Neuro - Phase 1 Flashcards

Question

**Overview of neurotransmitter physiology**

Answer 1

1. Synthesis – peptide transmitters in cell body then transported, non-peptide transmitters are synthesised and stored in the nerve terminal 2. Storage – occurs in vesicles within the active zone of the axon terminal 3. Release – influx of calcium due to depolarisation triggers calcium dependent exocytosis 4. Receptor binding – receptors on postsynaptic neuron may be rapid ionotropic (ligand gated ion channels) or slow metabotropic (second messengers) 5. Degradation – reuptake into neurons and glia, enzymatic breakdown of active component

Answer 2

**_Corticospinal tract_** carries motor signals from M1/SMA/PMA to LMNs in the spinal cord 1. primary neuron is an UMN originating in the motor cortices 2. travels down through internal capsule – genu and anterior portion of posterior limb (FAL) 3. decussation of some fibres at the pyramidal decussation creates two pathways: * lateral CST: 90% of fibres decussate in medulla and continue contralaterally in lateral SC * anterior CST: 10% of fibres remain ipsilateral and continue down in the anterior SC before later decussating at the level they innervate via the ventral white commissure 4. synapse onto secondary neuron which is LMN in the ventral horn of the spinal cord **_Corticobulbar tract_** Carries motor signals from M1/SMA/PMA to LMNs in motor cranial nerve nuclei 1. primary UMN from motor cortices travels down through genu of internal capsule 2. synapse onto secondary LMN in motor cranial nerve nuclei, most of these nuclei are supplied bilaterally from the left/right CBT with two exceptions * facial: upper facial nuclei have bilateral innervation, lower nuclei contralateral only * hypoglossal: primarily contralateral innervation **_Other non-pyramidal pathways include:_** * vestibulospinal – vestibular nuclei project to spinal cord for balance/posture * medial for bilateral head/neck control * lateral for ipsilateral proximal muscles * reticulospinal – two opposing pathways ipsilaterally control lower limb posture/walking * pontine/medial activates extensors * medullary/lateral inhibits extensors * rubrospinal – from red nucleus, complementary pathway to CST with unclear role * tectospinal – superior colliculus projects to SC to coordinate head/neck in visual reflexes

Answer 3

**Dorsal column medial lemniscus** – major sensory pathway for fine touch and proprioception 1. primary sensory neurons with cell bodies in dorsal root ganglia enter the spinal cord through the dorsal roots and form the ascending dorsal columns (gracile/cuneate fasciculi) 2. synapse onto secondary neurons in dorsal column nuclei of medulla 3. secondary neurons decussate as the internal arcuate fibres before travelling up to the thalamus as the medial lemniscus 4. synapse onto tertiary neurons in the VPL nucleus of the thalamus which continue up to S1 **Spinothalamic tract** – sensory pathway for pain and temperature 1. primary sensory neurons with cell bodies in dorsal root ganglia enter spinal cord via dorsal roots and synapse in dorsal horn at same level (or slightly above/below via Lissauer’s tract) 2. secondary neuron immediately decussates through ventral white commissure and ascends in the STT of the lateral funiculus 3. synapse onto tertiary neuron in the VPL nucleus of the thalamus before continuing to S1 Fibres within the STT also have a number of additional cortical connections * reticular formation – alertness due to pain * midbrain – periaqueductal grey for descending pain modulation * hypothalamus – SNS response to pain * limbic system – emotional response to pain

Answer 4

**Spinocerebellar tract** – unconscious proprioception involved in cerebellar function 1. primary sensory neurons synapse in dorsal horn of spinal cord 2. secondary neurons ascend to ipsilateral cerebellum via two pathways: * information from golgi tendon organs travel up ipsilaterally through dorsal SCT and inferior cerebellar peduncle * information from muscle spindles decussates and ascends through the ventral SCT contralaterally before decussating again in the brainstem and entering the ipsilateral cerebellum via the superior peduncle **Trigeminothalamic tract** – sensory information from the face 1. primary sensory neurons with cell bodies in trigeminal ganglia enter the brainstem and synapse in one of three sensory nuclei * mesencephalic (midbrain): proprioception * principal sensory nucleus (pons): fine touch * spinal trigeminal nucleus (medullar): pain and temperature 2. secondary neurons decussate and ascend through the TGT and synapse on tertiary neurons in the VPM nucleus of the thalamus

