Neuroscience And Mental Health Flashcards

Question

Describe cerebrospinal fluid.

Answer 1

CSF found in ventricular system and spinal canal into outer membrane of dura mater. The ventricles, aqueducts and canals of the brain are lined with ependymal cells (epithelial-like glial cells, often ciliated). In some regions of the ventricles, this lining is modified to form branched villus structures: the choroid plexus. CSF is produced by regions of choroid plexus in the cerebral ventricles: Capillaries leaky but local ependymal cells have extensive tight junctions with lots of transporters it pump fluid across. Secrete CSF into ventricles (lateral ventricles, 3rd ventricle via interventricular foramina, down cerebral aqueduct into 4th ventricle and into subarachnoid space via media and lateral apertures) - circulates Volume: 80-150 ml Functions: protection (physical and chemical), nutrition of neurones, transport of molecules Composition of plasma and CSF (mM/L) Diagram CSF has little protein to prevent damage by plasma protein entering which can lead to infection.

Answer 2

A blood-brain barrier is needed because the activity of neurones is highly sensitive to the composition of local environment, the CNS midst be protected from the fluctuations in the composition of the blood. Homeostasis is key for brain. BBB is at level with CNS capillaries. Exchange between blood and tissues occurs across capillary walls - continuous (moderately leaky), fenestrated - endocirne (leaky), sinusoid - liver, bone marrow (very leaky) BBB: the capillaries of the CNS parenchyma derived from surface pail vessels. Vessel BBB properties increased in deeper vessels. BBB capillaries have extensive tight junctions at the endothelial cell-cell contacts, massively reducing solute and fluid leak across the capillary wall. Local environment causes vessels to become BBB like. Differences between BBB and periphery capillaries: Brain capillary is continuous with little transcultural vesicular transport. Interendothelial junctions are tight junctions. Pericytes are closely approved to capillaries - maintain capillary integrity and functions. Periphery have sparse pericyte coverage whereas BBB have dense pericyte coverage. BBB covered with “end-feet” from astrocytes whicha ew important for maintaining BBB properties. Atrocytes in CNS can contact growth factors and other differentiation factors that cause vessels to become BBB like. Hydrophilic solutes such as glucose, amino acids, antibiotics, some toxins cannot cross BBB due to tight junctions. BBB controls the exchange of these substances using specific membrane transporters to transport into and out of CNS (influx and efflux transporters) Blood-borne infectious agents may have reduced entry - CNS infections most commonly affect the meninges .e.g. meningitis (Some evidence that loss of BBB can help with clearing some infections by allowing immune cells access) Lipophilic molecules (O2, CO2, alcohol) cross the BBB via diffusion down connetration gradients. Specific transport mechanisms for hydrophilic substances include: - water, via aqua-or in (AQP1, AQP4) channels - glucose, via GLUT1 transporter proteins - amino acids, via 3 different transporters - electrolytes, via specific transport systems Some areas of the brain have capillaries lack BBB properties and are found close to ventricles and are called circumventricular organs (CVOs). Capillaries are fenestrated. The ventricular ependymal lining close to these areas can be much tighter than in other areas, limiting exchange between them and CSF. These regions are generally involved in secreting into the circulation or need to sample the plasma. Eg. Posterior pituitary and median eminence secrete bgromones The area postrema samples the plasma for toxins and will induce vomiting Other are involved in sensing electrolytes and regulate water intake

Answer 3

Trauma to CNS results in loss of BBB. Pathological states such as inflammation, infection and stroke also lead to this. Pharmacology issue - May want some drugs to access brain but cannot, others access brain too readily and cause adverse effects. In treatment of allergy, H1 blockers are hydrophobic and can cross BBB by diffusion. Histamine is important in wakefulness and alertness so antihistamine made people drowsy. Nowadays, they’re used as sleep aids e.g. Nytol. Second generation antihistamines are polar (have hydrophilic attachment) so do not readily cross BBB and cause drowsiness. Dopamine cannot cross BBB so peripheral administration of dopamine cannot be used as Parkinson’s therapy. L-DOPA can cross BBB via an amino acid transporter and is converted to dopamine in brain however most circulating L-DOPA is converted to dopamine peripherally so less is available to access brain. Co-administration with the DOPA decarboxylase inhibitor, Carbidopa inhibits this conversion. It cannot cross BBB so does not affect the conversion in the brain.

Answer 4

The thalamus, subthalamus (subthalamic nucleus is target for deep brain stimulation in Parkinson’s; stop tremor through electrode) and hypothalamus are found in the diencephalon. Hypothalamus is just beneath lateral ventricles and divided in middle by 3rd ventricle. Thalamus sits ventral to the lateral ventricles and divided into 2 by 3rd ventricle. Organised into discrete nuclei, nuclei refer to collection of neuronal cell bodies in CNS, ganglia in PNS, basal ganglia is exception in CNS.

Answer 5

Relay site for numerous inputs and outputs (like Clapham J) Key relay centre to cortical sensory areas Involved in almost all sensory systems (except olfactory) Enhances or restricts signals Somatosensory pathway Primary somatosensory cortex found behind central gyrus in parietal lobe. To thalamus into gracile nucleus then cross over at second order neurone Signal sent down dorsal column, input from dorsal root ganglion through dorsal horn of spinal cord.

Answer 6

Intralaminar nuclei Intralaminar nuclei project to various medial temporal lobe structures (e.g. amygdala (emotions, fear, anxiety; anterior temporal lobe), hippocampus (memory; behind amygdala at floor of temporal), basal ganglia (movement) Mostly glutamatergic neruones (i.e. excitatory) Loss of neurones in this region associated with progressive supranuclear palsy (rare brain disorder causing problems with walking and balance) and Parkinson’s disease Reticular nucleus Forms the outer covering of the thalamus. Majority of neurones are GABAergic (e.g. inhibitory) Unlike other thalamic nuclei, they don’t connect with distal regions but with other thalamic nuclei Receive inputs from collaterals of their axons from thalamic nuclei therefore reticular nucleus acts to modulate thalamic activity (negative feedback). Reticular formation Set of interconnected pathways in the brainstem: send ascending projections to forebrain nuclei (ascending reticular activating system (ARAS)) Involved in consciousness and arousal: degrees of wakefulness depend on ARAS activity (increased activity = increased wakefulness) Both intralaminar and reticular nucleus receive inputs from ARAS.

Answer 7

Diagrams Hypothalamus Divided into two by 3rd ventricle Collection of individual nuclei with distinct functions Largely ipsilateral connections with other nuclei Involved in 4 functions: fighting, fleeing, feeding, mating (fight or flight) Function Hypothalamus has direct connections with ANS Connections with endocrine systems e.g. hypothalamic-pituitary axis Control of behaviour e.g. feeding behaviour Paraventricular nuclei send projections to ANS and posterior pituitary gland PVN also involved in feeding behaviour PVN lesions cause hyperplasia and weight gain PVN receives input from hypothalamic uncle I involved in feeding Suprachiasmatic nucleus (optic chiasm) Circadian rhythm, sleep wave cycles ANS connection via PVN Also connected to pineal gland so controls secretion of melanin. Lesions of SCN can cause disrupted sleep cycle

Answer 8

The part of the CNS, exclusive of the cerebellum, that lies between the cerebrum and the spinal cord. The major divisions: Medulla oblongata, pons, midbrain Sulcus limitans - separates cranial nerve motor nuclei (medial) from sensory nuclei (lateral). Diagram

Answer 9

From superior to inferior (Posterior) Pineal gland: melatonin release, circadian rhythm, light-dark cycle Superior colliculus: bump on back of brainstem, coordinated eye and neck movement Inferior colliculus: protective auditory reflex (loud bang heard, should I leave or stay) Trochlear nerve: only cranial nerve that emerges from back of the brainstem, supplies superior oblique muscle. Abducts, depresses eye. 4th ventricle: floor of 4th ventricle is back of the pons Dorsal columns: gracile = medial, from leg Cuneate = lateral, arms Everything is bilateral in brainstem except pineal gland on roof of brainstem Anteroinferior view Superior to inferior First 2 cranial nerves don’t emerge from brainstem, all neurones pass through cribriform plate of ethmoid bone to olfactory bulb. Olfactory - sense of smell, optic - light to retina to image Optic chiasm Pituitary stalk (infundibulum) immediately behind OC. Mammillary body: base of hypothalamus Cerebral peduncle: main sensory and motor tracts Oculomotor nerve: eye movement, also autonomic functions e.g. constriction Trigeminal nerve: sensory nerve of head and neck. Only one that emerges entirely from pons,3 divisions - touch+sensation, small root - motor function (chewing, mastication) Abducens, facial, vestibulocochlear nerve: controls lateral rectus - outward gaze, facial expression, sound + expression. Pyramids: cerebral peduncle emerges as pyramids. Motor problem: corticospinal tract = pyramidal symptoms, cerebellar/other = extra pyramidal symptoms Glossopharyngeal, vagus and accessory nerve: tongue and pharynx, parasympathetic, shoulder muscle - sternocleidomastoid and trapezius Hypoglossal: under tongue, supplies muscles of tongue Pyramidal decussation: contralateral motor control, cross over at base of medulla. External structures: cerebral peduncle, pyramid, pyramidal decussation

Answer 10

Stylomastoid foramen: facial nerve (7) exit, vertebral arteries, anterior and posterior spinal arteries Cribriform plate: olfactory nerve (1) Optic canal: optic nerve (2), ophthalmic artery Superior orbital fissure: oculomotor (3), trochlear (4), ophthalmic branch of trigeminal (5), abducens (6), superior ophthalmic vein Foramen rotundum: maxillary branch of trigeminal (5) Foramen ovale: mandibular branch of trigeminal (5) Foramen spinosum: middle meningeal artery Carotid canal: internal carotid artery Internal acoustic meatus: facial (7) entry, vestibulocochlear (8), labyrinthine artery Jugular foramen: glossopharyngeal (9), vagus (10), accessory (11) Hypoglossal canal: hypoglossal (12) Sigmoid sinus: internal jugular vein Foramen magnum: spinal fibres of accessory (11), inferior medulla

