the taste system.
  • Specific: Each receptor cell binds to specific chemical stimuli.
  • Sensitive: Some receptors take an extraordinarily small amount of chemical stimuli to be activated.
• TRANSDUCTION: There is no synapse between the olfactory cells and the CNS. The olfactory receptors go straight to the CNS.
  • Depolarization of the receptor occurs by a second messenger system: G-Protein ------> cAMP
• OLFACTORY BULB: Olfactory Receptors travel up through the Cribriform Plate to form the Olfactory Bulb.
  • SYNAPSE occurs in Olfactory Bulb, in a GLOMERULUS which are little balls of neuropil.
    • Mitral Cells and Tufted Cells: They get the synapses. A single one of these cells may receive up to 1000 olfactory receptors.
    • Periglomerular Cells and Granule Cells are inhibitory interneurons in the Glomerulus. They may serve an adaptation (desensitization) role -- to ignore frequent stimuli.
• OLFACTORY TRACTS: The axons of the second-order Mitral and Tufted Cells.
  • They then branch to form the Medial and Lateral Olfactory Stria.
• CNS OLFACTORY PROJECTIONS: The Olfactory Stria generally go through the Limbic System or Paleocortical System -- not through the Thalamus.
  • Anterior Olfactory Nucleus: Part of the Olfactory Tract.
  • Septal Nuclei: They send signals ------> Hypothalamus.
  • Piriform Cortex: Also called Paleocortex. They send signals ------> Entorhinal Cortex and Amygdala.
    • Amygdala: Limbic. Involved in affective components of odor.
    • Entorhinal Cortex: Limbic. They send signal to ------> Hippocampus where it connects odors to memories, so that a smell is associated with a memory.
  • Olfactory Tubercle: Base of the Olfactory Tract, part of Paleocortex. They send signal ------> Medial Dorsal Nucleus of Thalamus. This is conscious perception of odors.
    • ORBITOFRONTAL CORTEX: It receives the signals from the Thalamus and is responsible for the conscious perception of odor
  • SLEEP AND WAKEFULNESS
    
    </STRONG>
    ELECTROENCEPHALOGRAM (EEG): Electrodes are placed in five general regions bilaterally, over the five cortices.
    • The EEG measures only cortical activity -- not subcortical activity.
    RhythmDominant FreqAmplitudeState of ArousalBeta20 Hz High Frequency
    Low AmplitudeAlertness REM Sleep
    Alpha 10 Hz high frequency
    HighAlertness but with eyes closed; Relaxed wakefulness
    Theta3 - 7 HzHighSlow-Wave SleepDelta0.5 - 3 Hz Low Frequency
    HighSlow-Wave Sleep
    SLEEP STAGES:
    • Stage 1: Stage 1 and REM show the same patterns: beta-waves
    • SLOW-WAVE: Low sympathetic tone, regular breathing, normal muscle tone.
      • Stage 2: Transitional sleep.
      • Stage 3: Deep sleep, theta waves
      • Stage 4: Deep sleep, delta waves
    • REM: Rapid-Eye Movement.
      • Rapid eye movements, very low muscle tone (very still), high cortical activity (beta waves), penile erection is hallmark sign of REM sleep.
      • Dreaming. People aroused out of REM sleep remember their dreams vividly.
      • There is active cortical inhibition of spinal muscles thus resulting in low muscle tones. If it weren't for this active inhibition, then the subject would probably sleep walk or move during this period of sleep.
    • Normal Sleep Progression: 1, 2, 3, 4, 3, 2, REM, 2, 3, 4, 3, 2, REM, 2, 3, 4 ... etc.
      • As the evening progresses:
        • Each period of REM becomes longer.
        • Deep Sleep (3 and 4) becomes shorter until it no longer occurs.
        • Arousal usually occurs out of REM sleep
    • Sleep is an active process. It is not simply the absence of consciousness.
    Alpha Waves: Relaxed Wakefulness with the eyes closed.
    • The recording is most pronounced over the parietal and occipital lobes, and is least prevalent over the frontal lobe.
