9/20/2013 Flashcards
Diencephalon
Thalamus, Hypothalamus, Pineal Gland
Cerebral Aqueduct
Midbrain
4th Ventricle
Medulla, Pons
Forebrain
Diencephalon and Cerebral Hemispheres
Hindbrain
Brainstem and Cerebellum
Cervical
C1-C8 (Above cervical vertebrae)
Thoracic
T1-T12 (Below thoracic vertebrae)
Lumbar
L1-L5 (Below)
Sacral
S1-S5 (Below)
Coccygeal
Coccygeal C1 (Below)
Brainstem Functions
1) Cranial Nerve Nuclei
2) Passageway for tracts
3) Level of consciousness via forebrain projections of the reticular foramen
Cranial Nerve Entry & Exit
All on ventral surface, except trochlear (crosses and dorsal)
Olfactory & Optic – Entry Brain directly
Oculomoter – Between peduncles
Trochlear – Nucleus in caudal midbrain
Trigeminal – Largest; goes through mid-pons laterally via the middle cerebellar peduncle (primary nucleus is in the middle of pons; extends down to medulla where it is the spinal trigeminal nucleus; extends above primary nucleus to become mesencephalic nucleus in the midbrain)
Abducens, Facial, Vestibulocochlear – Medial to lateral at the junction of the pons and medulla
Glossopharyngeal & Vagus – Lateral Medulla
Spinal Accessory – Does not originate in the brainstem! Nucleus is technically in cervical spinal cord. Exits the lateral portion of the upper cervical spinal cord.
Hypoglossal – Between medullary pyramids and olive
Sensory vs. Motor Nuclei
Sensory neurons associated with ganglia (e.g. Trigeminal ganglia) – outside the CNS
Motor neurons associated with nuclei in brainstem
Generally, sensory nuclei found laterally and motor neurons are found more medially
Generally, caudal-rostral orientation of nuclei correlate with caudal-rostral functions of the nuclei
Temporal Lobe
Superior – Audition and language
Inferior – Visual processing
Recognizing stimuli
Insula
Visceral and autonomic function, including taste
Occipital Lobe
Vision
Frontal
Planning responses to stimuli
Parietal
Attending stimuli
Limbic
Emotion, Visceral motor
Septal or Basal Forebrain Nuclei
Base of the Forebrain, ventral to the basal ganglia
Modulate neural activity in cortex and hippocampus
Implicated in Alzheimer’s Disease – they degenerate
Anterior Commissure
Anterior, below lateral ventricles
Internal Capsule
Fibers descending and ascending to the cerebral cortex
Many axons arise or terminate in the thalamus
Some axons continue past the diencephalon to enter the cerebral peduncles of the midbrain (Corticobulbar and Corticospinal)
Blood supply of spinal cord
Vertebral arteries (branches of subclavian) Medullary arteries (branches of vertebral and aorta in the thoracic region)
Anterior – Anterior Spinal Artery
Posterior – Posterior Spinal Arteries
Blood supply of brainstem
Posterior cerebral artery Midbrain
PICA Medulla
AICA Pons
Blood supply of brain
Anterior circulation (forebrain) – Anterior and Middle Cerebral Arteries
Posterior circulation (posterior cerebral cortex, thalamus, and the brainstem) – Posterior cerebral, basilar, and vertebral arteries
Blood supply of basal ganglia, internal capsule, and hippocampus
Lenticulostriate arteries and Anterior Choroidal arteries (branches of middle cerebral)
Ventricle Landmarks
Septum Pellucidum – separates the anterior horns of the lateral venricles
Lateral Surface – Basal Ganglia
Thalamus is the wall around 3rd Ventricle
UMN Injury Clinical Signs
o Immediate flaccidity of muscles on contralateral side (above crossing)
Spinal shock – immediate decrease in spinal circuits because of lack of input from motor cortex and brainstem
o Acute manifestations tend to be most significant in arms and legs
o Trunk muscles usually preserved (brainstem pathways and bilateral projections of the anterior corticospinal tract that controls the midline)
o Several days after, the picture changes
Positive Babinksi (extensor instead of flexor) and Hoffman
Spasticity – increased muscle tone (resting muscle tension) because the efferent fibers are much more sensitive to stretch afferents, hyperactive reflexes (and clonus) due to loss of inhibition from UMNs; tested clinically by increased resistance to passive movement
• Much more severe stiffness when it follows damage to cortex/internal capsule than in spinal cord - if brainstem descending control is still intact, it exerts net excitatory effect (lesions above the spinal cord will leave brainstem paths intact)
Decerebrate rigidity (extensor muscles of the leg and flexor muscles of the arm), slowness of movement
Loss of ability for fine movements
LMN Injury Clinical Signs
o Flaccid paralysis/weakness to muscle depending on extent of injury
o Loss of muscle tone because of injury to alpha motor neurons (the reflex circuit is normally responsible for steady level of tension in muscles) and hyporeflexia
