Neuroscience review Brain Cerebrum o Grey Matter Large neurons: projection fibers (ascending and descending pathways) Medium

um neurons: commissural fibers (between hemispheres) Small neurons: association fibers (within hemisphere) o White Matter Corona Radiata Internal Capsule o Cortex: Frontal lobe: primary motor cortex, prefrontal cortex, premotor cortex, supplementary motor cortex Parietal lobe: primary somatosensory cortex Occipital lobe: primary visual cortex (calcarine sulcus) Temporal lobe: primary auditory cortex o Subcortical: Hippocampus Amygdala Basal ganglia Striatum (innervated by substantia nigra pars compacta, modulates input from cortex and output from thalamus, important in Parkinsons disease) o Dorsal Striatum: putamen, caudate nucleus o Ventral Striatum: nucleus accumbens, olfactory tubercle Globus pallidus (forms lentiform nucleus with putamen) Substantia nigra (pars compacta, pars reticulate) Lateral Ventricles Rhinencephalon Olfactory bulb, tract Anterior commissure Diencephalon o Epithalamus o Third Ventricle o Thalamus o Hypothalamus Optic Chiasma o Subthalamus o Pituitary gland Brain stem o Midbrain Tectum: inferior and superior colliculi Tegmentum: ventral tegmental area, Red Nucleus, crus cerebri Mesencephalic duct (of Sylvius) Cerebral peduncle Pretectum o Pons Respiratory centre: pneumotactic centre, apneustic centre Cranial nerve nuclei: pontine nucleus of trigeminal nerve sensory branches, motor nucleus for trigeminal nerve, abducens nucleus, facial nerve nucleus, vestibulocochlea nuclei, superior and inferior salivatory nuclei o Medulla Oblongata Medullary pyramids Cranial nerve nuclei: nucleus ambiguus, dorsal nucleus of vagus nerve, hypoglossal nucleus, solitary nucleus Cerebellum o Vermis o Hemispheres

Vascular supply - Vertebral Arteries Basilar Artery - Basilar Artery + Internal Carotid Arteries Circle of Willis o Anterior, Middle, Posterior Cerebral Arteries o Anterior, Posterior Communicating Arteries

Cranial nerves 1) Olfactory 2) Optic 3) Oculomotor 4) Trochlear 5) Trigeminal 6) Abducent 7) Facial 8) Vestibulocochlea 9) Glossopharyngeal 10) Vagal 11) Accessory 12) Hypoglossal Spinal Cord - Extends from foramen magnum, terminates in conus medullaris with filum terminale, forming cauda equina at L1-L2 - White matter: spinal tracts - Grey matter o Dorsal horn: sensory, Ventral horn: motor, Lateral horn (T1-L2): autonomic o Spinal nerve: union of dorsal sensory and ventral motor roots o Sympathetic fibers originate from lateral horn, exits spinal cord via ventral roots, white rami communicans to sympathetic ganglion, post-ganglionic grey rami communicans rejoins spinal nerves to innervate glands, smooth and cardiac muscle - 8 cervical (C1 above C1 vertebra, C8 below C7 vertebra), 12 thoracic, 5 lumbar, 5 sacral, 1 coccyx Pathways - Ascending (Sensory) o Spinothalamic: pain, temperature, touch, pressure Decussates at level of spinal cord o Dorsal Column Medial Lemniscus: vibration, conscious proprioception Decussates at level of medulla o Spinocerebellar: subconscious proprioception Does not decussate - Descending (Motor) o Pyramidal Corticospinal (rest of body) Decussates at level of medulla Corticobulbar (for head and neck) o Extra-pyramidal Tectospinal Vestibulospinal Reticulospinal Rubrospinal Sensory system - 1st order neuron o Receptors: Crude touch, pressure, pain, fine touch, vibration, conscious and subsconscious proprioception Skin, skeletal muscles, joints, viscera o Dorsal root ganglion o Synapses at dorsal horn of spinal cord nd - 2 order neuron o Axon travels along the ascending tracts o Decussates o Synapses at thalamus, cerebellum rd - 3 order neuron o Cerebral cortex or cerebellum Motor system - Upper motor neuron o Motor center of cerebral cortex o Axons pass through corona radiata, internal capsule, to midbrain and medulla oblongata o 80% decussate o Synapses at anterior horn of spinal cord

Lower motor neuron o Carries action potential to neuromuscular junction o Synapses on voluntary muscles

Organisation - Somatic nervous system o Sensory o Motor - Visceral nervous system o Sensory o Motor Sympathetic (T1-L2) Nicotinic acetylcholine receptor: ligand gated ion channel Parasympathetic (craniosacral outflow) Muscarinic acetylcholine receptor: GPCR that uses 2nd messenger to modify ion channels CN 3, 7, 9, 10 o 3: Intraocular muscle for pupil size and lens thickness o 7: Glands of head o 9: Parotid gland o 10: Parasympathetic stimulation of visceral organs up to 2/3 of proximal transverse colon S2-4: rest of GIT General Function - Sensory system: collect information about state of organism and environment - Motor system: organize and generate actions - Association systems: linking sensory and motor components to provide basis for higher order brain functions o Association cortex occupies majority of cortex (sensory and motor cortices account for ~20%)

Neurohistology - CNS o

Frontal: guiding complex behaviour by planning responses to ongoing stimulation Temporal: recognition and identification of highly processed sensory information Parietal: attention and awareness of the body and stimuli that act on it

Neurons: functional cells Induces depolarization along processes and axons Neurotransmitter production Glial cells: supporting cells Astrocytes: blood brain barrier Oligodendrocytes: myelination of nerve axons Ependymal cells: lining of ventricles Microglia: macrophages for brain Neurons: transmit signals Motor: neuromuscular junction Sensory: receptors (baro, chemo, mechano, noci, osmo, photo, proprio, thermo receptors) C fibers: slower due to unmyelinated fibers (thermal, mechanical, chemical) A fibers: faster due to myelination (sharp pain) Schwann cells: myelination of axons Satellite cells: similar to astrocytes and Schwann cells

PNS o

o o

Reflex - Pathway o Receptor responds to stimuli o Afferent sensory carries stimuli to CNS o Integration of information in CNS Monosynaptic Polysynaptic o Efferent motor neuron carries impulse Polysynaptic: involves inhibitory interneuron to relax opposing muscle o Effector: contraction and relaxation - UMN: loss of inhibition by UMN, hence hyper-reflexia and clonus may be observed - LMN: loss of innervation by LMN, hence muscle is unable to respond to stimulus

Neurophysiology - Action potential o Resting membrane potential At equilibrium, there is a balance of opposing forces Concentration gradient causing K+ to move out of the cell and Na+ to enter the cell Opposing electrical gradient that increasingly tends to stop K+ from moving across membrane Na+K+ ATPase: for every 2K+ transported into the cell, 3Na+ are removed Net loss of one positive ion from cell, leading to hyperpolarization o Ionic basis Na+ channels open, influx reaches threshold, firing off action potential Na+ channels closed and becomes refractory K+ channels are opened during depolarization and continues to leave the cell, causing membrane potential to return to resting state K+ channels are slow to close, causing hyperpolarization Factors affecting AP propagation

Axon diameter: larger less resistance Membrane conductance: leaks charge if poorly insulated Myelination: nodes of Ranvier saltatory conduction Membrane capacitance: current is used up charging the membrane o Clinical relevance: Multiple sclerosis: demyelination and inflammation along axonal pathways Toxins: tetrodotoxin (puffer fish) / saxitoxin (red tide) blocks Na+ channel -toxin (scorpion) slows inactivation of Na+ channel Dendrotoxin (wasp) / apamin (bee) blocks K+ channel Synapses o Transmission AP arrives at synaptic bouton, deploarization opens voltage gated Ca2+ channels Influx of Ca2+ promotes vesicle (containing neurotransmitter) attachment to presynaptic releasing sites Vesicle membrane fuses with presynaptic membrane and contents are released into synaptic cleft Transmitter diffuses across cleft and binds to postsynaptic receptors Excitatory or Inhibitory Bound receptors cause change in postsynaptic membrane potential, magnitude depends on amount Effect terminated by 1) enzymatic destruction, 2) reuptake, 3) outward diffusion, 4) uptake by glial cells Type: summation allows subthreshold EPSP/IPSP to influence AP production (balance) Excitatory Increases membrane permeability to Na+, increasing resting membrane potential Neurotransmitters: glutamate and aspartate Extremely widespread throughout CNS (cholinergic system is used in brain for learning and memory, and primarily in the PNS) Inhibitory Increases membrane permeability to K+ or Cl- reducing resting membrane potential Neurotransmitters: GABA and glycine Found mainly in spinal cord interneurons Amines: dopamine, noradrenaline, adrenaline, serotonin May be excitatory or inhibitory depending on the specific receptor Clinical relevance: Sarin and organophosphates inhibit acetylcholinesterase -bungarotoxin (Bungarus multicintus) irreversible nicotinic acetylcholine receptor inhibitor Atropine (Atropa belladonna) competitive muscarinic acetylcholinereceptor antagonist Aricept acetylcholinesterase inhibitor used for treatment of Alzheimers Disease

Spinal cord level - C3, 4 and 5 supply the diaphragm (the large muscle between the chest and the belly that we use to breath). - C5 also supplies the shoulder muscles and the muscle that we use to bend our elbow . - C6 is for bending the wrist back. - C7 is for straightening the elbow. - C8 bends the fingers. - T1 spreads the fingers. - T1 T12 supplies the chest wall & abdominal muscles. - L2 bends the hip.