    Synchronized -vs- Desynchronized:
    • Synchronized Waves characterizes slow-wave sleep. Synchronous discharge of neurons.
      • RETICULAR NUCLEUS of Thalamus is one of the major source of synchrony in the brain. It projects neurons onto itself and releases GABA as an inhibitory neurotransmitter to cause synchronization of discharge.
    • Desynchronized Waves: Neurons don't discharge at same time. Characteristic of arousal.
    Definitions:
    • Sleep: Normal, physiological alteration in consciousness and unconsciousness, which is freely reversible with appropriate stimulation.
    • Coma: A state of irreversible unconsciousness.
    • Concussion: Brief loss of consciousness after a blow to the head, with no permanent ramifications.
    • Syncope: Massive, widespread anoxia of cortical neurons. Fainting.
      • It happens from a hyperactive Vagus nerve that stops the heart from pumping enough blood to the brain. Fainting relieves the hyperactivity of the Vagus, and everything return to normal.
    CONSCIOUSNESS: Awareness of environment and self. It involves two systems.
    • RETICULAR ACTIVATING SYSTEM (RAS): It is responsible for the arousal aspect of Consciousness.
      • Activity of Reticular formation and some brainstem nuclei, which involve the Reticular Formation and Diffuse Thalamic Nuclei
    • CEREBRAL CORTEX: It is responsible for the content aspect of consciousness.
    • Anatomical Lesions that can produce coma:
      • Posterior Fossa: All of the subcortical structures, caudal to the Tentorium Cerebelli. A lesion to the posterior fossa will damage the Reticular Formation and can thus result in coma.
      • Uncal Herniation can press up against Tegmentum causing coma.
      • Metabolic Encephalopathy.
    • Tonic -vs- Phasic Modes of Consciousness:
      • TONIC MODE: Characteristic of Wakefulness and REM sleep.
        • High frequency (beta), continuous discharge of action potentials.
        • Na+ channels cause the action potentials.
        • Tonic mode has a resting potential that is just a few millivolts depolarized from phasic mode.
      • PHASIC MODE: Characteristic of Slow-Wave sleep.
        • Rhythmic, low frequency discharge of action potentials: An AP followed by 100 to 200 msec of silence.
        • Ca+2 channels cause these action potentials.
        • Phasic mode is just a few millivolts hyperpolarized from Tonic Mode.
    • Neurohormonal Systems of Arousal and sleep:
      • CHOLINERGIC SYSTEM: Raises the resting potential of thalamic and cortical neurons by a few millivolts and is related to the RAS.
        • NUCLEUS BASALIS (of Meynert): Basal forebrain.
      • NORADRENERGIC SYSTEM: Raises the resting potential of thalamic and cortical neurons by a few millivolts and is related to the RAS.
        • LOCUS CERULEUS, in the Midbrain, releases NorE.
      • SEROTONERGIC SYSTEM: Related to sleep and to the pain-control system.
        • Serotonin induces slow-wave sleep and comes from two-sources:
          • (Pain Control Pathway): Periaqueductal Gray ------> Nucleus Raphe Magnus ------> Dorsal Horn of Spinal Cord to inhibit pain. This pathway is also involved in causing sleep.
          • Preoptic Area (POA) of Hypothalamus: It also releases Serotonin.
    EPILEPSY: Two or more unprovoked seizures.
    • SEIZURE: Abnormal behavior resulting large amplitude hypersynchronous neuronal discharge.
    • ETIOLOGIC CLASSIFICATION of SEIZURES:
      • Acute Symptomatic: Non-Epileptic seizures caused by some explainable, reversible condition such as hypernatremia (high blood Na+).
        • By definition, acute symptomatic seizures are reversible.
      • Remote Symptomatic: Epileptic seizures caused by physical or metabolic trauma, such as an automobile accident, which resulted in incurable Epilepsy.
        • By definition, remote symptomatic seizures are irreversible.
      • Idiopathic: Genetic or unexplained Epilepsy.