o Fasciculations (loss of innervation leads to muscles producing more Ach receptors, more spontaneous firing)
o Eventually, muscle atrophy (not receiving direct innervation)
Motor Nerve Dysfunction Clinical Signs
o Usually asymmetric
o Usually distal
o Atrophy, fasciculation, cramps
o Neuropathies have a single large action potential when fired (due to regeneration of nerve fibers that are not as diversified) – unlike smooth movement that is produced by many action ptoentials
Neuromuscular Junction Dysfunction Clinical Signs
o Usually fluctuating and fatigable
Muscle Dysfunction Clinical Signs
o Usually proximal
o Usually symmetric
o Usually painless
o Usually non-fluctuating
o Myopathies have smaller action potential when fired
C3, C4, C5
Diaphragm
C5
Deltoid
C6
Biceps
C7
Triceps
C8-T2
Fingers
L4
Quadriceps
L5
Foot dorsiflexion
S1
Plantar flexion
S2-5
Sphincter control
Radiculopathy
Injury to nerve roots - LMN
Meylopathy
Injury to spinal cord – UMN
Fibrillation vs. Fasciculation
Fib – Individual muscle fiber that spontaneously fires (up–regulation of Ach receptors); not visible
Fas – Muscle fiber group that visibly contracts (common in peripheral motor nerve injury) – may be due to re-innervation; may not always indicate a pathology
Hypokinesia terms
Akinesia – lack of purposeful movements
Bradykinesia – Slow movements
Rigidity terms
Clasp-knife – sudden loss of rigidity at the end of external flexion
Cogweel – catch and release
Lead pipe – increased tone throughout passive movement
Hemiballismus
Injury to STN (infarct, tumor, surgery) – loss of indirect pathway, loss of inhibition
Uncontrolled flinging movements
Treated with dopamine agonists
Parkinson’s
Triad – Tremor, Rigidity, Bradkykinesia
Braak’s Hypothesis: Pre-motor (loss of smell, sleep issues, constipation) Motor Dementia, Neuropsychiatric issues
Neurodegenerative disease of substantia nigra pars compacta
10% Genetic
Huntington’s
100% Genetic – Triplet (CAG) repeat for glutamine, longer the repeat, the earlier the onset, autosomal dominant (toxic gain of function)
Degeneration of caudate and putamen, selectively for indirect pathway (loss of inhibition)
Many neuropsychiatric issues, late stage akinesia (ablation of cortex, brain as a whole)
Subarachnoid Hemorrhage
Presentation – Sudden headache “worst I’ve had in my life” – possibly due to irritating the Circle of Willis with nuchal rigidity
Lumbar puncture shows xanthochromia (yellow due to RBCs entering the CSF; when RBCs die, they release heme, which is degraded by enzymes into the yellow bilirubin)
Causes: Rupture of Berry aneurysm, AVM, and an anti-coagulated state
Berry Aneurysm
Most frequent cause of subarachnoid hemorrhage (85%)
Thin-walled out-pouching that lack a media (note intracranial arteries, in contracts to extra-cranial counterparts, have a smaller tunica media and lack external elastic lamina; this is particularly true at branch points where there is not a well-developed media layer), increasing its rupture risk
Most frequently located in the anterior circle of Willis at branch points of the communicating artery; posterior communicating might impinge on VIII
Associated with Marfan syndrome and autosomal dominant polycycstic kidney disease
Locked-in syndrome
Acute, bilateral paralysis: A patient is aware and awake but cannot move or communicate verbally due to complete paralysis of nearly all voluntary muscles in the body except for the eyes.
Causes:1) Stroke - Infarction of ventral pons, generally due to basilar artery embolism or thrombosis
2) Central pontine myelinolysis (demyelination disease that affects anterior of pons where the corticospinal tracts are) secondary to rapid IV correction of hyponatremia
Risk Factors: Alcoholics, Liver Disease
Pathogenesis: Lowered osmolytes in the brain cannot be as quickly replaced as the extracellular osmolarity increases, which leads to shrinkage of brain/loss of fluid from inside cells; the mechanism by which a rapid fall in brain volume results in demyelination is not completely understood. One possible mechanism is that osmotic shrinkage of endothelial cells opens the blood-brain barrier, allowing the entry of complement and other cytotoxic plasma components. Another proposed mechanism is that, during recovery from hyponatremia, the loss of cell water coupled with the movement of potassium and sodium back into the cells leads to an initial increase in cell cation concentration that occurs before the repletion of organic osmolytes. These combined changes may directly injure and induce apoptosis of astrocytes, leading to a disruption in the function of myelin-producing oligodendrocytes, release of inflammatory cytokines, and activation of microglia.
