Download UNIT XI

Motor Functions of the Spinal
Cord
BIEN 500
Steven A. Jones
Spinal Cord Function
• Conduct signals to the periphery of the
body.
• Process these signals as necessary
– Reflex actions
– More complicated actions, such as walking
Spinal Cord Divisions
• Anterior Motor Neurons
– Alpha Motor Neurons (large skeletal muscles)
• Type A nerve fibers
• Enervate large skeletal muscles
• Stimulate 3 to several hundred fibers each
– Gamma Motor Neurons
• Type A nerve fibers
• Send signals to muscle spindles
• Interneurons
– Perform Integrative functions
– Most signals in spine are processed through these
• Renshaw Cell Inhibitory System
– Suppresses spread of signals
– Located in the ventral horn
Motor Spindles
• Stimulated by stretching
• Send signals as a result of:
– Change in length of muscle.
– Change in tension on the muslce.
• Primary ending
– Group Ia fiber
– Important for sensing dynamic changes
• Secondary ending
– Group II fiber
– With Primary ending, sends a static response
Muscle Stretch Reflex
• Muscle stretch causes contraction
– First dynamic (short term), then static (long term)
– Shortening of muscle will cause inhibition
Anterior Horn
Motor Nerve
Proprioceptor Nerve (Ia)
Muscle Spindle
Posterior Horn
Force of Contraction
Feedback Function of Spindle
This effect is not surprising, is it?
With
Spindle
0
Without
Spindle
Time (s)
3
31% of the motor nerve fibers are gamma
efferent fibers
Gamma Motor System
• Excited by bulboreticular facilitory region
of the brain stem via:
– Cerebellum
– Basal ganglia (in the brain)
•
•
•
•
Caudate nucleus
Putamen
Globus pallidus
Substantia nigra subthalamic nucleus
– Crebral cortex
Muscle Length
Knee Jerk and Clonus
Clonus (think time delay)
Knee
Jerk
0
E.g. fatigue when standing
on tip toes.
Time (ms)
400
Golgi Tendon Organ
•
•
•
•
•
Detects tension rather than length.
Found between tendon and muscle.
Signals transmitted by type Ib nerve fibers.
Negative feedback to prevent overstimulation.
May help even out muscle load on fibers.
Tendon
Muscle
Golgi Tendon Organ
Flexor/Withdrawal Reflex
• Also called nociceptive reflex
• Pain initiates flexion, without passing
through brain
• Passes through interneurons
• Get extension in opposite limb
Flexor Reflex
Extensor Inhibition
Extensor Stimulation
Flexor Stimulation
Flexor Inhibition
Interneurons
Pain Signal from Hand
Reciprocal Inhibition: Stimulus exciting one muscle will
inhibit the antagonist muscle.
Spinal Cord Reflexes
• These responses occur in decerebrate
animlas.
– Walking
– Galloping
– Scratching
Muscle Spasm
• Broken bone
• Abdominal muscle spasm
• Muscle cramps
– Severe cold
– Lack of blood flow
– Overexercise
• Contraction may stimulate more
contraction – positive feedback.
Autonomic Spinal Cord Reflexes
• Vascular tone (e.g. change in skin
perfusion)
• Sweating
• Intestinal reflexes
– Control of gut muscles
– Inhibition of gastrointenstinal motility (e.g.
irritation)
• Bladder/Bowel control
Spinal Shock
• Occurs when spinal cord is deprived of
brain input.
• Spine recovers after days.
• Similar mechanism applies to most nerves
• Recovery may be excessive
• Affected functions:
– Arterial blood pressure
– Skeletal muscle reflexes are blocked
– Bladder/bowel control are lost (but recover)
Cortical and Brain Stem
Control of Motor Function
BIEN 500
Steven A. Jones
The Cerebellum, the Basal
Ganglia, and Overall Motor
Control
BIEN 500
Steven A. Jones
Organization of the Brain
Thalamus
Cerebellum
Regions of the Basal
Ganglia
Motor Functions of the Cerebellum
•
•
•
•
•
•
Running
Playing a musical instrument
Talking
Writing
Typing
I.e. Repeated, learned actions.