L3 straightens the knee. L4 pulls the foot up. L5 wiggles the toes. S1 pulls the foot down. S3, 4 and 5 supply the bladder, bowel and sex organs and the anal and other pelvic muscles.

Memory Basic processes - Encoding: perceptual and sensory information is transformed - Storage: process which information is retained - Retrieval: process which we recover information and become consciously aware - Stages: young tend to have problems with attention and encoding, elderly tend to have problems with retrieval o Sensory input sensory memory Unattended information is lost o Attention working (short term memory in hippocampus) Requires maintenance, unrehearsed information is quickly lost o Encoding long-term memory (in cortex) Some information may be lost over time o Retrieval to short-term memory Types Sensory Memory o Very short term, temporary recollection o Large capacity, very short duration, dependent on attention Attention is the gate that lies between sensory and working memory (very selective) Working Memory o Short term o Sensations which are attended to become encoded in short-term memory o Limited capacity, short duration o 7 +/- 2 bits of information, usually lasts about 30 seconds o Transferred to long term memory by encoding Long term Memory o Memories of the past which form knowledge base o Infinite in capacity and duration o Encoding depends on feelings, emotions, and is hence coloured (selective encoding) o Elaborative rehearsal to organise memory o 2 types of memory Explicit: items, events, meanings, episodic, semantic Implicit: unconscious, programmed into cerebellum, eg. cycling, etc o Problems lie in retrieval Tip of tongue Freudian slip Requires specificity as encoding (context, state, mood) Association networks: different parts of brain stores different parts of the same memory To retrieve information, brain performs complex chain of chemical and electrical functions As one ages, these cells, synapses and systems deteriorate and function less efficiently Aging does not generally affect sensory or long-term memory Short term memory declines with age o Mild decline in memory o Slowing in rate of information processing o But does not affect daily function, nor acutely exacerbate

Ageing -

Dementia - Clinical syndrome o Progressive o Global deterioration in cognitive function o In a clear state of consciousness o Sufficiently severe to interfere with social and occupational function - Epidemiology o Exponential increase in age specific dementia prevalence as age increases o Dementia prevalence in societies will increase due to increased life expectancy o Often unrecognised and misdiagnosed and viewed as inevitable ageing - Cost o Healthcare costs, lost productivity o Emotional, psychological and practical problems for caregivers o Early treatment Proven effective treatments available Prevents costly and inappropriate treatment Avoids trauma of misdiagnosis Prepares patients and families to settle financial, legal, treatment and care plan issues - Early symptoms o Difficulty learning and retaining new information o Language problems o Difficulty handling complex tasks o Alterations in behaviour o Loss of reasoning ability o Loss of spatial ability and orientation o No acute exacerbation: not to be confused with delirium (due to general medical condition) - Types o Alzheimers Disease (amnesia, aphasia, apraxia, agnosia) o Lewy Bodies o Vascular o Frontotemporal Types Progressive mutism Semantic dementia Early stages Personality changes Changes in social conduct Loss of emotional warmth - Prevention o Risk factors o Disease process and modifiers o Biomarkers and neuroimaging o Lifestyle interventions Social networks, mental activities, physical activity Reduce vascular risk Enhance cognitive reserve Reduce stress Diet: wine/alcohol o Pharmaceutical and non-pharmaeutical treatments Symptomatic treatment Cholinergic drugs (acetylcholinesterase inhibitors) o Tacrine, donepezil, galantamine, rivastigmine Glutaminergic drugs o Memantine Anti-psychotic drugs o Cultural issues - Imaging o Medial temporal lobe (hippocampus) o Increasing Alzheimers Disease enlarging temporal horn (normally not seen, indicates atrophy of hippocampus) o Modalities: CT, MRI, PET, MRA, fMRI - Markers o Beta amyloid and tau proteins

o o

Burden of disease (infarcts, white matter lesions) Neuronal loss

Communication Language - Interplay of: o Form: sounds, formation of sentences, function: verbal and non-verbal communication, content: meaning - And social interaction, different parts of the brain hold different skills, brain lesions may allow compensation of communication function - Good speech: cadence, speed, pitch, volume Communication deficits - Types o Aphasia o Apraxia o Dysarthria o Right hemisphere / cognitive communication deficits - Caused by: o Stroke o Dementia o Traumatic brain injury o Motor neuron disease o Cancer o Diseases of mouth, throat, lungs - Results in social isolation due to o Reduced communicative effectiveness o Difficulties with daily activities o Emotional frustration and reduced self-esteem Pathways - Somatosensory information is relayed to the primary sensory cortex - Sight is seen and relayed to the primary visual cortex - Speech is heard and relayed to the primary auditory cortex - Signals are propagated to Wernickes area where the signals are understood - Brocas area then responds with the desired expression and signals are sent to the primary motor cortex - Primary motor cortex then relays signals to the appropriate muscles for the production of speech Cognitive-neuropsychological model

Lesion Middle Cerebral Artery - Supplies lateral surface of brain o Upper division Motor and sensory of face, arm and hand: contralateral facial and upper limb weakness Frontal lobe Brocas area: non-fluent, expressive aphasia o Lower division Temporal lobe Wernickes area: fluent, receptive aphasia, auditory neglect

Aphasia - Brocas (non-fluent) o Good comprehension at simple level, slow, laborious expression, consists mostly of content words (nouns) o Short utterances, intact self-monitoring/awareness - Wernickes o Impaired comprehension o Long, grammatically accurate but empty speech, filled with neologisms or jargons, beating about the bush o Poor self-awareness - Global o Severe impairment in all language functions, stereotypical or over learned phrases o May be better at nonverbal tasks, due to impairments in understanding and talking Diagnosis - Past medical history, current case history, subjective assessment (physical status, behaviour) - Screen o Receptive language Understanding questions Following instructions (without visual cues) o Expressive language Naming objects (may need prompting, context of object) Conversation Reading Writing - Understanding o Attention: reduce distractions, face to face, one person at a time o Content: speak slowly, key words, break down instructions, repetition o Cues: supplement with gestures, pictures, drawings, elaborate with contextual information - Expressing o Time: allow time for them to think of words, search for clues o Questions: binary choices, yes/no questions o Alternatives: gestures, pointing to objects and pictures, writing, drawing Apraxia - Difficulties in speaking as a result of impairment in capacity to plan or program movements for speech - Due to damage to left side of brain o Left frontal, temporal, parietal lobe o Left insula and left basal ganglia - Co-occurs with aphasia in 80% of cases, not a result of muscle weakness - Clinical features: o Speech sounds in words may be distorted, left out or repeated o Difficulty in arranging order, groping for the right word o Difficulty with the correct word o Short functional phrases, writing may be better o Inconsistent errors, with slow labored rate of speech Dysarthria - Disturbance to muscular control, may involve damage to brain (cerebral cortex, cerebellum, basal ganglia) or physical structure (oral structures, throat, lungs) - 5 categories o Respiration: short phrases, running out of breath, uncoordinated speech-breathing pattern o Phonation: breathy, hoarse, strained/strangulated Parkinsons dysphonia: tremulous voice, watery and leaky o Articulation: slurred speech, unclear lip and lingual sounds o Resonance: hyper/hypo nasal speech Flaccid dysarthria: nasopharyngeal carcinoma, myasthenia gravis, LMN lesion Causing weakness of vocal muscles, leading to flaccid dysarthria and hyponasal speech o Prosody: monopitch, monoloud, uncontrolled changes in loudness and pitch Cerebellar dysarthria: lack of coordination, staccato, monotonous, may shout all the time UMN lesion: pseudobulbar (lesion above medulla) palsy, spastic dysarthria, gravelly voice, tongue is not moving well Pseudobulbar palsy UMN: dysphagia, distorted gag reflex, spastic tongue, brisk jaw jerk Bulbar palsy LMN: dysphgia, chewing difficulty, fasciculation of tongue, absent/normal reflexes Cognitive-communication deficits

Stress Stress -

Communication deficits often arising from right MCA infarct and traumatic brain injury Intact concrete and simple functional communication Deficits in cognition: attention, memory, problem solving Deficits in communication: pragmatics, higher level language function, difficulties with social rules of normal conversation