Osmolytes and cerebral adaptation to hyponatremia
The degree of cerebral edema and therefore the severity of neurologic symptoms are much less with chronic hyponatremia . This protective response, which begins on the first day and is complete within several days, occurs in two major steps.
1) The initial cerebral edema raises the interstitial hydraulic pressure, creating a gradient for extracellular fluid movement out of the brain into the cerebrospinal fluid
2) The brain cells then lose solutes, leading to the osmotic movement of water out of the cells and a decrease in brain swelling. Substantial depletion of brain organic osmolytes occurs within 24 hours, and additional losses occur over two to three days owing to downregulation of the synthesis and uptake of these solutes
Thrombotic Stroke, CNS
Due to rupture of atherosclerotic plaque
Usually develops at branch points (e.g. bifurcation of internal carotid and middle cerebral artery)
Results in pale infarct at the periphery of the cortex
Embolic Stroke, CNS
Due to thromboemboli, most commonly from the left side of the heart (e.g. secondary to atrial fibrillation)
Usually involves middle cerebral artery
Results in hemorrhagic infarct at the periphery of cortex
Lacunar stroke, CNS
Secondary to hyaline arteriolosclerosis (thickening of arteriole, mostly in kidney, with hyaline), which is a complication of hypertension/diabetes
Most common in lenticulostriate (caudate, putamen, globus pallidus) vessels, which are a branch of middle cerebral, which results in small “cystic” areas of infarction
Thalamic involvement causes sensory stroke
Internal capsule involvement causes motor stroke
Brain abscesses
Accumulation of pus – dead neutrophils – appear as ring-enhancing lesions on CT scan
60% are related to middle-ear infections
Cerebellar abscess is specifically associated with otitis media (think about anatomical location)
Middle-ear infection and sinusitis can cause frontal and temporal lobe abscesses
Anencephaly
Complete failure of higher brain structures to develop; accompanied by grossly deformed head with no cranial vault
Encephalocele
Protrusion of brain and meninges through a developmental defect in the skull
Hydranencephaly
Extreme form of porencephaly in which the cerebral hemispheres are destroyed; unlike anencephaly, the external head forms normally
Porencephaly
Cyst or cavity in brain that communicates with ventricles – may occur developmentally, or secondary to inflammatory disease or a vascular accident
Anterior vermis syndrome
Atrophy of rostral vermis most commonly caused by alcohol abuse → gait, trunk and leg dystaxia
Posterior vermis syndrome
Usually result of brain tumors in children (most commonly caused by medulloblastomas or ependymomas), involves flocculonodular lobe → truncal dystaxia
Cerebellum Hemispheric syndrome
Involves one hemisphere, often result of brain tumor (astrocytoma) or abscess (secondary to otitis media or mastoiditis) → arm, leg and gait dystaxia and ipsilateral cerebellar signs
Trisomy 13, Patau Syndrome
Affected infants usually die before 1 year of age, usually secondary to multiple congenital anomalies, particularly severe congenital heart defects; other features include holoprosencephaly (forebrain fails to develop into two hemispheres, causing defects in face development), micropthalmia (small eye), microcephaly, cleft lip/palate, polydactyly, congenital heart disease, severe mental retardation
Benign essential tremor
Familial, progressive, bilateral, symmetric postural tremor of the upper extremities that is not typically associated with other neurologic symptoms; generally increases with increasing age and is more prevalent in patients with a positive family history; primarily affects the arms in 6-12 Hz frequency; head (titubation) may also be involved
Syringomyelia
Cystic degeneration of spinal cord due to an occlusion in the central canal right above the anterior commisure. A syrinx results when a watery, protective substance known as cerebrospinal fluid, that normally flows around the spinal cord and brain, transporting nutrients and waste products, collects in a small area of the spinal cord and forms a pseudocyst (e.g. obstruction in CSF flow caused by Chiari can be redirected to cyst?)
Arises with trauma or in association with an Arnold-Chiari malformation
Usually occurs at C8-T1 (cervical region)
Expansion of cyst (“synrix”) over time leads to involvement of other spinal tracts, leading to muscle atrophy and weakness with decreased muscle tone and impaired reflexes – damage to LMNs. It can also lead to Horner syndrome due to disruption of the lateral horn of the hypo-thalamospinal tract (sympathetic input for face; arises from hypothalamus and synapses on the lateral horn at T1 superior cervical ganglion eyelids, pupil, skin of face)
Horner Syndrome
Droopy eyelid, miosis, and anhidrosis (decreased sweating) – lack of decreased sympathetic innervation of eye
Tabes dorsalis
Syphilitic myelopathy – slow degeneration (de-myelination) of nerves in the dorsal columns of the spinal cords (proprioception, sensation, vibration)
Tertiary Syphilis (decades later of untreated syphilis)
Argyll-Robertson pupils: Accommodates, but doesn’t react (constrict) to light
Clinical Nerve Conduction Study
The stimulation electrode depolarizes all of the axons in the nerve, causing them to simultaneously fire action potentials. The signal obtained at the recording electrode represents a summation of the action potentials of the individual nerve fibers. It is examined for velocity, amplitude and for the shape of the waveform.
