The Central Nervous System

The Brain

The embryonic structure that gives rise to CNS structures is the neural tube.

When the neural tube is formed it differentiates into the brain rostrally and spinal cord caudally.

Anteriorly begins to expand and forms the three primary brain vesicles.

Primary brain vesicles

Prosencephalon (forebrain)

Mesencephalon (midbrain)

Rhombencephalon (hindbrain)

Secondary brain vesicles – by 5th week

From Prosencephalon:

Telencephalon

Sprouts “ears” – cerebral hemispheres

Also gives rise to lateral ventricles and superior part of 3rd ventricle

Diencephalon

Thalamus, hypothalamus, epithalamus

Most of 3rd ventricle

From Mesencephalon:

Mesencephalon  

Brain stem: midbrain

Cerebral aqueduct

From Rhombencephalon:

Metencephalon

Brain stem: pons

Cerebellum

4th ventricle

Myelencephalon

Brain stem: medulla oblongata

4th ventricle

Flexures develop due to restriction of skull

Midbrain and cervical flexures bend forebrain toward brain stem

Cerebral hemispheres grow posteriorly and laterally in a horseshoe shape, creases and folds to form convolutions

Increases surface area accomodates around one trillion neurons

 

Regions and Organization of the Brain

Regions

Cerebral hemispheres

Diencephalon (sometimes grouped with either brain stem or cerebrum)

Brain stem

Cerebellum

Organization of CNS

Spinal cord – central cavity surrounded by gray matter surrounded by white matter

Brain – central cavity surrounded by gray matter surrounded by white matter with some exceptions: Outer cortex of gray matter in cerebrum and cerebellum, scattered gray matter (nuclei) within white matter or brain stem

Ventricles of the Brain

Spaces within the brain

Connected to each other and the spinal cord’s central canal

Lined with ependymal cells

Lateral ventricles (1st and 2nd ventricles)

One in each cerebral hemisphere

Close anteriorly, separated by septum pellucidum (thin membranous structure

Connected to 3rd ventricel by interventricular foramen (Foramen of Monro)

Third ventricle

Located in diencephalon

Cerebral aqueduct connects to 4th ventricle

Fourth ventricle

Dorsal to pons and superior to medulla

Continuous with central canal of spinal cord inferiorly

Connected to subarachnoid space by 2 lateral apertures and median aperature

 

Cerebral Hemispheres

Features

Gyri  (Jeer-ee) – folds

Sulci (sul-kee ) – grooves

Fissure – deep groove

Longitudinal fissure separates hemispheres

Transverse fissure separates cerebrum from cerebellum

Central sulcus – separates frontal lobe from parietal lobe

Precentral gyrus – anterior

Postcentral gyrus - posterior

Parieto-occipital sulcus separates parietal lobe and occipital lobe

Lateral sulcus separates temporal lobe from parietal and frontal lobes

Insula – 5th lobe, buried in lateral sulcus

 

Cerebral Cortex

Features

Seat of consciousness

Gray matter – cell bodies, dendrites, unmyelinated axons, glia, blood vessels; no fiber tracts

Brodmann areas

52 different areas mapped by variations in thickness and structure of neurons

Functional aspects: domains

Specific motor and sensory functions localized in domains

Accommodates the Regional Specialization Theory (Structurally distinct areas have specific functions)

Higher mental functions (memory and language) have overlapping domains, or at least receive input from and send output to different domains

Accommodates the Aggregate Field View (Cortex acts as a whole to carry out mental functions)

 

Generalizations

Three functional areas: motor, sensory, and association

Contralateral innervation

Lateralization of function

All functional areas interact with other areas in some way

Motor Areas

Primary motor cortex (somatic motor cortex)

Located in precentral gyrus of frontal lobe of each hemisphere

Directs conscious movement of SkM

Axons of pyramidal cells in precentral gyrus run down spinal cord; form voluntary motor tracts called pyramidal tracts or corticospinal tracts

All other descending motor tracts come from brain stem nuclei and have 2 or more neurons in a chain

Somatotopy and the motor homunculus – localization of body structures to neurons that control them

Actually shown that neurons innervate more than one muscle (synergists)

Muscles receive input from more than one site on the cortex

Premotor cortex

Anterior to precentral gyrus

Controls practiced motor skills of a repetitive nature; coordinates movement of several muscle groups simultaneously

Typing
Musical instrument

Broca’s area

Anterior to the inferior region of the premotor cortex

Thought to be present in only one hemisphere – usually the left – concerned with motor speech; direction of muscles used to speak

Broca’s area and a corresponding area in the other hemisphere both are active just before speech and during the “planning” phase preceding other voluntary motor activities.

Frontal eye field

Anterior to premotor coretex and superior to Broca’s area

Controls voluntary eye movements

Sensory Areas

Somatosensory areas

Primary somatosensory cortex

Postcentral gyrus

Receive input from general sensory receptors in skin and proprioceptors in SkM

Identify region being stimulated – spatial discrimination

Somatosensory homunculus

 

Somatosensory association area

Posterior to the primary somatosensory cortex

Integrates and analyzes somatic sensory input

Lets you stick your hand in your pocket and know what you’re grabbing

Visual areas

Primary visual cortex

Located on posterior tip of occipital lobe and within calcarine sulcus on the medial aspect of the occipital lobe

Largest cortical sensory area

Receives input from retinas

Contralateral – right half of visual space from each eye sends input to the left visual cortex and vice versa

Visual association area

Surrounds primary visual area

Interprets visual stimuli, enables recognition

Damage to primary visual cortex = blindness; damage to visual association area = see it but don’t know what it is

Auditory areas

Primary auditory cortex

superior margin of temporal lobe

input from cochlear receptors of inner ear

Auditory association area

Integrates; tells you what you heard

Sound memories stored here (what it is, not so much what it means)