Answer 11

Spinal nerves and cranial nerves General somatic afferent (GSA): sensation from skin and mucous membranes General visceral afferent (GVA): sensation from GI tract, heart, vessels and lungs General somatic efferent (GSE): muscles for eye and tongue movements General visceral efferent (GVE): preganglionic parasympathetic Cranial nerves Special somatic afferent Vision, hearing and equilibrium Special visceral afferent Smell and taste Special visceral efferent - only related to head and neck Muscles involved in chewing, facial expression, swallowing, vocal sounds and turning head

Answer 12

Lateral medullary syndrome; Thrombosis of vertebral artery of PICA (posterior inferior cerebellar artery) - ischaemia - vertigo (vestibular nuclei) - ipsilateral cerebellar ataxia (unsteady of feet) (inferior cerebellar peduncle - inf coming from musculature to cerebellum - loss of balance/gait) - ipsilateral loss of pain/ thermal sense (face) (spinal nucleus (trigeminal)) - horner’s syndrome - loss of sympathetic control, droopy eyelid (sympathetic tract - upper brainstem, loss of sympathetic innervation of eye area) - hoarseness, difficulty swallowing (Nucleus ambiguus - musculature of throat) - contralateral loss of pain/ thermal sense (trunk and limbs) (spinothalamic tract)

Answer 13

A modality is a type of stimulus. Modalities have specialised receptors, which will transmit info through specific anatomical pathways to brain. Sensory nerve endings (axons) are specific to different modalities. Touch/ pressure/ vibration —> mechanoreceptor (proprioception )(enclosed nerve endings: mechanoreceptors) Temp —> thermoreceptor (free nerve endings: thermoreceptors and nociceptors) Nociception —> nociceptor (pain) Classification of sensory neurones: Alpha beta-fibres: innocuous (not harmful) mechanical simulation (large and myelinated therefore fast) E.g. Merkel cells (light touch and superficial pressure), Pacinian corpuscle (detects deep pressure, high frequency vibration and tickling) Alpha delta-fibres: noxious (harmful) mechanical and thermal stimulation (less fast) C-fibres: noxious mechanical and thermal and chemical stimulation (no myelinated, slower, achy pain)

Answer 14

Receptors are transducers that convert energy from the environment into neuronal action potentials. A threshold is the point of intensity at which the person can just detect the presence of a stimulus 50% of the time = absolute threshold Need a stimulus to be strong enough to send a.p. (generator potential to action potential) Adaptation: tonic receptors Detect continuous stimulus strength Continue to transmit impulses to the brain as long the stimulus is present, keeps the brain constantly informed e.g. Merkel cells - slowly adapt allowing for superficial and fine touch to be perceived (stroking) Adaptation: - phasic receptors Detect a change in stimulus strength Transmit an impulse at the start and the end of the stimulus e.g. Pacinian receptor - sudden pressure excites receptor, transmits a signal again when pressure is released The receptive field is the region on the skin which causes activation of a single sensory neurone when activated. - Small receptive fields allow for the detection of fine detail over a small area - precise perception e.g. fingers have many densely packed mechanoreceptors with small receptive fields - Large receptive fields allow the cell to detect changes over a wide area (less precise perception) Two point discrimination is the minimum distance at which two points are perceived as separated. Related to the size of the receptive field. (Smaller, more denser) Quantity sensory testing used to test sensitivity (13 tests) can be used for pain e.g. brush. Lateral inhibition: a receptive field can overlap with another receptive field. Difficult to distinguish between 2 stimulus fields. Lateral inhibition prevents the overlap of receptive fields. Facilitates pinpoint accuracy in localisation of the stimulus. Mediated by inhibitory interneurones within dorsal horn of spinal cord. Facilitates enhanced sensory perception (discrimination) The difference between adjacent inputs is enhanced by lateral inhibition. Lateral inhibition is the process by which stimulated neurons inhibit the activity of nearby neurons. Prevents spreading in lateral direction.

Answer 15

Alpha delta fibres mediate sharp, intense or first pain Type 1: noxious mechanical Type 2: noxious heat C fibres mediate dull, aching or second pain Noxious thermal, mechanical and chemical stimuli (polymodal) ``` Lateral spinothalamic tract (sensory component) Spinoreticular tract (emotional) Peripheral sensitisation (decrease thresholds to peripheral stimuli at the site of injury) Central sensitisation (decrease thresholds to peripheral stimuli at an adjacent site to the injury, expansion of receptive field, spontaneous pain) ```

Answer 16

Inhibition of primary afferent inputs before they are transmitted to the brain through ascending pathways. Activation of alpha beta fibres activates inhibitory interneurones to block projection neurones activated by c-fibres .e.g. rubbing to reduce pain

Answer 17

Alpha beta fibres enter via the dorsal horn and enter the dorsal column pathways. Information conveyed from lower limbs and body (below T6) travel ipsilaterally along the gracile tract. Information conveyed from upper limbs and body (above T6) travel ipsilaterally along the cuneate tract. 1st Oder neurones terminate in the medulla: Fibres in the gracile tract have their first synapse in the gracile nucleus. Fibres in the cuneate tract have their first synapse in the cuneate nucleus. 2nd order neurones cross in the medulla: Second order axons decussate (cross the midline) in the caudal medulla Forms the contralateral medial lemniscus tract. 2nd order neurones terminate in the thalamus: The axons terminate in the ventral posterior lateral nucleus of the thalamus (VPL) 3rd order neurones terminate in the somatosensory cortex: 3rd order neurones from the VPL project to the somatosensory cortex. Size of the somatotopic areas is proportional to density of sensory receptors in that body region (somatosensory homunculus) Pain and temperature location not as precise

Answer 18

Spinothalamic (anterolateral) pathway Pain and temperature sensations ascend within the lateral spinothalamic tract Crude touch ascends within the anterior spinothalamic tract 1st order neruones terminate in the dorsal horn: Primary afferent axons terminate upon entering the spinal cord. Second order neurones decussate immediately in the spinal cord and form the spinothalamic tract. 2nd order neurones terminate in the thalamus: 2nd order neurones terminate int he ventral posterior lateral (VPL) nucleus of the thalamus

Answer 19

Blocked anterior spinal artery causes ischaemic damage to the anterior part of the spinal cord. Spinothalamic tract damage causes pain and temperature loss below the level of the lesion. Retained light touch, vibration and 2 point discrimination due to intact dorsal columns.

Answer 20

An unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage. Neuropathic pain: pain caused by a lesion or disease of somatosensory nervous system .e.g. diabetic, sciatica, trauma, post-surgical, chemotherapy Pain in area of neurological dysfunction Sharp burning electric shocks Poor response to usual analgesic drugs .eg. Opiates Nociceptive: noxious stimulation of a nociceptor (somatic or viscera) e.g. skin, muscles, joints, bones Alloy is: pain due to a stimulus that does not normally provoke pain e.g. brush Hyperalgesia: increased pain from a stimulus that normally provokes pain Primary hyperalgesia describes pain sensitivity that occurs directly in the damaged tissues. Secondary hyperalgesia describes pain sensitivity that occurs in surrounding undamaged tissues. Sensitisation: increased responsiveness of nociceptive neurones to their normal input. Hypoalgesia: diminished pain in response to a normally painful stimulus. Parathesia: abnormal sensation whether spontaneous/ evoked.

Answer 21

Facilitation and inhibition of nociceptive processing in the dorsal horn. The periaqueductal gray (PAG, also known as the central gray) is a nucleus that plays a critical role in autonomic function, motivated behavior and behavioural responses to threatening stimuli. Monoamines: Serotonin (facilitate - harmful) Noradrenaline (inhibits - protective) Pain relief: Opioids (endogenous and exogenous) inhibit pain. Reduce pain transmission in dorsal horn by inhibiting glutamate release .i.e. activation of spinothalamic neurones. Antidepressants: TCA, SNRI, SSRI - target adrenaline

Answer 22

Functional segregation: motor system organised in a number of different areas that control different aspects of movement. Hierarchical organisation: high order areas of hierarchy are involved in more complex tasks (programme and decide on movements, coordinate muscle activity) - more than one muscular system coordinated Lower level areas of hierarchy perform lower level tasks (execution of movement) - carry out instructions

Answer 23

Location: Precentral gyrus, anterior to central sulcus in frontal lobe. Function: control fine, discrete, precise voluntary movement Receives info from other cortical areas and sends descending signals to thalamus and brainstem to execute movement. There’s a somatotopic organisation - Penfield’s motro homunculus

Answer 24

Primary motor cortex contain Betz cells (pyramidial cells - neurones) -> fibres pass through internal capsule of basal ganglia -> cerebral penducle in midbrain -> pass through pons into pyramids -> cross over - decussation at bottom of medulla -> descend through corticospinal tract -> project to ventral root of spinal cord at appropriate level and synapse with lower motor neurones (alpha neurones) -> project out to musculature through VR?? By spinal nerves. Remaining 5-10% of fibres don’t cross at medulla, stay ipsilateral and descend in anterior corticospinal tract. Decussation happens at level of spinal cord. Largely input to thorax, intercostal muscles, axial musculature.

Answer 25

Referring to motor neurones in brainstem - cranial nerve nuclei. The corticobulbar tract is a two-neuron path which unites the cerebral cortex with the cranial nerve nuclei in the brainstem involved in motor functions (apart from the oculomotor nerve).