    • BEHAVIORAL CLASSIFICATIONS OF SEIZURES:
      • Generalized: At Onset, a seizure that starts by virtually all neurons of the cortex synchronously discharging.
        • Tonic-Clonic: Alternative behavior of stillness (tonic) followed by rocking and jerking (clonus).
        • Abscence: Brief
      • Partial: At Onset, a seizure that starts by a localized region of cortex discharging.
        • Secondary Generalization: Partial seizures can and often do spread to become generalized seizures. But, they are classified by how the seizure starts.
        • Simple Partial: The patient has full recollection of the seizure. The patient does not have retrograde or anterograde amnesia surrounding the event.
        • Complex Partial: The patient does not recall the seizure or the events immediately preceding it. Retrograde and possible Anterograde amnesia.
    • Dilantin is a drug that is effective in treating partial seizures.
    SLEEP APNEA:
    • SYMPTOMS: Excessive daytime sleepiness, resulting from waking up many times during the night due to obstructed airways.
      • Hypercapnia, Hypoxia, Compensated Respiratory Acidosis, morning headaches.
      • Complications: Cor Pulmonale (Right-Heart Failure), Pulmonary Hypertension, Systemic Hypertension
      • Inordinately loud snoring
    • Types:
      • Obstructive Sleep Apnea: Sleep Apnea due to obstructed or collapsed upper airways. Essentially a respiratory problem.
        • Most common type: 98% of cases.
        • Respiratory effort is still evident: expanded chest, etc.
        • Snoring only occurs with this form.
      • Central Sleep Apnea: Sleep Apnea due to a loss of the CNS drive to breathe -- i.e. sleep somehow inhibits the Phrenic Nerve from firing on the diaphragm.
        • This is much rarer and is essentially a neurological problem.
        • Snoring is absent.
    • Treatment:
      • Continuous Positive Airway Pressure (CPAP): Physically keep upper airways open, for obstructive apnea.
      • Tracheostomy, or procedures to surgically widen the space in the nasopharynx are also options.
      • Medroxyprogesterone can be given to women to stimulate breathing in the case of central apnea.
    • THE HYPOTHALAMUS
      
      
      Anatomy of Hypothalamus: The Hypothalamus forms the walls of the Third Ventricle.
      • Borders:
        • Optic Chiasm: Anterior-Ventral border
        • Anterior Commissure: Posterior-Rostral border.
        • Mamillary Complex: Forms the Ventral-Caudal border. It is very easy to see on the gross-brain but we don't know its function.
      • BLOOD SUPPLY:
        • Hypothalamic Arteries: They come off the Circle of Willis.
        • Superior Hypophyseal Artery: Supplies the basal hypothalamus (median eminence) and then goes on to supply the Adenohypophysis (anterior pituitary).
          • So, the anterior pituitary gets blood that came directly from the hypothalamus. It receives no direct arterial blood of its own.
        • Inferior Hypophyseal Artery: It supplies the Neurohypophysis (posterior pituitary).
          • So, the posterior pituitary gets fresh arterial blood, rather than blood that has come from hypothalamus.
        • Hypophyseal Vein: The neurohypophysis dumps its contents (oxytocin, ADH) out of hypothalamic nerves, and into the hypophyseal vein, where it then makes its way into the general circulation.
      CONNECTIONS to Hypothalamus: Most of the neural connections with the Hypothalamus are part of the Limbic System.
      • MAMILLOTHALAMIC TRACT: Mamillary Complex (posterior part of Hypothalamus) ------> Anterior Thalamus
        • • These fibers are heavily myelinated and constitute a major nerve tract.
      • FORNIX: Hippocampus ------> Hypothalamus (Pre-Optic Area) ------> Mamillary Bodies
      • STRIA TERMINALIS: Amygdala ------> Hypothalamus
        • This tract also goes from Amygdala to other area of the brain.
      • MEDIAL FOREBRAIN BUNDLE: Locus Ceruleus of Brainstem ------> Hypothalamus
        • This is the only place in the brain where Norepinephrine is used as a Neurotransmitter. All the nerves come from the Locus Ceruleus.
