Neurosciences and genetics

Question 1

Macroscopic changes in Alzheimer’s

Answer 1

1) Cortical Atrophy (hippocampus, parahippocampal gyrus, temporal amygdala esp parietal and frontal lobes)
2) low brain weight
3) ventricular dilation
4) Depigmentation of locus coeruleus

Question 2

Microscopic changes in Alzheimer’s (5)

Answer 2

1) extracellular senile plaques (Beta amyloid plaques in grey matter - made from APP, concentrated in synapses)
2) Intracellular neurofilbillary tangles - hyperphosphorylated tau (a MAP)
3) Gliosis - increases in activated microglia and reactive astrocytes near amyloid plaques
4) Degeneration of the nucleus of Meynert (cholinergic neurones in basal forbrain, specifically in the Substantia innominata)
5) Hirano bodies (in hippocampi) - similar to LB but without ubiquitin (Eosinophilic, football shaped inclusion seen in neurons of the brain - also seen in normal ageing) - composed mainly of ACTIN

Question 3

Pineal Gland secretes:

Answer 3

Melatonin

Question 4

Macroscopic pathological findings in Huntington’s (3)

Answer 4

Frontal atrophy
Marked bilateral atrophy of the caudate and putamen = chorea
Enlarged ventricles

Question 5

Microscopic pathological findings in Huntington’s (3)

Answer 5

Neuronal loss and gliosis in the cortex
Neuronal loss in the striatum
Inclusion bodies in the neurons of the cortex and striatum

Question 6

Huntington’s genetics and EEG:

Answer 6

• Trinucleotide repeat - CAG, Chrom 4
• More repeats = more severe illness
• CAG length is more unstable when inherited from the father
• shows anticipation

Normal CAG = repeated 27 times. More in Huntingtons

EEG - Flattened trace

Question 7

Knight’s move inheritance is seen in:

Answer 7

X-linked conditions

Question 8

A phenotype is:

Answer 8

An individual’s observable traits. It results from the interaction between the genotype and the environment.

Question 9

A genotype is

Answer 9

an individual’s collection of genes

Question 10

A haplotype is:

Answer 10

a set of DNA variations, or polymorphisms on a chromosome, that tend to be inherited together

Question 11

A karyotype is:

Answer 11

An individual’s collection of chromosomes.
The process of paring, ordering, and visualising the chromosomes is called karyotyping.

Question 12

Penetrance vs Expressivity

Answer 12

Penetrance describes the proportion of a population of individuals who carry a disease-causing allele who express the related disease phenotype.
Penetrance describes ‘how likely’ it is that a condition will develop
examples of conditions with incomplete penetrance include retinoblastoma and Huntington’s disease

Expressivity describes the extent to which a genotype shows its phenotypic expression in an individual.
Expressivity describes the ‘severity’ of the phenotype
a condition with a high level of expressivity is neurofibromatosis

Question 13

Mitrochondrial inheritance:

Answer 13

Males and females affected, but always being maternally inherited
An affected male does not pass on his mitochondria to his children, so all his children will be unaffected

Question 14

Components of the Basal Ganglia:

Answer 14

1) Striatum (caudate, putamen, nucleus accumbens (CPN)
2) Subthalamic nucleus
3) Globus pallidus
4) Substantia nigra (divided into pars compacta and pars reticulate)

(putamen and globus pallidus are collectively referred to as the lenticular nucleus.)

Question 15

Four main conditions resulting from problems with the BG:

Answer 15

1) Huntington’s chorea (caudate nucleus)
2) Wilson’s disease (copper deposition in basal ganglia)
3) Parkinson’s disease (substantia nigra)
4) Hemiballism (subthalamic nucleus)

Question 16

Sensory Cranial Nerves:

Answer 16

1 - Olfactory
2 - Optic
5 - Trigeminal*
7 - Facial*
8 - Vestibulococlear
9 - Glossopharyngeal*
10 - Vagus*

Question 17

Motor Cranial Nerves:

Answer 17

3 - Occulomotor
4 - Trochlear
5 - Trigeminal*
6 - Abducens
7 - Facial*
9 - Glossopharyngeal*
10 - Vagus*
11 - Accessory
12 - Hypoglossal

Question 18

A young person presenting with atypical psychosis, seizures, and movement abnormalities - diagnosis? 2 main categories?