Used to detect demyelination, which is shown by:
1) decreased conduction velocity (demyelinated nerves will not be able to pass along the action potential effectively because of decreased resistance and increased capacitance forces – back to current model)
2) decreased signal amplitude (determined by the # of axons firing, so decrease indicates axonal loss or complete conduction block for some of the fibers)
3) Abnormal waveform (due to combo of myelinated and demyelinated fibers)
Peptide vs. Small Molecule Neurotransmitter
Peptide – synthesized in cell body; larger (3-36 amino acids)
Small molecule – synthesized in nerve terminal (enzymes synthesized in cell body); individual amino acids
Organophosphates
Inhibit ACheE; initially an over-stimulation, then paralysis (completely depolarized and cannot be responsive to further innervation)
Nicotinic ACh Receptor
- Ionotropic cation channel
- Need to bind two molecules of Ach (thus, high concentrations needed to activate)
- Nicotonic receptors activated by “nicotine” and other toxins (e.g. snake toxin); found in the NMJ and pre-ganglionic synapses
Muscarinic Ach Receptor
- Metabotropic, mediate most things in the brain, all glands and parasympathetic effector organs
- Muscarinic receptors are activated by muscarine, a poisonous alkaloid in mushrooms
- Remember – atropine is a muscarinic receptor antagonist!
Glutamate Toxicity
Follows acute brain injury – neurons in ischemic areas exhibit increased glutamate, which contributes to toxic levels for the cell (mechanism unknown – glutamate receptors literally “excite” neurons to death)
Glutamate
Acetylcholine
Glial Cells
- Outnumber neurons
- Astrocytes – maintain appropriate environment for neural signaling
- Oligodendrocytes – myelin
- Microglial – macrophages
Ionotropic Glutamate Receptors
AMPA and NMDA are the big ones; non-selective cation influx
Note NMDA:
• Mg-block relieved by depolarization (e.g. repetitive firing leads to summation and massive depolarization, role in plasticity)
• Requires glycine as co-transmitter
• Allows calcium inside the cell, which can serve as a second messenger
• Slower-acting than AMPA
Most cells have NMDA and AMPA receptors
Metabotropic Glutamate Receptors
- Second messenger responses can either be excitatory or inhibitory
- Varied roles and responses to pharmacological agents
GABA
- Inhibitory (except for developing brains when the concentration of chlorine is higher inside)
- Most commonly found in local circuits (also as a projection cell in Purkinje cells of cerebellum)
- Date Rape drug causes symptoms due to the byproduct of GABA degradation
GABA-A, GABA-C
- Ionotropic
- Influx of chlorine
GABA-B
- Metabotropic
- Activates K+ channels
- Blocking Ca2+ channels
Alcohol-mediated alterations in GABA Receptors
Ethanol potentiates GABA-receptor actions (treat withdrawal with benzodiazepines); Initially alcohol potentiates GABA receptors, but chronic use causes a down-regulation of GABA receptors and reduced neurotransmission - these changes are responsible for alcohol withdrawal symptoms (increased excitability) and increased reduced tolerance to alcohol
Glycine
- Inhibitory, very similar to GABA-A (influx of chlorine)
- Half of inhibitory synapses in spinal cord use glycine
Catecholamine
- Dopamine, Norepinephrine, and epinephrine
- All derived from tyrosine
Dopamine
- Substantia Nigra & Ventral Tegmental Area
- Actions: Motor, Milk, Mind, eMesis Motivation
- Cocaine inhibits DAT
- Amphetamines are a stimulus-independent release of dopamine by reversing DAT pump
Norepinephrine
- Locus Ceruleus
- Sleep and wakefulness, attention, and feeding behavior
- Note that DBH catalyzes the production of NE from dopamine
- Mutation in NET causes orthostatic intolerance (less BP)
- Epi is found in brain at lower concentrations than NE, function not known (need PNMT enzyme)
Histamine
- Tuberomammillary nucleus of hypothalamus
- Arousal and attention (anti-histamines make you sleepy) and vestibular function (antagonists of H1 receptor are used for motion sickness; note that H2 receptors are involved in secretion of gastric acid)
Serotonin
- Raphe nuclei (pons and upper brainstem)
- Regulate sleep and wakefulness, affect, appetite, aggression, thermoregulation
Ascending Arousal System (Major NTs, pathways)
The level of consciousness or arousability is controlled by an ascending
system of connections from the brainstem; two main groups:
1) Cholinergic neurons are active during wakefulness and REM sleep. In the pons, the laterodorsal and pedunculopontine tegmental nuclei (LDT/PPT) project to subcortical targets such as the thalamus. These probably play a role in cortical activation and help produce REM sleep.