Answer 5

ischaemic (80%) * embolism, thrombosis, systemic hypotension, cerebral venous sinus thrombosis haemorrhagic (20%) * intracerebral – bleeding within the brain due to ruptured blood vessel * subarachnoid – bleeding outside the brain in subarachnoid space commonly due to hypertension, bleeding disorders, aneurysm, trauma

Answer 6

Neuronal cell death occurs due to excitotoxicity, extracellular glutamate is normally tightly regulated by sodium dependent reuptake systems in neurons and glia which become dysfunctional in ischaemia due to the loss of ATP 1. ischaemia/hypoxia results in inability to maintain normal gradients 2. accumulation of intracellular Na+ and extracellular K+ inhibits glutamate uptake systems and lack of ATP limits conversion of glutamate to glutamine in glia 3. extracellular glutamate levels increase resulting in excess stimulation of NMDA receptors leading to excessive depolarisation – Na+ and Ca2+ entry * Ca2+ increases AMPA receptor expression, causing further excitation * excess K+ is not removed due to lack of ATP, disrupts membrane and leads to excessive depolarisation 4. intracellular calcium overload is toxic and activates enzymes that initiate apoptosis

Answer 7

motor loop – refining movement sequences oculomotor loop – inhibition of saccades to focus via frontal eye field limbic loop – reward and pleasure cognitive loop – movement planning and decision making

Answer 8

Basal ganglia play a key role in motor planning and modulation of movement, the initiation and termination of a movement program is determined by two parallel pathways which are activated/deactivated by neurotransmitters in the striatum acting on medium spiny neurons * direct pathway – initiates movement, increased dopamine from SNpc * indirect pathway – terminates movement, increased ACh from within striatum ***DIRECT PATHWAY*** Activated due to dopamine from SNpc activating D1 neurons and inhibiting D2 neurons 1. excitatory signals descends from motor cortex to D1 neurons 2. D1 neurons inhibit the GPi/SNpr 3. reduces inhibition by the GPi/SNpr on the PPN and thalamus 4. increased output from PPN and thalamus resulting in greater SC output ***INDIRECT PATHWAY*** Activated due to ACh from large aspiny striatal neurons activating D2 neurons via M1 receptors and inhibiting D1 neurons via M2 receptors 1. excitatory signal descends from motor cortex to D2 neurons 2. D2 neurons inhibit the GPe 3. reduces inhibition by the GPe on the STN 4. increased excitatory output from STN on the GPi/SNpr 5. greater inhibition from GPi/SNpr on thalamus and PPN 6. decreased output from PPN and thalamus results in diminished SC output

Answer 9

**_Parkinson’s disease_** – unclear cause results in degeneration of dopaminergic neurons in the SNpc leading to a shift towards ACh in the striatum and the indirect pathway * major clinical signs: bradykinesia, rigidity, resting tremor * pharmacological management delayed as much as possible, mainstay is levodopa + carbidopa to restore dopamine in the striatum while limiting peripheral excess **_Huntington’s disease_** – neurodegenerative disease that primarily affects GABAergic neurons of the indirect pathway and cholinergic aspiny neurons of the striatum * occurs due to autosomal dominant mutation in the huntingtin protein resulting in CAG repeats that produce a polyglutamine tail in the dysfunctional gene product * clinical signs: chorea, decreased muscle tone * managed with antipsychotics, antidepressants, counselling/support

Answer 10

Risk factors – folate deficiency, increased maternal age, family history, obesity, medications rostral end: anencephaly caudal end: spina bifida (varying degrees shown below)