Answer 18

Autoimmune Encephalitis
1) Antibodies against neuronal cell surface/ synaptic receptors
- usually treatable
2) Antibodies against intracellular antigens
- less responsive to treatment, assoc with tumours (ab’s include anti-Hu and anti-ma)

NB: Learn specific abs
(Anti-NMDAR is the most commonly associated)

Question 19

Small class 1 neurotransmitters include: (1)

Answer 19

Acetylcholine

Question 20

Small class 2 neurotransmitters include: (5) - Amines

Answer 20

Dopamine
Histamine
Serotonin
Noreinephrine
Epinephrine

Question 21

Small class 3 neurotransmitters include: (4) - Amino acids

Answer 21

GABA
Glycine
Glutamate
Aspartate

Question 22

Small class 4 neurotransmitters include: (2)

Answer 22

Carbon monoxide
Nitric oxide

Question 23

Large neurotransmitters include:

Answer 23

Endorphins
Neuropeptides
Oxytocin
Cannabinoids
(Large: CONE)

Question 24

Excitatory neurotransmitters include:

Answer 24

Acetylcholine
Epinephrine
Norepinehrine
Dopamine*
Serotonin
Glutamate

GAS DEN

Question 25

Inhibitory neurotransmitters include:

Answer 25

Dopamine* Glycine GABA

Question 26

Ionotropic Receptors:

Answer 26

mediates its effect by opening an ion channel on the surface of a cell short lived effect specific rosette shaped

Question 27

Metabotropic receptors:

Answer 27

G-protein coupled - when activated imitates a reaction within the cell. Longer lasting effects Diffuse rather than specific effects

Question 28

What is a Circumventricular Organ?

Answer 28

Unique areas of the brain that lack a blood-brain barrier, allowing them to directly interact with substances in the bloodstream. These regions have an endocrine function and play crucial roles in homeostasis by monitoring and responding to changes in body fluid composition. - midline structures around 3rd and 4th ventricles - in contact with CSF and blood - highly permeable capillaries

Question 29

6 circumventricular organs:

Answer 29

3x chemosensory - Area Postrema (vomiting centre) - Vascular Organ of Lateral Terminalis - Subfornical Organ (regulates thirst) VOLT, SO AP 4x secretory - Pineal Body - Posterior pituitary - Median Eminence - Subcommisural Organ SOME PP PB

Question 30

Blood Brain barrier facts:

Answer 30

Endothelial Cells - joined by tight junctions Lipid soluble and small molecules pass through easily Water soluble and large molecules do not pass through easily Fenestrated at the circumventricular organs Increased permeability when inflamed Serves to separate the blood from the BECF (brain extracellular fluid)

Question 31

Lewy Bodies are:

Answer 31

- intracellular protein aggregates primarily composed of alpha-synuclein (in neurones) - present particularly in those areas with high concentrations of dopaminergic neurons such as the substantia nigra and basal forebrain - accumulation leads to neuronal dysfunction and eventual death, resulting in a decrease in dopamine levels.

Question 32

Spongiform changes in the cortex - seen in:

Answer 32

Prion diseases e.g CJD

Question 33

Macroscopic changes in LBD (2)

Answer 33

1) Cerebral atrophy (but less marked than in Alzheimer's) 2) Pallor of the substantia nigra and of the locus coeruleus

Question 34

Microscopic changes in LBD (3)

Answer 34

1) Lewy bodies - intracellular deposits consisting mostly of alpha synuclein and get degraded by ubiquitin - NB can also be found in Amygdala in Alzheimer's 2) Neurofibrillary tangles and senile plaques 3) Neuronal loss and gliosis are usually restricted to brainstem regions, particularly the substantia nigra and locus ceruleus.