Mechanism of Action of Cerebellum
• Sequences motor activities
• Monitors and corrects motor activities to
conform to signals from the motor cortex &
other parts of the brain.
• A negative feedback system.
Anatomy
Anterior Lobe
• Afferent – Incoming
– From brain
– From periphery
Posterior
Lobe
• Efferent – Outgoing
– From brain
– From periphery
Flocculonnodular Lobe
Oldest, Vestibular
(equilibrium) control
The Purkinje Cell
Molecular
Layer
Billions of Parallel
Nerve Fibers
Purkinje (Inhibitory)
Constantly firing
Purkinje Layer
Granule Layer
Granule Cells
Input from
Inferior Olive
(Climbing Fiber)
strong stimuli
Output
Deep Nuclear Cell
Constantly firing
Multiply by 30,000,000
Deep Nuclei
Input from Elsewhere
(Mossy Fiber)
weak stimuli
Learning (Perkinje Cells)
• Inferior olivary complex receives intent and
execution information – sends error signal.
• Climbing fiber rate – 1 per second
• Mismatch between desired movement &
actual movement increases/decreases rate.
• Firing rate changes sensitivity of perkinje
cells.
• Error signal is then stopped.
Feedback Control of the Distal Limb
Motor Cortex
Thalamus
Intermediate
zone of
cerebellum
Red
Nucleus
Feedback from Cerebellum
Intended
Movements
Actual Movements
Muscles
Generally important for movements that are too fast to be corrected on the fly.
Effects of Cerebellar Damage
• Slow development of movements
• Weak development of force
• Overshoot of motion
Thus, the cerebellum functions to plan,
sequence and time complex motions.
Non-Motor Functions of the
Cerebellum
• Estimation of speed.
• Prediction of timing.
• Interpreting spatiotemporal relations.
Abnormalities of the Cerebellum
• Dysmetria and Ataxia/Past Pointing
– Discoordinated movements/Overshoot
• Dysdiadochokinesia – don’t know where
your body parts are in fast motion.
• Dysarthria – cannot coordinate speech
• Intention tremor – movement overshoot
• Cerebellar nystagmus – tremor of the
eyeballs
• Hypotonia – loss of muscle tone.
Basal Ganglia
• Include the following components of the brain:
–
–
–
–
–
Caudate nucleus
Putamen
Globus pallidus
Substantia nigra
Subthalamic nucleus
• Located lateral to the thalamus
• Nearly all motor & sensory nerves from the
crerebral cortex pass between the caudate
nucleus and putamen.
Basal Ganglia
Thalamus
Putamen and
Globus Palidus
Amygdala
Cerebellum
Caudate Nucleus
Basal Ganglia
• Control complex motor activity
– E.g. writing letters of the alphabet
– Cutting paper with scissors
– Shooting a basketball
– Hammering nails
– Throwing a football/baseball
Parkinson’s Disease
• Destruction of the pars compacta in the
substantia nigra
• Prevents activity of dopamine-secreting
nerve fibers to the caudate nucleus.
• Dopamine = Inhibitor
• Causes
– Rigidity of musculature
– Involuntary tremor (3-6 Hz)
– Difficulty initiating movements
Treatment for Parkinson’s
• L-Dopa
– Gets converted to dopamine
– Dopamine will not pass the blood-brain barrier
• L-Deprenyl
– Inhibits monoamine oxidase, which destroys dopamine.
– Helps slow destruction of dopamine producing neurons
– Can be combined with L-Dopa
• Transplanted fetal dopamine cells
– Cells do not persist for more than a few months.
– Raises the abortion issue.
• Destruction of feedback circuitry in the basal ganglia
The Cerebral Cortex; Intellectual
Functions of the Brain; and
Learning and Memory
BIEN 500
Steven A. Jones
Cerebral Cortex
• Largest part of the nervous system
• Functional part: 2 – 5 mm thick layer of
neurons
• Total area ~ 1 m2
• ~ 100 billion neurons
• Three types of cells
– Granular (or stellate)
– Fusiform
– pyramidal
Granular Cells
• Pyramidal in shape
• Short axons – function as intracortical
neurons
• Excitatory – Glutamate
• Inhibiroty - GABA
Pyramidal Cells
•
•
•
•
Source of output fibers
Larger, more numerous than fusiform cells
Nerve fibers go down to spinal cord.