        • The Locus Ceruleus also sends NorE neurons to other locales, but the Medial Forebrain Bundle is the one that goes to the Hypothalamus.
      POSTERIOR PITUITARY PATHWAY: Paraventricular Nucleus ------> Superoptic Nucleus ------> (Arcuate Nucleus ------> Infundibulum) ------> Neurohypophysis
      • MAGNOCELLULAR NEURONS: Neurons that follow this path and make the hormones Oxytocin + ADH.
        • These neurons have larger cell bodies.
      • PARVICELLULAR NEURONS: These neurons have smaller cell bodies and make the small peptides (releasing factors) that control the adenohypophyses.
      NUCLEI, PARTS, and FUNCTIONS OF THE HYPOTHALAMUS:
      • Mamillary Bodies: The most caudal part of the hypothalamus.
      • Pre-Optic Area: The most anterior part of the Hypothalamus, near the optic chiasm.
      • Paraventricular Nucleus: Above the pre-optic area, surrounding the third ventricle on either side. The sites of origin of the Neurohypophyseal hormones.
      • Superoptic Nucleus: Near the paraventricular nucleus. The sites of origin of the neurohypophyseal hormones (Oxytocin, ADH).
      • Suprachiasmatic Nucleus: Right above the optic chiasm, it regulates circadian rhythms.
      • Arcuate Nucleus: Sits right above the pituitary gland. All pituitary factors pass through this nucleus before reaching the pituitary.
        • Median Eminence is next to Arcuate Nucleus, and is where a lot of the neurons terminate on blood vessels.
      • Ventral Medial Nucleus: Important in feeding behavior and emotional behavior.
        • Lesion of this nucleus can result in Rage, as Amygdala becomes dominant to Hypothalamus.
        • This nucleus contains the satiety center which tell you when you are full.
      • Dorsal Medial Nucleus:
      Functions of Hypothalamus:
      • ENDOCRINE: Hypothalamus is the ultimate homeostasis machine.
      • AUTONOMIC: Hypothalamus plays important roles in regulating autonomic system.
      • EMOTION: Hypothalamus does not originate emotions, but it integrates them. Emotion has two mental components.
        • Cognition: An awareness of what is going on in your environment.
        • Conation: The urge to act on feelings.
        • RAGE EXPTS: Lesion of Ventral Medial Nucleus results in uncontrolled rage. This is because there is a BALANCE between Hypothalamus and Amygdala in controlling emotional behavior
          • Amygdala dominant (as in above) ------> RAGE results.
          • Hypothalamus dominant (as in a lesioned Amygdala) ------> PLACID, FLAT behavior results.
        • KLÜVER-BUCY SYNDROME results when both Amygdala and Hypothalamus are lesioned.
          • Extremely docile, eat a lot, hypersexual.
        • SEX BEHAVIOR: Androgens play primary role in regulating sexual behavior. At least that's true in animals. Humans, it may be less true as higher cortical functions are more dominant.
          • There are androgen-receptors in both hypothalamus and amygdala.
      • MOTIVATIONAL STATES
        • FEEDING:
          • Lateral Hypothalamus is the HUNGER CENTER. Stimulate it and you eat.
          • Ventromedial Nucleus is the SATIETY CENTER. Stimulate it and you feel full.
            • It has some CCK-Receptors, and this may play role in satiety. There are also some local CCK neurons, and they don't know whether the CCK is originating locally or from the digestive system.
        • THIRST: Two primary determinants of thirst. Subfornical Organ, in the wall of third ventricle, is the primary thirst-inducer.
          • Tissue Osmolarity: High osmolarity in hypothalamus stimulates the sensation of thirst. Subfornical organ has osmole receptors to sense this.
          • Blood Volume: Low blood volume stimulates thirst. Subfornical organ has Angiotensin II receptors to sense low blood volume.
          • Fever and dry mouth also have an effect.