Answer 26

Promotor cortex Location: frontal lobe anterior to M1 Function: planning of movements Regulates externally cued movements .e.g. seeing an apple and reaching out for it requires moving a body part relative to another body part (intra-personal space) and movement of the body in the environment (extra-personal space) Supplementary motor area Location: frontal lobe anterior to M1, medially Function: planning complex movements; programming sequencing of movements Regulating internally driven movements (e.g. speech) SMA becomes active when thinking about a movement before executing that movement. Association cortex Brain areas not strictly motor areas as their activity does not correlate with motor output/ act Posterior parietal cortex: ensures movements are targeted accurately to objects in external space - motor learning and planning (don’t think about wearing clothes) Prefrontal cortex: involved in selection of appropriate movements for a particular course of action (personality input into movement, based on previous experience, touch hot plate -> burned -> don’t do again (prevent harm) )

Answer 27

Lower motor neurone: spinal cord (ventral horn), brainstem (bulbar) - SC neurones to muscles Upper motor neurone: corticospinal, corticobulbar (Betz cells and projection to spinal cord/ brainstem) Pyramidal: lateral corticospinal tract Extrapyramidal: basal ganglia, cerebellum

Answer 28

Upper motor neurone lesion: Loss of function (negative signs): -paresis: graded weakness of movements -paralysis (plegia): complete loss of muscle activity Increased abnormal motor function (positive signs) due to loss of inhibitory descending inputs: -spasticity: increased muscle tone -hyper-reflexia: exaggerated reflexes -clonus: abnormal oscillatory muscle contraction Babinski‘s sign Apraxia A disorder of skilled movement. Patients are not parotid but have lost information about how to perform skilled movements e.g. riding bicycle Lesion of inferior parietal lobe, the frontal love (premotor cortex, supplementary motor area) Any disease of these areas can cause apraxia, although stroke and dementia are the most common causes. Lower motor neurone lesion Weakness Hypotonia (reduced muscle tone) Hyporeflexia (reduced reflexes) Muscle atrophy Fasciculations: damaged motor units produce spontaneous action potentials, resulting in a visible twitch - uncontrolled Fibrillations: spontaneous twitching of individual muscle fibres; recorded during needle electromyography examination. Motor neurone disease (MND) Progressive neurodegenerative disorder of the motor system Spectrum of disorders Amyotrophic lateral sclerosis (ALS) -Amyotrophic lateral sclerosis (ALS), also known as motor neurone disease (MND) or Lou Gehrig's disease, is a specific disease that causes the death of neurons controlling voluntary muscles. Both upper and lower neurones affected. Progress from distal to proximal, from legs. Kills = respiratory musculature not functional ``` Upper motor neurone signs: Increased muscle tone (spasticity of limbs and tongue - more rigid) Brisk limbs and jaw reflexes Babinski‘s sign Loss of dexterity (dyspraxia) Dysarthria (problems speaking) Dysphagia ``` ``` Lower motor neurone signs: Weakness Muscle wasting Tongue fasciculations and wasting Nasal speech Dysphasia ```

Answer 29

Extrapyramidal - not part of corticospinal tract Includes: Caudate nucleus (like a tadpole in anterior-posterior plane, most anterior) Lentiform nucleus (putamen + external globus pallidus), separated from caudate by internal capsule Subthalamic nucleus (beneath thalamus) Substantia nigra (midbrain projecting to basal ganglia) Ventral pallidum (dopaminergic neurones projecting to areas of brain), claustrum (thing layer of grey matter), nucleus accumbens (reward centre), nucleus basalis of Meynert (cholinergic neurones projecting to cortex, have sensory function, primary site of damage in Alzheimer’s) Functions Elaborating associated movements (e.g. swinging arms when walking; changing facial expression to match emotions) Moderating and coordinating movement (suppressing unwanted movements) Performing movements in order

Answer 30

The primary pathology involves the neurodegeneration of the dopaminergic neurones that originate in the substantia nigra and project to the striatum. Tremor in hand, problem initiating movement (want to get up, hard to get up) Lewy body - abnormal accumulation of protein Main motor signs: - bradykinesia (slowness of (small) movements e.g. doing up buttons) - hypomimic face (expressionless, mask-like - absence of movements that normally animate the face) - akinesia (difficulty in the initiation of movements because cannot initiate movements internally) - rigidity (muscle tone increase, causing resistance to externally imposed joint movements) - tremor at rest (starts in one hand (pill-rolling tremor) with time spreads to other parts of the body - can become bilateral)

Answer 31

Genetic neurodegenerative disorder Chromosome 4 (gene for Huntington protein), autosomal dominant CAG repeat, triplet repeat disorder >/equal to 35 Degeneration of GABAergic neurones in the striatum, caudate and then putamen Motor signs Choreic movements (chorea): rapid jerky involuntary movements of the body; hands and face affected first; then legs and rest of body. Speech impairment Difficulty swallowing Unsteady gait Later stages, cognitive decline and dementia