Brain -

Threat or perceived threat to organisms homeostasis Evokes reaction in the brain That activates physiological symptoms in the body Response is proportional to the significance of the stressor, intensity and chronicity o Acute: minutes, hours immune enhancement o Chronic: hours, days onwards immunosuppression Function may be enhanced with stress, but if cannot be resolved through adaptation, results in withdrawal or anxiety o Extremes: mutism, confrontational Amygdala o Inner most part of brain, anterior to hippocampus o Fear, stress response, elicits and sustains anxiety symptoms Locus ceruleus o Bluish tint grossly o Releases norepinephrine and induces corticotrophin releasing hormone from hypothalamus (adrenal glands) Nucleus accumbens o Reward mechanisms with fibres to prefrontal cortex Thalamus o Arousal, sleep, sensorimotor gating Hypothalamus o Stress response, sleep/wake/appetite regulation Hippocampus o Memory and emotion, storage of anxiety related information Prefrontal cortex o Decides actions and responds accordingly, motor cortex fibres as well Responds via sympathetic nervous system, and hypothalamus-pituitary axis (primarily stress hormones cortisol, adrenaline) GIT o Least important to stress, hence to the extent of expulsion and defecation o Limbic system increases stimulation of mast cells in the enteric nervous system inflammatory bowel disease Brain o Increased glucocorticoids decreased brain derived neurotrophic factor decreased dendritic branching neuron atrophy and death o Chronic stress hippocampus atrophy, amygdala hypertrophy Increased risk of premature death (suicides), higher frequency of adverse health behaviours, increased risk of IHD and respiratory problems Overall: o Fight or flight: aggression, conflict, flee, withdrawal

Body -

Clinical significance - Early depression: if untreated may cause hippocampus to decrease significantly in size o Due to possibility of neurogenesis in adults, where regenerated neurons will migrate to area of need o Decreased BDNF in depressed patients Stress coping - Problem solving: solve problems of stress, organization - Emotion oriented Neurobiology

Avoidance oriented: avoid activities that induce stress, or cause regret in future Supportive behaviour: befriending Counteract: tone down expectations

Sleep and wake Definition - Reversible state of decreased responsiveness to the environment - Behavioural quiescence - Species specific posture - Sequence of physiologic sleep stages Why Restorative function Thermoregulation, energy conservation Memory consolidation and information processing, brain development and growth: spatial memory replay during sleep in hippocampus, synapses and connections strengthen during sleep performance is proportional to hippocampus activity Development of oculomotor control Immune function, preservation and protection Synaptic plasticity and remodelling: inspires insight increased ability to see patterns

Sleep-wake behaviour - Wakefulness: aware of oneself and the environment, cerebral cortex is active - REM sleep: unconscious, cerebral cortex is active, paralysis of skeletal muscles, dreams and saccadic eye movements - Non-REM sleep: unconscious, with reduced cortical activity, reduced muscle tone Tests Sleep-wake scoring o Electroencephalogram, electrooculogram, electromyogram Reflects summation of extracellular currents (microvolt scale with poor spatial resolution) During sleep, neurons tend to fire with increased synchronicity, EEG shows large steady waves Clinical sleep study o Electrocardiogram, airflow sensors, oximetry, nasal pressure, oesophageal pressure, body position, respiratory effort Awake with eyes closed o EEG: predominance of alpha wave activity in 8-13 Hz range o EOG: predominance of alpha wave activity in 8-13 Hz range (leak from EEG channel) o EMG: tonic Stage 1 sleep: transition from wakefulness to non-REM sleep o EEG: disappearance of alpha wave activity, appearance of low voltage theta activity in 4-7 Hz range o EOG: appearance of slow eye movements, undulating waves o EMG: tonic, but slightly attenuated Stage 2 sleep o EEG: appearance of K complexes (large fluctuations) and sleep spindles (fast frequency) on background of mixed frequency o EOG: no eye movements, may have deflection o EMG: tonic Slow-wave sleep (stage 3 and 4) o EEG: appearance of high amplitude delta activity <4 Hz o EOG: delta activity from EEG observed o EMG: reduced muscle tone REM sleep o EEG: appearance of low voltage mixed frequency (resembles stage 1 sleep pattern) o EOG: rapid eye movements o EMG: loss of muscle tone

States -

Determinants - Homeostatic process o Sleep pressure builds up with increased awake time, can only be dissipated by sleep itself o Probably adenosine levels - Circadian process o Alertness and sleepiness vary with time of day, regulated by internal biological clock Neurochemistry of arousal - Acetylcholine: pedunculopontine and dorsolateral tegmental nuclei (PPT/LDT), basal forebrain o Essential for midbrain pontine function, acetylcholine neurons in pons - Noradrenaline: locus ceruleus (LC) - Serotonin: raphe nuclei

Dopamine: ventral tegmental area Histamine: tuberomamillary nucleus (TMN) Orexin: lateral hypothalamus

Sleep circuits - REM sleep o Acetylcholine neurons in PPT/LDT and basal forebrain exhibit high activity: fibres to thalamus (monaminergic) and descending motor pathway (inhibitory) Activating the cortex, causing dreams Muscle atonia, rapid eye movements Autonomic fluctuations - Non-REM sleep o Synchronous cortical activity (ventrolateral pre-optic area (VLPO) and GABA, Gal): anterior part of hypothalamus, inhibitory to TMN, raphe, LC and PPT/LDT Difficult to wake out of deep sleep Fewer dreams, tonic muscle tone, no eye movements Increased parasympathetic tone - Arousal o Orexin: stimulatory to TMN, raphe, LC and PPT/LDT TMN, raphe, LC further stimulate PPT/LDT PPT/LDT sends excitatory signals to motor neurons in descending tract Model: Mutual inhibition between wake-promoting (monaminergic) and sleep-promoting (VLPO) neuronal cell groups Orexin is thought to stabilize sleep-wake transitions Circadian rhythm - Superior chiasmatic nucleis in the anterior hypothalamus is the master circadian clock: generates 24 hour rhythm in petri dish - Rhythm is generated endogenously, does not require sleep o Melatonin starts to increase before bed time Both circadian and light regulation o Cortisol starts to increase before actual waking - Nuclei o Superior chiasmatic nucleus Light enters the eye and signals are sent along the retinal hypothalamic tract to the SCN o Paraventricular hypothalamic nucleus o Pineal gland Signals eventually end up here, and inhibitory signals from the pineal gland suppress melatonin rhythm Performance - Day time: performance peaks just before bed o Homeostatic component: accumulation of hypnotoxins, sleep drive increases o Circadian component: responds by increasing alertness during the day - Night time: performance is worst just out of bed o Homeostatic component: sleep drive dissipates during sleep, and is very low in second half of the night o Circadian component: sleep drive increases allowing sustained sleep Tests Psychomotor vigilance test o Responds to stimuli on screen, tests reaction time

Chronic 2 weeks of suboptimal sleep equivalent to not sleeping for 10 days consecutively 24 hours of wakefulness equivalent to 0.08 blood alcohol concentration

Effects of under-sleeping - Increased propensity of errors - Increased risk of heart disease, type 2 diabetes - Chronic shift work is carcinogenic - Growth suppression, impaired immune responses - Associated with mood disorders Lesions -

VLPO: insomnia SCN: loss of circadian rhythm LHA (orexin nucleus): destabilizes sleep-wake transitions, also under circadian control of SCN Arousal system (TMN, LC) sleepiness

Prion disease: fatal familial insomnia

Sleep disorders - Insomnia: inability to fall asleep or remain asleep o Most common sleep complaint, often a symptom of other disease or condition o Experience stress or worrying o Medication cause - Obstructive sleep apnoea: breathing is briefly and repeatedly interrupted during sleep o OSA can cause low blood oxygen levels, leading to hypertension and heart disease o Obesity increases risk due to increased obstruction due to fat o OSA can lead to excessive daytime sleepiness: reduced deep sleep due to repeated wakings to gasp for air o Snoring: indicator of OSA - Periodic limb movements: repetitive cramping or jerking of the legs during sleep - Restless legs syndrome: uncomfortable sensation in legs that can only be alleviated by moving or stretching the affected limb o Worse in evening and night time, not present during day time - Narcolepsy: excessive daytime sleepiness and frequent daytime sleep attacks o Extreme drowsiness every 3-4 hours o Dream-like hallucinations between sleep and wakefulness o Sleep paralysis when first waking up o Cataplexy: sudden loss of muscle tone while awake, often caused by emotion o Due to orexin nuclei loss, causing increased sleep-wake transitions due to loss of regulation o Narcoleptics are less prone to addiction - Delayed sleep phase disorder: stable sleep schedule that is much later than desired o Characterized by sleep onset insomnia and extreme difficulty waking in the morning o Most common in adolescents o Exposure to bright light in the morning can help to shift the sleep-wake cycle earlier Insufficient sleep - Reasons o o o o o

Sleep disorders Depression Stress or anxiety Not enough time in bed Poor sleep environment Sleeping with lights/TV on Noisy environment during sleep Uncomfortable mattress or pillows Too hot or cold in room Poor sleep habits/hygiene Watching TV or surfing internet before bedtime Keeping irregular bedtimes Taking caffeine close to bedtime Most widely used drug in the world Stimulant, half-life ~ 5 hours Exercising just before bedtime Caffeine prior to bedtime