      • TEMPERATURE REGULATION: The hypothalamus contains the thermostat for regulating our body temperature.
        • Anterior Hypothalamic Area is the Warm Sensitive area. It tries to get rid of heat (sweating and vasodilation)
          • Loss of the Anterior Hypothalamus result in Hyperthermia.
        • Posterior Hypothalamic Area is the Cold Sensitive area. It tries to create more heat (shivering)
        • FEVER: Bacterial infection releases endotoxins that causes release of interleukins by circulating blood cells, especially IL-1. In the brain, IL-1 causes the hypothalamus to reset the thermostat to a higher level.
      • CIRCADIAN RHYTHMS: Mediated by Suprachiasmatic Nucleus.
        • Temperature regulation: You have higher temperature in morning, and while you're awake, than when you are sleeping.
        • Melatonin has a circadian rhythm: It is released at night, during sleep, but not during day.
        • ACTH / Cortisol has circadian rhythm.
      • HIGHER CORTICAL FUNCTION
        
        
        ALLOCORTEX: All cortical structures below the Rhinal (Collateral) Sulcus. It contains the following (The neocortex is everything else)
        • Hippocampus
        • Parahippocampal Gyrus
        • Entorhinal Cortex
        CORTICAL NEURONS:
        • Pyramidal Cells have long axons that project to other lobes of the brain or to subcortical structures.
          • They are excitatory neurons and use glutamate as neurotransmitter.
        • Fusiform Cells have long axons
        • Granule (Stellate) Cells are interneurons with short axons.
          • These neurons project to neighboring neurons in the same region of the brain.
          • These interneurons can be either excitatory (glutamate) or inhibitory (GABA)
        CORTICAL LAMINA: Layers of the Cerebral Cortex
        • Layers I-III: SUPRA GRANULAR LAYERS, most superficial layers.
          • Cortico-cortical inputs (associations) terminate primarily in one of these layers.
        • LAYER IV: GRANULAR LAYER. It contains granule cells.
          • Thalamic projections (subcortical information) terminates primarily in this layer.
        • Layer V: Output in this layer projects primarily to the Brainstem.
        • Layer VI: Deepest layer, next to white matter. Output in this layer projects primarily to Thalamus.
        CYTOARCHITECTURE:
        • GRANULAR CORTEX: The primary sensory regions of the cortex, which cytologically contains granules: Somatosensory (Brodmann 1-3), Visual (17), and Auditory (41).
        • AGRANULAR CORTEX: The motor regions of the cortex (4), which do not contain granules.
        BRODMANN'S AREAS
        
        Area 3a, 3b, 1, 2Primary and secondary somatosensory corticesArea 17Primary Visual (Striate) CortexArea 41Primary Auditory CortexArea 42Secondary Auditory Cortex (Wernicke's Area)Area 4Primary Motor CortexArea 6Premotor CortexArea 8Frontal Eye FieldsArea 5, 7Posterior Parietal Cortices
        ASSOCIATION CORTICES: The sign of higher intelligence. There are three association cortices.
        • POSTERIOR PARIETAL ASSOCIATION CORTEX: The convergence of somatosensory, visual, and auditory association cortexes. This is basically the area where we process special-sensory stimuli.
        • LESIONS = Neglect Syndrome, Astereognosias, Aphasias.
        • PREFRONTAL ASSOCIATION CORTEX: Short-Term Memory, foresight, and judgment.
          • SHORT-TERM MEMORY EXPT: Lesion in this area in monkeys, and they cannot select food under an opaque cup that was just placed there ten seconds ago.
          • Dopamine is a prominent
        • LIMBIC ASSOCIATION CORTEX: Memory, olfaction, and emotion.
          • Cingulate Cortex Lesion ------> Sham Rage in monkeys. Motor actions of rage without provocation.
          • Orbitofrontal Cortex Lesion ------> Decrease normal aggressiveness and emotional response.
            • Frontal Lobotomies, historically, were attempts to flatten behavior by lesioning the orbitofrontal cortex.