Olfactory cortex

Piriform lobe in medial aspect of temporal lobes

Part of rhinencephalon, now associated with emotion and memory (limbic system)

Gustatory cortex

Insula, deep to temporal lobe

Visceral sensory area

Posterior to the gustatory cortex in the insula

Conscious perception of visceral sensations

Vestibular (equilibrium) cortex

Posterior part of insula

Conscious perception of balance

Multimodal Association Areas

Any cortical area that doesn’t have primary in its name (not primarily linked to one sensory or motor area)

Communicate with the motor cortex and other sensory association areas; analyze, recognize, act on input

Have multiple inputs and outputs independent of primary sensory and motor areas

Anterior Association Area (Prefrontal cortex)

Most complicated cortical region

Intellect, complex learning, personality

Abstract ideas, judgment, reasoning, persistence, planning concern for others, and conscience

Linked to limbic system, role in mood

Prefrontal lobotomy – treatment of severe mental illness (‘30s to ‘50s); reduced anxiety (and judgment, initiative, spurred abnormal personality changes, caused epilepsy, etc.)

Posterior Association Area (General interpretation area or gnostic area)

Regionally diffuse

Input from all sensory association areas

Storage site for complex memories associated with sensation

Integrates input into understanding of situation, sends assessment to prefrontal cortex

Prefrontal cortex adds emotion and decides on response

Damage to this area results in inability to interpret situations (imbecility) Found in one hemisphere only (usually left)

Language areas – included in posterior association area

Wernicke’s area

Occurs in posterior temporal lobe of one hemisphere (usually the left)

Speech area; once thought to be the only area responsible for understanding both written and spoken language

May be the phonics area; comprehension may occur in prefrontal areas

Geschwind's territory

A newly discovered brain region, implicated in language.

Connects Broca's and Wernicke's areas via a region of the parietal lobe of the cortex, and may be important for the acquisition of language in childhood.

Apparently the last area in the brain to mature, the completion of its maturation coinciding with the development of reading and writing skills.

Affective language areas

Present in hemisphere opposite Broca’s and Wernicke’s areas

Affect – tone, both to impart and to interpret

Add emotional input to speech, interpret emotional content of speech

Limbic Association Area

Cingulate gyrus, parahippocampal gyrus, and the hippocampus

Provides emotional impact and helps establish memories

Lateralization of Cortical Functioning

Division of labor

Most functions performed by both hemispheres

Some dominance of tasks by one side or the other

Cerebral dominance

The hemisphere that is dominant for language (also tends to have greater control over mathematical abilities and logic)

Left side in about 90% of people

Other side does visual-spatial skills, intuition, emotion, appreciation of art and music; poetic, creative

Usually left dominant people are right handed

Other 10% either reversed or “bilateral”

Typically left handed (although most lefties are left dominant, just right motor dominant)

Ambidexterity sometimes, sometimes cerebral confusion; dyslexia?

Communication and control over each other

Rational brain keeps emotional brain from running amuck, emotional brain keeps rational side from intellectualizing everything to death

Function together, not as separate units

He Brain vs She Brain

Males exhibit proficiency at spatial-visual tasks early, females more proficient at verbal skills throughout life (selective use of part of hemisphere?)

Injury to dominant hemisphere compromises language abilities in males more than in females (greater use of other hemisphere?)

Structural differences – Male synaptic pattern develops in preoptic nucleus of hypothalamus in response to testosterone, female pattern is the default.

Region in anterior hypothalamus involved in male-typical sexual behavior is larger in males than females or homosexual males.

Planum temporale (area of temporal lobe involved in language and auditory function) cortical granular layer neuron density higher in females.

Females have longer temporal lobe and posterior region of corpus callosum is wider.

Some neurons innervating external genitalia much larger in males than females, contain receptors for testosterone but not estrogen.

Cerebral White Matter

Deep to gray matter

Communication between cerebral areas, cerebral cortex and lower CNS

Consists mainly of tracts, classified by direction they run

Commissural fibers (commissures) (horizontal)

Connect corresponding areas between hemispheres

Corpus callosum – largest

Anterior commissure

Association (horizontal)

Conduct within the same hemisphere

May be short, between gyri

Long – connect different lobes

Projection  (vertical)

Ascending tracts – enter from cord and lower brain centers

Descending tracts - leave cortex and run to lower centers

Internal capsule – band of projection fibers on either side of upper brain stem

Passes between thalamus and some of the basal ganglia, then radiates through cerebral white matter to cortex – corona radiata

 

Basal Ganglia

Really nuclei, but historically called ganglia

Consist mainly of caudate nucleus and the lentiform nucleus

Lentiform nucleus = putamen + globus pallidus

Fibers make up the corpus striatum

Internal capsule fibers run past and impart a striped appearance

 

Amygdaloid nucleus – grouped anatomically (sits on tail of caudate nucleus) with the basal ganglia but functionally part of the limbic system

Basal ganglia receive input from other nuclei, cerebral cortex, and each other.

Centre median nucleus of thalamus

Subthalamic nucleus

Substantia nigra of midbrain

The globus pallidus (output nucleus of the basal ganglia) and the substantia nigra project to premotor and prefrontal cortices through thalamic relays and so have indirect influence on voluntary muscle movements.