2) Neurons of the basal forebrain (nucleus basalis of Meynert, diagonal band of Broca, etc.) use Ach, glutamate and GABA to directly activate cortical and subcortical targets, promoting EEG activation and learning.
3) Monoaminergic neurons are active during wakefulness, slow-down in NREM, and are silent in REM sleep. These project directly to cortex and most subcortical regions.
4) Norepinephrine (NE) – mainly from locus coeruleus (LC); helps promote
vigilance and attention
2) Serotonin (5HT) – mainly from raphe nuclei; influences mood
3) 3) Histamine (HIST) – only from tuberomammillary nucleus (TMN); promotes arousal
4) Dopamine (DA) – promotes movement and motivation, but source of wake-promoting DA unclear, possibly ventral periaqueductal grey or ventral tegmental area.
5) The reticular system is a heterogeneous population of midline neurons that extend from the caudal medulla to the midbrain. Mainly, it is an older term that encompasses the wake-promoting systems listed above, but there may be other wake-promoting neurons within this system that have not yet been discovered. Stimulation produces awakening, and lesions produce coma or hyper-somnolence.
Peptidergic neurons containing orexin (also known as hypocretin) in the lateral hypothalamus send excitatory projections to all these arousal systems. The orexin system probably helps stabilize wakefulness through activation of all the other arousal regions. People lacking orexin have narcolepsy. Orexin antagonists are being developed as a new treatment for insomnia.
How does orexin stabilize the awake/sleep cycle?
Coma
Coma - occurs with lesions of this ascending arousal system or with diffuse, bihemispheric dysfunction
REM
- unconscious but cortex active, dreaming, paralysis of all muscles except respiratory and oculomotor, saccadic eye movements (activity of PPRF), penile/clitoral tumescence, possibly memory consolidation function, increased pulse, increased blood pressure,
- 25% of sleep cycle; occurs every 90 minutes, duration increases during the night
- Same EEG patterns as wakefulness (fast, low amplitude)
- Ach is the principal neurotransmitter; NE/Serotonin reduces REM sleep
Mechanism of REM Sleep
Note that ACh major neurotransmitter during REM sleep; aminergic input (e.g. NE, serotonin) will decrease REM sleep
Non-REM
- unconscious with little cortical activity
- increased parasympathetic activity
- sleep-walking, night-terrors, bedwetting most common during REM stage 3
Mechanism of Non-REM Sleep
Ventrolateral preoptic area (VLPO) neurons are active during sleep,
and VLPO lesions produce fragmented light sleep. VLPO neurons send inhibitory, GABAergic projections to the TMN and other arousal regions such as the LC and DR. These VLPO neurons are especially active during slow wave sleep and some also continue to fire in REM. VLPO neurons may be activated by sleep-producing chemicals (somnogens) such as adenosine (the effects of which are blocked by caffeine), inflammatory molecules (PGE, etc.)
EEG
The EEG is a measure of the summed electrical activity between 2 scalp
electrodes. This activity results from extracellular current flows generated by synaptic potentials (EPSP’s and IPSP’s) in cortical pyramidal cells. During wakefulness, the EEG has a low amplitude and consists predominantly of fast waves. This is due to a lack of synchronized activity across the cortex. High amplitude waves characteristic of deep sleep are due to the synchronized activity of millions of cells. This synchronization
arises from the interaction of neurons in the reticular nucleus of the thalamus, thalamocortical relay neurons, and cortical neurons.
Frequency of EEG waves parallels wake/sleep state and arousability (“BATS”):
Awake (eyes open) – Beta (highest frequency)
Awake (eyes closed) – Alpha
Stage 1 (Light Sleep) – Theta
Stage 2 (Deeper Sleep, Grinding of Jaw) – Sleep spindles* and K complexes**
Stag 3 - (Deepest non-REM sleep) – Delta (lowest frequency, highest amplitude)
REM - Beta
*During sleep these spindles are seen in the brain as a burst of activity immediately following muscle twitching. Researchers think the brain, particularly in the young, is learning about what nerves control what specific muscles when asleep. Sleep spindle activity has furthermore been found to be associated with the integration of new information into existing knowledge.
**K-complexes have two proposed functions: first, suppressing cortical arousal in response to stimuli that the sleeping brain evaluates not to signal danger, and second, aiding sleep-based memory consolidation.
Developmental Changes in Sleep Cycle
Total sleep time is highest in children and then plateaus during young adulthood. REM sleep is the predominant sleep state during infancy, gradually decreasing during childhood and then essentially stable throughout adulthood. Slow wave sleep declines with age. This decline in deep sleep probably accounts for why many people wake from sleep more frequently as they age, but people still require the same total amount of sleep through adulthood.