Answer 32

``` Sits in posterior cranial fossa. Tentorium cerebelli (dura) covers it. ``` 3 layer cortico structure. No. Of different inputs to cerebellum but only one output via purkinje fibres to white matter nuclei Outermost layer = molecular later - not many neurones Next = purkinje cell layer Next = granular cell layer Divisions of the cerebellum Vestibulocerebellum -regulation of gait, posture and equilibrium Coordination of head movements with eye movements (close connection with superior caniculi) ``` Spinocerebellum -coordination of speech -adjustment of muscle tone -coordination of limb movements (Inferior cerebellar peduncle from spinal cord fibres up to cerebellum) ``` Cerebrocerebellum - coordination of skilled movements - cognitive function, attention, processing of language - emotional control

Answer 33

Vestibulocerebellar syndrome Damage (tumour) causes syndrome similar to vestibular disease leading to gait ataxia and tendency to fall (even when patient sitting and eyes open) Spinocerebellar syndrome Damage (degeneration and atrophy associated with chronic alcoholism) affects mainly legs, causes abnormal gait and stance (wide-based) Cerebrocerebellar or lateral cerebellar syndrome Damage affects mainly arms/skilled coordinated movements (tremor) and speech Main signs of cerebellar dysfunction Deficits apparent only upon movement - Ataxia: general impairments in movement coordination and accuracy. Disturbances of posture or gait: wide-based, staggering (“drunken”) gait - dysmetria: inappropriate force and distance for target-directed movements (knowcking over a cup rather than grabbing it) - intention tremor: increasingly oscillatory trajectory of a limb in a target-directed movement (nose-finger tracking), just thinking evokes a tremor. - dysdiadochokinesia: inability to perform rapidly alternating movements, (rapidly pronating and supination gets hands and forearms) - scanning speech: staccato, due to impaired coordination of speech muscles

Answer 34

Allows for contact from neurone to muscle or from neurone to neurone. Arrangements can be simple or complex; contact ratio - ranges from 1:1 for muscle to 103:1 in the CNS The membrane potential of the post synaptic neurone can be altered in two directions by inputs: It can be made less negative .i.e. be brought closer to threshold for firing; this is an excitatory post synaptic potential (EPSP) It can be made more negative .i.e. be brought further away from threshold for firing; this is an inhibitory post synaptic potentials (IPSP) Graded effects = summation, the degree of summation will determine how readily a neurone can reach threshold to produce an a.p. Neuromuscular junction A specialised synapse between the motor neurone and the motor end plate, the muscle fibre cell membrane Activation: When an action potential arrives at the NMJ, Ca2+ influx causes ACh release. ACh binds to receptors on motor end plate. Ion channel opens - Na+ influx causes action potential in muscle fibre. At rest, individual vesicles release ACh at a very low rate causing miniature end-plate potentials - constant release

Answer 35

These are the lower motor neurones of the brainstem and the spinal cord. They innervate the (extrafusal) muscle fibres of the skeletal muscles - voluntary muscle contraction; their activation causes muscle contraction The motor neurone pool contains all alpha motor neurones innervation game a single muscle

Answer 36

A single motor neurone together with all the muscle fibres that it innervates. Stimulation of one motor unit causes contraction of all the muscle fibres in that unit. Types of motor units: Slow (S, type 1) - smallest diameter cel bodies Small dendritic trees Thinnest axons Slowest conduction velocity (Unmyelinated) Fast, fatigue resistant (FR, type IIA) - larger diameter cell bodies Larger dendritic trees Thicker axons Faster conduction velocity Fast, fatiguable (FF, type IIB) - larger diameter cell bodies “”””” The 3 different motor unit types are classified by the amount of tension generated, speed of contraction and fatiguability of the motor unit.

Answer 37

Recruitment and race coding Recruitment Motor units are not randomly recruited. There is an order: -governed by the size principle Small units are recruited Friday (these are generally the slow twitch units) -as more force is required, more units are recruited -this allows fine control (e.g. when writing), under which low force levels are required Rate coding A motor unit can fire at a range of frequencies. Slow units fire at a lower frequency. As the firing rate increases, the force produced by the unit increases. Summation occurs when units fire at frequency too fast to allow the muscle to relax between arriving action potentials.

Answer 38

Are a type of growth factor. Prevent neuronal death. Promote growth of neurones after injury Can modify activity of motor unit

Answer 39

Fibre types can change properties under many different conditions. Type IIB to IIA most common following training e.g. athlete training - fatigue resistant Type I to II possible in cases of severe reconditioning or spinal cord injury. Microgravity during space flight results in shift from slow to fast muscle fibre types. Ageing associated with loss of type I and II fibres but also [referential loss of type II fibres. This results in larger proportion of type I fibres in aged muscle - slower contraction times.

Answer 40

A reflex is an automatic and often inborn response to a stimulus that involves a nerve impulse passed inward from a receptor to a nerve centre and then outward to an effect or (muscle or gland) without reaching the level of consciousness. Different reflex arc diagram Supraspinal control Clenching teeth/making a fist while having patellar tendon tapped -> hyperexcitability in patella reflex (bigger swing) = Jendrassik manoeuvre Higher centres of the CNS exert inhibitory and excitatory regulation upon the stretch reflex. Inhibitory control dominates in normal conditions. Decerebation reveals the excitatory control from supraspinal areas. Rigidity and spasticity can result from brain damage giving overactive or tonic stretch reflex. Diagram Higher centres influence reflexes by: 1) activating alpha motor neurones 2) activating inhibitory interneurones 3) activating propriospinal neurones 4) activating gamma motor neurones - control muscle fibre length based on afferent movement, respond to movement to tense or not muscle fibres 5) activating terminals of afferent fibres Higher centres & pathways involved are: Cortex – corticospinal (fine control of limb movements, body adjustments) Red nucleus – rubrospinal (automatic movements of arm in response to posture/balance changes) Vestibular nuclei – vestibulospinal (altering posture to maintain balance) Tectum – tectospinal (head movements in response to visual information) Intrafusal muscle fibres - respond to change in length of fibres (gamma neurones) Extrafusal muscle fibres - under alpha neurone control (voluntary) Gamma reflex loop If knee is extended and muscle goes slack, the spindle is shortened to maintain its sensitivity. The gamma loop is made up of alpha and gamma motor neurons, sensory neurons, muscle spindles, and skeletal muscle. The gamma loop operates between the spinal cord and the muscles, quickly and automatically regulating the level of tension in our muscles. Alpha motor neurons control the contraction of skeletal muscle, while gamma motor neurons control the contraction of muscle fibers located within the muscle spindle. When our brain sends the message down to the alpha motor neurons to contract a muscle, our gamma motor neurons get the message to contract the muscle fibers within the muscle spindle as well. This is called alpha-gamma coactivation, and it occurs so that the muscle spindle always stays active and able to sense changes in muscle length. there are sensory neurons wrapped around the muscle spindle. These sensory neurons sense changes in the length of the muscle spindle and send this information to the alpha motor neuron, allowing it to regulate the length of the skeletal muscle. So, our muscle length is determined both by descending messages from the central nervous system (CNS) and by the automatic activity that occurs within the gamma feedback loop. Hyper-reflexia e.g. due to a stroke, loss of descending inhibition Clonus - ankle spasms Babinski sign - toes flex Hypo-refelxia • Below normal or absent reflexes • Mostly associated with lower motor neuron diseases

Answer 41

Outer ear focuses on the tympanic membrane (eardrum) that boosts sounds and creates pressure waves Middle ear Increases pressure of vibration by: -focussing vibrations from the larger tympanic membrane to the smaller oval window -the incus has a flexible joint with the stapes so that ossicles can use leverage to increase force on the oval window Protective mechanisms: the stapedius and tensor tympani muscles can contract when noise is loud to restrict the movement of the ossicles to protect the inner ear from excessive volumes. Inner ear Cochlea - to transduce vibration into nervous impulses -In doing this, the cochlea produces a frequency/pitch and intensity analysis of the sound. -made up of 3 compartments: Scala vestibuli - contains perilymph fluid Scala tympani - contains perilymph fluid Scala media - contains endolymph fluid The basilar membrane is sensitive to different frequencies at different points along its length (high proximal, low distal) Protective mechanisms: the auditory tube allows equilibrium of air pressure on either side of the tympanic membrane Organ of Corti - collectively describes the hair cells surrounded by supporting cells - Stria vascularis secretes the endolymph (high K+, low Na+) - the tectorial membrane is gelatinous and does not vibrate with sound Hair cells - have many stercocilia per cell, 2 types: -Inner hair cell- 3500 cells arranged in a single row, densely innervated by around 10 sensory acorns per cell -outer hair cell - 20000 cells arranged in 3 rows, sparsely innervated by 1 axon for several cells Both types of hair cells respond to sound but it’s the inner cells that transmit signals to the brain Higher amplitudes of sound will cause a greater deflection of stercocilia and K+ channel opening

Answer 42

Occurs in inner ear 1) Basilar membrane vibrates to sound 2) upward movement displaces stercocilia away from modiolus: K+ channels open —> K+ enters from endolymph —> hair cell depolarises 3) depolarisation opens Ca2+ channels in the body of hair cell 4) glutamate released from base depolarises axon of spiral ganglion cell —> action potential 5) downward movement displaces stercocilia towards modiolus: K+ channels close —> hair cell hyperpolarises The mechanism is highly sensitive - threshold sound requires 0.3 nm deflection The system depends upon the maintenance of the endolymph being +80mV by the stria vascularis.

Answer 43

Spiral ganglion cells from each cochlea project via CN VIII (vestibulocochlear nerve) to the ipsilateral cochlear nuclei (monaural neurones) After that, all connections are bilateral Thus deafness in one ear must be caused only by problems in the cochlear nucleus or CN VIII nerve (rare). Hearing is tonotopically organised in the brain

Answer 44

Sound is compressed and rarefied air waves. Humans hear between 20 and 20000 Hz, most sensitive between 1000 and 3000 Hz. -high frequencies vibrate the basilar membrane closer to the base -low frequencies vibrate the basilar membrane closer to the apex Loudness is measured on a logarithmic decibel scale (0dB-120dB) - the scale is logarithmic because the ears’ response to sound is not linear but logarithmic - 120dB = thunder, 60dB = conversational speech Hearing loss increases with age, particularly the higher frequencies of sound associated with human speech.

Answer 45

Otoscopy - torch with a clean funnel on to look into ears -used to inspect the tympanic membrane and to measure light reflection, differentiations of its parts and mobility Tuning fork tests - differentiates between conductive (outer or middle ear) and sensorineural (inner ear) hearing loss - air conduction - fork placed 2cm from EAC opening - bone conduction - foot plate placed on mastoid bone - Rinner and Weber tests Assessment of hearing Audiometry – measuring the acuity for variations in sound intensity and frequency. o An audiometer produces sound of varying intensity and frequency and a pure tone audiogram can be generated to discover where the hearing loss is. Tympanometry – examination used to test conduction of middle ear, mobility of tympanic membrane and the conduction bones by creating variations of air pressure in the ear canal. o Tympanograms can commonly show; A (normal compliance), C (negative middle ear pressure) or B (non-vibration of tympanic membrane) – non-vibration of TM can be due to: middle ear effusion, perforation of TM, Eustachian tube dysfunction or occluded ear canal. Spontaneous Otoacoustic Emission – OAEs are low-intensity sounds generated by the cochlea outer hair cells.

Answer 46

Types of Hearing Loss - Conductive hearing loss – an outer or middle ear problem. - Sensorineural hearing loss – an inner ear problem. - Mixed hearing loss Types of Hearing Loss – Conductive Hearing Loss: Outer-ear conductive hearing loss: o Congenital malformations. Congenital atresia – collapse or closure of the ear canal. o Impacted wax. o Foreign bodies. o External otitis – inflammation of the passage of the outer-ear. Otorrhea – abnormal fluid. Pain on mobilisation of the ear and tragus and can lead to systemic symptoms. o Exostosis – benign bony growths in the ear canal due to repeated exposure to cold water. Usually multiple and bilateral  leads to accumulation of ear wax and external repeat ear infections. Middle-ear conductive hearing loss: o Acute otitis media – inflammation of the middle-ear. o Otitis media with effusion – inflammation of the middle-ear with fluid accumulation. o Chronic otitis media – can be of two forms: No cholesteatomatous: • Without perforation —> retraction of the TM to Pars Tensa or Pars Flaccida. • With perforations —> active or inactive perforation of TM. Cholesteatoma – destructive and expanding growth consisting of keratinizing squamous epithelium in the middle ear and/or mastoid process. o Otosclerosis – soft, spongy growth of new bone mostly near the oval window. In 90% of cases, no symptoms but can reduce mobility of stapes —> hearing loss and thus a stapedectomy can be performed (mostly affects women). Types of Hearing Loss – Sensorineural Hearing Loss: Inner ear sensorineural hearing loss: o Prebyacusis – age-related hearing loss. Is gradual and symmetric and is due to the aging European population. It affects frequencies of speech for the 5th decade of life. Men are 2x more affected and tinnitus is often associated. o Sudden hearing loss – greater than 30dB hearing reduction over >3 contiguous frequencies, occurring over a period of 72 hours or less. Unexplained rapid loss of hearing usually in one ear. o Ototoxic drugs – e.g. diuretics, beta-blockers, TCAs, antibiotics etc. o Infections – e.g. mumps, measles, chicken pox, influenza and syphilis. o Noise-induced hearing loss – two forms: Acoustic trauma – brief exposure to very intense sounds and HL may be severe but substantial recovery is common. Long-term noise exposure – damage results from long-term exposure usually in one frequency. • Common in occupational settings.

Answer 47

The Labyrinth Organs Semi-circular canals – stimulated by ANGULAR acceleration. o This gives a signal of approx. angular velocity. Otolith organs – stimulated by LINEAR acceleration and GRAVITY force. o This gives a signal of head acceleration and tilt. Otolith Organs There are 2 otolith organs: o Utricle – senses movement in the horizontal plane. o Saccule – senses movement in the vertical plane. The otoconia is a layer of calcium carbonate on top of a gelatinous layer and as it is heavy, movements of the head displace the otoconia and thus pull the hair cells. o Linear acceleration will also move the heavy otoconia layer. There is ONE kinocilium per hair cell and movements towards the kinocilium stimulate the cell whilst movements away from the kinocilium do not. These organs are OMNI-DIRECTIONAL. Semi-circular Canals There are 3 semi-circular canals and these each join into an ampulla that contains a capula full of hair bundles. Displacement of endolymph in the canals will move the capula and thus fire off APs from the hair cells. o I.E. picture is head turning left. Linear acceleration produces equal force each side of the capula so there is no net movement. When the head turns left for example, the movement is towards the kinocilium in the horizontal canal in the left ear but in the right ear it is away from the kinocilium  hence there is a depolarisation in the left ear and a hyperpolarisation (inhibition) in the right ear. There is a constant tonic firing when at rest.

Answer 48

Vestibular disorders can be structural, functional or both – achieving a diagnosis does not occur in 40%: o Structural – destructive or irritative disease. o Functional – misinterpretation of sensory input, mal-adaptation, loss of rules of correspondence. o Both – structural disorder provoking chronic dysfunction. Disorders of the vestibular system include: o Vertigo – false perception of movement in space. -Can last anywhere between seconds and continuous. Minutes most common possibly due to vertebrobasilar insufficiency (migraine). Hours of vertigo caused by Meniere’s syndrome. o Vestibular ataxia – instability of gait and posture. o Vestibular nystagmus – UNILATERAL vestibular lesions. o Oscillopsia – BILATERAL vestibular lesions. o Motion sickness – loss of co-ordination on directional reorientation, oversensitivity to visual motion in the environment. o Acute phase of vestibular loss – slight impairment of orthostatic control —> severe nausea and vomiting.

Answer 49