Starting

Stopping

Monitoring

Especially slow and sustained or stereotyped motions

Regulate intensity

Impairment results in postural and muscle tone problems, tremors, abnormal slowness of movement (Parkinson’s)

Also have a role in cognition and memory

Diencephalon

 

Thalamus

80% of diencephalon

Bilateral masses of gray matter connected by the intermediate mass (midline commissure)

Receives afferent impulses from all parts of the body and relays to appropriate area of cortex

Relays sensory impulses involved with similar functions to both sensory cortex and cortical association areas – crude recognition of pleasant vs. unpleasant sensation

Integrates some sensory input before relay to association areas

Relays hypothalamic afferents dealing with emotion and regulation of visceral activity

Relays cerebellar afferents (regulation of motor control)

Nuclei:

Dorsal nuclei

Medial

Lateral dorsal – integration of sensory input and relay to cortical association areas

Lateral posterior - integration of sensory input and relay to cortical association areas

Ventral nuclei

Ventral anterior – basal nuclei to cortex relays

Ventral lateral – cerebellum to cortex relay

Ventral posterior lateral – major synapse point for fibers carrying impulses from the general somatic sensory receptors

Anterior nuclear group – relays from hypothalamus (emotion and visceral function)

Reticular nucleus

Pulvinar – posterior extremity of the thalamus; integration of sensory input and relay to cortical association areas

Medial geniculate body – auditory relay center

Lateral geniculate body – visual relay center

Summary of roles: mediating sensation, motor activity, cortical arousal, learning, and memory

 

Hypothalamus

Inferior to thalamus, caps brainstem

Mammillary bodies – paired nuclei, protrude anteriorly; olfactory relays

Infundibulum – stalk connecting hypothalamus to pituitary, runs between the optic chiasma and mammillary bodies

Main visceral control center, lots of nuclei

Homeostatic roles

Autonomic control center

Controls autonomic centers in brain stem and spinal cord

Blood pressure, heart rate, contractility, digestive tract motility, respiratory rate and depth, pupil size, etc.

Center for emotional response and behavior (CERAB)

Inputs from limbic system

Perception of pleasure, fear, rage; biological rhythms, drives (sex)

Autonomic expressions of emotion – fight or flight

Body temperature regulation

Hypothalamic neurons sense blood temperature

Hypothalamic nuclei initiate cooling or heat-retention mechanisms as needed

Regulation of food intake

Hunger and satiety

Regulation of water balance and thirst

Osmoreceptors excite nuclei that trigger ADH release

Thirst centers stimulate drinking

Regulation of sleep-wake cycles

Suprachiasmatic nucleus – the biological clock times sleep wake cycle in response to light signals from visual pathways (receptors for melatonin)

Control of endocrine system functioning

Releasing and inhibiting hormones to stimulate anterior pituitary

Release of ADH (supraoptic nucleus) and oxytocin  (paraventricular nucleus) from posterior pituitary

Epithalamus (roof of third ventricle)

Pineal gland -  melatonin (sleep-wake cycle and mood)

Choroid plexus – manufacture of cerebrospinal fluid

Brain Stem

 

 

Midbrain

Between diencephalon and pons

Fiber tracts:

Ventral aspect contains cerebral peduncles

Fiber tracts containing pyramidal motor tracts

Medially, sort of, contains medial lemniscus

Spinothalamic sensory tracts - specific ascending pathways, inputs from a single type or a few related types of sensory receptor that can be localized precisely on the body surface.

Fasiculus cuneatus and fasiculus gracilis of spinal cord synapse with 2nd order neurons in the nucleus cuneatus and nucleus gracilis in medulla, continue on to terminate in the ventral posterior nuclei of the thalamus.

Between dorsal border of substantia nigra and red nucleus medially.

Dorsal aspect contains superior cerebellar peduncles

Fiber tracts connecting midbrain to cerebellum

Cerebral aqueduct

Connects 3rd and 4th ventricles

Separates cerebral peduncles from the tectum

Surrounded by gray matter

Tectum

Dorsal aspect of midbrain (the “roof”)

Nuclei:

Periaqueductal gray matter

Nuclei that are part of the body’s endogenous pain suppression mechanism and link the amygdala (fear sensing) to the fight or flight ANS centers

Oculomotor nuclei (cranial nerve III)

Trochlear nuclei (cranial nerve IV)

Substantia nigra

Deep to cerebral peduncles

Largest nuclei in midbrain

Pigmented with melanin, the dopamine precursor

Functionally linked to basal ganglia, involved in motor control activity

Red nuclei

Between substantia nigra and cerebral aqueduct

Pigmented – iron

Well vascularized

Relay nuclei in descending motor pathways involving limb flexion

Reticular formation nuclei also present

Corpora quadrigemina (4)

Superior colliculi

Paired

Visual reflex centers

Coordinate head and eye movements during tracking a moving object

Involuntary head movement in response to detection of peripheral motion

Inferior colliculi

Auditory relays

Startle reflex – turning to an unexpected sound

Pons

Composed primarily of tracts

Projection fibers between cord and higher brain centers

Relay fibers between pontine nuclei and cerebellum

Connect motor cortex with cerebellum

Form middle cerebellar peduncles

Nuclei:

Give rise to cranial nerves V, VI, and VII

Reticular formation nuclei

Pontine respiratory centers – coordinates medullary respiratory centers

Medulla Oblongata

Tracts:

Pyramids

Pyramidal tracts from motor cortex

Decussation just above cord

Contralateral voluntary motor control

Inferior cerebellar peduncles – dorsal connections to cerebellum

Medial lemniscus

Somatic sensory tract from cord to somatosensory cortex

Nuclei:

Inferior olivary nuclei

Relay between proprioception pathways and cerebellum

Cochlear nuclei

Auditory inputs (vestibulocochlear nerves)

Vestibular nuclei

Make up the vestibular nuclear complex

Mediate equilibrium maintenance responses

Inputs from ampullae, utricle, and sacculae

Outputs to postural and neck muscles, cerebellum, reticular formation, thalamus, and the contralateral vestibular complex