Answer 11

Hydrocephalus = increased CSF within the cranial cavity * primary: non-communicating hydrocephalus caused by obstruction of normal CSF flow, causes may include congenital malformation (e.g. Chiari), inflammation, haemorrhage * secondary: communicating hydrocephalus due to atrophy of the brain with CSF filling the larger ventricular space

Answer 12

_GLIOMAS_ * glioblastoma* – high grade anaplastic glioma which can be either a very aggressive primary cancer or can develop secondarily from a lower grade glioma * astrocytoma* – relatively common with diffuse (worse) or localised (better) forms * oligodendroglioma* – slow growing but highly infiltrating with late presentation * ependymoma* – solid or papillary masses in ventricular system * ganglioglioma* – mixed CNS cancer with neurons and glia typically in superficial temporal lobe *_OTHERS_* * medulloblastoma* – embryonal tumour most common in children, aggressive + rapid spreading * meningioma* – meningeal cancer may be idiopathic or associated with radiotherapy * schwannoma* – benign nerve sheath tumour often in vestibulocochlear nerve

Answer 13

Different consequences/considerations depending on level of injury, major concerns include: * neurogenic shock: loss of sympathetic tone * autonomic dysreflexia: loss of inhibitory spinal signals can result in SNS overstimulation causing uncontrolled hypertension * respiratory compromise: impairment of muscles of breathing

Answer 14

_vestibulocerebellum_ = floculonodular lobe role: position of head in space and subsequent maintenance of balance 1. vestibular information relayed via CN8 and vestibular nuclei 2. enters cerebellum and relayed to vestibulocerebellum via deep nuclei 3. efferents travel back to deep nuclei as well as to vestibular nuclei (vestibulospinal tract) and reticular formation (reticulospinal tract) _spinocerebellum_ = vermis + paravermal zone role: proprioception of the trunk to maintain balance/posture 1. input from ipsilateral SCT via inferior (ventral SCT) and superior (dorsal SCT) peduncles 2. relayed to spinocerebellum via deep cerebellar nuclei 3. efferents travel out to contralateral motor cortices to control muscle movements ipsilateral to the initial input _cerebrocerebellum_ = lateral lobes role: planning of movement patterns for the cortex 1. information from contralateral cortex descends and decussates in pons 2. enters via middle peduncle and relayed to lateral hemispheres by deep nuclei 3. efferents travel out via superior peduncle, decussate in pons and relayed to contralateral motor cortices via thalamus

Answer 15

Schizophrenia is a psychiatric disorder characterised by severe disturbance in perception of reality including thinking, language, behaviour The DSM criteria include: * at least two of the following for one month: **delusions, hallucinations, disorganised speech**, grossly disorganised or catatonic behaviour, negative symptoms * level of functioning is significantly lowered * continuous signs of disturbance for at least 6 months * no other cause – other psychiatric disorder, substance abuse, medical condition positive symptoms – delusion, hallucination, disorganised speech/thought negative symptoms – anhedonia, avolition, alogia, asociality, blunted affect often coincides with cognitive and mood dysfunction as well

Answer 16

It is believed that dysregulation of dopamine signalling plays a significant role in the pathogenesis of schizophrenia, this is supported by the dopamine inhibiting effects of most antipsychotic medications Different dopaminergic pathways are thought to be responsible for different symptoms * mesolimbic: hyperactivity = positive symptoms (D2) * mesocortical: hypoactivity = negative symptoms (D1) * nigrostriatal: extrapyramidal side effects * tuberoinfundibular: hyperprolactinaemia side effects

Answer 17

* modifiable* – substance use/abuse * non-modifiable* – genetics, FHx, paternal age, obstetric complications, childhood trauma, migrant status, urban upbringing

Answer 18

Extrapyramidal side effects – primarily associated with typical or first-generation antipsychotics, these are associated with blockade of D2 receptors in the nigrostriatal pathway (ADAPT) * acute dystonia * akathisia * Parkinsonism (resting tremor, bradykinesia, cogwheel rigidity) * tardive dyskinesia Hyperprolactinaemia – from blockade of the tuberoinfundibular pathway resulting in increased release of prolactin, causes galactorrhea, infertility, menstrual dysfunction, erectile dysfunction Metabolic side effects such as increased appetite, weight gain, insulin resistance, obesity and type 2 diabetes mellitus are more associated with atypical antipsychotics Cardiovascular disease including myocarditis, arrhythmias, hypertension Clozapine has a number of specific side effects that need to be closely monitored particularly agranulocytosis, seizures, and CNS depression

