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Final - Review Notes (Lec 22-35) PSYCH 2NF3

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McMaster University
Gautam Ullal

PSYCH 2NF3 2013 QuickNotes – Final Content (Lectures 22-35) Electrophysiological Investigations of the Brain 1. Electroencephalogram (EEG) – refer to Midterm 2 QuickNotes 2. Magnetoencaphalogram (MEG) – measures magnetic field generated by neurons, no skin or scalp artifacts or contact, more directly reflects activity of neurons, better temporal and spatial resolution than EEG, requires superconducting coils, magnetic shields and superconducting quantum interference devices (SQUID), expensive 3. Electrocorticogram (ECoG) – craniotomy (hole in skull), record electrical activity directly from brain surface, better resolution than EEG, target epileptic focus, anesthetic can be used but keeping patient aware is beneficial, can use before epilepsy surgery or removing tumor (brain cells have no pain receptors) 4. Stereotactic Recording and Microdialysis – localized stimulation by targeting electrodes to specific area to record electrical activities, invasive (in vivo), MRI first to obtain 3D map for guiding tool o Microdialysis – microelectrodes implanted stereotactically; infuse chemicals locally 5. Slice Studies – slice (eg/ hippocampus) in fluid medium, stimulate then record activity; multiple-electrode grid to record different regions and see interaction 6. Voltage Clamp 7. Photon-Uncaging 8. Patch Clamp Neural-Network Modeling  Use simple to complex algorithms and computer simulations  Kindling – progressive neuronal activity following repeated stimulation of forebrain areas – model for learning and epilepsy  Manifests as progressively longer “EEG-After Discharges” induced by progressively lower thresholds  Neurons assigned 1/0 firing pattern (all-or-none neuron)  Model synapse by varying weight of excitatory and inhibitory inputs on neuron  Incorporate Hebbian Rule  Network after 10 suprathreshold stimuli – tends to recover to resting state  Network after 30 suprathreshold stimuli – remains most often in higher activity state; kindling  Rate of kindling is inversely proportional to number of neurons; higher the number of neurons, greater the variability of kindling Split-Brain  Consciousness – process of awareness of own self (through environment etc)  Self – who one is (based on memories, personal experiences etc)  Split-Brain Surgery – cutting corpus callosum; confine abnormal firing to one side; can do partial callostomy if problem is localized  Split Brain Syndrome o Two minds in one brain – eg/ turn TV on with one hand, turn off with other o Reading a book held in left hand – left brain is engaged (reading), right brain is not engaged (holding book) and thus left hand drops book; can train brain to work together o Holding flower, smell flower, pick flower – left hand holds flower, right nostril smells flower (right brain; olfaction same side  left brain does not get signal), cannot pick the flower (left brain)  right brain knows which flower was smelled, but left brain cannot give indication (left brain = speaking brain) o See, pick, speak (KEY left side (right brain); RING right side (left brain)) – tachistoscope (split screen), words flashed for 0.1 seconds on screens; sees “ring” on right side (left brain); can say “ring” (left brain); picks up key with left hand (right brain sees KEY) Neglect  Unilateral Neglect (hemineglect) – left half of body does not exist/belong to me; sensations intact, problem with attention; damage to right parietal lobe (often due to stroke)  Neglect of left space o May be selective – able to appreciate shape, but not attend to details in left space o Could involve mental space – distorted special orientation; unable to attend to spatial maps on one side of brain; mental recall of objects on left side effected  Reduced blood flow to different cortical areas o Viewer Centered/Egocentric Neglect – hyperfusion of right angular gyrus and supramarginal gyrus; divide space depending on my position (I am center); eg/ draw right half of entire picture o Stimulus/Object Centered/Allocentric Neglect – hypofusion of right superior temporal gyrus; eg/ draw right half of all objects in picture  Right side of body gets attention from both