Nucleus gracilis and Nucleus cuneatus

Relays associated with medial lemniscal tract

General somatic sensory information from cord to somatosensory cortex

Visceral motor nuclei – inputs through reticular formation nuclei from hypothalamus

Cardiovascular center

Cardiac center

Vasomotor center

Respiratory centers

Rate and depth of breathing

Vomiting center

Inputs from stomach and duodenum – distension

Tickling back of the throat

Painful injury to the genitourinary system

Dizziness

Chemicals (emetics) through receptors in the stomach or duodenum

Floor of the fourth ventricle (chemoreceptor trigger zone) – lies on blood side of blood-brain barrier

Swallowing center

Regulation of hiccuping, coughing, and sneezing

Reticular formation nuclei (Raphe nucleus, medial nuclear group, lateral group)

Projections to hypothalamus, thalamus, cerebellum and cord

Cerebellum

Anatomy of the Cerebellum

Hemispheres (2)

Vermis – connects hemispheres medially

Folia – gyri; all sulci are transversely oriented so gyri are parallel

Lobes – each hemisphere divided into 3 lobes by deep fissures (Primary fissure and horizontal fissure)

Anterior and Posterior Lobes

Overlapping sensory and motor maps of body

Medial portions (vermis) receive inputs from axial part of body

Influence motor activity of trunk and girdle muscles

Relay information to cerebral motor cortex

Intermediate portions of the hemisphere control distal parts of limbs and skilled movements

Lateral portions of each hemisphere receive inputs from cerebral association areas

Integrative areas

Role in planning movements

Flocculonodular Lobes

Deep to vermis and posterior lobe

Receive inputs from equilibrium apparatus

Maintain balance and control some eye movements

Cortex of gray matter

Stellate

Basket

Granule

Purkinje cells

Only cortical neurons that synapse with central nuclei of cerebellum

Mediate most output of cerebellum

Internal white matter

Branches like a tree

Known as arbor vitae because of branching pattern

Dentate nuclei – most familiar of the deep, paired masses of gray matter

Cerebellar Peduncles

Ipsilateral innervation

Superior cerebellar peduncles

Connect to midbrain

Efferents from deep cerebellar nuclei

Connect to cerebral cortex through thalamic relays

Middle cerebellar peduncles

Connect to pons

Fibers from pontine nuclei relay voluntary motor information to cerebellum from cerebral cortex

Inferior cerebellar peduncles

Connect to medulla

Afferent sensory tracts from muscle proprioceptors and vestibular nuclei (equilibrium)

Cerebellar Processing

  1. Input from frontal motor association area through collateral fibers of pyramidal tracts notifies cerebellum of intended motor activity [from pons through middle cerebellar peduncles]

  2. Input from proprioceptors, visual, and equilibrium pathways allows cerebellum to determine where the body is in space and how it is moving [from medulla oblongata through inferior cerebellar peduncles]
  3. Integrates the sensory input, calculates coordination plan for force, direction, and extent of muscle contraction; prevents overshoot, maintains posture, ensures smooth, coordinated movements

  4. Sends coordination blueprint [through superior cerebellar peduncles to midbrain] to motor cortex through thalamic relays, which can make adjustments in motor program

    Also sends output to brainstem nuclei (i.e. red nuclei of midbrain) which project to motor neurons of spinal cord

Cognitive Functions of the Cerebellum

Recognizes and predicts sequences of events to adjust for multiple forces exerted on a limb during complex movements involving several joints

Word association

Puzzle solving

Functional Brain Systems

Limbic System

Group of structures on medial aspect of each cerebral hemisphere and diencephalon

Cerebral structures

Septal nuclei

Cingulate gyrus

Parahippocampal gyrus

Dentate gyrus

Hippocampus

Amygdala

Diencephalon

Hypothalamus

Anterior nuclei of the thalamus

Linked by fiber tracts (including the fornix)

Emotional brain, especially amygdala and anterior part of cingulate gyrus

Connections between lower and higher brain regions, responds to wide variety of stimuli

Hypothalamus – subject to emotional input and control of autonomic functioning; severe stress can lead to emotion-induced illness (psychosomatic illness), i.e. hypertension, irritable bowel syndrome, ulcers, and cardiac arrest

Interaction with higher cortical areas, link between feelings and conscious thought

Hippocampus and amygdala also involved in memory

Reticular Formation

System of loosely clustered neurons extending through brainstem

Found in 3 columns

Raphe nuclei (midline)

Medial (large cell) group

Lateral (small cell) group

Projections

All over -

Hypothalamus

Thalamus

Cerebellum

Spinal cord

Functions

Arousal of brain

Reticular Activating System

Receive sensory inputs from all ascending sensory tracts

Send impulses to cerebral cortex through thalamic relays

Maintains cortex in alert conscious state, enhances excitability

Filters out repetitive, familiar or weak signals

Brings attention to unusual, significant, or strong impulses

Role in learning and memory; part of “reward pathway”

Damped by sleep centers of hypothalamus, etc.