Fibers also connect major regions of the
brain.
• Fusiform cells provide similar functions.
Layers of the Cerebral Cortex
I.Molecular Layer
Large Numbers
of Neurons
II. External Granular Layer
Intracortical
Association Functions
III.Pyramidal Cells
IV. Granular Cells, Output fibers to thalamus
V. Large fibers to brain stem and cord
VI. Fusiform or polymorphic cells. Output signals
VII. Output signals
Divisions of the Cerebral Cortex
Eye
Tuning
Thought
Supplementary Motor
Synergies
Hand
Skills
Speech
Bilateral
Vision
Contralateral Vison
Functional Areas of the Cerebral
Cortex
Motor
Planning
Movement,
Thought
Spatial
Coordinates
of Body and
Surroundings
Word
Formation
Vision
Broca’s Area
Behavior, Emotion,
Motivation (Limbic)
Language
Comprehension,
Intelligence
Interesting Brain Regions
• Broca’s Area – word formation
• Angular Gyrus
– Interpretation of visual information
– Associated with dyslexia
• Wernicke’s Area
– More developed in dominant side of brain
– General interpretive area
– Stimulation may produce complex visualization,
hallucinations, complex statements, hearing a musical
piece
• Limbic Association Area – behavior, emotion,
motivation.
• Facial Recognition Area (large)
Dominant Hemisphere
• Wernicke’s area more developed on one
side.
– Important for language, mathematics, logic.
• Left hemisphere more dominant for 95%
– More than 50% larger in over 50% of neonates.
– Other 5% is either dual- or right-dominant.
– Related to right-handedness.
• Hemispheres communicate via corpus
callosum
Non-Dominant Hemisphere
•
•
•
•
•
•
•
Understanding/Interpreting music
Nonverbal visual experiences
Spatial relations with surroundings
Interpretation of “body language”
Interpretation of vocal intonation
Somatic experiences
Non-symbolic interpretation
Effects of Prefrontal Lobotomy
•
•
•
•
•
Inability to solve complex problems
Inability to combine tasks to reach goals
Inability to multitask
Loss of aggressiveness/ambition
Inappropriate social responses (w.r.t.
morals/sex/body functions)
• Inability to produce trains of thought
• Rapid mood changes
• Normal motor function, but often without purpose
Interpretation of Prefrontal Lobotomy
• Passiveness/Inappropriate social responses
– Probably relates to limbic system
• Inability to follow through sequences
– Easily distracted from the central theme
– Lack of “working” (Cache) memory disables
•
•
•
•
•
Prognostication
Planning for the future
Delay of impulses
Consideration of consequences of actions
Solving complicated problems
Aphasia
• Wernicke’s Aphasia
– Damage to Wernicke’s area in the dominant
hemisphere
– Can understand the words, but not the thought.
• Broca’s Aphasia
– Damage to Broca’s area
– Unable to form motor control
• Other areas
– Cerebellum, basal ganglia, sensory cortex
– Total or partial inability to speak
Contralateral Control
• Right side of brain controls left side motor
coordination & vice versa
Corpus Callosum
Corpus Callosum
• Transfers information from Wernicke’s area to
contralateral motor cortex
• Prevents somatosensory information from
contralateral hemisphere from reachig
Wernicke’s area
• Severing is a treatment for epilepsy
• If severed
– Can still perform subconscious motor functions on
ipsilateral side
– May do things without knowing why
Thought
• Holistic theory
– Thought results from a pattern of stimulation
– Involves cerebral cortex, thalamus, limbic system,
upper reticular formation (URF)
– Thalamus, limbic system and URF determine:
•
•
•
•
Pleasure
Pain comfort
Modalities of sensation
Crude localization on the body
– Cerebral cortex determines:
• Fine localization on the body & in space
• Texture
• Recognition of geometric patterns
Memory
• Caused by new neural pathways or facilitated
pathways.
• Occur at all levels of the nervous system.