Improving sleep hygiene - Maintain regular bed and wake time schedule, including weekends - Establish regular relaxing bedtime routine - Create sleep-conducive environment that is dark, quiet and comfortable - Sleep on comfortable mattress and pillows - Use bedroom only for sleep - Finish eating 2-3 hours before regular bedtime - Exercise regularly but avoid just before bedtime - No smoking, alcohol (may aid in falling asleep, but may disrupt sleep cycle in the night) - Napping o 20-30 minutes may help to improve mood, alertness and performance, and redue sleepiness o Too long nap in the day may reduce quality and quantity of night time sleep

Balance and co-ordination Neuroanatomy - Cerebral cortex o Pre-frontal cortex Judgements and decisions o Motor Pre-central gyrus: primary motor cortex Secondary motor cortex Supplementary motor area: motor planning Pre-motor cortex: intentions, visual and sensory inputs o Somatosensory Post-central gyrus: primary sensory cortex Secondary sensory cortex Somesthetic association areas: stereognosis, identification of 3D objects Inferior parietal lobule: body proprioception and spatial relationships o Auditory o Sensory speech o Motor speech - Pathways o Descending: Somatotopic Arrangement rostral spinal cord travels medially, distal spinal cord travels laterally

Corticospinal: control of movements that are voluntary, discrete and skilled UMN arises from cerebral cortex (including corticobulbar tract for facial muscles) o Passes through corona radiate, internal capsule, crus cerebri (midbrain)

o o

o o

Majority decussates at lower medulla lateral corticospinal tract Minority decussates at spinal cord ventral corticospinal tract Synapses to LMN at ventral horn of spinal cord Extra-pyramidal system: influences muscle tone, reflexes, posture and movement (postural) UMN arises from: o Red nucleus in mid brain rubrospinal: excitatory to flexor muscles Subconscious regulation of upper limb o Vestibular nucleus in pons/medulla vestibulospinal: balance and posture Lateral vestibulospinal tract From lateral nucleus, affects extensor muscles (tone and equilibrium) Medial vestibulospinal tract From medial nucleus: corrects position of head and neck (extensors) o Superior colliculus in midbrain tectospinal Responds to visual stimuli, mediates reflex movements Pupil size, thickening of lens Evasion of danger o Reticular formation spread over brainstem reticulospinal Influences reflexes, muscle tone, voluntary movements and vital functions Cardiovascular and respiratory function Dorsal column medial lemniscus Cerebellar Function Control centre for equilibrium Receives steady stream of information concerning equilibrium state, position and state of muscles and joints, and orders from cerebral cortex Able to integrate information and by feedback pathways, regulate and control motor activity, equilibrium and muscle tone automatically and at a subconscious level Left controls left side, right controls right side: may cause motor problems as infracted/lesioned cerebellum is unable to signal back to the contralateral pre-motor cortex Tracts Vestibulocerebellar Spinocerebellar/trigeminocerebellar: proprioception, and pain/discomfort Cerebrocerebellar Vestibular/labyrinthe system Hearing and visual pathway Visual: collateral fibres are sent to the superior colliculus and pretectum after the optic chiasma Superior colliculus: external ocular muscles Pretectal nucleus: photo-pupillary and accomodation

Neurophysiology - 2 important centres of coordination: both initiation and performance, with spatial and temporal coordination o Basal ganglia: gating proper initiation of movement Intended movement is released during competing process of inhibition and disinhibition

Direct pathway o Cerebral cortex sends stimulatory signals to striatum (caudate/putamen) o Striatum sends inhibitory signals to globus pallidus internus (disinhibition) o Globus pallidus internus normally inhibits thalamus, inhibition of globus pallidus internus allows tonic activity of thalamus to resume o Excitatory signals from ventral anterior/ventral lateral (VA/VL) thalamus are then sent to motor cortex to cause movement Indirect pathway o Cerebral cortex sends stimulatory signals to striatum o Striatum sends inhibitory signals to globus pallidus externus o Globus pallidus externus normally sends inhibitory signals to subthalamic nucleus, inhibition of globus pallidus externus allows activation of subthalamic nucleus o Subthalamic nucleus sends increased excitatory signals to parts of globus pallidus internus and substantia nigra pars reticulate o These 2 nuclei (GPI and SNPR) are then driven to produce inhibitory signals to VA/VL thalamus, inhibiting movement This reduces activation of motor cortex, allowing the suppression of competing movements and the activation of the intended movement Disorders: Parkinsons Disease o Decreased dopaminergic (stimulatory) inputs from substantia nigra pars compacta o Reduced stimulation of striatum (caudate/putamen) reduced disinhibition o Chorea-form Parkinsons is a result of overstimulation of brain by dopaminergic drugs o 4 hallmarks of Parkinsons Disease Rest tremor: starts on one side, eventually moves to the other, gets more obvious with distraction Rigidity Bradykinesia/hypokinesia slower movements, fingers touching slower Loss of balance Other symptoms: hypomimia, mask like face, decreased arm swing, magnetic gait, small shuffling steps, difficulty in turning Huntingtons Chorea o Projection from striatum is diminished (due to loss of striatal medium spiny neurons) o Allowing for increased activity of globus pallidus externus inhibition of subthalamic nucleus inhibition of GPI and SNPR reduced inhibitory signals to VA/VL thalamus o Hyperkinesia (indirect pathway affected)

o Cerebellum: sensory motor coordination of ongoing movement, detect movement errors away from intended
Tracts Cerebrocerebellum dentate nucleus pre-motor cortex (planning) Spinocerebellum interposed and fastigial nuclei motor cortex and brainstem (execution) Vestibulocerebellum vestibular nuclei LMN in spinal cord and brainstem (balance and vestibulo-ocular regulation) Error detection and modulation Climbing fibre: from inferior olivary nucleus o Detection of motor errors o Directly modulates mossy fibres (2 views, activated climbing fibres causes synchronously activated parallel fibre synapses to be either strengthened or weakened) o Stimulates Purkinje cell and deep cerebellar nuclear cell

Purkinje cell inhibits deep cerebellar nuclear cell Mossy fibre: from pontine nuclei (cerebral cortex), spinal cord and vestibular system o Stimulates deep cerebellar nuclear cell Signals are passed on to thalamus toward motor cortex o Stimulates granule cell Granule cell gives rise to parallel fibres Up to 200 thousand parallel fibres may provide input to 1 Purkinje cell Stimulation of Purkinje cell Results: o Cortical inhibitory loop: via excitatory signals to Purkinje cell from parallel fibres (mossy fibres granule cells parallel fibres) and from climbing fibres o Deep excitatory loop: via excitatory signals to deep cerebellar nuclear cell from climbing fibres and mossy fibres

Vestibular system - Organs o Otolith: 3 translational (displacement or acceleration detected) Utricle: horizontal, Saccule: vertical Otoconia: calcium carbonate crystals to add weight to gelatinous mass Movement causes displacement of gelatinous mass causing movement toward kinocilum (producing depolarization via mechanically gated transduction channels) or movement away fro mkinocilum (causing hyperpolarization, reducing activation) Otolith organs are mirror images on each side of the head, tilt of head to one side depolarization of one side and hyperpolarization of contralateral otolith organ o Semicircular canals: 3 rotational Cupula: gelatinous mass that encases hair bundles, viscous barrier which endolymph cannot circulate Head movement in the plane of semicircular canals inertia of endolymph produces force across cupula Distending it away from the direction of head movement, displacement of hair bundles within crista Linear accelerations equal forces on both sides of cupula non-displacement of hair bundles Entire population of hair cells in cupula have the same polarization Movements toward the right/left will cause activation of ipsilateral semicircular canal Physiology o Vestibular: contributes to perception of self motion, head position and spatial orientation relative to gravity Helps to stabilize gaze, head and posture o Peripheral: contains vestibular labyrinth Inner ear structures of system function as miniaturized accelerometers and inertial guidance devices Continually reports information about the motion and position of the head and body to integrative centres in the brainstem, cerebellum and somatic sensory cortices o Central: vestibular nuclei directly innervates motor neurons controlling extra-ocular, cervical and postural muscles o Labyrinth: transduces motion from head movements, inertial effects due to gravity and ground borne vibrations

Vestibular ocular reflex - Functions to stabilize image in retina during head rotation o Reflex causes eyes to turn in the contralateral direction of head movement - Ipsilateral canal hair cells are depolarized increased activity activates contralateral abducens nucleus and motor neurons of ipsilateral oculomotor nucleus both eyes turn in contralateral direction - Nystagmus: resets eye position during sustained rotation of the head o Physiological: when movement is sustained o Pathological: due to imbalance in semicircular firing

Postural control and balance - Anticipatory responses depend on feed-forward control expected disturbances - Postural adjustments depend on feedback control unexpected disturbances - Cerebellar lesions: ataxia, impaired in making adaptive changes in postural control - Vestibulospinal and cervicospinal reflexes act synergistically to maintain body posture of head/neck and trunk

Clumsiness History Weakness

Exam Asymmetric Symmetric

Monoplegia Hemiplegia Tetra/para-plegia: Spastic Flaccid Nystagmus Rombergs test Finger-nose

Site Neuro-, plexo-, radiculopathy Brain/brainstem Spinal cord (UMN) Neuro-, myo- pathy (LMN) Extra-pyramidal Vestibular Proprioceptive Visual Cerebellum