          • Inferior Temporal Lobe: This portion of limbic association cortex is concerned with long-term memory. Stimulation of this region resulted in vivid hallucinations of past experiences.
            • KLÜVER-BUCY-SYNDROME: Lesion of the inferior temporal lobe results in hypersexuality, oral exploration, and excessive hunger in monkeys.
        CORTICAL HEMISPHERES:
        • DOMINANT HEMISPHERE: Is defined as that one which contains specialized language areas, Wernicke's Area. Wernicke's area will be larger on the dominant side.
          • The relationship between hemispheric dominance and handedness is complex. They often correspond but not always.
          • For right or left-handed individuals, the left hemisphere is most often dominant, then codominance. Right-hemisphere dominance is least common.
        • SODIUM AMYTAL TEST: Test to see which hemisphere is dominant. Put this barbiturate into each of the Carotid Arteries, and have the subject count down from 10. When you have injected it into the dominant hemisphere, the subject will stop counting.
        • CORPUS COLLOSECTOMY: Split the interconnections between left-brain and right-brain, such that left and right-brain function cannot communicate. If a subject is presented an apple in exclusively one visual field or the other:
          • RIGHT VISUAL FIELD ------> Left Visual Cortex ------> the subject is able to verbally identify the object as an apple.
          • LEFT VISUAL FIELD ------> Right VIsual Cortex ------> The subject could not identify it as an apple, even though he knew it was, because he had no access to language acquisition.
            • The subject was still able to pick it out from among different objects or identify it in other non-verbal ways.
        • NON-DOMINANT (RIGHT) HEMISPHERE:
          • Contains lots of association areas
          • Concerned with spatial-perceptual orientation
          • Facial recognition.
        Language:
        • APHASIAS: Disturbances of language production, comprehension, or both.
          • This is not a strict motor problem, but one where problem lies in higher cortical centers. Some strictly motor problems:
            • Dysarthria: Inability to articulate language. Strict motor deficit.
            • Dysphonia: Lack of control over vocal cords. Strict motor deficit.
          • WERNICKE'S APHASIA: Deficit in comprehension of language.
            • Empty Speech: Verbal output is fluent but it is meaningless.
          • BROCA'S APHASIA: Deficit in forming meaningful language.
            • Verbal Output is possible but it is not fluent.
            • Verbal comprehension is normal.
          • CONDUCTION APHASIA: Damage to the Arcuate Fasciculus, which interconnects Broca's and Wernicke's areas.
            • Speech comprehension is good, but incorrect words may be used.
            • Impaired writing.
        • Language Areas:
          • Wernicke's Speech Reception Area (42): Speech comprehension.
            • Posterior Superior Temporal Lobe
          • Broca's Motor Speech Area: Speech formation; formation of fluent, meaningful speech.
          • ARCUATE FASCICULUS: The pathway that interconnects the two above.
        • WERNICKE-GSCHWIND MODEL: Describes the neural pathway by which a person reads a word and then vocally says what the word is. The pathway goes in the following order:
          • Visual Stimulus ------> ------> Visual Cortex ------> Visual Association Cortex ------> Angular Gyrus (in Parietal Association cortex): This step turns the written word into an auditory signal. Language is stored primarily as an auditory signal.
          • Angular Gyrus ------> Wernicke's Area: Interpretation of what the auditory signal means
          • Wernicke's Area ------> Arcuate Fasciculus ------> Broca's Area: speech formation signals are generated
          • Broca's Area ------> Facial part of motor cortex: The word is vocalized.
        • ALEXIA: Inability to read, resulting from damage to Angular Gyrus.
        • APROSODIA: Deficit in singing, intonation, or inflection of voice. A flat affect to the voice.
          • This results from a lesion to the speech-area on the non-dominant side, which is responsible for emotional inflection of voice.
        • AGRAPHIA: Inability to write. Also from damage to angular gyrus.
          • This can occur when visual symbols cannot gain access to the language system.
        • APRAXIA: Inability to perform learned motor movement, such as a saluting or flipping a coin.