Question 35

3 lobes of the cerebellum

Answer 35

Flocculonodular lobe Anterior lobe Posterior lobe

Question 36

3 functional divisions of the cerebellum:

Answer 36

1) vestibulocerebellar - balance, spatial orientation 2) Spinocerebellum - fine-tuned body movements (Vermis and intermediate zones - midline) 3) cerebrocerebellum (lateral hemispheres) - planning movement, conscious assessment of movement

Question 37

4 anatomical areas of the cerebellum:

Answer 37

Vermis - assoc with bodily posture and locomotion Folia - pleat-like gyri on surface Arbor Vitae - "tree of life" - cerebellar white matter Cerebellar peduncles - 3 pairs, used to communicate with the nervous system AV CP F V

Question 38

Lesions in Dominant Parietal Lobe (5):

Answer 38

1) Gerstmann's Syndrome - includes agraphia, acalculia, finger agnosia, left-right disorientation 2) Language disorders including aphasia 3) Alexia - inbility to read 4) Anomia - can't find right word 5) impaired writing and mathematics

Question 39

Lesions in Non-dominant Parietal Lobe (7):

Answer 39

1) Spatial disorientation including limbs 2) Hemispatial neglect on opposite side 3) Prosopagnosia (can't recognise faces) 4) Constructional Aphasia 5) Dressing Apraxia 6) Topographical disorientation 7) Anosognosia (inability to acknowledge illness)

Question 40

Kluver-Bucy syndrome

Answer 40

Amygdala lesion - bilateral temporal lobes Hypersexuality, hyperorality, hyperphagia, visual agnosia, blunted affect with apathy

Question 41

Balint's Syndrome

Answer 41

Bilateral Parieto/Occipital lesion Can't direct eyes to specific point in visual field (occulomotor apraxia) Optic ataxia - difficulty interacting with objects in visual field Simultanagnosia - can't perceive multiple objects at once

Question 42

Variant CJD vs Sporadic CJD (6)

Answer 42

Duration: v - longer, >1 year S - shorter, months Symptoms v - psychiatric and behavioural, later neurology S - neurological MRI and EEG v - Pulvinar sign ( bilaterally hyperintense pulvinar nuclei of the THALAMUS on FLAIR or diffusion-weighted MRI images), generalised slowing on EEG but nothing specific S - Bilateral anterior basal ganglia high signal, EEG - biphasic and triphasic waves 1-2/sec Origin and age of onset v - infected meat products, younger people 25-30 S - genetic mutation, older people 55-65 Note: Detection of 14-3-3- proteins in the CSF is highly specific for CJD and can be particularly helpful in diagnosing sporadic CJD

Question 43

8 candidate genes for schizophrenia and which chromosome:

Answer 43

DISC1 (c.1) Dysbindin DTNBP1 (c.6) Neuregulin NRG1 (c.8) COMT (c.22) G72 (c.13) RGS4 (c.1) DAOA (c.13) DRD2 (c.11)

Question 44

COMT in schizophrenia

Answer 44

- Role in dopamine metabolism esp in prefrontal cortex. clears dopamine from synapses - Strongest association gene - Role in degradation of catecholamines - Low activity of COMT = assoc with schiz and OCD - Chrom 22 (assoc w/ velocardiofacial disorder - 20% of these patients have psychosis)

Question 45

Neuregulin in schizophrenia

Answer 45

- NRG1 = growth factor that stimulates neuron development and differentiation - Increased neuregulin signaling in schizophrenia may suppress the NMDA receptor, leading to lowered glutamate levels - Chromosome 8

Question 46

Dysbindin in schizophrenia

Answer 46

- Expression decreased in schizophrenia - may reduce glutamate levels - chromosome 6 - MOST CONSISTENT CANDIDATE GENE in schizophrenia

Question 47

DISC 1 in schizophrenia

Answer 47

- DISC1 encodes a multifunctional protein that influences neuronal development and adult brain function - Disrupted in schizophrenia - Chromosome 1