Rigidity Unsteadiness

Festinant Ataxic

History - Onset o Sudden (stroke), insidious (deficiency) - History of preceding symptoms o Flu, diarrhoea Guillain-Barre syndrome, trauma cervical myelopathy - Presenting features o Fever (infection) - Progression of disease o Tumour, Guillain-Barre syndrome - Dietary/travel history o Deficiency states - Previous sexual exposure o Exposure to syphilis, AIDS - Family history o Spinocerebellar ataxia - Antenatal history o Developmental disorders Aetiology - Vascular: brain (stroke), spinal cord (infarction) - Infective: brain (syphilis), spinal cord (epidural abscess, syphilis) - Toxic: brain (alcohol) - Autoimmune: brain (SLE), spinal cord (SLE) - Metabolic: brain (hypoglycaemia), spinal cord (Vit B12 deficiency) - Iatrogenic/inflammatory: brain (multiple sclerosis), spinal cord (multiple sclerosis) - Neoplastic: brain (astrocytoma), spinal cord (metastatic) - Seizure - Congenital - Degenerative Motor neurone pattern UMN Hyper-reflexia Hyper-tonia Muscle wasting not severe May have sensory level Bladder and bowel may be involved (spinal cord LMN Hypo/normo-reflexia Hypo-tonia Distal muscle wasting Glove/stocking sensory loss (stockings before gloves) Bladder/bowel usually not involved

Smell Function - Important protective function o Supply essential information about environmental dangers o Fire, spoiled food, gas leaks - Appreciate aesthetic properties of everyday objects - Combined with taste, appreciate flavour of food experiences Anatomy - Cells o

Olfactory Epithelium Small region of nasal mucosa located high up within nasal vault, 1 cm2 on each side of nose Situated behind the 1mm wide olfactory cleft, difficult to visualise Bounded by: Under surface of cribriform plate Medial surface of superior turbinate Upper septum Medial surface of middle turbinate Mucosa and lamina propria Olfactory Receptor Neuron (bipolar) Projects single dendrite to surface of olfactory epithelium and single axon to olfactory bulb 10-20 million in nasal cavity Contains immotile cilia to increase surface area Odour molecules bind to receptors on cell membrane of cilia Unmyelinated axons join together into fascicles Become myelinated filia olfactoria Pass through 15-20 foramina in each cribriform plate Forms first order synapse in olfactory bulb Sustenacular cells Supporting cells surrounding ORNs Maintains ionic milieu for signal transduction Basal cells Stem cells of olfactory epithelium Participates in normal cell turnover Can allow regeneration of damaged components, neuronal stem cells Bowmans glands

Pathways o Accessory inhalant pathway Ophthalmic and maxillary branches of trigeminal nerve contribute to olfaction Detection of irritants like ammonia Plays important role in nasal reflexes Sneezing and holding of respiration when noxious substance is inhaled Central connections occurs within thalamus o Central olfactory pathway Olfactory bulb lies in anterior cranial fossa subjacent to frontal cortex 2 types of principal cells within olfactory bulb Axons of tufted and mitral cells form lateral olfactory tract Fibres project caudally and terminate in olfactory cortex in ventral surface of telencephalon Connections from olfactory cortex to hippocampus links olfactory input with learning and behaviour Smells can evoke strong memories

Produces olfactory mucus, travels through Bowmans duct Secreted on surface of olfactory epithelium Cilia suspended within mucous layer Microenvironment is necessary for sensory transduction

Physiology - Normally 15% of inspired air passes olfactory epithelium - Sniffing increases turbulence in airflow and delivery of airflow to this area - Retronasal olfaction important in detecting odours from oral cavity and pharynx (when eating) - Patients confuse loss of smell with loss of taste - Small amount of odorant molecules pass through nasopharynx into nose - Appreciation of certain flavours within food

Odorant molecules transported across olfactory mucus Binds to olfactory receptor located on olfactory receptor nerve Activates olfactory specific G-protein second messenger pathway o ATP cAMP influx of Na+ and Ca2+, release of K+ depolarisation, firing of AP along axon to olfactory bulb

Taste Anatomy - Taste bud o Basic unit of taste o Taste occurs when chemical substances stimulate gustatory receptor cells contained within taste buds o Location: Tongue primarily Contained within papillae Three types: (filiform papillae does not contain taste buds) o Fungiform: anterior 2/3 of the tongue o Circumvalate: forms inverted V separating anterior 2/3 from posterior 1/3 o Foliate: posterior 1/3 of tongue Also on pharynx, larynx, soft palate and epiglottis o Taste buds contains:

Innervation o Several cranial nerves Facial nerve: supplies anterior 2/3 of tongue and soft palate via chorda tympanic branch and greater superficial petrosal branch to geniculate ganglion Glossopharyngeal: supplies posterior 1/3 of tongue Vagus nerve: supplies pharynx and larynx o Each nerve fiber responds to broad class of stimuli o However, particular class of taste may produce greatest stimulus in certain nerves Facial: more responsive to sweet and salty stimulus Glossopharyngeal: more responsive to sour and bitter stimuli o Pathway: Nerve fibres project to the nucleus tractus solitarius First gustatory station within brainstem, receives all afferent gustatory fibres Fibres then project to primary taste cortex Or cross to contralateral side forming synapses in thalamic taste nucleus Then project to primary taste cortex

Taste receptor cells: turn over periodically every 2 weeks (rapid turnover affected by chemotherapy) Basal cells: replace population of taste receptor cells Edge cells

Physiology - 2 methods of transduction o Activates GPCR various 2nd messengers o Directly binds to apical ion channels on taste bud cells Saliva Taste Important role in taste process Transports solubilised taste molecules to cell membranes of taste receptor cells Role in taste bud maintenance Removes tastants once stimulation of taste receptors occur, decreasing tendency for taste to linger 4 main taste qualities: salt, sweet, bitter and sour 5th: umami, elicited by MSG, enhances flavour

Swallowing Function - Passage of food from oral cavity to stomach via pharynx and oesophagus - Passes over the entrance of the larynx - Requires coordinated activity of muscles in 1) oral cavity, 2) pharynx and larynx, 3) oesophagus Sequence of events - Oral phase o Voluntary, food enters mouth, reduced and mixed with saliva by chewing movement o Uses combination of muscles: masseter, temporalis, medial pterygoid o Sealed by action of orbicularis oris, returned from cheek by buccal muscles o Preparation of bolus, elevated by intrinsic and extrinsic muscles toward soft palate o Tongue is flattened, bolus moves back to enter pharynx o Soft palate elevated by levator and tensor veli palatine to close and protect nasopharynx - Pharyngeal phase o Involuntary, reflex initiated once bolus leaves oral cavity and enters pharynx o Ventilatory stream and alimentary stream cross in this phase, protection of airway o Diaphragmatic contraction to prevent breathing and swallowing simultaneously o Protection of larynx Laryngeal elevation, moving it closer toward epiglottis Contraction of epiglottis which moves downwards to block airway opening Closed in purse-string fashion via contraction of interarytenoid, aryepiglottic and thyroglottic muscles Vocal cords close, respiration is suspended Cough reflex in case food enters larynx - Oesophageal phase o Upper oesophageal sphincter opens by relaxation of cricoesophageal muscle o Bolus moves along oesophagus by peristalsis into stomach o Laryngeal vestibule also opens, allowing breathing Neural control - Divided between cerebral cortex and brainstem - Cortex: voluntary initiation of swallow - Brainstem: coordination and control of swallowing (especially medulla) o Input from muscles of jaw, lips tongue, sensory receptors from oral cavity, epiglottis, oropharynx, muscles involved o Output to vagus nerve (muscles of palate, pharynx and larynx), hypoglossal nerve (tongue), and trigeminal and facial nerves (muscles of jaws and lips) Disorders Olfaction Described by normosmia, anosmia, hyposmia, dysosmia and flavour - 2 types of losses o Conductive: secondary to obstruction of airflow to olfactory cleft by Nasal polyps Allergic rhinitis, rhinosinusitis Tumours o Neural: secondary to damage of olfactory nerves anywhere from olfactory receptors to bulb to processing centres Trauma (oedema, shearing, damage) URTI (permanent damage to olfactory epithelium) Toxins Alzheimers disease Gustatory Described by hypogeusia, ageusia, dysgeusia - True loss of taste is rare, most is due to olfactory dysfunction - 2 types of losses o Mucosa of tongue, oral cavity, pharynx Infections Mucositis (radiation, etc) Aging Smoking o Nerves Chorda tympani (via ear pathology or surgery) Lingual or pharyngeal branches of glossopharyngeal nerve during tonsillectomy or uvulopalatopharyngoplasty (UPPP) Tumour of glossopharyngeal or vagus nerves

Swallowing - Motor neuron, sensory neuron or swallowing centre may be damaged - Causes dysphagia, choking and other symptoms, but taste and smell is not affected