``` These signals are used to: Control balance. o Dysfunction leads to ataxia. Provide spatial reference for other motor actions. o Dysfunction leads to ataxia. Provide compensatory reflexes (VOR). o Total loss dysfunction leads to oscillopsia (objects oscillate). o Unilateral loss dysfunction leads to nystagmus. Provide proprioception. o Dysfunction leads to dizziness. Tune CVS for re-orientations. o Dysfunction leads to hypotension. ``` Unusual stimulation of the balance organs provokes motion sickness.

Answer 50

Vertigo – feelings of intense spinning. The vestibular projections go via the thalamus to the temporo-parietal cortex and regulate perception of motion in space. Unilateral lesion – the tonus of the intact canal gives a signal as if the head is rotating to the intact side (as the other side has lost its intrinsic tone). As you can see on the left, episodes of vertigo can last from seconds to days to even continuous and the causes are varied. o BPPV – Benign, Paroxysmal Positional Vertigo. -Accounts for a 1/3rd of all incidences of vertigo and is caused by otoconial debris in the canals. -BPPV is transient and provoked by head movement. -Debris floating in the canals stimulates the ampulla causing false signals of head rotation – vertigo. -Treated by vigorous head rotation to flush debris. Nystagmus Acute unilateral vestibular disorder – the unopposed tone of the intact canal causes the eyes to be driven to the lesioned side (vestibular-ocular reflex). The movement is detected by the brainstem which then corrects eye position with fast movements. This effect is minimised by visual suppression mechanisms.

Answer 51

Superior and medial vestibular neurons project to motor nuclei supplying the extraocular muscles. Axons ascend in the MLF (Medial Longitudinal Fusciculus) and excite the ipsilateral oculomotor (CN III) nucleus and the contralateral abducens (CN VI) nucleus. VOR – when the head rotates to the left, the eyes rotate to the right and saccade (a rapid movement of the eye between fixation points) to the left. VOR acts to maintain gaze on a selected target. o So continuing head rotation cause a physiological vestibular nystagmus. Dysfunctions Oscillopsia  Loss of vestibular function impairs eye stabilisation during rapid head movements as the VOR is the only mechanism to drive fast compensatory reflex. The diagnosis is done with the “Head shaking test” – head is oscillated and the eyes monitored. o Bilateral loss – the eyes will be taken off target by the head swing and multiple catch-up saccades will be made to regain the target. o Unilateral loss – detected my discrete fast swings of the head – during a fast swing to the good side, the eyes will remain on target whilst a swing to the lesioned side will result in catch-up saccades. Vestibular ataxia Vestibular Ataxia Bilateral – mild gait ataxia that is worse at speed, when negotiating rough ground or when vision is reduced. Unilateral – tendency for the body and head to lean and fall to the lesioned side which becomes pronounced in difficult balancing situations. Tracts: o Lateral vestibulo-spinal tract – descends ipsilaterally in ventral funiculus of spinal cord. Axons terminate in lateral ventral horn and influence motor neurons to the limbs. o Medial vestibulo-spinal tract – descends bilaterally in MLF to cervical and upper thoracic spinal cord. Axons terminate in medial ventral horn and influence motor neurons to neck and back. As you can see by where the tracts go from the vestibular nucleus, lesion can bring about; hypotension, respiratory dysrhythmia, HR, nausea and vomiting (motion sickness).

Answer 52

Calorics Measure: nystagmus duration, peak velocity and subjective sensation. Interpretation: o Small amplitude, short duration to both hot and cold ipsilateral – canal paresis. o Bilateral small short responses – bilateral hypofunction. o Asymmetry of hot/cold responses – of little significance/normal. Acute Vestibular Lesions Symptoms include: o Ipsilateral tilt, attempted compensation and/or an ipsilateral head tilt and skew. Treatments include: o Reassurance of patient, drugs (steroids, anti-virals etc.), treatment of associated anxiety etc., cognitive behaviour therapy with desensitisation and physiotherapy, behavioural anxiolytic tactics and minimise risk factors – ALSO LOOK TO BPPV HEAD TILTING. Motion sickness: o Primary symptoms – pallor, sweating, nausea, vomiting. o Associated symptoms – headache, dizziness + nystagmus, instability, restlessness, drowsiness, feeling of eye strain. o Treatment – Cognitive behaviour therapy with desensitisation in SMALL doses + behavioural anti-emetic and anxiolytic (something used to reduce anxiety) exercises.

Answer 53

Benign paroxysmal positional vertigo Problem in inner eat Symptoms are repeated, brief periods of vertigo with movement - spinning sensation when changing head position Red flags - headache - atypical nystagmus

Answer 54

Inner ear mechanism detects head movement Semicircular canals detect angular acceleration Vestibulocochlear-ocular reflex stabilises gazing space. Move head to right, eyes look left and vice versa If you lose both peripheral vestibular labyrinths, when head moves, world wobbles —> oscilllopsia (indicates a nystagmus)

Answer 55

BPPV Vestibular neuritis - subacute onset, continuous vertigo, normal gait, red flags - headache, gait ataxia Migrainous vertigo Stroke (cerebellar) - poor balance, headache

Answer 56

Eyes - gaze - VOR - Doll’s eyes’ reflex - eyes should be stationary when head tilted Ears -otoscopy Legs - gait - tandem walking - Romberg - eyes closed and maintaining balance

Answer 57

- minimal movement - reduced responsiveness to external stimuli - reversible with stimulation unlike coma, anaesthesia or death EEG, EOG, EMG

Answer 58

Awake -very active, fast movements Stage 1 and 2 NREM - light sleep - slowly become drowsy - no eye movement and general muscle activity is reduced - slow rhythm Stage 3 and 4 NREM - deep sleep - minimal eye movement - continued relaxation of muscles - slowest rhythm Stage 5 REM - back to fast rhythm brain activity - REM - muscle activity is lowest - paralysed Each sleep cycle lasts around 90 minutes

Answer 59

Maintenance of arousal -RAS - reticular activating system controls consciousness Originates from brainstem and then goes upwards to thalamus and cortex Control fo sleep/wake cycle - lateral hypothalamus promotes wakefulness (orexin/hypocretin - neurotransmitter) (positive on RAS) LH - ventrolateral preoptic nucleus (anterior hypothalamus) promotes sleep (negative on RAS) VLP Circadian synchronisation of sleep/ wake cycle Suprachiasmatic nucleus synchronises sleep with falling light level Activates pineal gland releases melatonin which is linked to light Inhibits LH and activates VLP

Answer 60

``` • Psychiatric and neurological – Sleepiness, irritability, stress, mood fluctuations, depression, impulsivity, hallucinations • Neurological – Impaired attention, memory, executive function – Risk of errors and accidents – Neurodegeneration (?) • Somatic – Glucose intolerance – Reduced leptin/increased appetite – Impaired immunity – Increased risk of cardiovascular disease and cancer – Death ```

Answer 61

Reduced latency to sleep onset - faster to sleep Increase of slow wave sleep (NREM) Increase of REM sleep (after selective REM sleep deprivation)

Answer 62

``` • Restoration and recovery – but active individuals do not sleep more • Energy conservation – 10% drop in BMR – but lying still is just as effective • Predator avoidance – but why is sleep so complex? • Specific brain functions – memory consolidation ```