left and right parietal lobe – no right hemineglect with lesion on left parietal lobe  Rivalry – examiner presents fingers to both visual fields; hemineglect patient cannot count on left visual field because of rivalry – may be able to count if fingers presented one-after-another Phantom Limb Syndrome  Amputated limb “coexists” as normal, limb has “telescoped/shrunk”, limb fixed in awkward posture, limb exists close to other body part not related earlier, amputated limb is “paralyzed” or painful  Develops following traumatic amputation (patient is not mentally prepared) – due to denial, persistence of nerve network, nerve plasticity  Rubber Hand Illusion – phenomenon of extended body ownership; brushing of rubber hand, real hand hidden; brain misinterprets visual schema for tactile schema o fMRI shows increased activation of premotor cortex (plans for movement) besides parietal (sensory) cortex during illusion  Parietal lobe activation when hand is brushed 1 PSYCH 2NF3 2013  Premotor activation when subject points to rubber hand as own Temporal Lobe  Temporal Lobe/Cortex – connects auditory, visual, olfactory, vestibular, spatial and touch sensations; associates with emotions (through amygdala), forms contextual memories (through hippocampus) o Functions – process auditory, visual, gustatory, olfactory, somatosensory and vestibular inputs; emotions; empathy (mirror neurons); theory of mind; language and music; verbal and non-verbal memory; spatial map (place cells and grid cells); time  Anatomical Landmarks – Inferior Temporal (TE); visual areas= 20, 21, 37, 28; auditory = 22, 42, 41  Medial Temporal Cortex – amygdala, hippocampus, insula (buried inside temporal lobe)  Lateral Temporal Cortex – auditory cortex, visual cortex, gustatory cortex, uncus (smell) (part of temporal lobe)  Clusters of neurons organized in columns of the Inferior Temporal Cortex in Monkeys, perpendicular to the cortical surface – show selective responses to specific shapes; different temporal lobe neurons activated depend on visual stimulus  Auditory Cortex (humans) – Wernicke’s area; larger on left side; responsible for interpretation and processing speech  Epilepsy – repeated episodes of (all or some) altered states of consciousness, strange feelings (de ja vu, ja mais vu), hallucinations (auditory, olfactory, visual), altered behaviour (eg/ violence, ecstasy, melancholy, fear), amnesia to the episode o Patient HM – generalized seizures for years uncontrolled by medication; bilateral temporal lobe resection controlled seizures but causes anterograde amnesia with normal retrograde memory, IQ, language and social behaviour  Fear-Conditioning and Avoidance –sensory input through medial nucleus of amygdala; motor responses through central nucleus of amygdala (amygdala is key mediator)  Urbach-Wiethe Syndrome – amygdala degeneration; autosomal recessive bilateral disease; inability to recognize fear in faces, no memory loss, other facial expression recognition not impaired as much o Patient SM – shows no fear to any life situations o High CO2levels inhaled - normal individuals show panic attack; patient with amygdala lesion shows panic response stronger than control  Kluver-Busy Syndrome – amygdala lesion; following bilateral anterior temporal lobectomy (including amygdala); excessive tameness (flat affect), oral exploration, agnosia, indiscriminate dietary behaviour, autoeroticism (sexual mounting inanimate objects); follow meningitis, trauma and brain tumors  Insula (insular cortex) – triangular island under temporal cortex; gustatory, vestibular (balance) and remote (eg/ empathy) sensations/functions o Integrates the emotional, cognitive and sensory components of pain perception; link subjective conscious “pain experience” with conscious “emotional experience” of expression (eg/ activated when disgust is experienced) o Primary-taste area o Damage to insula results in failure to experience disgust or empathy for pain in others  Couvade Syndrome – sympathetic pregnancy; men groan as if in labour-pain while wives deliver baby blissfully  Theory Of Mind – innate ability to understand the state of another’s mind (eg/ empathy) o Impaired in children <4-6 years, people with autism, schizophrenia, frontotemporal dementia and anosognosia (no insight about stroke or blindness) o