Depressed by alcohol, sleep-inducing drugs, tranquilizers

Severe injury results in unconsciousness (permanent = coma)

Damping removed by LSD and other hallucinogens

Motor arm projects to spinal cord

Helps control skeletal muscles during coarse movement of limbs

Autonomic functions

Include vasomotor, cardiac, and respiratory centers of the medulla

Higher Mental Functions

Brain Wave Patterns and the EEG

Normal Frequency Classes

Alpha waves – awake, calm, relaxed

Beta waves – higher frequency, more irregular; awake and mentally alert or concentrating

Theta waves – more irregular, seen in stage 3 NREM sleep, common in children but not normal in awake adults

Delta waves – high amplitude low frequency (< 4Hz); deep sleep, anesthesia (RAS damped), indicate brain damage in wakeful adults

Abnormal Electrical Activity of the Brain: Epilepsy

Epileptic seizures

Abnormal discharge of groups of neurons

Blocks activity of other neurons during discharge

Not associated with or cause of intellectual impairment

Can be genetic or caused by injury of some kind

Blows to the head

Stroke

Infections

Autoimmunity

Prolonged fever

Tumors

Partial seizures result in relatively localized activity

Motor cortex origin

Localized contraction of contralateral muscles

Temporal-lobe epilepsy or psychomotor epilepsy

Originates in the limbic lobe (medial asect of cortex, borders on the brainstem)

Results in illusions (hallucinations, flashbacks, emotional outbursts, rampages) and semi-purposeful motor activity

Generalized seizures involve wide areas of the brain and loss of consciousness

Absence (Petit mal) seizures

Transient loss of consciousness (blank expression and facial twitches)

Usually seen in children

Often disappears by age 10 or so

Tonic-clonic (Grand mal) seizures

Loss of consciousness for longer periods

Tonic phase – generalized increase in muscle tone

Clonic phase – series of jerky movements

May result in broken bones, tongue biting, bowel and bladder evacuation

Auras

Result of origin of seizure in somatosensory cortex

Visual cortex – visual aura

Auditory cortex – auditory aura

Vestibular cortex – feeling of spinning

Olfactory cortex - odors

Control with anticonvulsant drugs or vagus nerve stimulator

Drugs stimulate amount of GABA (inhibitory NT)

Valproic acid – non-sedating

Phenobarbital – classic sedating

Klonopin

Consciousness

Grades

Alert
Drowsy or lethargic
Stupor
Coma

Definition: Holistic information processing

Involves simultaneous activity of large areas of the cerebral cortex

Superimposed on other types of neural activity

Totally interconnected

Loss of consciousness represents impairment of brain function (except for sleep)

Syncope or fainting – ischemia due to hypotension

Coma – total unresponsiveness for an extended period of time

Sleep and Sleep-Wake Cycles

Types of Sleep

NREM Sleep

Stage 1 – Relaxation begins, vital signs normal, EEG shows alpha waves

Stage 2 – EEG becomes irregular, sleep spindles appear (short high-voltage wave burst)

Stage 3 – delta waves appear, vital signs begin to decline, SkM relaxation, some dreaming, especially nightmares

Stage 4 – delta waves

REM sleep

Occurs about 90 minutes after sleep begins

Paradoxical – EEG looks like alpha waves

Vital signs increase but SkM inhibited

Most dreaming occurs

Sleep Patterns

Circadian rhythm

Suprachiasmatic nucleus of hypothalamus receives input from retina, forms biological clock

Preoptic nucleus is the sleep-inducing center

RAS inhibition probably not important, actually mediate some parts of sleep, especially dreaming

REM begins about every 90 minutes

REM lasts 5-10 minutes in first cycle and gets progressively longer, up to about 50 minutes

Awakening occurs when neurons of the dorsal raphe nuclei of the midbrain reticular formation fire at maximal rates – this appears to be tied to a rise in core body temperature

NT changes in sleep: NE declines (regionally), serotonin levels rise

NE (released by the locus ceruleus in the pons) may induce transient paralysis of REM sleep

Importance of Sleep

Slow-wave appears to restorative

REM sleep may involve dealing with emotional crap, unlearning meaningless communications that occur during the day

Alcohol and barbituates suppress REM sleep

Benzodiazapines reduce slow-wave sleep more than REM

Requirement declines with age

Homeostatic Imbalances of Sleep

Narcolepsy

Involuntary sleep during normal waking hours

May be triggered by some pleasurable event

Last about 15 minutes, EEG looks like REM

Usually get less REM than normal at night

Insomnia

Amount

Quality

Language

Involves almost all of the dominant hemisphere’s cortical association areas.

Broca’s area, Wernicke’s area, and the basal nuclei analyze input and organize output related to word sounds and grammatical structure.

These areas are surrounded by cortical areas that join them to other cortical regions that hold concepts and ideas.

Lesions to Broca’s area produce aphasia characterized by an understanding of language but difficulty with speaking and sometimes writing, typing, and sign language.

Lesions to Wernicke’s area produce aphasia characterized by difficulty understanding language and nonsensical speaking referred to as “word salad”.

Affective language areas are found in the same areas of the opposite hemisphere and are involved in emotional aspects of language (body language, tone, gestures)

Memory

Stages of Memory

Short-term memory (STM)

Working memory

Preliminary step to LTM

Limited to 7 or 8 bits of information (phone number)

Long-term memory (LTM)

Limitless capacity

Ability to store and retrieve declines with age

Some sensory input selected for transfer to STM, may or may not decide to transfer to LTM

Transfer from STM to LTM affected by:

Emotional State – best when alert, motivated, aroused

Rehearsal

Association with pre-existing information already in LTM

Automatic memory – some LTMs are formed unconsciously

Memory consolidation – file new information into existing categories already stored

Categories of Memory

Declarative (fact) memory

Related to conscious thought and language ability

Often forgotten quickly but may be filed in LTM in context

Nondeclarative memory

Less conscious or unconscious, noncontextual, best remembered through doing

Procedural (skills) memory

Motor memory

Emotional memory

Brain Structures Involved in Memory

Declarative memory: hippocampus and amygdala (limbic system), diencephalon (thalamus and hypothalamus), ventromedial prefrontal cortex, and basal forebrain (cluster of ACh-secreting neurons anterior to the hypothalamus)

Sensory perception ® cerebral sensory cortical neurons send impulses along parallel circuits to  hippocampus and amygdala ® both send information to diencephalon, basal forebrain and prefrontal cortex; Basal forebrain ® sensory cortical areas the sensory information came from