Vision Perception - Begins at the retina and continues to the visual cortex of the brain - Eyes merely begin the visual process, and the brain interprets the information, allowing us to see - Visual sensation: light falling onto retina of eye - Visual perception: interpretation of sensory information coming from eye Refraction - Cornea: 3/4 of refractive power, fixed focus, 45 dioptres - Lens: variable focus, 1/4 refraction, 18 dioptres, 60% water, 5 mm thick, 9 mm wide Lens Anatomy o Arranged in layers Capsule Epithelium Dividing cells are on the outermost layer, and keep growing Older cells get pushed and compressed in the middle o Accommodation

Distance: ciliary muscle relaxes zonular ligaments become taut thins lens: less refraction Near: ciliary muscle contracts zonular ligaments relax lens becomes more globular: more refraction

Conditions - Myope: longer eyeball, short-sightedness - Hyperope: shorter eyeball, long-sightedness - Aging: o Lens becomes progressively stiffer due to continuous regeneration and compression at nucleus o At age 40, the lens loses half the ability to accommodate and becomes symptomatic o Hyperopes are more likely to be long-sighted at age 40 Lens becomes more rigid 1000 fold at nucleus Loss of ciliary muscle efficiency - Cataract: clouding of lens o Senile: age related, lens fibres laid down and compacted o Congenital, juvenile o Associated: ocular injury or disease, lens protein becomes exposed and inflammatory response ensues o Systemic disease: diabetes, hypocalcaemia, etc Retina - Cells o

Photoreceptors Rods and cones Convert light energy into electro-chemical signal (phototransduction) o Bipolar cells o Retinal ganglion cells Axons make up the optic nerve, which brings the signal to the primary visual cortex Layers (from the direction which light travels) o Stratum opticum o Ganglionic layer Nerve fibers fold and leave by crossing a part of the retina Does not have any receptors (blind spot) Colours in blind spot is filled in by brain (from other eye, and from surrounding vision) o Inner plexiform layer o Inner nuclear layer o Outer plexiform layer o Outer nuclear layer o Layer of rods and cones o Pigmented layer (black): to reduce reflection and noise to provide clear accurate picture

Pathway

Retina optic nerve optic chiasma optic tract lateral geniculate nucleus optic radiation visual cortex

Duplex nature of retina - 2 mechanisms of vision

o o

Vision in dim light Vision in bright light

Rods and Cones - Membrane discs and folds contain photosensitive pigment - 11-cis-retinal (vitamin A derivative) plus protein (opsin) - Rods: rhodopsin, cones: 3 different pigmented photoreceptor proteins, maximally sensitive to light of different wavelengths Comparison Rods Outer segment is rod shaped 109 cells per eye, distributed throughout retina, peripheral vision Density is highest 30 degrees from fovea, absent from fovea Good sensitivity 1 type: monochromatic Many rods connected to one bipolar cell: poor acuity and poor resolution Cones Outer segment is cone shaped 106 cells per eye, found mainly in fovea, images in centre Density is highest at fovea centralis Poor sensitivity 3 types: colour vision Each cone is connected to one bipolar cell: good acuity and good resolution

Photoreception - Opsin activation occurs when a photon hits rhodopsin - Opsin activates transducin, transducin activates phosphodiesterase - cGMP levels decline and gated Na+ channels close - Rate of neurotransmitter release declines o Dark current no longer being produced Bleaching and regeneration of visual pigments - Post-photon induction 11-trans-retinal is produced, causing bleaching - Enzymatic regeneration of 11-cis-retinal using ATP requires about 15 minutes to restore eye to maximum sensitivity of rods o Hence: dark adaption is maximal at 15-20 minutes Tests Electroretinogram o Photoreceptor hyperpolarisation: a-wave o Bipolar cell depolarisation: b-wave Spatial resolution o Character chart, focuses on minimum angle of resolution (30 seconds 1 minute of arc on clock face) o Visual acuity declines away from the fovea because cones are more widely separated o Standard optotype: 5 minutes of arc (6/6: at 6 meters, optotype is 5 minutes of arc, 6/12: at 12 meters, etc) o At 6 meters, lens is focusing at infinity, hence there is no real accommodation

Colour vision - Wavelength of light determines the colour that the brain perceives from it - Shortest wavelengths are perceived as violet, longest as red - Cones are stimulated by all visible wavelengths, but are maximally stimulated by red, green and blue - Collectively, the photoreceptors are most sensitive to bright green tending toward yellow (530-555 nanometers) Colour vision defects - Particular cone may be deficient or insufficient - Colour calculations cannot take place - Classified as: o Protan-: red o Deutan-: green o Tritan-: blue o opia: blind o omaly: weak - Type: o Congenital or inherited: genetic disorder, usually affects only one type of cone, may affect two or even three (blue colour disorder is the rarest), both eyes are affected o Acquired, either eye or both, macular (blue-yellow), optic nerve (red-green) or cortical lesions - Achromatopsia o Do not have normal cone vision o Totally colour blind or almost totally colour blind, poor visual acuity Tests Pseudoisochromatic colour confusion charts (Isihara chart, at least 13) Hue arrangement task (Farnsworth Munsell 100 Hue) Lantern detection tests (Edridge-green) Anomaloscope (Colour matching)

Visual field - 90 degrees temporally - 60 degrees nasally - 50 degrees superiorly - 70 degrees inferiorly - Blind spot at 15-17 degrees temporal to fixation Field of vision - Superior field is projected on inferior retina of both eyes - Inferior field is projected on superior retina of both eyes - Nasal field is projected on temporal retina of both eyes - Temporal field is projected on nasal retina of both eyes Pathway - Vision generated by photoreceptors in retina - Signals are gathered by ganglion cells of the retina - Information leaves the eye via the optic nerve - Partial crossing of axons at optic chiasm - After the chiasm, axons are called optic tract - Optic tract wraps around midbrain to get to lateral geniculate nucleus, where all axons synapse - Lateral geniculate nucleus axons fan out through the deep white matter of the brain as optic radiations o Meyers loop: temporal pathway, responsible for superior visual field o Baums loop: parietal pathway, responsible for inferior visual field - Which travel back to the primary visual cortex at the occipital lobe Retinotopic organisation - Central 10 degrees of vision is represented by 55% of primary visual cortex (calcarine sulcus) - 30 degrees of vision 80% of cortex Lesions

1) Eye various visual field defects

a. Glaucoma b. Optic nerve neoplasm c. Papilloedema d. Retinal detachment e. Retinitis pigmentosa f. Macular oedema g. Diabetes, hypertension Optic nerve left/right eye blindness Optic chiasma bitemporal hemianopia Optic tract left/right homonymous hemianopia Optic radiation left/right superior/inferior quadrantanopia Striate cortex left/right homonymous hemianopia with macular sparing (due to dual blood supply, in ischaemic damage)

2) 3) 4) 5) 6)

Testing - Confrontation - Tangent screen - Perimetry o Good for 120 degrees o 2 types: Kinetic Good for defining border of visual field defect Operator dependent Less accurate for follow-up Static Sensitive and repeatable More accurate for follow-up Difficult to define border

Hearing Anatomy and function - Function of peripheral ear is to collect and convert sound energy o Development of ear is to allow for aquatic to land transition loss of energy - To be analysed by the central system, auditory and association cortices - Embryology: o Ear is formed by branchial apparatus

Ear has 3 parts o External Pinna

1st and 2nd arch: external pinna 1st cleft: external ear canal 1st pouch: middle ear cavity Junction between 1st cleft and 1st pouch: tympanic membrane Inner ear: from otic placodes (neuroectoderm) Significance: external structure may be malformed but inner ear may be intact

FIbrocartilage lined with skin Skin is adherent to perichondrum Ear lobe is devoid of cartilage Function: o Serves as fibrocartilaginous structure to collect sound into meatus o Protection of external acoustic meatus External auditory canal 1 inch long Lateral 1/3: hair bearing skin on cartilage Medial 2/3: bony tympanic ring of temporal bone Canal curves inferiorly and forward medially o Function: objects that manage to enter the ear hit the ear canal instead of eardrum Narrowest point: 5mm lateral to tympanic membrane o Function: foreign bodies are lodged here without damage to eardrum Wax (from ceruminous glands) o Function: protective due to insect repelling smell, and enzymes that alter protective function against bacteria Function: Accentuates sound from 45 degrees left/right as pinna points forward Accentuates 2-5 kHz sounds (speech typically lies in this range) Malformations: no ear canal, no pinna (may be associated with middle ear malformation), treated by bypassing malformed organ, or reconstruction

Middle Ear drum Lateral border of middle ear Squamous epithelium outerl ayer, respiratory epithelium inner, fibrous mesodermal layer Mesotympanum, epitympanum, hypotympanum (recesses) Pars tensa, pars flaccida Ossicles Developed by mesoderm 3 bones: malleus, incus, stapes (leads to oval window at basal turn of cochlea) Ossicular chain o Malleus handle, malleus head, incus head, long process, stapes, oval window o Free floating in middle ear o Function: amplification 30 fold, 50-60 dB drop in volume with loss of ossicular chain Mastoid sinus Mastoid air cells help provide equilibration in Eustachian tube malfunction Related to temporal lobe, sigmoid sinus Function: Adapt to hearing on land 30% of hearing, concentration function of eardrum Inner