Two determinants of sleep
1) Homeostatic control: Prolonged wakefulness will produce longer, deeper sleep with more stage 3 NREM sleep. This is often referred to as the homeostatic component of sleep, the presumption being that sleep mechanisms are trying to restore the brain to some equilibrium.
2) Circadian clock: Sleepiness is dependent on the time of day. If you stay up all night, you feel pretty sleepy around 3 am, but by 10 am that sleepiness is not as intense even though you have been awake longer. This is referred to as the circadian component of sleep. Daily 24 hour rhythms known as circadian rhythms have a strong influence on sleep, wakefulness, body temperature, growth hormone, cortisol, and nearly every biologic parameter. These rhythms are mediated by the suprachiasmatic nuclei, small clusters of neurons just above the optic chiasm. SCN neurons act as a pacemaker with a 24 hour cycle of activity. These neurons receive a direct input from retinal ganglion cells containing the novel photopigment melanopsin (even if you lack cones and rods you can still regulate clock). This luminance signal entrains the pacemaker, synchronizing behavior to the external light-dark cycle
Functions of sleep
- Ecological – safer to be asleep than out in the environment
- Energy conservation – sleep burns fewer calories
- Memory – many memories are consolidated during sleep, improving
performance - Cellular restoration – Neurons may require periods of reduced activity
NTs that are on or off in Wake, Non-REM, REM
ACh is dominant in REM, Aminergic dominant in non-REM
Insomnia
A. About 15% of the population has long-term problems initiating or maintaining sleep. Short term insomnia occurs in ~30% of people.
B. Chronic insomnia is often associated with depression or anxiety, maladaptive behavior (psychophysiological), medications, EtOH and other drugs.
Circadian Rhythm Disorders
A. Circadian phase delay (staying up late and then sleeping late in AM) is very common in teens and young adults.
B. Treated with consistent sleep routine, bright light in AM, sometimes melatonin at night.
Parasomnias
A. NREM sleep: sleepwalking, confusional arousals, and night terrors
B. REM sleep: REM sleep behavioral disorder (failure of paralysis during dreams), strongly associated with Parkinson’s Disease and similar disorders.
Sleep apnea
Obstructive sleep apnea: upper airway occlusion during sleep due to obesity, small airway, allergies, etc. Treatment: CPAP, surgery, dental device, weight loss.
From FirstAid:
• Repeated cessation of breathing > 10 seconds during sleep, which causes disruption and daytime sleepiness
• Note that increased hypoxia will leap to more EPO, higher hematocrit
• Central – no respiratory effort (medulla isn’t sensing CO2) – headache early morning (would they wake up?)
• Obstructive – respiratory effort against airway obstruction, associated with obesity, loud snoring, systemic/pulmonary hypertension, arrhythmias, and possibly sudden death
Distinctive Features of Visceral Motor System
1) No medial-lateral anatomical organization like somatic motor
2) LMNs are located OUTSIDE of the CNS in paravertebral or prevertebral ganglia
3) Diffuse contacts between the visceral motor neurons and viscera (axons are highly branched and contain varicosities
4) Whereas motor is controlled by the motor cortical areas in the posterior frontal lobe, much more diffuse control “central autonomic network”
5) Diverse NTs
Edinger-Westphal Nucleus
Pre-ganglionic nucleus in midbrain that synapses on the ciliary ganglion via the oculomotor nerve to mediate the parasympathetic constriction in response to light
Mesencephalic Nucleus
Superior and Inferior Salivary Nuclei
Pre-ganglionic nuclei in the pons and medulla that mediate the parasympathetic production of tears/salivary glands via VII and IX
Nucleus Ambiguus
Medulla pre-ganglionic nucleus – motor innervation of the pharynx, larynx, and upper esophagus via X and IX
Dorsal Motor Nucleus
Medulla pre-ganglionic nucleus of X – sends autonomic fibers to the heart, lungs, and upper GI
Anatomical difference between sympathetic and parasympathetic fibers
Sympathetic ganglion have more dendrites and more fibers converge onto it than parasympathetic ganglia
Organs that only receive sympathetic innervation
Sweat glands, adrenal medulla, piloerector muscles, most arterial blood vessels
Myenteric Plexus
Also known as Aeurbach’s Plexus – intrinsic to gut
Between the two muscle layers
Regulates the musculature of the gut
Submucus Plexus
Also known as Meissner’s Plexus
Located in submucosa, concerned with glandular secretion and chemical monitoring
What are the two important functions of afferent activity arising from viscera?
1) Provides feedback input to local reflexes that modulate moment-to-moment visceral activity within individual organs
2) Informs higher integrative centers of more complex patterns of stimulation that may signal threatening conditions or require coordination of other things
Nucleus of Solitary Tract
Central structure in the brainstem (medulla) that receives visceral sensory information (includes chemoreceptor and baroreceptor) and distributes it accordingly
What is responsible for poor localization of visceral pain and referred pain?