Question 48

Define x3 (Affinity, Potency, Efficacy) of drug in relation to receptors

Answer 48

1) Affinity - How avidly the drug binds to the receptor 2) Potency - The concentration or dose of a drug required to produce 50% of the drug's maximal effect. Potency depends on both the affinity of a drug for its receptor, and the efficacy with which drug-receptor interaction is coupled to response 3) Efficacy - Also referred to as 'intrinsic activity' of a drug is the ability of the drug to elicit a response when it binds to the receptor

Question 49

3 genes of importance in EOFAD (Early Onset Familial Alzheimer's Disease)

Answer 49

N.B very rare - only 1-6% Alzheimer's cases PSEN-1 - 30-70% (Chrom 14) - most common APP - 10-15% (Chrom 21) PSEN-2 5% (Chrom 1) The presenilins are components of enzymes that cleave APP to produce amyloid beta fragments of different lengths. Mutations in the presenilins account for the majority of genetic early-onset Alzheimer's cases. Autosomal Dominant

Question 50

Glial cytoplasmic inclusion bodies visible in the CNS, found in Multi-System Atrophy

Answer 50

Papp-Lantos Bodies

Question 51

Large, dark-staining aggregates of proteins in neurological tissue found in FTD

Answer 51

Pick Bodies

Question 52

Round, concentrically laminated, pale eosinophilic cytoplasmic inclusions (aggregates of alpha-synuclein)

Answer 52

Lewy Bodies, found in PD and LBD

Question 53

1) Acidophilic, stellate inclusions in giant cells 2) Concentrically laminated inclusions (up to 50µm) in giant cells Both found in sarcoidosis and berylliosis

Answer 53

1) Asteroid bodies 2) Schaumann cells

Question 54

Inactivated X chromosome - dark staining mass in contact with the nuclear membrane

Answer 54

Barr Bodies

Question 55

Alcoholic hyalin - eosinophilic intracytoplasmic inclusions in hepatocytes: intermediate filaments, predominantly prekeratin

Answer 55

Mallory Bodies - found in alcoholic hepatitis, alcoholic cirrhosis, Wilson's disease, primary-biliary cirrhosis

Question 56

Palisaded lamellated membranous cytoplasmic bodies seen in macrophages

Answer 56

Zebra bodies - Niemann-Pick disease, Tay-Sachs disease, or any of the mucopolysaccharidoses

Question 57

Nuclei of damaged cells with bound anti-nuclear antibodies which become homogeneous and loose chromatin pattern

Answer 57

LE bodies (hematoxylin bodies) - seen in lupus

Question 58

Palisades of nuclei at the end of a fibrillar bundle, seen in Schwannoma

Answer 58

Verocay bodies

Question 59

Kayser-Fleischer rings

Answer 59

Seen on the cornea in wilson's disease

Question 60

Kuru plaques

Answer 60

Composed partly of a host-encoded prion protein, sometimes seen in CJD

Question 61

Gyri of Parietal lobe (3):

Answer 61

1) Angular - maths, language, cognition (anomic aphasia if lesion - AAA) - area affected in GERSTMANN SYNDROME 2) Post-central - touch 3) Supramarginal - empathy PArietal lobe is SUPER

Question 62

Gyri of temporal lobe (2):

Answer 62

1) Fusiform - Face and body recognition, word and number recognition (visual) - involved in facial recognition 2) Superior temporal - Language Comprehension (Wernicke's area), and sensation of sound. **Reduced gray matter volumes in the superior temporal gyrus (STG) have been reported in patients with schizophrenia**

Question 63

Gyri of Frontal lobe (2):

Answer 63

1) precentral- voluntary movement and control 2) superior frontal - laughter and self-awareness

Question 64

Gyri related to hippocampus (2):

Answer 64

1) Parahippocampal - surrounds the hippocampus - involved in memory, can be asymmetrical in schizophrenia 2) Dentate: Formation of episodic memory

Question 65

Lingual and cingulate gyri (location and function):