Test – Sally and Anne doll test o Von Economo Neurons (humans, great apes) – large bipolar, spindle-shaped neurons in insula, amygdala, anterior cingulate and orbito frontal cortex; develop by 4 years of development; connect some brain regions; polymodal integration of internal and external sensations and emotions  Poorly developed in autism; degenerate in frontotemporal dementia and AD; less density in early-onset Schizophrenia  Mirror Neurons – group of neurons extending from inferior parietal cortex/lobule to premotor and prefrontal cortex; activated when observing behaviour; important for imitation, language acquisition, understanding others feelings (empathy) and intentions; implicated in autism o Involved in understanding a command (idea), observe someone performing, mental rehearsal, others intentions, empathy, social communication, imitation of an action, pantomime, understanding metaphors, inside, humor  Booba-Kiki Effect – shapes mirror sounds (shape and word pairs); evidence for “mirror neurons” in occipitotemporal cortex; explanation of synesthesia (stimulus in one precept triggers precept in other sensory modality)  Mirror Neurons in Monkeys o Watch human hand place food pellet – some neuron firing o Watch monkey hand place food pellet – large amount of neuron firing o Watch human hand use pliers to place food – no neuron firing (monkey doesn’t know how to use pliers)  Superior Temporal Sulcus (STS) – activated on perceiving biological motion (eg/ facial perception); inputs into premotor areas via mirror neurons  Amnesia (typically anterograde) o Left lobe lesion – impaired recall of verbal material presented visually or aurally; verbal memory tested with word pairs and short story recall o Right lobe lesion – impaired recall of non-verbal material (geometric shapes, faces, tunes); test by copying drawing then recalling 45 minutes later  Space Perception o Place Cells – hippocampal neurons that fire in response to specific locations; independent of head orientation; rely on several sensory inputs (vision most important) o Head Direction Cells – hippocampal neurons that fire to specific orientation; independent of location o Grid Cells – sensitive to location, head orientation, speed of movement etc; environments represented as a grid on the entorhinal cortex 2 PSYCH 2NF3 2013 o Electrical activity recorded hippocampus, parahippocampus, amygdala and frontal lobe with multiple electrodes (6-14) placed bilaterally in 7 epileptic patients undergoing surgery exploring a virtual town  Place Cells – right hippocampal neurons showed maximum firing to specific locations  Orientation Sensitive Cells – right parahippocampal neurons showed maximum firing to specific orientation  Distance, Time, Direction o Dead reckoning – navigation based on self-generated, movement related cues (distance, time taken, direction); return to location faster, hippocampus and entorhinal cortex process cues  Eg/ Mouse gathers candy around cage, then returns to burrow by a different, quicker path, due to cues o Food storing chickadee has larger hippocampal volume than non-food storing sparrow Meninges  Meningitis Symptoms (from vignette) – short duration of headache, high fever, neck stiffness, increased respiratory rate and pulse, positive Brudzinski sign (bending neck causes bending of legs due to inflamed/irritated meninges)  Skull o Skull Bones – flat bones separated by suture lines; fontanel (gaps between suture lines) fused 1-2 years after birth (helps with baby delivery and allows for brain development) o Craniosynostosis – premature fusion of suture lines result in distorted shape and brain cannot develop properly  Brain Stem – has vital centers (cardiovascular and respiratory functions), reticular formation (network of neurons important for arousal, attention and muscle tone), cranial nerve nuclei (highway for sensory and motor neurons) o Medulla oblongata of brain stem passed through foramen magnum  Layers of Meninges th 1. Dura Mater – outermost, dense, thickest layer; dense innervation by pain-fibers via trigeminal nerve (5 cranial nerve); pain receptors  Outer layer attached to skull, inner layer folds along sagittal and transverse planes that scaffolds hemispheres; folds contain venous sinuses that receive venous blood from brain  Arachnoid granulations (mushroom-shaped projections attached to venous sinus openings) drain the CSF from subarachnoid space into dural sinuses  Not high pressure area  Head Injury  skull fracture  dural tear  venous blood  brain pressure on vein causes lucid interval (bleeding stops temporarily; symptom free)  bleeding ensues after 1-2 hours (can be fatal if not treated early)  Hematoma = pooling of blood outside of blood vessel  Herniation (protrusion) of hippocampus, brain stem, cerebellum through foramen magnum – caused by increased intracranial pressure (can be caused by bleeding); can result in sudden death due to pressure on vital centers; diagnosed by CT scan 2. Arachnoid Mater – middle layer, web-like, minimal sensory inputs 3. Pia Mater – innermost layer, closest to brain o Meninges (3 layers) envelopingthe spinal cord merge with the peripheral nerves o Failure of neural tube closure leads to meningomyelicele (herniation of meninges and spinal cord; type of spina bifida (undeveloped spinal cord))  Cerebral Spinal Fluid (CSF) – watery fluid circulating around brain and spinal cord, between cerebral ventricles and subarachnoid space; shock absorber for brain buoyancy (1400g50g), drains metabolic products from brain to veins, provides nutrition, vehicle for chemical messengers to distant targets, diagnostic window particularly for meningitis o Normal pressure (intracranial tension/pressure) = 5-15 mm Hg o Normal volume of CSF = 125 mL; replaced 4-5 times/day o Lumbar Puncture/CSF Tap – needle inserted between L3-L4 (spinal cord end at lumbar vertebrate L2); small quantity of CSF collected to diagnose meningitis; suspect infection if CSF is turbid  Do lumbar puncture with caution if raised intracranial tension  Ventricles – two lateral ventricles (1 in each hemispheres)  opens into third ventricle (near thalamus and hypothalamus)  opens into fourth ventricle (between pons, medulla and cerebellum)  Secretion of CSF – aqueduct connects 3 and 4 ventricle; CSF produced in choroid plexus (outpunching capillaries that form a network; not found in ducts but in ventricles)  Circulation of CSF – cillary ependymal glial cells (finger-like processes that oscillate) line cerebral ventricles and facilitate circulation of CSF  Hydrocephalus (obstructive) – increase in ventricular volume, water in brain; may be due to obstruction in CSF circulation (from increased pressure or normal pressure but atrophy of brain); brain eventually gets squeezed and damages skull in babies o Aqueduct could be blocked due to projection, tumor or hindered development o Shunt-Surgery – needle inside ventricle drains CSF when pressure builds up in abdominal cavity adjacent to peritoneum or blood vessel direction o AD – normal pressure; enlarged ventricles due to brain atrophy, brain gets filled with CSF but pressure remains normal; not caused by obstruction  Difficult surgery because have to go through pons o Schizophrenia – increased ventricle size without increase in pressure Cerebral Blood Flow  Circle of Willis – circular arrangement of vessels at base of brain that is fed into by 2 internal carotid arteries and 1 basilar artery; communicating system between the internal carotid and basilar arteries; branches that go to brain (middle cerebral artery, posterior communicating artery and arterial cerebral artery) o Blocked vessel  Slow developing problem – Circle of Willis allows for proper blood flow (clockwise or counter clockwise blood flow) 3 PSYCH 2NF3 2013  Sudden (acute) – circular pathway cannot adjust in time  leads to stroke  Middle cerebral artery covers most of cerebral cortex; anterior and posterior cerebral arteries cover remaining cerebral cortex  Internal Capsule – dense collection of motor and sensory nerves going to and from cerebral cortex  Middle Cerebral Artery – supplies internal capsule; often implicated in stroke  Autoregulation – internally/self-regulated; automatic internal regulation of blood flow Micro-adjustments of blood flow depending on local demands a) Cerebral Microvasculature – branching pattern of blood vessels b) Windkessel Design – smooth muscle valves regulate blood flow rate to adjacent area by increasing/decreasing diameter Provide constant blood flow to brain despite wide fluctuations in peripheral mean arterial pressures c) Munroe-Kelly Principle – brain, flood and CSF share fixed limited volume of rigid skull; keeps blood flow constant (brain tissue 1400mL, cerebral blood flow 150 mL, cerebrospinal fluid 150 mL) d) Role of Medullary Vasomotor Centers – detect changes in blood pressure in incoming blood vessels and reflexively regulate blood flow to brain via autonomic nervous system (ANS); medulla oblongata regulates respiratory and cardiovascular systems e) Neurovascular Network and Astrocytes – blood flow must increase to particular area to perform a function  Strategy 1 – steal blood from neighboring area  impairs area that lacks blood; impair body functions  Strategy 2 – steal blood in a distributed fashion with quicker response due to neurovascular network  Neurovascular network – tells blood vessels to increase or reduce blood pressure; regulates regional cerebral blood flow o Network of nerve fibers that connect blood vessels; orchestrated by major areas such as basalforebrain; chemical cues stimulate increase/decrease of diameter (increase in2O or GABA – vasoconstriction; 2O and Glutamate – vasodilation); astrocyte major component  Orientation columns – support via glia o Astrocyte has good network and doesn’t need neurotransmitter – can send electrical signals (Ca signals) rapidly Blood Brain Barrier (BBB)  Brain is 2% body weight  20% of brain is blood, 20% oxygen, 20% glucose 2  1g of brain shares ~200cm of surface area with blood  Length of blood vessels lining the cortex = ~400 miles  WBC, RBC, chemical substances cannot enter brain – important for neuronal and synaptic function; metabolites of WBC and RBC are neurotoxic  Goldmann’s Classical Experiment – Tryptan blue injected into 1. Blood; did not stain brain or CSF 2. CSF; stains brain  impermeable barrier between blood and CSF, and blood and brain  Components of BBB o Blood Brain Barrier (BBB) – selective physiochemical barrier between blood and brain o Endothelial cells – line capillaries o Tight Junctions (TJ) – between blood vessel and endothelial cells; only seen in brain capillaries, not general capillaries  Made of occcludins and claudins; destroyed by trauma, epileptic seizures and AIDS o Basement Membrane (BM) – additional barrier that reinforces BBB; semipermeable o Astrocytes and Pericytes – important for TJ and BM synthesis o Microglia and Astrocytes – act as local police o Enzymes of endothelium, astrocytes and pericytes – destroys invading chemicals o Abundant mitochondria, TJ and astrocytes in brain capillary system – not general capillary system o Astrocytes – extend between ependymal of ventricle, neuron and blood vessel with extensive branches; foot processes wrap tightly around blood vessels o Pumps – expel toxic substances (eg/ glutamate pumps expel excess glutamate from neuron)  Crossing BBB o O 2nd CO –2can cross easily; lipid soluble o Glucose – requires transporter(GLUT) o Psychoactive Drugs – can cross; lipid and water soluble o DOPA (dihydroxyphenylalanine) – cannot cross; needs to be L-DOPA  Parkinson’s Disease – deficiency of dopamine, but if dopamine administered, cannot permeate BBB  L-DOPA (precursor) can cross – 50% to neuron, 50% to blood vessel; administered with carbidopa (prevents L-DOPA conversion to dopamine in blood vessel) o Transport Systems  Passive transport of lipid soluble substances  Carrier-mediated transport – eg/ GLUT (for glucose); amino acid transporters (L-DOPA), vitamin-transporters  GLUT-1 Defects  lowers GLUT-1  lowers efficiency to transport glucose to brain  seizures and mental retardation; microcephaly  Microcephaly – small head circumference (does not grow through development); developmental delay, learning disabilities, mental retardation, uncontrolled epileptic seizures; treat with early intake of special ketogenic (high in fat) diet (nourish neurons instead of glucose)  Ion pumps – eg/ Na+, K+, ATPase  Receptor mediated endocytosis – peptides and proteins bind to receptors on neuron and endocytosed; masqueraders are toxic  Breaking BBB o Certain chemicals open BBB and allow drug entry – mannitol and arabinose often injected with other anticancer medication to break BBB for short period of time; sugars break BBB because of high osmotic gradient  Disadvantage – other substances can cross BBB  Leaks in BBB 4
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