This pathway makes the perception more durable (a memory)

Retrieval from LTM by prefrontal cortex

Nondeclarative memory (habit system): Sensory input ® Cerebral cortex ® corpus striatum ® brain stem nuclei, promotes motor response

Cerebellum also involved for conditioning of voluntary muscle contractions

Mechanisms of Memory

Hard to study, but probably involves the glutamate – NMDA – calcium – NO long term potentiation pathway mentioned earlier

Activation of genes that code for synaptic proteins in postsynaptic cells includes cAMP-CREB and BDNF

Protection of the Brain

Meninges – 3 connective tissue membranes covering the CNS

Functions:

Cover & protect the CNS

Protect blood vessels & enclose venous sinuses

Contain CSF

Partition the skull

Dura Mater

Outermost, consists of 2 layers of fibrous connective tissue (periosteal layer attached to inside of skull – fused to periosteum, present in skull only, meningeal layer covering the brain and spinal cord, forms the dural sheath of the spinal cord in the vertebral canal).

Layers separate in brain, enclose dural sinuses, which collect venous blood from the brain and send it to the internal jugular veins.

Dural septa - Meningeal layer extends inward to form partitions subdividing the cranial cavity and limiting movement of the brain inside the skull.

Falx cerebri – fold in the longitudinal fissure, attached to crista galli (ethmoid bone) anteriorly

Falx cerebelli – inferior posterior continuation of falx cerebri, folds along the vermis

Tentorium cerebelli – folds into transverse fissure between cerebral hemispheres and cerebellum

Arachnoid Mater

Deep to the dura mater, separated by the subdural space, which is filled with serous fluid.

Consists of fine elastic connective tissue with weblike extensions inward to attach to the underlying pia mater.

Subarachnoid space (between arachnoid and pia mater) is filled with CSF and contains the largest blood vessels of the brain.

Projections that extend exteriorly into the superior sagittal sinus form arachnoid villi, which return CSF to the venous blood

Pia Mater

Fine connective tissue, highly vascular, clings tightly to surface of the brain

Cerebrospinal Fluid

Protection:

Brain and spinal cord float in CSF, which reduces pressure of brain against skull and keeps brain from collapsing under its own weight.

Cushions CNS against trauma.

Nourishes brain and spinal cord

Carries chemical signals from one area of brain to another (hormones, sleep- and appetite-controlling molecules)

Production:

Filtered from plasma at the choroid plexuses

Clulsters of thin-walled, permeable capillaries surrounded by pia mater and ependymal cells in the ventricles.

Tissue fluid is filtered continuously from blood

Ependymal cells modify filtrate by pumping only specific ions into CSF and removing waste products and unnecessary solutes.

Water follows solutes by osmosis, across ependymal cells and  into the CSF in the ventricles.

Average adult formation of CSF is about 500 ml per day.

Composition:

Less protein, Ca++, and K+ than plasma, more Na+, Cl-, and H+.

Circulation:

CSF moves through ventricles, and from fourth ventricle moves through median and lateral apertures into subarachnoid space or inferiorly into the central canal of the spinal cord.

Cilia of ependymal cells wave to circulate CSF, which baths surface of CNS in subarachnoid space and returns to venous circulation at the arachoid villi.

 

Blood-Brain Barrier

Consists of:

Continuous endothelium of capillary walls, endothelial cells joined by tight junctions.

Thick basal lamina around each capillary.

Regulated by foot processes of astrocytes, stimulate tight junction formation between endothelial cells.

Maintain relatively constant environment in CNS by only allowing nutrients like glucose, essential amino acids, and some elecrolytes passage (by facilitated diffusion) while blocking bloodborne metabolic wastes, proteins, some toxins, and most drugs.

Some nonessential amino acids and K+ moved by active transport from brain into blood.

Fat soluble substances (lipids, O2, CO2, some drugs, and alcohol) pass through easily.

Absent at vomiting center (brainstem) and hypothalamus, where blood contents need to be sampled.

Homeostatic Imbalances of the Brain

Traumatic Brain Injuries

Coup and contrecoup

Concussion

No permanent neurological damage, symptoms include dizziness, confusion, maybe momentary loss of consciousness, headache

Contusion

Tissue destruction, may be the result of repeated insult (lots of concussions); symptoms depend upon area affected

Brainstem contusions can cause coma; damage to RAS

Hemorrhage

Compression of tissue

Cerebral edema

Exudate formation

Water uptake by tissues

Treat with anti-inflammatories

Cerebrovascular Accidents (CVAs)

Most common NS disorder

3rd leading cause of death in the US

Ischemia leading to anoxia, glutamate, etc.

Causes:

Blockage of arteries

Thrombosis

Atherosclerosis

Compression of tissue

Hemorrhage

Edema

TIAs (transient ischemic attacks)

Last 5-50 minutes

Temporary numbness, paralysis, impaired speech, higher level processing

Partial blockage due to thrombosis, vasospasm, or embolism

May be predictive of stroke to come

Treat with clot busters (tPA, streptokinase) or clotting inhibitors (aspirin, warfarin/Coumadin)

Treatment within 3 hours increases chances of survival without permanent damage by 50%

Degenerative Brain Diseases

Alzheimer’s

Progressive degeneration of cholinergic neurons in cortex and hippocampus

Neurofibrillar tangle formations

Mutated tau protein

Mediates microtubule formation

Mutation results in neurofibrillary tangles within neurons

Senile plaque formation

Cells and fibers surrounding a core of b-amyloid

Amyloid Precursor Protein normally broken down by both secretory pathways and lysosomal degredation

Cognitive effects

Short-term memory loss

Attention deficits

Disorientation

Personality changes

Language loss

Parkinson’s

Degeneration of dopamine producing neurons in substantia nigra – project to corpus striatum (basal nuclei).