1) Far fewer visceral sensory neurons than somatic
2) In the dorsal horn, many of the second-order neurons that receive visceral sensory input (goes through DRG) are part of the anterolateral system, which also receives nociceptive input from more superficial surfaces – pain from viscera can be “referred” to these areas
Reticular Formation
Outdated term; refers to the heterogeneous collection of distinct neuronal clusters in the brainstem tegmentum that modulate the excitability of neurons in the forebrain and spinal cord or coordinate the firing patterns of more local lower motor neuronal pools engaged in reflexive or stereotypical somatic motor and visceral motor behavior (e.g. PPRF)
Broadly speaking, modulatory functions are found in the rostral sector and premotor functions are localized in more caudal regions
What is the target of sensory input from visceral systems?
Nucleus of solitary tract
Visceral motor centers in the medullary reticular formation
Sensory fibers related to viscera convey limited amount of information to consciousness (except pain)
Where do afferent visceral fibers arise?
Cell bodies in the DRG (spinal visceral sensory neurons) and sensory ganglia associated with IX and X (i.e. general visceral sensory information from organs and viscera in the thorax, upper abdomen, head and neck; in the abdomen, visceral afferents generally follow pathway of sympathetic nerves)
Visceral Reflex Arc
Some afferent fibers via DRG synapse in the lateral horn where the visceral motor neurons are located
Dorsal Column Pain Pathway
Some pain fibers, especially visceral pain fibers, ascend in the dorsal column and terminate in the dorsal column nuclei and eventually are relayed to thalamus
Premotor cortices
Responsible for planning and selecting movements, esp. movements that are triggered by sensory cues or internal motivations (the primary motor cortex on the other hand is more involved with the direct execution of skilled movements of the limb and facial muscles)
Hypothalamus Input and Output
Sensory inputs (visceral and somatic, chemosensory, and humoral) + Contextual information (cerebral cortex, amygdala, hippocampal formation)
Compares input to biological set-point; Output to visceral motor (autonomic premotor centers in brainstem and pre-ganglionic neurons in brainstem and spinal cords), somatic motor, neuroendocrine, behavioral responses
Horner’s Syndrome
Ptosis, Miosis, Sunken Eye, Decreased sweating (if the descending pathway is affected)
Relative Speed of Ganglionic Synapses
Nicotonic/Pre-ganglionic: Fast (ion channel)
Muscarinic/Adrenergic/Post-ganglionic: Slower (G-proteins)
What integrates ascending sensory information and cortical input for voiding?
Periaqueductal Grey – when socially acceptable, there is increased parasympathetic outflow (S2, S3, S4) and disinhibition of the skeletal muscle of the sphincter (S2, S3, S4)
What would happen to urine control without descending control of the sacral spinal cord?
Incomplete bladder emptying – no dishinibition of the motor neurons and/or not enough increased para-sympathetic activity; this leads to chronic UTIs in paraplegic patients
What causes clitoral/penile erection?
NO released by parasympathetics causes filling of the cavernous venous sinuses (also glandular secretions); afferent stimulation conveyed centrally through somatic sensory endings, which causes increased parasympathetic response and somatic excitation in certain muscles, which causes orgasm
Supraoptic and Paraventricular Nuclei
Hypothalamus
Supraoptic Area
Synthesizes ADH, oxytocin, CRH (Corticotropin-releasing hormone)
Anterior Nucleus
Hypothalamus
Supraoptic Area
Temperature regulation (heat dissipation); lesion leads to hyperthermia (body produces more heat than it is able to dissipate)
Preoptic Area
Hypothalamus
Releases gonadotropic hormones. Sexual dimorphic nucleus, which has a role in sexual behavior, mating, and partner preference.
Lesion leads to arrested sexual development, impotence, amenorrhea.
Suprachiasmatic Nucleus
Pre-Optic
Regulates circadian rhythms (e.g. cyclic release of CRH, melatonin from pineal gland). Input from retina (melanopsin), output to pineal gland.
Dorsomedial Nucleus
Hypothalamus, Tuberal Region.
Almost all major pathways feed into this nucleus; also regulates autonomic function(s); stimulation can lead to obesity
Posterior Nucleus
Hypothalamus
Posterior
Temperature regulation (heat conservation). Lesion leads to poikilothermia (poor thermoregulation). Stimulates the sympathetic nervous system.
Lateral Nucleus
Hypothalamus
Posterior
Feeding center. Stimulation leads to increased eating (lateral nucleus causes you to grow laterally). Lesion leads to starvation.
Mamillary Body
Hypothalamus
Posterior
Damaged in Wernicke Encephalopathy/Korsakoff psychosis (confabulation, amnesia, ataxia). The circuit is from hypothalamus to fornix to mammillary body.