Answer 63

``` • Can occur in REM and NREM sleep • Most frequent in REM sleep • More easily recalled in REM sleep • Contents of dreams are more emotional than ‘real life’ • Brain activity in limbic system (consciousness, emotional) higher than in frontal lobe during dreams ``` Function • Safety valve for antisocial emotions • Disposal of unwanted memories • Memory consolidation

Answer 64

Insomnia • Causes of chronic cases: – physiological e.g. sleep apnea, chronic pain – Brain dysfunction eg. depression, fatal familial insomnia, night working • Treatment – sleep hygiene .e.g. establishing fixed times for going to bed, avoiding caffeine before bad, don’t use back-lit devices shortly before going to bed – hypnotics (most enhance GABAergic circuits) – sleep CBT Hypersomnia - excessive daytime sleeping Primary causes - narcolepsy, post-traumatic brain injury Secondary causes due to poor quality overnight sleep - obstructive sleep apnoea, anxiety Epworth sleepiness scale used to determine daytime sleepiness ``` Narcolepsy • Falling asleep repeatedly during the day and disturbed sleep during the night • Cataplexy (sudden, brief loss of voluntary muscle tone, often triggered by strong emotions e.g. laughter) • Dysfunction of control of REM sleep • Orexin/hypocretin deficiency ``` ``` Shift work • Night working causes physiological processes to become desynchronised • This can lead to sleep disorders, fatigue and an increased risk for some conditions such as obesity, diabetes and cancer ``` Sleep and neurological disease - consequence or cause

Answer 65

The state of being aware of and responsive to one’s surroundings Mechanisms RAS • The reticular formation (RF) regulates many vital functions. The degree of activity in the reticular system is associated with alertness/levels of consciousness • RF projects to the hypothalamus, thalamus and the cortex • Ventral tegmental area (dopaminergic neurones) (midbrain) • Locus coeruleus (noradrenergic neurones) (pons)

Answer 66

Coma (absent wakefulness and absent awareness) -a state of unrousable unrepsonsiveness lasting more than 6 hours Vegetative state (wakefulness with absent awareness) - destruction of cortex and hemispheres, intact ascending RAS - sleep cycles present Minimally conscious state (MCS - wakefulness with minimal awareness)

Answer 67

``` Higher frequency neural oscillations Awake = beta waves Drowsy relaxed = alpha waves Stage N1 sleep = theta waves Stage N2 sleep = sleep spindles Stage N3 sleep = delta waves REM sleep = fast, random ```

Answer 68

Glasgow coma scale Scores for eyes open, verbal responses, motor responses ``` Causes of coma Metabolic – Drug overdose – hypoglycaemia – diabetes – "the failures" – hypercalcaemia ``` ``` Diffuse intracranial – head injury – meningitis – SAH – encephalitis – epilepsy – hypoxic brain injury ``` ``` Hemisphere lesion – cerebral infarct – cerebral haemorrhage • subdural • extradural – abscess – tumour ``` ``` Brain stem – brainstem infarct – tumour – abscess – cerebellar haemorrhage -cerebellar infarct ```

Answer 69

There are 3 types of tear production: o Basal tears. o Reflex tears – in response to irritation. Afferent CN V1, Efferent PNS. o Crying tears. Lacrimal system – tears produced in lacrimal glands —> drain through two puncta —>through sup. and inf. Canaliculi —> collect in tear sac and drain through tear duct into nose.

Answer 70

``` Properties: o Maintains smooth corneal-air surface. o Facilitates oxygen supply to cornea. o Removes debris. o Bactericide. ``` Composed of three layers: o Superficial oily layer – reduce tear film evaporation. Produced by Meibomian glands. o Aqueous layer – produced by tear gland. o Mucin layer – maintains wet corneal surface.

Answer 71

Conjunctiva – a thin transparent tissue that covers the outside surface of the eye. - Begins at the outer edge of the cornea and covers the visible surface of the eye and lines the eyelids. - Nourished by near-invisible blood vessels. Coat of the Eye There are 3 layers to the coat of the eye: -Retina – a thin layer of photo-sensitive tissue that captures light rays. -Choroid – is a component of the uvea (iris, ciliary body and choroid) and is composed of layers of blood vessels. -Sclera – a tough opaque white tissue that covers the outside of the eye and is CONTINUOUS with the cornea. High water content. Cornea -LOW water content. -Provides 2/3rds of the eye’s focussing power. -Higher refractive index than air, convex. -There are 5 layers: 1. Epithelium. 2. Bowman’s membrane. 3. Stroma – thickest layer, contains nerve endings. 4. Descemet’s membrane. 5. Endothelium – pumps fluid OUT of cornea and prevents corneal oedema. Only 1 cell thick and has NO capacity to regenerate. Cell density decreases with age and can result in corneal oedema and corneal cloudiness.

Answer 72

Uvea – the vascular coat of the eye ball that lies between the sclera and the retina. - Composed of 3 parts; iris, ciliary body and choroid. - Close connections of the structures mean disease of one often affect the other two. Lens Zonules -The lens is suspended by a fibrous ring called the lens zonules and consists of passive connective tissue. Optic Nerve and Macula - The optic nerve connects at the back of the eye near the macula and the visible part is called the optic disc. - The macula is located temporal to the optic nerve and is a small and highly sensitive part of the retina involved in detailed central vision. The fovea is the very centre of the macula.

Answer 73

``` Segments -The segments are divided by the lens. -Anterior: o Between the cornea and the lens. o Filled with clear fluid and provides nutrients. -Posterior: o Filled with vitreous humour. ``` Ciliary Bodies Normal pressure: 12-21mmHg. -The ciliary body located here ACTIVELY produces aqueous (no correlation with BP). -Aqueous production: o Aqueous flows into the posterior chamber down the green arrow —> flows into the posterior chamber —> into the scleral angle (with trabecular meshwork). o The aqueous is then absorbed via two methods: Uveal-scleral Outflow – aqueous leaks between the sclerous and the choroid. • 20% of drainage. • Prostaglandin analogues target this. Schlemm’s canal & TM – aqueous goes to blood stream. • 80% of drainage.

Answer 74

Glaucoma – a disease of sustained high intraocular pressure (a risk factor). -Characteristics are retinal ganglionic cell death and enlarged optic disc cupping (the optic disc enlarges due to absence of retinal ganglionic cells that have died). -Results in visual field loss and blindness. -Types of glaucoma: o Primary open angle glaucoma (most common): -Trabecular meshwork dysfunction. o Closed angle glaucoma (acute or chronic): -The increased IOP causes the lens/iris to bulge out and restrict access to the TM and thus limit outflow. Risk factors include having a small eye and having a naturally small angle. -Treated with peripheral laser iridotomy to create drainage holes.

Answer 75

Macula and Fovea - The macula is located roughly centre of the retina, temporal to the optic disc. - The fovea is the very centre of the macula. - The macula has the HIGHEST concentration of CONES but the LOWEST concentration of RODS. - The fovea can be clinically assessed using OCT (Optical Coherence Tomography). Vision -Central vision – macular degeneration affects ACUITY: o Detailed day vision. o For reading and facial recognition. o Assessed by the visual ACUITY assessment. -Peripheral vision: o For shape, movement and night vision. o Assessed by the visual FIELD assessment. Retinal Structure Light comes in to hit the RPE. - Outer layer – 1st order neurones (photoreceptors), detection of light. - Middle layer – 2nd order neurones (bipolar cells), regulate/improve sensitivity and process light. - Inner layer – 3rd order neurones (Retinal ganglionic cells), transmission of signal to brain. Retinal Structure -Rod photoreceptor: Scotopic = rod vision. o Longer outer segment that is 100x more sensitive to light. o It has a SLOW response to light. o Responsible for peripheral, night vision and recognises motion. o 120m rods. -Cone photoreceptor: Photopic = cone vision. o Less sensitive to light but a FASTER response. o Responsible for central colour, day vision and detail. o 6m cones. There are NO rods found in the fovea at all.

Answer 76

Frequency Spectrum -Commonest form of colour vision deficiency is red-green confusion or Deuteranomaly (M-cone peak shifted to L-cone peak). o M- and L-cone peaks are VERY close to each other. -500nm is the wavelength of the rods peak sensitivity. Frequency Spectrum - Ishihara test is a colour perception test and tests for red-green deficiencies. - Patients that suffer from deuteranomaly will not be able to distinguish the numbers from the backgrounds. Light-Dark Adaptation -Dark adaptation: o There is an increase in light sensitivity in the dark. o Biphasic process: Cone adaptation – 7 minutes. Rod adaptation – 30 minutes (to regenerate the rhodopsin). -Light adaptation: o Occurs over 5 minutes. o Occurs via; neuro-adaptation, bleaching of photo-pigments and inhibition of rod/cone function. -Pupil adaptation – a minor effect of pupil constriction.

Answer 77

Refraction -The index of refraction is measured by: n=(speed of light in a vacuum (c))/(speed of light in substance (v)) -As c is a set limit and the denominator cannot be greater than it, the value will always be >= 1. -Mediums SLOW down light below c. -Light bends towards the normal when slowing down (entering a new medium). -Some light reflects and some refracts when entering a new medium. Lenses -Converging (convex) lens focuses light rays onto a single point. o Used for glasses (long-sighted or hyperopic people) and cameras. -Diverging (concave) lens diverge light rays.