          • This occurs from a Disconnection Syndrome and involves disruption of pathways going from Wernicke's Area to Premotor Cortex.
        LEARNING AND MEMORY:
        • REFLEXIVE MEMORY: Remembering how to do something, like riding a bike.
          • CONDITIONING: Classical condition is a form of reflexive memory. Pavlov's dog salivates when he hears the bell rings, after constantly being presented with a bell followed by food.
            • Conditioning Stimulus: The bell
            • Unconditioned Stimulus: The food
          • CEREBELLAR NUCLEI have been discovered to play a role in reflexive memory.
          • Operant Conditioning: Conditioning of behaviors based on the consequences (reward / punishment).
        • DECLARATIVE MEMORY: Conscious memory and recall.
          • TWO-STAGE MODEL of Memory Processing: Memories are formed by putting information in short-term memory into long-term memory.
          • HIPPOCAMPUS is known to perform the function of consolidating short-term memory into long-term memory.
            • Lesion of Hippocampus causes anterograde amnesia, inability to remember things after the point of injury.

THE LIMBIC SYSTEM


Anatomical Structures of the Limbic System:

• NEOCORTEX: Two structures located lateral, rather than medial, to the Sylvian Sulcus.
  • DORSOLATERAL CORTEX: Pre-Frontal Association Cortex.
    • INPUT: Dorsomedial Nucleus of the Thalamus.
    • OUTPUT: It projects to the Entorhinal Cortex
    • FNXN: It has marginal association with the Limbic System. It is involved in motivation and in the planning of emotions.
  • ORBITOFRONTAL CORTEX: It is involved in the motor events associated with emotion.
    • INPUT: Dorsomedial Nucleus of the Thalamus.
• ALLOCORTEX:
  • CINGULATE GYRUS: PALEOCORTEX (most primitive)
    • FNXN: Integral part of Papez' Circuit
    • INPUT: Anterior Nucleus of the Thalamus.
  • PARAHIPPOCAMPAL GYRUS: PALEOCORTEX (most primitive)
  • HIPPOCAMPAL FORMATION: The only structure that is exclusively part of limbic system. Locale is at the base of the Temporal Lobe.
    • Order of Signal: Entorhinal Cortex ------> Dentate Nucleus ------> Hippocampus
    • HIPPOCAMPUS: Receives input directly from Dentate Gyrus
      • Structure: Three layers containing Pyramidal Cells
        • Molecular Layer: Receives input from Dentate Nucleus
        • Pyramidal Cell Layer: Pyramidal cell bodies.
        • Polymorphic Layer: Output through Fornix or to other Hippocampal structures.
      • Anoxia: The hippocampus is extraordinarily sensitive to Anoxia.
      • OUTPUTS: The hippocampus has several outputs.
        • Back to Neocortex: Consolidation of Short-Term Memory into Long-Term Memory.
        • Fornix ------> To Hypothalamus: Modulate autonomic / hypothalamic behavior.
        • Septum: A way station for information headed to the hypothalamus.
      • FNXN: Hippocampus general function is to consolidate short-term memory into long-term memory
        • LESION of only hippocampus results in anterograde amnesia. Patient would be no longer able to remember new things, but previous memories would remain intact.
    • DENTATE NUCLEUS: Receives input directly from Entorhinal Cortex
      • Structure: Three layers containing Granule Cells
        • Molecular Layer: Outer layer, receives input from Entorhinal Cortex
        • Granule Cell Layer: Granule Cell bodies
        • Polymorphic Layer: Inner Layer, sends output to the Hippocampus
    • SUBICULUM:
    • ENTORHINAL CORTEX: In Papez' The primary input to the Hippocampus.
      • INPUT: It receives direct olfactory input, as well as association input for the other senses.
      • OUTPUT: The Dentate Nucleus.