• Intellectual memory mostly in cerebral cortex
• Mind ignores much (unimportant information)
• Mind remembers important information
– Pain
– Pleasure
Classification of Memories
• Short term
– Last seconds or minutes
– May be converted to long-term memory
– Classic example – phone number
• Intermediate long-term
– Last days to weeks, but fade
• Long-term
– Can be recalled years later
– Pathways to complex memories may be difficult to
find
Explanations of Short-Term Memory
• Reverberating neurons
• Presynaptic facilitation or inhibition
• Enhanced synaptic conduction/
accumulation of calcium
Mechanism for Intermediate Memory
• Temporary chemical or physical changes
at presynaptic terminals or postsynaptic
membranes
Facilitator Neuron
Sensory Neuron
cAMP
Serotonin
Ca++
Facilitatory neuron prevents habilitation and enhances
synaptic response.
Molecular Path in Intermediate Memory
• Habituation caused by closure of Ca++ channels.
• Serotonin activates adenylcyclase, forms cAMP.
• cAMP activates protein kinase, blocks K+
conductance (up to several weeks), prolongs
action potential (AP).
Facilitator Neuron
• Prolonged AP releases
Ca++ Channel
large amounts of Ca++.
Serotonin
• Facilitatory neuron can
cAMP
also act on postsynnaptic membrane.
++
K+ Channel
Ca
Long-Term Memory
• Caused by structural changes.
– Increase in no. of neural transfer vesicles
– Increase in no. of neural transfer vesicle
release sites
– Increase in no. of presynaptic terminals/length
of dendrites
Neural Development
• Excess neurons at birth
• Axons that do not connect or connect with wrong
type of cell dissolve
• Nerves will not develop for a blocked eye.
• 50% or more of original neurons in parts of
cerebral cortex are eliminated.
• This is a type of memory.
• Plasticity continues to a lesser extent in later life.
– E.g. can recover after stroke (sensory and motor).
Consolidation Time
• Minimal consolidation 5-10 minutes
• Strong consolidation 1 hour
• Determined by shock experiments
– Provide strong sensory input
– Convulsive shock after a time period
– Determine whether subject remembers or not.
Rehearsal
• Repeating something over in the mind.
• People tend to do this with “interesting”
things.
• If wide awake, remember better than when
in mental fatigue.
• None of this is particularly surprising, is it?
Computer Memory
Short Term
Long Term
Hard
Disk
(slow,
large)
RAM
(fast,
“small”)
Cache
Memory
(faster,
smaller)
On Chip
Memory
(fastest,
smallest)
CPU
Removable
Storage
(slowest,
“largest”)
Computers are designed to account for
tradeoffs of speed and size. Fast memory
tends to be more expensive.
Files are not “erased.” Rather the information that points to them is
deleted, allowing information to be overwritten.
Programs can retrieve these files after deletion if they have not been
(completely or partially) overwritten.
Associative Memory
Clock
Piano
Time
Hands
Music
Fingers
Score
Metronome
Toes
Four score and
seven years
ago today, our
forefathers …
Uh … Dang!
Metric
Meters
Lincoln’s
Gettysberg
Address
Feet
Length
Gettysberg
Corn
Wheat
Civil War Battles
Codification of Memory
• Same as “association.”
• Organization of memories helps in retrieval.
• Complex memories can be stored, but not
immediately accessible.
• My personal hypothesis on dreams
– Random access of complex stored memories
– Delete “links” to useless information
– Similar to disk defragmentation?
Role of Thalamus in Memory
• Damage may cause retrograde amnesia
without anterograde amnesia
– Forget things
– Forget recent things more than older things
• Thalamus may affect memory “search.”
Role of Hippocampus in Memory
• Hippocampus output is reward/punishment
• Removal of hippocampus
– Inability to form new long term
verbal/symbolic memories
• Referred to as anterograde (ante=before) amnesia
• You do not “forget” things.
• You just cannot remember new things.