Cochlea: 2.5 turns Semicircular canals: vestibule Function: balancing, angular movement of head

Housed in petrous apex of temporal bone, densest Membranous labyrinth: contains endolymphatic sac Bony labyrinth: separated from membranous labyrinth by perilymph

Cochlea

Sound pathway - Oval window: allows transmission of mechanical energy to fluid filled cochlea - Scala vestibuli: sound waves vibrate Reissners membrane, causing vibrations in scala media o Scala media: endolymph (produced by striae vascularis) high K+, low Na+, maintains +80 mV Congenital hearing loss: connexin gap, incretin protein forming Na+K+ gate is defective, unable to generate appropriate potential Scala tympani: filled with perilymph (vestibuli too), high Na+, low K+ Round window o Allows pressure wave to exit the cochlea, decreasing resistance, allowing sound to preferentially enter the cochlea Function: if sound enters vestibular system, may cause dizziness on hearing sounds

Tonotopicity - Higher frequency at basal turns, lower frequency at higher turns, due to membrane thickness decreasing at higher turns - Traveling wave theory: different frequencies preferentially vibrate segments of the membrane of varying thickness Physiology - Vibrations of scala media cause displacement of the basilar membrane - Outer hair cells accentuate stimulation of inner hair cells o Pulls tectorial membrane down to enhance sensitivity via prestin protein (contractile) - Inner hair cells are stimulated and send signals via neurotransmitter Ascending auditory pathway - Cochlear nucleus - Superior olivary (some fibres come here) o Receives signals from both ears, sound localization function Low frequency: phase difference (time, which ear receives sound first) High frequency: intensity difference (which ear receives louder sound) o Reflexes: stapedius muscle contracts to dampen stapes, dampening sound concentration - Lateral lemniscus: may cross midline near 4th ventricle - Inferior colliculus: receives both ipsilateral and contralateral nerve endings - Medial geniculate body in thalamus: first place to reognize sound - Primary auditory cortex: pattern recognition - Broadmanns area 41 o Tonotopicity is preserved o Some fibres are sent to motor system, hypothalamus (for physical reflex and psychological/emotional response) Hearing loss - Severity o Normal, Mild hearing loss, Mild hearing loss in noise, Moderate loss, Severe (deafness) - Assessment o Subjective: tester records response Play audiometry: requires child conditioning to understand task, child is ordered to do a task over a microphone with a controlled volume Conventional audiometry: adult presses buzzer in silent room when sound is played/heard o Objective: testing of hair cells, auditory pathways that can be measured Otoacoustic emission Based on response of outer hair cells in response to sound Outer hair cell contraction can be measured using a sensitive microphone in ear Used for newborns who cannot reply to sound Auditory brainstem response Electrodes to measure auditory pathway, various nuclei

Wave form can be seen with sound stimulus, patient cannot move, else muscular electrical activity will interfere (may require sedation) Steady state evoked potential (similar to above) Output: audiogram typically demonstrates 30-40 dB loss, affected in mild hearing loss (normal talking volume)

Pathology - Conductive: bone conduction mimics air conduction line, due to conductive chain lesions o External ear o

Fungal/bacterial infection Middle ear

Acute otitis media, children with flu (pus/fluid accumulation dampens ossicular chain) o Chronic suppurative otitis media May cause rupture/perforation of eardrum
o o Cholesteatoma

Whitish keratinising squamous neoplasm, may erode into brain, perforation of eardrum Otosclerosis

New bone formation around stapes, autosomal condition, treated by prosthetic stapes Sensory neural: damage to inner ear hair cells, auditory neural pathway o Noise induced deafness Excessive headphone usage Outer hair cells gets damaged due to: fatigue, oxidative damage 4 kHz region most typical, possibly due to more tenuous vascular supply (prone to ischaemia) Law: 85 dB > 8 hours a day with ear plugs is not allowed Exponential decrease in exposure with increase in dB o Presbyacusia Age induced, >60 years incidence increases to 23-30% Due to chronic damage o Ototoxicity Drug induced, bilateral, aminoglycosides, loop diuretics (disruption of electrolyte balance in scala media) o Acoustic neuroma Vestibular schwannoma, presses on nerve Unilateral in nature MUST be excluded (MRI to check) May press on brainstem, cerebellum, 5th nerve, 7th nerve late presentation: clumsiness o Central auditory processing disorder Anything along pathway Sound interpretation problems, unable to understand instructions Singapore tests have not found local normal yet

Assistive devices - Hearing aids o Amplifies sound o Processor that digitizes and filters sound o May be behind ear or in canal - Bone anchored hearing aids o Aids in improving bone conduction - Implantable hearing aid o Clipped to ossicles o Magnetic vibrator to enhance ossicular vibration - Cochlear implants o Electrodes coiled around cochlea o Direct nerve stimulation, coiled around full length of cochlea o Able to mimic tonotopicity - Brain stem implant, cochlear nucleus

Touch Dermatomes

Neuroaxis - Skin - Peripheral nerve o Compression Median nerve: wrist (carpal tunnel syndrome), cubital fossa Ulnar nerve: wrist, medial epicondyle Radial nerve: proximal to wrist, elbow, spiral groove of humerus (most common) o Peripheral neuropathy Genetic: Friedreichs ataxia, Charcot-Marie-Tooth syndrome Metabolic: diabetes mellitus (most common, symmetrical), chronic renal failure, porphyria, amyloidosis, liver failure, hypothyroidism Toxic: drugs, organic metals, heavy metals, excess vitamin B6 Inflammatory: Guillain-Barre Syndrome, systemic lupus erythematosus, Sjogrens syndrome Vitamin deficiencies: B12, A, E, B1 Others: malignancy, HIV, radiation, chemotherapy - Nerve roots/plexus - Spinal cord o Brown Sequard Syndrome: ipsilateral UMN weakness, ipsilateral proprioception and vibration loss (dorsal column medial lemniscus), contralateral pain and temperature loss (spinothalamic) - Brain o Stroke May have sensory stroke/transient ischaemic attack (loss of sensory but no motor weakness)

Summary

Pain -

Unpleasant sensory and emotional experience associated with actual or potential tissue damage Protective mechanism: to remove tissue from pain stimulus

Classification - Duration: acute, chronic - Region and system o Location: headache, back pain, pelvic pain, etc o Body system: myofascial, rheumatic, neurologic, vascular - Aetiology o Somatogenic Nociceptive Stimulation: thermo-, chemo-, mechano- receptors Superficial or deep Neuropathic Peripheral or central Burning, tingling, electrical, stabbing, or pins and needles o Psychogenic Nociceptors - Pain receptors do not adapt, continuous excitation will become progressively greater (hyperalgesia) Classification Fast pain Slow pain Description Sharp, pricking, acute, electric Burning, aching, throbbing, chronic Location Superficial tissues Skin and deep tissues Transmission A fibres (myelinated) 6-30 m/second C fibres (unmyelinated) 0.5-2 m/second Analgesia - Input: peri-aqueductal grey (midbrain), raphe magnus nucleus (lower pons), pain inhibitory complex (spinal cord) - Opiate system: endorphins and encephalins are endogenously produced, opiate receptors present in CNS Treatment - Chronic pain o Diagnosis: location, mode of onset, provoking and relieving factors, quality of pain, duration, severity o First tier: NSAIDs, transcutaneous electrical nerve stimulation (TENS), psychological therapy, nerve blocks o Second tier: opioids, neurolysis, thermal procedures o Advanced: neurostimulation, implantable drug pumps, surgical intervention, neuroablation - Medication: nociceptors (analgesics, NSAIDs, opioids), neuropathic (anti-depressants, anti-convulsants), anti-spasms

Adjunct: injections (anaesthetics, steroids), nerve blocks, physiotherapy, TENS, acupuncture, psychological support, surgery

Movement Tract Cortex: higher functions o Integration of sensory inputs (somatosensory, visual, auditory, olfactory cortices) o Understanding of sensory inputs (Brocas area, Wernickes area, visual association, auditory association cortices) o Processing of algorithms (frontal lobe) o Planning and decision (pre-frontal area) o Execution of motion (motor cortex) Brainstem: conduit for essential tracts and repository of nuclei for cranial nerves Cervical cord: conduit for essential tracts, primarily serves upper limb function Thoracic cord: conduit for essential tracts, primarily serves chest and abdomen Lumbar cord: conduit for essential tracts, primarily serves lower limbs Sacral cord: conduit for essential tracts, primarily serves perineum (and bottom of feet)