Answer 65

1) Lingual - occipital lobe, dreaming and visual word recognition 2) Cingulate - adjacent to the corpus collosum, for emotion, memory and learning

Question 66

Broca's vs Wernicke's:

Answer 66

Brocas: Broadmanns 44, 45, frontal lobe, motor Damage causes BROKEN words i.e non-fluent aphasia. Expressive aphasia - have understanding but can't express it (can be caused by occlusion of MCA) Wernicke's: Broadmanns 22, posterior part of the superior temporal gyrus in the dominant hemisphere (next to primary audotory area) Damage causes fluent aphasia - normal words but nonsensical - WACKY. Receptive aphasia - can't understand speech

Question 67

Two main types of Acetylcholine receptors:

Answer 67

Nicotinic - ionotropic, stimulated by ACh and nicotine - increases dopamine Muscarinic - metabotropic, stimulated by muscarine and Ach (5 subtypes)

Question 68

4 major pathways of dopamine:

Answer 68

Mesolimbic (VTA to NA) -Reward pathway Mesocortical (VTA to cortex) - hypofunction = Neg sx Nigrostriatal (SN to striatum) (Blockage = ESPEs) Tuberoinfundibular (Hypothalamus to pituitary) - (blockage = Increased PROLACTIN)

Question 69

What is the Ventral Tegmental Area?

Answer 69

The ventral tegmental area (VTA) is a group of dopaminergic cells located in the midbrain that are involved in reward and pleasure. Start of both the mesolimbic and mesocortical pathways Along with the NA the VTA plays acentral role in reward processing and therefore drug addiction.

Question 70

Acetylcholine 1) Source 2) breakdown 3) re-uptake 4) function 5) sites of release

Answer 70

1) Choline and Acetyl co-A - catalysed by choline acetyltransferase (SITE: nucleus of Meynert in Basal Forebrain) 2) metabolite - choline. Catalysed by Acetylcholinesterase 3) no re-uptake, degraded choline is recycled 4) arousal modulation, learning, thirst, memory, REM, pain, perception 5) forebrain, brainstem

Question 71

5 types of Muscarinic (ACh) receptors:

Answer 71

M1 - Exocrine function, inhibits dopamine release, affects cognitive function and seizure activity M2 and M3 - mainly involved in smooth muscle contraction. M2 causes bradycardia, M3 inhibits dopamine release M4 and M5 - ONLY in CNS - facilitate dopamine release.

Question 72

Lyonisation:

Answer 72

Process of X-inactivation Normal in females - inactivates one of X chrom, so genetic info not duplicated Inactivated X chromosome = Barr body Affects phenotype in Kleinfelter's (XXY)

Question 73

Genomic Imprinting:

Answer 73

Refers to a situation where a piece of DNA can behave differently depending on whether it is inherited from the mother or the father Eg: Angelmann's vs Prader-Willi syndrome - both due to deletion of 15q but A = from mother, PW = from father

Question 74

Chromosomes with small p arms, that can be involved in Robertsonian translocations:

Answer 74

Acrocentric Chromosomes

Question 75

A chromosome with equally sized p and q arms is referred to as:

Answer 75

Metacentric

Question 76

RNA differs from DNA in 4 ways:

Answer 76

1) single stranded 2) much shorter 3) Base U instead of T 4) nucleotides contain ribose, rather than deoxyribose

Question 77

3 main types of RNA:

Answer 77

1) Ribosomal RNA (rRNA) is what ribosomes are made up of and provides a place for mRNA and tRNA to attach during translation. 2) Messenger RNA (mRNA) is the RNA that carries information from DNA from the nucleus to the ribosomes. 3) Transfer RNA (tRNA) bring amino acids to the ribosome during translation

Question 78

Transcription vs translation of RNA:

Answer 78

Transcription is the synthesis of RNA from a DNA template (i.e copying) Uses RNA polymerases 3 steps - initiation, elongation, termination Translation refers to the synthesis of polypeptides (proteins) from mRNA. Translation takes place on ribosomes in the cell cytoplasm, where mRNA is read and translated into the string of amino acid chains that make up the synthesized protein. Uses mRNA, tRNA and rRNA Same 3 stages as above