Ventromedial Nucleus
Hypothalamus
Tuberal Region
Satiety Center. Stimulation leads to decreased eating (ventromedial nucleus causes you to shrink medially). Lesion leads to obesity, hyperphagia, “savage” behavior
Arcuate Nucleus
Hypothalamus
Tuberal Region
Produces hypothalamic releasing and inhibiting factors that act on the anterior pituitary. Inhibits prolactin release via dopamine (aka prolactin-inhibiting factor).
Where is Wernicke’s area?
• Posterior part of superior temporal gyrus; that is why Wernick’es aphasia may also be associated with a contralateral upper quadrant field cut (temporal lobes)
Where is Broca’s area?
• Inferior frontal gyrus; part of pre-motor cortex
Gerstmann’s syndrome
Arises from lesions in the left angular gyrus (junction of parietal and temporal lobes)
– Agraphia
– Acalculia
– Finger agnosia
– Right-left disorientation
Fourth Nerve Palsy
- Hypertropic (elevated slightly)
- Head tilt away from the lesion (normally intorts, so extorting)
- Fourth nerve has a very long path, tumor can be involved
- Loops up when medial
- Double vision when reading a book
Sixth Nerve Palsy
- Diabetes, Hypertension
- Intercranial pressure (90 degree exit off pons into the brain)
- Can’t look laterally in the eye that is affected, but medial horizontal movement in other eye is not impaired
- Bilateral: Can’t look lateral in either direction
UMN Lesion of VII Clinical Presentation
- Note that UMN innervation of VII in the upper half of the face is bilateral so that if you destroy cortical input from one side, the upper facial movement is conserved, but the lower face movement on the contralateral side of the lesion is not
- To summarize: You would see deficits in the lower half of the face on the contralateral side
Identify and explain.
Intracellular hyper-phosphorylated Tau proteins; seemed to be caused by the “toxic” AB amyloid neuritic plaques that are formed
What are the round plaques?
Neuritic plaques – extracellular; comprised of hydrophobic, beta-sheet stacked AB amyloid with entangled neuritic processes and can be associated with microglia
May deposit around vessels, increasing the risk for hemorrhage
What is the histological hallmark of spongiform encephalopathy?
Spongy degeneration (damage to neurons and glial cells is characterized by intracellular vacuoles)
Three proposed stages of memory processing
The role of the hippocampus and parahippocampal areas are crucial for establishing long-term memories. When sensory input is received it is encoded into short term memory (hippocampus-independent). This information is held in working memory (tested in tasks such as counting backward from 100) and if consolidated (hippocampus-dependent) is stored as long term memory which can later be retrieved.
Note that: Implicit (or non-declarative) memory such as learning motor skills is not dependent on the hippocampus. H.M., a man who had his hippocampi (and large amounts of the parahippocampal areas) removed bilaterally for epilepsy could no longer encode new explicit memories. He could learn to ride a bike—he would do better each day but have no memory of riding a bike before. In 1997, an MRI study was done to see the extent of the surgical resection.
Papez Circuit
Limbic system circuit that plays a role in memory and emotion; although it is not a true circuit, structures of the circuit contribute to memory and emotional processing that is part of the limbic system
The Papez circuit begins with fibers arising from the subiculum of the hippocampal formation, which enter the fornix and travel forward to both the medial and the lateral mammillary nuclei. The medial mammillary nucleus then projects through the mammillothalamic tract to the anterior thalamic nucleus. Recall that the anterior thalamic nucleus also receives a direct projection from the fornix. The anterior thalamic nucleus next projects through the internal capsule to the cingulate gyrus. Finally, a prominent white matter pathway underlying the cingulate gyrus called the cingulate bundle, or cingulum, passes from the cingulate cortex to the parahippocampal gyrus. From the parahippocampal gyrus, projections continue to the entorhinal cortex and hippocampal formation, completing the loop.
Tumor
Pilocytic Astrocytoma
(Child) - Histology
- GFAP
- Rosenthal fibers
Tumor
Medullo-blastoma
(Child) - Histology
Homer-Wright rosettes
Tumor
Hemangio-blastoma
(Child) - Histology
- Foamy cells
- High vascularity
Tumor
Glioblastoma Multiforme
(adult) - Histology
- GFAP
- Pseudopalisading necrosis
Tumor
Glioblastoma Multiforme
(adult) - Gross
“Butterfly”
What are the consequences of subfalcine herniation?
In this type of hernation, the cingulate gyrus herniates under the falx cerebri, which can compress the anterior cerebral artery
What are the consequences of uncal herniation into the tentorium cerebri?
Crushes CN III (down and out with dilated pupil)
Compression of PCA can lead to contralateral homonymous hemianopia
Rupture of paramedian arteries that perforate from basilar into midbrain and thalamus, causing hemorrhage
Wallerian Degeneration
In the periphery, the axon and myelin get degraded & phagocytosed, THEN Schwann cells proliferate!