Somatotopy - Motor homunculus o Legs: central area, face: parietal area, hands: in between specific infarction may result in specific motor loss - Spinal cord o Syringomyelia: widened central canal within spinal cord compresses upper limb fibres, leaving lower limb motor and sensory function relatively intact, also, the lesion tends to widen laterally and rostral/caudally, leaving the dorsal column medial lemniscus tract intact and the paralysis may spread to involve the lower limb Neuroaxis - UMN lesion: hyper-reflexia, hypertonia o Cortex Infarction/lesion contralateral UMN hemiplegia + contralateral 7th nerve UMN palsy Middle cerebral artery: most common artery to be blocked, requires at least 15 ml/100g/min of blood flow Below threshold levels in haemorrhage/thromboembolism damage occurs Seizure: inappropriate neuron firing, epilepsy: recurrent seizures (injury, malformation, etc) Subcortical area Diencephalon: CN I, II Brain stem Midbrain: CN III, IV III: eye is down and out, testing of 4th nerve causes intorsion of eyeball (look at medial vessels), ptosis (LPS, compensated by frontalis), loss of accommodation (ciliary muscle) o Recovery horizontal movement may return first o Eye lesions: linked to thyroid and myasthenia gravis (orbit or muscle problems) Medial longitudinal fasciculus (MLF), parapontine reticular formation (PPRF) lesion o Frontal eye field pushes eyes to opposite side, damaged in stroke eyes may be diverted to the ipsilateral side as the lesion o Frontal eye field (Brodmanns area 8) when activated sends signals to MLF of ipsilateral eye and PPRF of contralateral eye, causing activation of the medial rectus of the ipsilateral eye and lateral rectus of contralateral eye allowing coordinated movement o Lesion in MLF: failure to adduct eye on the same side of lesion causing nystagmus in contralateral eye when looking away from the lesion due to diplopia: internuclear ophthalmoplegia Horners syndrome: sympathetic interruption ptosis, miosis, enophthalmos, +/- anhidrosis Eye problems: look for lipid deposits, xanthylasmata at eye bags, arcus cornealis around iris Pons: CN V, VI, VII, VIII VI: longest intracranial course easily damaged Pons infarction/lesion contralateral UMN hemiplegia + ipsilateral 7th nerve LMN palsy o Bells phenomenon: eye rolls up as attempt is made to close eye, due to 7th palsy, orbicularis oculi is unable to completely close eye VII: common sites posterior fossa, pons, petrosal, parotid, peripheral (5 Ps) o Bells palsy: 7th nerve lesion, UMN contralateral face below brows affected, LMN ipsilateral face above and below brows affected o Common causes: inflammation (treated with steroids, acyclovir), good recovery o May have synkinesis: false innervation due to wrong nerve regeneration Medulla: CN IX, X, XI, XII XII: stick out tongue, innervation responsible for pushing tongue in contralateral direction, lesion to nerve will cause the tongue to point toward affected side (+ fasciculation and atrophy in LMN)

o o

o Cerebellum: look at balance and coordination

o Spinal cord Lumbar signs may be due to thoracolumbar spinal cord lesions, as the fibres may continue down before exiting the spinal column Spinal shock: in the first week of damage, UMN damage may present as LMN due to spinal shock

LMN lesion: hypo-reflexia, hypotonia o Anterior horn cells Non-length dependent pattern of weakness and loss of reflexes proportionate to weakness Reflex loss due to denervation and atrophy Fasciculations and wasting Wallerian degeneration/death of anterior horn cells causes sporadic random firing of neuron causing fasciculations and twitching of specific muscle fibres Example: amyotrophic lateral sclerosis (Lou-Gehrigs disease, Motor Neurone Disease) Not length dependent, furrows on tongue with fasciculation, involvement of swallowing muscles, speech loss, respiratory muscles weakness may also be present, bulbar atrophy o Spinal roots: radiculopathy/polyradiculopathy specific root motor and sensory function may be lost o Plexus Important due to co-localization of many peripheral nerves o Peripheral nerve Demyelinating disease: reflex is lost due to increased transmission time Symptoms: weakness, loss of reflexes, relatively little wasting, sensory abnormalities, proximal and distal neurological deficits Mononeuritis multiplex: classic cause Mycobacterium leprae o Sciatica: Foot drop, numbness, weakness of dorsi/plantar flexion, eversion and inversion o Upper limb: median nerve on one arm, ulnar on the other o Sural nerve below lateral malleolus grossly thickened Axon disease: length dependent deficit (Wallerian degeneration from point of damage) Symptoms: weakness, loss of reflexes, wasting, loss of sensation, paraesthesia, dysaesthesia, lancinating pain, allodynia, hyperalgesia (abnormal sensations), length dependent deficits Mononeuropathy: one nerve, mononeuritis multiplex: single nerve damage in multiple locations Diffused polyneuropathy: glove and stocking deficits, stockings before gloves, length dependent o Diabetes mellitus, Guillain Barre syndrome Specific examples Median neuropathy o Thenar eminence atrophied o Sensation: loss of sensation over median 3.5 fingers o Benedicts sign: thumb and index finger are extended when hand/fingers are flexed Ulnar neuropathy o Guttering on dorsum of hand due to atrophy of intrinsic muscles (interosseous), abduction of fingers and extension of interphalangeal joints are lost, allowing for unopposed flexion of proximal finger flexors producing a claw o Claw: ulnar paradox, more distal the damage, the worse the claw appears o Sensation: loss of sensation of medial 1.5 fingers o Froments sign: flexor pollicis longus (median nerve) compensates for weak adductor muscle (ulnar nerve), causing flexion of the interphalangeal joint of the thumb to maintain grip Radial neuropathy o Signs: wrist drop (extensor weakness), decreased elbow flex (brachioradialis weakness) o Commonly due to compression of radial nerve at spiral groove of humerus weak extensors but triceps are normal (Saturday night palsy) Others o Hip adduction: obturator nerve o Extension of knees: femoral nerve abnormal knee reflex Neuromuscular junction

Most common disorder: myasthenia gravis ACh receptors are targeted by immune system decreased receptors and resulting in failure of transmission Common presentation: ptosis, diplopia due to fatigue, dysphonia, dysarthria, respiratory weakness, proximal weakness o Edrophonium/Tensilon test: reversible ACh-esterase inhibitor increases ACh in NMJ by reducing breakdown o In myasthenia gravis, muscle weakness is reduced, in muscle weakness from cholinergic crisis resulting from too much stimulation, increase in ACh will worsen weakness o Treatment: allow receptors to regenerate by stopping the immune process

o Muscle

Lambert Eaton Myasthaenic Syndrome (LEMS): autoantibodies targeting presynaptic voltage gated Ca2+ channels at NMJ o 60% associated with underlying malignancy, especially small cell lung cancer

Intrafusal muscle fibres innervated by alpha motor neurons, interneurons of anterior horn, gamma motor neurons, Renshaw cells, granule cells Weakness may be due to muscle not in optimal position Tends to show patchy muscle weakness, not glove and stocking loss in the case of peripheral length dependent neuropathy

Abnormal movement - 4 categories o Automatic: learned, conditioned, packaged algorithm o Voluntary Parakinesia: intentional movement to hide involuntary movement Supranuclear gaze palsy: failure of depression and elevation, but physical manipulation allows eyes to increase range o Semi-voluntary Tourettes syndrome: motor ticks, can be controlled, but the urge is uncomfortable o Involuntary: unable to be controlled Benign essential tremors: no resting tremors, no akinesia, no rigidity, tremor of voice, intention tremors Chorea: involuntary, irregular, purposeless, non-rhythmic, abrupt, rapid, unsustained movements that seem to flow from one body part to another (extra-pyramidal system) Associated with: CHOREA o Cirrhosis: Wilsons disease o Hereditary: Huntingtons Disease, Acanthocytosis o Oestrogens: Chorea gravidarum (in pregnancy), oral contraceptive pill (OCP) o Rheumatic fever: Sydenhams chorea o Endocrinopathy: Diabetes mellitus (hyperglycaemic hemi-chorea, damage to basal ganglia), thyrotoxicosis o Autoimmune disease Athetosis: similar to chorea, slow, writhing continuous, involuntary and fluid movements Ballismus: violent large amplitude choreic movements of proximal parts of limbs, causing flinging and faliling limb movements Lesion in contralateral subthalamic nucleus and/or connections or contralateral striatum Myoclonus: sudden, brief, shock-like involuntary movements caused by contractions or inhibition, usually arrhythmic, but can be rhythmical May have specific triggers (sound, light), may be generalised or focal Causes: cortical (myoclonic epilepsy), brainstem (hyperekplexia), spinal cord (segmental or propriospinal myoclonus) Normal myoclonus: hypnogogic myoclonus, in response to stimuli - Tone o Generalised dystonia Twisted, eyes closed Abnormal tone May have blepharospasm o Psychogenic dystonia with sensory trick o Paroxysmal dyskinesia: various dyskinesia that occur, persist for a length of time, and disappear - Spasticity o Advantage Helps patients to ambulate, stand or transfer Maintains muscle bulk Prevents DVT, osteoporosis, pressure ulcer formation over bony prominences o Disadvantage Deformities (dislocation, contractures, or scoliosis) Impaired activities of daily living, decreased mobility Skin breakdown, pain/abnormal sensory feedback Poor weight gain Sleep disturbance, depression Treatment for hyperkinetic disorders - Treat underlying condition - Benzodiazepines - Neuroleptics - Dopamine depletors - Surgery - Botulinum toxin Red flags - Symmetry of signs - No tremulousness - Rapid deterioration - Autonomic symptoms predominate - Pyramidal or cerebellar signs

Alien limb phenomenon Poor response to dopaminergic drugs