Answer 19

**Persecutory** – affected person feels they are being harassed/stalked/conspired against Delusion of **grandeur** – heightened sense of greatness or influence Delusional **jealousy** – belief that a spouse or partner is being unfaithful Delusion of **control** – belief that somebody else is in control of one’s behaviour/thoughts Delusion of **reference** – thinking everything is related to them e.g. people talking about them

Answer 20

Major depressive disorder (MDD) = mental disorder characterised by a pervasive low mood and loss of interest in normally enjoyable activities The DSM criteria include 5 or more of the following 9 symptoms in the same 2-week period: * **depressed mood** * **loss of interest or pleasure** * change in weight/appetite * insomnia or hypersomnia * psychomotor agitation or retardation * loss of energy or fatigue * feelings of worthlessness/guilt * impaired concentration * thoughts of death or suicidal ideation/attempts Mnemonic is SIGECAPS – sleep changes, interest, guilt, energy, cognition/concentration, appetite, psychomotor, suicide Persistent depressive disorder (PDD/dysthymia) = mood disorder consisting of symptoms of MDD persisting for at least two years in adults or one year in children/adolescents Postpartum depression = symptoms of MDD arising within one month of parturition, may be associated with hormonal imbalances

Answer 21

As with other psychiatric conditions, the underlying cause of depression is likely to be a complex interplay between biological, environmental, and psychological factors, there are several theories of physiological dysregulation thought to be involved: * **_monoamine deficiency theory:_** dysregulation of neurotransmitter systems particularly serotonin, dopamine, and noradrenaline – each of these can be linked to groups of symptoms and have a number of interactions with each other * **_HPA axis dysfunction:_** chronic activation of the HPA axis is implicated, cortisol acts in a feedback loop with the anterior pituitary and hypothalamus + evidence of hippocampal atrophy which may be the basis of dysfunction * associated with neurotransmitter systems * increased risk of cardiovascular disease * **_second messenger system dysfunction_**

Answer 22

Bipolar disorder = mental disorder characterised by episodes of depression and abnormally elevated mood also known as mania/hypomania * mania: euphoria, grandiosity, pressured speech, impulsivity, diminished need for sleep, may include delusion or hallucinations * hypomania: manic symptoms for at least four days but without functional decline and no psychosis * depressive symptoms are in line with those of major depressive disorder _bipolar I_ – at least one manic episode, may be preceded or followed by episodes of depression or hypomania but these are not necessary for diagnosis _bipolar II_ – one or more episode of hypomania and one or more episode of MDD _cyclothymia_ – history of hypomania and depressive symptoms (not qualifying for MDD) over at least two years

Answer 23

(DIGFAST) Distractibility Impulsivity Grandiosity Flight of ideas Agitation (psychomotor) Sleep (decreased need) Talkativeness or pressured speech

Answer 24

The limbic system is a grouping of brain structures which supports a variety of structures including emotion, behaviour, and memory Limbic structures – amygdala, hypothalamus, hippocampus, fornix, nucleus accumbens

Answer 25

Two types of memory: * explicit: semantic = facts, episodic = experiences * implicit = skills and procedural memory Stages of memory formation: * sensory memory holds sensory information for less than one second to help form a smooth sense of the world around you * short term or working memory allows recall for seconds to a minute without rehearsal but has limited capacity, able to be measured * long term memory theoretically has unlimited capacity and is believed to be stored in neurological circuits throughout the entire brain