Answer 78

Emmetropia – adequate correlation between axial length and refractive power. -This is NORMAL and parallel light rays will always fall on the retina with NO accommodation required. Ametropia – mismatch between axial length and refractive power. -Parallel light rays do NOT fall on the retina with NO accommodation. -Forms of Ametropia include; o Myopia (near-sightedness) or hyperopia (far-sightedness). o Astigmatism. o Presbyopia. Ametropia – Myopia: -Rays converge at a point ANTERIOR to the retina. -The aetiology of myopia is unclear but may be genetic. -Causes include: axial myopia (long eyeball/globe), refractive myopia (excessive refractive power). o Axial myopia is most common. -Treatments include: concave lens, contact lens, laser treatment to remove part of the lens (lens = 20 dioptres). Ametropia – Hyperopia: -Rays converge at a point POSTERIOR to the retina. -The aetiology of myopia is unclear but may be genetic. -Causes include: axial hyperopia (short eyeball/globe), refractive hyperopia (insufficient refractive power). o Axial hyperopia is most common. -Symptoms include: o Visual acuity blurs relatively early. o Asthenopic symptoms; eye pain, frontal headache, blepharoconjunctivitis. -Amblyopia = uncorrected hyperopia > 5 dioptres. -Treatments include: convex lens, remove lens with laser treatment and have a greater power lens, contact lens or intra-ocular lens. Ametropia – Astigmatism: -Rays come to focus on 2 focal lines rather than a single focal point. -Aetiology is hereditary. -The cause is: the refractive media is not spherical so rays refract differently along one meridian than an adjacent one thus producing more than one focal point. -Symptoms include: o Asthenopic symptoms. o Blurred and distorted vision. o Head tilting and turning. -Treatments include: o Regular astigmatism – cylindrical lenses +/- spherical lenses. o Irregular astigmatism – rigid contact lenses +/- surgery. Near-Response Triad -Mediates the response for near-vision. -The triad consists of: o Sphincter pupillae – pupillary miosis to increase depth of field. o Circular ciliary muscle – accommodation to increase refractive power of the lens. o Medial rectus – align both eyes towards a near object. Presbyopia – the naturally occurring loss of accommodation with age. - Onset from 40 years of age and distant vision remains intact. - Corrected by reading glasses (convex lens) to increase the refractive power of the eyes. - Treatment includes; reading glasses, bifocal, trifocal and progressive power glasses.

Answer 79

Types of Optical Correction -Spectacle lenses: o Monofocal lenses – spherical or cylindrical lenses. o Multifocal lenses. -Contact lenses: o Higher quality optical image (less influence on the size of the retinal image than spectacle lenses). o Can be worn for sports and for aesthetic reasons but require careful daily cleaning and are expensive. o Complications include; infectious keratitis, giant papillary conjunctivitis, severe chronic conjunctivitis. -Intraocular lenses: o Replacement of cataract crystalline lens. o Give the best optical correction for aphakia and avoid the magnification/distortion caused by spectacles. -Surgical correction: o Keratorefractive surgery. o Intraocular surgery – clear lens extraction with or without intra-ocular lens. A small flap of the eye is made and then the laser changes the refractive power of the cornea and the epithelial flap is then re-sewn back onto the eye. An extra intra-ocular lens can be placed on top of the physiological lens of the eye or the old lens can be removed by laser activity (phaco tip).

Answer 80

Accommodation Mechanism: o Circular ciliary muscle (located around ciliary bodies) contracts. o Relaxes the zonules that are usually taught (the zonules are passive elastic bands with no active contractile activity). o In the absence of zonular tension, the lens returns to the natural convex shape —> increases natural power of lens. Mediated by CN III (oculomotor). For near vision, the ciliary muscles contract and the central lens thickness increases to increase its power.

Answer 81

1. Eye. 2. Optic nerve – ganglion nerve fibres. 3. Optic chiasm – half of fibres decussate here. 4. Optic tract – ganglion fibres exit as optic tract. 5. Lateral Geniculate Nucleus – ganglion fibres synapse in nucleus. 6. Optic radiation – 4th order neuron. 7. Primary visual cortex OR Striate Cortes (occipital lobe). Visual pathway retina -First order neurons – Rod and Cone retinal photoreceptors. -Second order neurons – Retinal bipolar cells. -Third order neurons – Retinal ganglionic cells. o Travel down the length of the optic nerve and have a PARTIAL decussation (53% cross) at the optic chiasm. o Fibres synapse in the LGN (Lateral Geniculate Nucleus) located within the thalamus.

Answer 82

Receptive Field – The activity of each neuron in the retina: -The further away from the fovea, the larger the receptive field. -Receptive field – the retinal space within which incoming light can alter the firing pattern of a neuron. -Convergence – number of lower order neurons field synapsing on the same higher order neuron. The cone system has a lower order of convergence than the rod system (as the cones tend to be one-to-one whereas many photoreceptors link to a single RGC in the rod system). Receptive Field – The activity of each neuron in the retina: - Cone system convergence < Rod system convergence. - Central retina convergence < peripheral retinal convergence. - Low convergence – small receptive field, fine visual acuity, low light sensitivity. - High convergence – large receptive field, course visual acuity, high light sensitivity.

Answer 83

-RGCs are split into on-centre and off-centre cells. -On-centre ganglionic cells: o Stimulated by light at the CENTRE of the receptive field. o Inhibited by light on the EDGE of the receptive field. -Off-centre ganglionic cells: o Inhibited by light at the CENTRE of the receptive field. o Stimulated by light at the EDGE of the receptive field. -This is important for – contrast sensitivity and edge detection. Optic Chiasma 53% of fibres cross. - Lesions anterior affect SINGLE eyes only. - Lesions posterior affect BOTH eyes equally. - Crossed fibres – originate from nasal retina, responsible for temporal visual field. - Uncrossed fibres – originate from temporal retina, responsible for nasal visual field

Answer 84

Visual field defects: o Lesion at optic chiasma – damages crossed RGC fibres from nasal retina in both eyes —> temporal field deficit in both eyes – Bitemporal hemianopia. o Lesion posterior to optic chiasma – Right = left homonymous hemianopia in both eyes. Left = right homonymous hemianopia in both eyes. o Bitemporal hemianopia – caused by enlargement of pituitary gland tumour. o Homonymous hemianopia – caused by stroke. -In a macular sparing disorder, you have a loss of peripheral vision but you retain central acuity. -Glaucoma often affects the HORIZONTAL plane of loss of vision. -Neurological problems often affect the VERTICAL plane of loss of vision.

Answer 85

-Primary visual cortex OR Striate cortex: o Situated along the Calcarine fissure. o Characterised by a distinct stripe derived from the myelinated fibre of the optic radiation projection. -Representation: o Disproportionately large area representing the macula – due to a higher density of RGCs (lower convergence). o Visual fields: -Superior visual field projects BELOW the Calcarine fissure. -Inferior visual field projects ABOVE the Calcarine fissure. -Left hemi-field projects to the right. -Right hemi-field projects to the left. Organisation: o Organised as columns with unique sensitivity to visual stimulus of a particular orientation. o Right and left eye columns intersperse each other. Macular sparing homonymous hemianopia: o Commonly due to damage of the primary visual cortex. o Often due to stroke. o Contralateral homonymous hemianopia with central macula sparing. Macula is spared due to dual blood supply. Extrastriate cortex Extrastriate Cortex – the area surrounding the visual cortex. -Converts basic visual information, orientation and position into complex information. -Dorsal pathway: o Primary visual cortex  posterior parietal cortex. o Motion detection, visually-guided action. o Damage results in motion blindness. -Ventral pathway: o Primary visual cortex  Inferiotemporal cortex. o Object representation, face recognition, detailed fine central vision and colour vision. o Damage results in cerebral Achromatopsia.

Answer 86

Pupillary Function -In light – decreases spherical aberrations and glare, increases depth of field, reduces bleaching of photopigments. o Constriction mediated by PNS nerve within CN III. -In dark – allows more light into eye. o Dilation mediated by SNS nerve. Pupillary Reflex -Afferent pathway (red & green): o Rod and cone photoreceptor —> bipolar cells —> RGCs —> nerves exit at posterior 1/3rd of optic tract and enter LGN —> synapse at brainstem (Pretectal nucleus) —> synapse at Edinger Westphal nucleus. -Efferent pathway (blue): o Edinger Westphal —> oculomotor nerve efferent —> synapse at ciliary ganglion —> short posterior ciliary nerve —> pupillary sphincter. -Note that the afferent pathway on either eye stimulates the efferent pathway in BOTH eyes. o Direct light reflex – constriction of pupil of the light stimulated eye. o Consensual light reflex – constriction of pupil of the other eye. Afferent Vs. Efferent Defect - Right afferent defect (damage to CN II) – no pupil constriction in both eyes when right is stimulated, pupil constriction in both eyes when left eye is stimulated. - Right efferent defect (damage to right CN III) – no right pupil constriction at all, left eye constricts whether left or right is stimulated. Swinging Torch Test Done to demonstrate weakness of the afferent pathway. -The damage to the afferent pathway is usually incomplete or relative. -E.G. Relative afferent pupillary defect in right eye. o Both pupils constrict when light swings to left eye with intact pathway. o Both pupils will paradoxically dilate when light swings to the right eye as a result of relatively reduced drive for pupillary constriction in both eyes.

Answer 87

-Six extraocular muscles innervated by three cranial nerves. -Movement: o Duction – eye movement in one eye. o Version – eye movement in both eyes in the same direction, dextro- is to the right, levo- is to the left. o Vergence – eye movement in both eyes in opposite directions. o Convergence – simultaneous adduction (inwards) movement in both eyes when viewing a near object. -Speed: o Saccade – short, fast burst of movement (900deg/second) – reflexive saccade, scanning saccade, predictive saccade and memory-guided saccade. o Smooth pursuit – sustained slow movement (60deg/second) – driven by motion of a moving target across the retina. ``` Muscles: 4 straight muscles: o Superior rectus – moves eye up. o Inferior rectus – moves eye down. o Medial rectus. Occulomotor innervation (plus all above). o Lateral rectus. Abducens innervation. 2 oblique muscles: o Superior oblique – attached high on temporal side of eye and passes under superior rectus, moves eye down and in. -Trochlear innervation. o Inferior oblique – attached low on nasal side of eye and passes over inferior rectus, moves eye up and out. -Occulomotor innervation. ``` Eye Movement Testing The muscles must be isolated to test nerve and muscle function: -Lateral rectus – abduction (away from midline). -Medial rectus – adduction (towards midline). -Superior rectus – elevated and abducted. -Inferior rectus – depressed and abducted. -Inferior oblique – elevated and adducted. -Superior oblique – depressed and adducted. 3rd Nerve Palsy - The affected eye droops and abducts and the eyelid droops. - As the third nerve is affected, the unopposed lateral rectus takes over (abducts) and the superior oblique also takes over. 6th Nerve Palsy - The affected eye is unable to abduct and deviates to the midline (adducts). - Double vision worsens on gazing to the side of the affected eye. Optokinetic Nystagmus Reflex - Nystagmus – oscillatory eye movement. - Optokinetic nystagmus – smooth pursuit + fast paced reset saccade. - This reflex is used to test visual acuity in pre-verbal children by observing presence of nystagmus movement. - The reflex being present is physiological and a sign the child has the visual acuity to perceive motion.