Results in tremor, slowed movement, rigidity.

Treated with l-dopa (crosses blood-brain barrier, is converted to dopamine in CNS) and drugs that enhance the effects of dopamine.

When response to drugs declines deep brain stimkulation with electrode implants can inhibit tremors.

Gene therapy to enhance GABA secretion could inhibit abnormal brain activity and the use of stem cells has shown promise.

Huntington’s

Autosomal dominant genetic disorder that manifests in middle age, causes accumulation of mutant huntingtin protein in brain, causing degeneration of basal nuclei followed by degeneration of cerebral cortex.

Early signs are involuntary "dancing" movements (chorea). Cognitive function degenerates later in the disease, which is progressive and fatal, usually within 15 years of onset of symptoms.

Treatments are designed to inhibit dopamine activity and stem cell implants may offer some hope in the future.

The Spinal Cord

Gross Anatomy and Protection

Foramen magnum to 1st or 2nd lumbar vertebra (just inferior to ribs)

Conus medullaris – tapered end of cord

Nerve roots extend to appropriate level before exiting: Cauda equina

Reflex center

Coverings

Dura mater – spinal dural sheath

Not attached to vertebrae

Epidural space

Between dura and inner vertebral wall

Filled with fat and veins

Arachnoid

Subarachnoid space between arachnoid and pia

Filled with CSF

Extends to S2 with dura

Lumbar puncture – done in subarachnoid space in meningeal sac inferior to conus medullaris, no cord, roots located laterally to exit at appropriate intervertebral foramina

Pia extends to coccyx and attaches to anchor cord (filum terminale)

Lateral extensions of pia anchor cord to vertebra throughout length – denticulate ligaments

Enlargements

Cervical and lumbar – site of nerves that serve upper and lower limbs

Spinal Cord Cross-Sectional Anatomy

Structural features

Flattened from anterior to posterior

Two grooves on surface

Anterior median fissure
Posterior median sulcus

Gray Matter and Spinal Roots

H - or butterfly shaped, joined by gray commissure

Dorsal horns – posterior projections

Interneurons receiving sensory input

Sensory neurons have cell bodies in dorsal root (dorsal root ganglion)

Receive both somatic sensory and autonomic (visceral) sensory input

Ventral horns – anterior projections

Nerve cell bodies of somatic motor neurons

Axons exit via ventral roots to SkM

Amount of gray matter corresponds to amount of muscle innervated

Lateral horns – present in thoracic and superior lumbar segments

Autonomic motor neurons of the sympathetic division

Serve visceral organs

Axons exit via ventral roots

White Matter

Composed of nerve fibers that run in 3 directions: Ascending, descending, and transverse

Divided into columns or funiculi

Posterior, lateral, or anterior

All major spinal tracts are part of multi-neuron pathways

Contain spinal cord neurons, and parts of peripheral neurons and brain neurons

Generalizations:

Most pathways cross over at some point

Most consist of chains of 2 or 3 neurons

Most exhibit somatotopy

All pathways and tracts are paired

Ascending Pathways to the Brain

Typically chains of 3 neurons

Three main pathways on each side of spinal cord: specific (dorsal column-medial lemniscal), nonspecific (spinothalamic), and spinocerebellar.

Specific Ascending Pathways (dorsal column-medial lemniscal system)

Transmit to sensory cortex: conscious interpretation

Contralateral innervation

Found in the posterior funiculus (dorsal white column)

Fasciculus cuneatus and fasciculus gracilis

Synapse with nucleus cuneatus and nucleus gracilis in medulla oblongata

Medial lemniscal tracts

Originate in the medulla, synapse with ventral posterior nuclei in the thalamus and with reticular formation nuclei.

Carry sensory input concerning fine touch, pressure receptors, joint proprioceptors

Discriminative touch and conscious prorioception

Can localize source of input precisely on body surface

Nonspecific Ascending (anterolateral) Pathways (spinothalamic)

Lateral and anterior spinothalamic tracts

Synapse with reticular formation nuclei, and thalamic nuclei

Carry sensory input concerning pain, temperature, deep pressure, coarse touch

Ascending Spinocerebellar Tracts

Transmit proprioceptor information to the cerebellum, no conscious perception

Ipsilateral innervation

Anterior and posterior spinocerebellar tracts

Terminate in cerebellum

Tabes dorsalis

Progressive deterioration of posterior white matter tracts and associated dorsal roots

Caused by syphilis

Poor muscle coordination and unstable gait due to destruction of joint proprioceptor tracts

Invasion of sensory roots by bacteria causes pain, pain passes when dorsal root is completely destroyed

Projection – phenomenon where brain refers sensations to their usual point of stimulation no matter where they arise (can directly stimulate cortex and think you “felt” it on the surface of the skin)

Descending (Motor) Pathways and Tracts

Direct (Pyramidal) Tracts

Originate as pyramidal neurons in precentral gyrus, send impulses through brain stem (corticospinal tracts) and synapse with interneurons or ventral horn motor neurons in spinal cord.

Both tracts transmit motor impulses to spinal cord neurons that activate contralateral skeletal muscles.

Lateral corticospinal

Anterior corticospinal

Indirect (Extrapyramidal) System

Brain stem motor nuclei and all motor pathways except pyramidal pathways.

Most receive projections from and are influenced by pyramidal tract neurons – not really extrapyramidal, more multineuronal.

Complex, multisynaptic, involved in reglation of:

Axial muscles that maintain blance and posture

Muscles controlling coarse limb movements

Head, neck, and eye movements that track objects in visual field

Most activities depend on reflex activity

Tectospinal

Originates in superior colliculus of midbrain – coordinates head and eyes toward moving visual targets.