Answer 26

Papez’s circuit = hypothesised limbic circuit for memory consolidation 1. Entorhinal cortex receives input from all cortical regions and projects to hippocampus 2. Axons from hippocampus form the fornix which spits into two pathways at the anterior commissure * precommissural fibres – septal area + NAc, reward component of memory * postcommissural fibres – 90% of fibres travel to mamillary bodies which are a hypothalamic nucleus, these project to thalamus via mammillothalamic tract 3. Thalamus projects to cingulate cortex, from here the memory can either return to the beginning of the loop for layering/consolidation or is stored by some means

Answer 27

The amygdala consists of a number of nuclei which are thought to be key in linking sensory perception with emotional responses – receives input from sensory fields, insula, memory Two major outputs: * amygdalofugal – decision about movement via learned responses of reward/punishment * stria terminalis – output to hypothalamus for visceral activation when anxious/stressed

Answer 28

Dorsolateral – executive functions including decision making, working memory and planning Ventromedial – emotional responses, self-control, morality

Answer 29

_Psychosocial interventions_ Cognitive behavioural therapy (CBT) is based on the assumptions that mood disorders are accompanied by systematic distortions in thinking and that this interpretation events influences how they affect us Techniques include: * challenging negative beliefs * monitoring thoughts, feelings, and behaviours * activity scheduling * behavioural experiments to disprove negative predictions Other forms of therapeutic counselling include: * psychodynamic therapy – interpretation of mental and emotional processes to help patients find patterns in their emotions/thoughts/beliefs * family therapy – focus on improving communication and resolving conflicts _Non-pharmacological interventions_ * electroconvulsive therapy (ECT) = uses electric current to induce seizures as a treatment for severe depressive and psychotic symptoms * transcranial magnetic stimulation (TMS) = similar premise to ECT using magnetic fields to stimulate neural circuits within the brain * vagal nerve stimulation (VNS) = stimulator device implanted in the chest sends regular pulses of electricity to the brain via the vagus nerve to influence neural networks

Answer 30

The DSM criteria for delirium includes: * disturbance in attention and awareness/orientation * develops over a short period of time and fluctuates throughout the day * decline in cognitive functioning * not explained by another neurocognitive disorder with evidence that the disturbance is a direct consequence of another medical condition or medication/drug use/withdrawal

Answer 31

Toxicity – medications, illicit drugs Metabolic disturbance – hypoglycaemia, hyperglycaemia, ketoacidosis, electrolyte imbalance Neurological – brain tumour, TIA, stroke, meningitis/encephalitis Hypoxia or hypercapnia Acute urinary obstruction Thyrotoxicosis or myxoedema coma

Answer 32

Group of symptoms which are associated with use of multiple serotonergic medications or drugs which can be a medical emergency – results from excess serotonin in the CNS * signs/symptoms: high body temperature, agitation, sweating, mydriasis, seizures, rhabdomyolysis * treatment involves discontinuing medications, serotonin antagonists, active cooling

Answer 33

Personality disorders are pervasive and inflexible patterns of experience and behaviour that deviate markedly from expectations of an individual, categorised into three types: * eccentric/erratic * emotional/reactive * rigid functioning e.g. borderline personality disorder, 10 main criteria (5 needed) including frantic efforts to avoid abandonment, identity disturbance, mood swings, inappropriate intense anger, impulsivity

Answer 34

Mental illness = presence of one or more of the following: * delusions * hallucinations * serious disorder of thought form * severe disturbance of mood * sustained irrational behaviour suggesting any of the above symptoms Person with mental illness is somebody exhibiting a mental illness with reasonable grounds to believe that temporary care and control are necessary for the safety of the person and others Mentally disordered person is someone who has behaviour so irrational that temporary care and control is necessary to protect them or others from serious harm Involuntary admission is a complex process initiated if a person is believed to be mentally or disordered and there are no other less restrictive means of care available * involves multistep series of evaluations by medical professionals * review by mental health inquiry + tribunal

Answer 35

by Arch --\> not sure about pharynx deviation (that aahh test is for uvula CN 10) CN 9 test = gag reflex/swallowing water palsy = loss of taste/sensation to posterior 1/3 of tongue + can't swallow properly