Answer 88

1) association fibres: connect areas within the same hemisphere; short fibres between adjacent parts of the cortex and help coordinate function 2) commissural fibres: connect left hemisphere to right hemisphere e.g. corpus callosum 3) projection fibres: connect cortex with lower brain structures (e.g. thalamus), brainstem and spinal cord; corticospinal tract

Answer 89

Layer 1-3: mainly cortico-cortical connections; layer 1 = glial cells Layer 4: input from thalamus Layer 5-6: connections with subcortical, Brian stem and spinal cord; output, Bet cells * Neocortex is arranged in layers (lamina structure) and columns * More dense vertical connections – basis for topographical organization * Neurons with similar properties are connected in the same column Neocortex is comprised of different lobes: - frontal lobe - temporal lobe - parietal lobe - occipital lobe ``` Primary cortices: -function predictable -organised topographically -right-left symmetry E.g. primary motor cortex, primary somatic sensory cortex, primary auditory cortex ``` Association cortices: -function less predictable -not organised topographically -left-right symmetry weak or absent (Connect primary cortical and other areas) E.g. motor association area (premolar cortex), sensory association area, visual association area (colour recognition), auditory association area, prefrontal association area (behaviour, personality changes)

Answer 90

Visual association cortex: Image attributes are processed separately e.g. What colour, form, where (spatial relationships) There are two pathways from occipital lobe - what pathway (ventral stream) and where pathway (dorsal stream) Lesions of the visual posterior association area (fusiform gyrus) can result in the inability to recognise familiar faces or learn new faces - a deficit called prosopagnosia (aka face blindness) e.g. stroke Frontal cortex lesions: Characterised by a lack of planning, behaviour becomes disorganised , attention span and concentration diminish, self-control is hugely impaired Frontotemporal dementia - can be sexually inappropriate Parietal cortex lesions: -posterior parietal association cortex creates a spatial map one the body in surroundings, from multi modality info -injury may cause disorientation, inability to read maps or understand spatial relationships, apraxia, hemispatial neglect In Alzheimer’s - starts of in temporal lobe (inhibitory to memorise things), A’s disease progresses through cortex into parietal = disorientation Temporal cortex lesions: Language, object recognition, memory, emotion Injury leads to agnosia (loss of recognition), receptive aphasia (failure to understand outside world), anterograde amnesia (unable to lay down new memories) Hemispheric specialisation: Patients who have had a callosotomy (split brain) have lateralised deficits in function No corpus callosum born or transect e.g. epilepsy don’t want to spread from one side to another Right can’t share info with left e.g. drawing and saying diagram (left verbal processing) Input from the left field of view is processed by the right hemisphere and vice versa Diffusion tensor imaging, a form of MRI - tractography shows integrity of functional pathways

Answer 91

Transcranial magnetic stimulation (TMS) The magnetic field induces an electric current in the cortex, causing neurones to fire This can be used to test whether a specific brain area is responsible for a function e.g. speech Transcranial direct current stimulation (TDCS) Changes the local excitability of neurones, increasing or decreasing the firing rate (NB: does not directly induce neuronal firing); sensitivity of neurones changed Recent research suggests that TDCS could be used to reduce motion sickness by suppressing the area of the cortex associated with processing vestibular info

Answer 92

Position emission tomography (PET) - radioactive substances injected Magnetoencephalography (MEG): meanders magnetic fields Electroencephalograph (EEG): measures electric fields MEG and EEG test sensitivity of motion part of visual cortex Functional magnetic resonance imaging (fMRI) - measures brain activity by detecting changes in blood flow and utilisation of O2 When participants imaged positive events in the future or the past, the amygdala and rostral anterior cingulate cortex were more active than when they imagined negative events

Answer 93

Olfactory epithelium at top of nose and following are found: -bipolar olfactory neurones - receptive component externally into nose, cell body and then projection up through cribiform plate in ethmoid bone to olfactory bulb (sits underneath frontal lobe) -sustentacular cells -basal cells Progressive loss with age Olfactory bulb: bipolar olfactory receptor cells synapse with mitral cells in glomerular type organisation Second-order olfactory neurones project back to brain via olfactory tract • Olfactory bulb (mitral cells) • Olfactory tract -split into 2 stria • Olfactory stria - 1) piriform cortex -medial temporal lobe, 2) orbital frontal cortex (front cortex just aligned next to orbit) • Piriform and orbitofrontal cortex • Connections to brainstem promote autonomic responses .e.g salivating to olfactory stimulus • Clinical deficit: Anosmia (loss of sense of smell) - Parkinson’s, Alzheimer’s • Prodromal auras: lots of people with epilepsy know they’re going to have a seizure. A lot of epileptics are temporal lobe based, if around piriform cortex, can smell something to warn a seizure = prodromal aura Side note: the nose in Parkinson’s has brown staining - a moral protein

Answer 94

System responsible for processes aimed a survival of the individual: ❖ maintenance of homeostasis via activation of visceral effector mechanisms, modulation of pituitary hormone release and initiation of feeding and drinking ❖ agonistic (defence & attack) behaviour: fight or flight ❖ sexual & reproductive behaviour ❖ memory Subcortical structures: - frontal lobe - thalamus - hippocampus - lying in the floor of the inferior horn of the lateral ventricle in temporal lobe - amygdala - anterior to hippocampus - hypothalamus - olfactory bulb

Answer 95

Neocortex —> cingulate cortex —> hippocampus (via Cingular bundle) —> mammillary bodies in hypothalamus - 2 spheres in base (via fornix) —> anterior nucleus of thalamus (via MTT = mamallothalamic tract) —> cingulate cortex Neocortex = emotional colouring - coloured by previous experience Anterior nucleus of thalamus —> cingulate cortex = emotional experience (lay down new memories) Hypothalamus —> anterior nucleus of thalamus = emotional expression - reaction to outside world (greatly hypothalamic) Cingular bundle = longitudinal fibres above corpus callosum Cingulate cortex = just above corpus callosum Start at hippocampus Neocortex = all other cortical areas can feed int this circuit

Answer 96

Main connections: - afferent: perforant pathway - from ectorhinal cortex right next to it - helps develop memories - efferent: fibrin - when directly attached to hippocampus/fornix - when break away Functions: -memory and learning Clinical: -Alzheimer’s disease, epilepsy Hippocampus is found in the medial temporal lobe within inferior horn of lateral ventricle Hippocampus circuitry - diagram

Answer 97

Cortical atrophy - front lobe atrophy - cortex shrink, temporal lobe atrophy - hippocampus shrink - enlargement of ventricles Plaques Can use silver staining Tangles Disrupted nerve cell ``` Anatomical progression • Early ❖ Hippocampus and entorhinal cortex ❖ Short-term memory problems • Moderate ❖ Parietal lobe - disorientation ❖ Dressing apraxia - not sure where fingers are, can’t carry out complex tasks • Late ❖ Frontal lobe - personality change ❖ Loss of executive skills - loss of decision making skills ```

Answer 98

• Main connections: ❖ Afferent: Olfactory cortex (e.g. gas leak), septum, temporal neocortex, hippocampus, brainstem ❖ Efferent: Stria terminalis - goes to anterior part of hypothalamus • Functions: ❖ Fear & anxiety ❖ Fight or flight • Clinical: ❖ Kluver-Bucy syndrome - hyperorality - like baby, examine objects by putting in mouth -loss of fear -visual agnosia -hypersexuality Syndrome originally described in monkeys with bilateral temporal lobectomy Grey matter nucleus embedded in white matter of anterior temporal lobe in front of ventricle Multiple nuclei within amygdala each differentials susceptible to neurodegeneration Side note: - bilateral damage to temporal lobes anteriorly = trauma .e.g car accidents - temporal lobes crashing against cranial fossa = bilateral amygdala damage

Answer 99

• Structures shown experimentally to be associated with aggression ❖ Hypothalamus - anterior parts ❖ Brainstem (periaqueductal grey) - grey matter around aqueduct ❖ Amygdala • 5-HT in raphe nuclei - 5-HT (serotonin) is neurotransmitter found in rap he nuclei

Answer 100

Septum lies between lateral ventricles anteriorly • Main connections: ❖ Afferent: Amygdala, olfactory tract, hippocampus, brainstem ❖ Efferent: Stria medularis thalami, hippocampus, hypothalamus • Functions: ❖ Reinforcement & reward “Good feeling” - therapeutic - treat tremor in Parkinson’s - subthalamic nucleus

Answer 101

Mesolimbic pathway: Ventral tegmental area to cortex, nucleus accumbens and amygdala va median forebrain bundle - dopamine release (Not same as Parkinson’s - dopamienrgic projectons from substantia nigra up to basal ganglia) • Opioids, nicotine, amphetamines, ethanol and cocaine (acts on reuptake - reuptake inhibitor - prolongs DA in synpase) all increase DA release in nucleus accumbens • Stimulate midbrain neurons, promote DA release or inhibit DA reuptake • Other neurotransmitters also modify this system L-Dopa in Parkinson’s, dopamine agonist given when stop working Dopaminergic side effects, stimulates nucleus accumbens, obsessive compulsive behaviour e.g. online gambling