Vestibulospinal

Originates in vestibular nuclei in medulla, maintains muscle tone, activates ipsilateral limb and trunk extensors and head to maintain balance during standing and moving.

Rubrospinal

Originates in Red nucleus of midbrain, controls some upper limb movement (flexors).

Reticulospinal

Originates in reticular formation nuclei of pons and medulla, controls muscle tone, visceral motor functions, may control most unskilled movements.

 

Spinal Cord Trauma and Disorders

Spinal Cord Trauma

Damage causes either sensory loss or motor function loss.

Paralysis

Flaccid

Damage to ventral root or ventral horn cells stops impulses from reaching muscles served.

No movement, atrophy

Spastic

Only upper motor neurons of primary motor cortex damaged.

Spinal motor neurons, muscles stimulated by spinal reflex activity

No voluntary control but don’t atrophy as much (become shortened)

Transection

Total motor and sensory loss in regions inferior to site of damage

Paraplegia – transaction between T1 and L1, both lower limbs affected

Quadriplegia – damage in cervical revion, all four limbs affected

Hemiplegia – paralysis of one side only, usually due to brain injury

Spinal shock

Transient period of functional loss following traumatic cord injury.

Immediate depression of all reflex activity below site of injury: bowel and bladder reflexes stop, BP drops, all muscles are paralyzed and insensitive.

Function usually returns within a few hours, if not by 48 hours paralysis is usually permanent.

Poliomyelitis

Transmitted by ingestion of fecally contaminated water.

The virus first invades lymph nodes of the neck and small intestine. 

Symptoms:

Headache

Sore throat

Fever

Stiffness of the back and neck

Occasionally paralysis (less than 1%)

Viremia and spinal cord involvement may follow, including destruction of ventral horn motor neurons.

Death may occur by respiratory failure or cardiac arrest depending on muscles affected.

Most cases are mild or asymptomatic.  Vaccines keep the incidence low in the US.

Vaccines:

Salk (IPV) (1954) - Formalin-inactivated virus; Requires boosters.

Sabin (OPV or TOPV) (1963) - Contains three strains of live virus – trivalent; Administered orally, no boosters.

Postpolio Syndrome – Experienced by some survivors of polio epidemic of 40’s and 50’s.

Extreme lethargy, musclar burning pains, progressive muscle weakness and atrophy. 

May be due to normal loss of neurons in aging with inability to recruit nearby neurons to compensate for losses (already recruited these neurons to compensate for loss of neurons due to infection).

Amyotrophic Lateral Sclerosis

Progressive destruction of ventral horn motor neurons and pyramidal tract fibers.

Results in loss of ability to speak, swallow, and breathe, with death occuring typically within 5 years.

Idiopathic in 90% of cases although may be due to glutamate excitotoxicity, autoimmune reactions, or a combination.

Riluzole inhibits glutamate release, only drug developed in last 50 years to treat ALS.

Diagnostic Procedures for Assessing CNS Dysfunction

Reflex tests

CT

MRI

PET scans

Clot busters for stroke (tPA)

Cerebral angiography can show location of clot so tPA can be applied directly, also used for patients who have had warning strokes or TIAs.

Ultrasound – cheaper and less invasive than angiography

 

Developmental Aspects of the Central Nervous System

Neural Plate

Arises from ectoderm of dorsal midline  - 3rd week of pregnancy

 

Invaginates, forms the neural groove flanked by neural folds.

Neural Folds

Superior edges fuse over deepening groove to form the neural tube. Some neural fold cells migrate laterally and form the neural crest.

Neural Tube – by 4th week

Detaches from surface ectoderm, differentiates into brain rostrally and spinal cord caudally.

Neuroblasts migrate outward from the neural tube and form the alar plate dorsally and the basal plate ventrally by the 6th week.

Basal plate neuroblasts form motor neurons.

Alar plate neuroblasts form interneurons, which, along with some basal plate neuroblasts form the white matter of the spinal cord.

Neural Crest

Formed from neural fold cells

Gives rise to sensory neurons (dorsal root ganglia) and some autonomic neurons.

Cerebral palsy - brain damage causes voluntary muscles to be paralyzed or poorly controlled.

Spasticity, speech difficulties and other motor difficulties are seen and may be accompanied by visual impairments, seizures (about half), mental retardation (about half), and deafness (about one third).

Cerebal palsy is not progressive but is irreversible. Possible causes include lack of oxygen during delivery or maternal exposure to radiation, alcohol and other drugs, infection, or smoking during pregnancy.

Anencephaly - neural folds don't fuse rostrally, causing the cerebrum and part of the brain stem to be lacking (anencephaly = "without brain").

There is no ability to see, hear, process other sensory input, initiate voluntary muscle movement, or think. Death occurs soon after birth.

Spina bifida - due to incomplete formation of the vertebral arches (laminae and spinous processes are missing on at least one vertebra).

Usually occurs in the lumbosacral region. Neural deficits are seen in severe cases.

Spina bifida occulta is the least serious (and most rare) type, involves one or a few vertebrae, and causes no neural problems. A small dimple or tuft of hair may be seen over the site but there are no other external manifestations.

Spina bifida cystica is more common and severe, with a saclike cyst protruding dorsally from the spine.

Meninogoceles contain meninges and cerebrospinal fluid.

Myelomeningoceles contain portions of the spinal cord and spinal nerve roots.

Larger cysts with more neural structures cause greater neurological problems, whith may include bowel incontinence, bladder paralysis, lower limb paralysis and continual infections. 90% of cases are accompanied by hydrocephalus.

Inadequate amounts of folate in the maternal diet have been implicated in about 70% of cases in the past but the incidence has dropped significantly since mandatory supplementation of bread, flour, and pasta products started.