– Can also cause some retrograde amnesia
• Not important in reflexive learning (e.g.
sports)
Behavioral and Motivational
Mechanisms of the Brain – The
Limbic System and the
Hypothalamus
BIEN 500
Steven A. Jones
Regulatory Functions
• Cardiovascular
• Body Temperature
• Fluid regulation
– Thirst
– Excretion of water into the urine
• Reproduction
– Uterine contraction
– Milk ejection
• Feeding
– Hunger (lateral hypothalamic area)
– Satiety (in the ventromedial nucleus)
– Licking lips, swallowing (mamillary bodies)
• Control of pituitary gland
Emotional Effects of Hypothalamus
• Lateral hypothalamus
– Thirst, eating
– Increased activity level
– Rage and fighting
• Ventromedial nucleus
– Reward centers
– Opposite of lateral hypothalamus
• Thin zone of periventricular nuclei & central gray area of
mesencephalon
– Fear and punishment
• Anterior & Posterior regions (and others)
– Sexual drive
Hippocampus
• Hippo – horse (e.g. hippopotumus=river
horse).
• Three nerve cell layers instead of six.
• Filtering of incoming sensory information
• Stimulation – rage, passivity & sex drive
• Weak stimulation can lead to seizure
– Localized
– Olfactory, visual, auditory, tactile hallucinations
Hippocampus and Learning
• Role in learning discussed previously
• Originally part of olfactory cortex.
• Smells important to eating & sex drive.
Amygdala & Hypothalamus
• Bidirectional connections with hypothalamus.
• Effects mediated through hypothalamus:
– Control of arterial pressure, heart rate
– Control of gastrointestinal motility & secretion
– Defecation & micturation
– Pupillary dilation and (rarely) constriction
– Secretion of pituitary hormones, especially:
• Gonadotropins
• Adrenocortocopic hormone
Amygdala Stimulation
• Tonic movement (raising head, bending
body)
• Circling movments
• Clonic, rhythmical movements
• Olfaction/Eating movements (licking,
chewing, swallowing)
• Rage, escape, punishment, fear
Similar to
Hypothalamus
• Reward & pleasure
Amygdala Bilateral Ablation in
Monkeys
•
•
•
•
•
•
•
•
Klüver-Bucy syndrome
Excessively examine objects orally
Loss of fear
Decreased aggressiveness
Tameness
Herbrivore may become carnivorous
Sometimes psychic blindness
Excessive sex drive
Limbic Cortex
• Surrounds the limbic structures.
• Not well understood:
– Stimulation yields little information
– Ablation of anterior temporal cortex usually also damages
amygdala.
• Ablation of Posterior Orbital Frontal
– Insomnia
– Motor restlessness
• Ablation of Anterior Cingulate & Subcallosal Gyri
– Nothing to filter rage from hypothalamus
• Regions of cortex appear to cause association of
limbic functions with nearby regions of cerebral
cortex. (e.g. connecting sensations with feelings)
States of Brain Activity – Sleep;
Brain Waves; Epilepsy;
Psychoses
BIEN 500
Steven A. Jones
Types of Sleep
• Slow-wave sleep
– The largest proportion of a given sleep period
– Deep, restful
• Rapid-eye-movement (REM) sleep [Paradoxical
or Desynchronized Sleep]
– Occur periodically (ca. every 90 minutes for 5-30
minutes)
– About 25% of time for young adult
– Associated with vivid dreaming
– Duration increases as person becomes less tired.
Slow Wave Sleep
• Decrease in body functions (10 – 30%)
– Peripheral vascular tone
– Blood pressure
– Respiratory rate
– Basal metabolic rate
• Dreams & sometimes nightmares do occur.
– Less likely to be remembered.
– I.e. consolidation of dreams in memory does
not occur.
REM Sleep
•
•
•
•
•
•
•
•
Usually associated with dreaming
Harder to wake subject, yet …
People usually awaken naturally during REM
Strong suppression of muscle tone (but not the
eye muscles, obviously).
Irregular heart rate/respiratory rate
Increase of brain metabolism of ~20%.
EEG patterns similar to wakefulness
Brain is active, just not connected to the world
Theories of Sleep
• Passive theory
– Brain becomes fatigued and inactive
• Active theory
– Brain is actively inhibited
– Transecting brain stem in midpontile region
prevents sleep (based on EEG)
– I.e., something below midpontile region
causes sleep by inhibiting parts of the brain.
Areas where stimulation causes
sleep
• Raphe nuclei in medulla & lower half of pons
– Nerve fibers extend to reticular formation, thalamus,
neocortex, hypothalamus & limbic system.
– Can inhibit incoming pain signals
– Release serotonin
• If serotonin formation is blocked, no sleep but …
• Serotonin levels are decreased during sleep.