  • AMYGDALA: Attaches the subjective components of emotions and feelings to autonomic components. Amygdaloid Nuclei:
    • CORTICOMEDIAN GROUP: Processes Olfactory Information
      • Corticomedian Group ------> Hypothalamus
      • Corticomedian Group ------> Stria Terminalis ------> Septum
    • BASOLATERAL GROUP:
      • Basolateral Nuclei <====> Neocortex
      • Basolateral Nuclei ------> Dorsomedial Nucleus of Thalamus ------> Pre-Frontal Cortex
      • Basolateral Nuclei ------> Nucleus Accumbens
    • CENTRAL NUCLEUS: Main cells that provide info to the hypothalamus.
      • Some info also sent to brainstem nuclei in Pons.
    • TWO MAIN OUTPUTS: The Hypothalamus and Stria Terminalis.
• DIENCEPHALON:
  • FORNIX: The tract over which the Hippocampus sends information to the Hypothalamus.
  • SEPTUM: A way station between the Hippocampus and Hypothalamus.
    • INPUT: Receives input from the Amygdala and Hippocampus.
    • OUTPUT: Sends info to the Hypothalamus
    • Nucleus Raphe Magnus (Serotonin) and Locus Ceruleus (Norepi) synapse on the Septum in a "diffuse" way and can therefore influence its output.
  • ANTERIOR NUCLEUS, THALAMUS:
    • OUTPUT: It sends output to the Cingulate Gyrus, in Papez' Circuit.
  • MEDIAL DORSAL NUCLEUS, THALAMUS:
    • OUTPUT: It sends output to the neocortical structures, Orbitofrontal and Dorsolateral Cortices.
    • INPUT: Receives motor information from the Ventral Globus Pallidus of Striatum.
  • HYPOTHALAMUS:
• STRIATUM (BASAL GANGLIA): Modulates motor activity in the Limbic System.
  • NUCLEUS ACCUMBENS:
    • CLOSED CIRCUIT: Nucleus Accumbens ------> Globus Pallidus ------> Dorsomedial Nucleus of Thalamus ------> Orbitofrontal Cortex
      • This circuit modulates the motor behaviors associated with emotion.
      • It is referred to as a "closed circuit"

PAPEZ CIRCUIT: The fundamental interaction between higher sensory input from the cortex and more primitive functions from the sub-cortex and the rest of the body.

• POSTERIOR PARIETAL ASSOCIATION CORTEX: Information that enters Papez' Circuit originates from the sensory association cortex (combination of visual, auditory, somatosensory)
  • OLFACTION: Olfactory information, on the other hand, enters the Limbic System directly.
• INCOMING SIGNAL: Association-Cortex ------> Cingulate Gyrus ------> Hippocampal formation ------> Entorhinal Cortex (synapse) ------> Hippocampus
• OUTGOING SIGNAL: Hippocampus ------> Fornix ------> Mamillary Bodies ------> Mammillothalamic Tract ------> Anterior Nucleus of Thalamus

KLÜVER-BUCY SYNDROME: Hypersexual horniness. Lesion of the Amygdala and Hypothalamus.
SCHIZOPHRENIA: A splitting of the cognitive with the emotional aspects of behavior.

• DOPAMINE: Two Dopaminergic systems are implicated in Schizophrenia.
  • MESOLIMBIC SYSTEM: Provides Dopaminergic neurons to the Nucleus Accumbens.
  • MESOCORTICAL SYSTEM: Projects dopaminergic neurons to PreFrontal Cortex.
• POSITIVE SYMPTOMS: Overproduction of Dopaminergic Mesolimbic Neurons ------> over expression of limbic system
  • This problem could be treated with dopamine antagonists
  • Positive Symptoms = hallucinations and uncontrolled emotions
• NEGATIVE SYMPTOMS: A decrease in dopaminergic output of the mesocortical system ------> pre-frontal cortex. They think this may be involved.
  • This problem could theoretically be treated with dopamine itself, but that treatment doesn't work.
  • Negative Symptoms = lack of motivation, lack of planning, lack of foresight

hi,lyuda,
cant help praising you for the great work.is this from road map? or any other book.can u please specify
well done