• Parts of nucleus of the tractus solitarius
– Region of medulla & pons for visceral signals
– Depends on presence of raphe nuclei
• Regions of diencephalon
Transmitter Substances & Sleep
• Muramyl peptide
– Low molecular weight
– Accumulates in blood/cerebral spinal fluid in
sleep deprivation
• A nonapeptide (found in sleeping animals)
• “A third factor” found in neuronal tissue
after sleep-deprivation
Causes of REM Sleep
• Possibly associated with acetylcholine
from upper brain stem reticular formation.
• Cyclic behavior of sleep not well
understood.
Effects of Lack of Sleep
• Sluggishness
• Irritability
• Psychosis
Epilepsy
EEG
• Grand Mal Epilepsy
(high voltage)
• Petit Mal Epilepsy
(spike & dome pattern)
• Focal Epilepsy
100 m
Grand Mal Epilepsy
•
•
•
•
•
•
•
Neural discharges in all areas of the brain
Tonic seizures of the body
Tonic-clonic seizures (near the end)
Swallowing tongue, difficulty breating
Sometimes defication, urination
Duration: seconds to 4 minutes
May lead to stupor/fatigue/sleep
afterwards.
Petit Mal Epilepsy
• Probably involves thalamocortical brain
activating system
• 3 to 30 seconds of unconsciousness or
diminished consciousness
• Twitching, blinking
• Remains conscious afterwards
• Onset in late childhood, disappear at ~
age of 30.
• May trigger Grand Mal
Focal Epilepsy
• Can occur anywhere in the brain
• Usually caused by localized lesion
• E.g. when occurs in motor cortex, causes
“progressive march of muscle contractions
on contralateral side (jacksonian epilepsy)
• May trigger Grand Mal
• Interesting case – psychomotor seizure
Psychomotor Seizure
• May involve
–
–
–
–
–
Short period of amnesia
Attack of abnormal rage
Sudden anxiety, fear, discomfort
Moment of incoherent speech, mumbling trite phrase.
Motor act (attack, rub face)
• Subject may not remember activities
• May remember he/she did them, but not know
why.
Depression
• Depression
– Diminished formation of norepinephrine, serotonin or
both? (probably others)
– Depression may involve
•
•
•
•
Grief, unhappiness, despair, misery
Loss of appetite, sex drive
Insomnia
Psychomotor agitation (despite the depression)
• Manic Depression (biopolar disorder)
– Alternating between depression & mania
– Lithium diminishes norepinephrine/serotonin
Treatments for Depression
• Drugs
– Monoamine oxidase inhibitors
• Block destruction of norepi and serotonin
– Tricyclic antidepressants
• E.g. imipramine, amitriptyline, many newer ones.
• Block norepi & serotonin reuptake
– Drugs that enhance effect of serotonin
• Electroconvulsive therapy
– Enhances norepinephrine transmission efficiency
– “Here. This ought to snap him out of it!”
Schizophrenia
• Symptoms (not “split personality”):
– Hearing voices
– Delusions of grandeur
– Paranoia, sense of persecution
– Incoherent speech
– Dissociation of ideas, abnormal thought
sequences
– Witdrawn, abnormal posture, rigidity
Possible causes of schizophrenia
• Multiple prefrontal lobe areas where signals are
blocked or dysfunctional
• Excessive excitement of dopamine secreting
neurons in behavioral centers
– Parkinsons patients given L-Dopa can develop
schizophrenia
– Drug treatments reduce dopamine release
• Abnormal function of limbic behavioral control
system (hippocampus)
– Hippocampus is often reduced in size
– Regions connected to hippocampus are hyperfunctional
Alzheimer’s Disease
• Premature aging of the brain
• Loss of memory function
• Patients have amyloid plaques (10 – several
hundred m) in cortex, hippocampus, basal
ganglia, thalamus, cerebellum
• Metabolic degenerative disease
• Consistently find loss of limbic memoryrelated neurons
The Autonomic Nervous
System; the Adrenal Medulla
BIEN 500
Steven A. Jones
Cerebral Blood Flow, the
Cerebrospinal Fluid, and Brain
Metabolism
BIEN 500
Steven A. Jones