Question 79

Dysarthria - 5 types

Answer 79

Spastic (UMN) Flaccid (LMN) Hypokinetic (extrapyramidal) Hyperkinetic (extrapyramidal) Ataxic (cerebellar)

Question 80

Spastic Dysarthria (features, conditions, localisation)

Answer 80

Explosive and forceful, at a slow rate Pseudobulbar palsy, spastic hemIplegia UMN

Question 81

Flaccid Dysarthria (features, conditions, localisation)

Answer 81

Breathy, nasal, imprecise consonants Myesthenia Gravis LMN

Question 82

Hypokinetic vs Hyperkinetic dysarthria

Answer 82

Both: extrapyramidal Hypo: slow, quiet, monotonous, tremor - seen in PD Hyper: strained, stoppages at inappropriate moments, variable rate - seen in tardive dyskinesia, Huntingtons, Sydenham's chorea

Question 83

Ataxic dysarthria (features, conditions, localisation)

Answer 83

rapid, slurred, mono-pitched - seen in Friedrich's ataxia, alcohol abuse - cerebellum

Question 84

3 types of white matter tracts:

Answer 84

Projection tracts: Connect higher centers of the brain (those beyond the brain stem) with lower centers (e.g. brainstem and spinal cord) Commissural tracts: Connect the two hemispheres together Association tracts: Connect regions of the same hemisphere. Note: Long association connect separate lobes together whereas short association fibers connect separate gyri of the same lobe

Question 85

5 examples of projection white matter tracts:

Answer 85

Corticospinal and corticobulbar - connect motor cortex to brain stem and spinal cord Corona Radiata - from cortex to brainstem via the internal capsule Internal capsule - Major conduit of fibers to and from the cerebral cortex Geniculocalcarine Tract (optic radiation) - connects LGN to occipital (primary visual) cortex

Question 86

2 types of commisural white matter tracts

Answer 86

1) Corpus Collosum - largest white matter bundle, connects two cerebral hemispheres 2) Anterior/ commissure AKA pre-commissure - crosses through the lamina terminalis (lateral wall of 3rd ventricle). Connects temporal lobes and amygdala and olfactory bulbs. Its anterior fibers connect the olfactory bulbs and nuclei; its posterior fibers connect middle and inferior temporal gyri

Question 87

7 types of Association White Matter Tracts:

Answer 87

6 = Faciculus (faSIXulus) 1 = Cingulum (1 = SINGLE-um) 1) Cingulum - connects cingululate gyrus and enthorinal cortex (limbic system) 2 and 3) Superior and Inferior Orbitofrontal Faciculus - connect frontal and occipital lobes 4 ) Superior Longitudinal faciculus - Connects the frontal lobe cortex to parietal, temporal, and occipital lobe cortices (the largest association bundle) 5) Inferior longitudinal (occipitotemporal) faciculus - Connects temporal and occipital lobe cortices 6) Uncinate Faciculus - Connects the orbital and inferior frontal gyri of the frontal lobe to the anterior temporal lobe, connecting orbitofrontal cortex with parts of the limbic system 7) Arcuate - connects Brocas to Wernickes

Question 88

Localise the lesion: - Hemiparesis of the contralateral foot and leg (more severely than the arm) - Sensory loss of the contralateral foot and leg - Transcortical motor aphasia (lack of fluency with intact comprehension and repetition) - Abulia, disinhibition, executive dysfunction, anosognosia (lack of insight), emotional lability, frontal release signs (re-emergence of primitive reflexes)

Answer 88

Anterior cerebral artery (ACA occlusion) - suspect if frontal signs

Question 89

Localise the lesion: - Hemiparesis of the contralateral face and limbs - Sensory loss of contralateral face and limbs - Dysphasia / aphasia (when dominant hemisphere affected) (Broca and Wernicke) - Contralateral neglect - Homonymous hemianopia or quadrantanopia without macular sparing (macular vision not preserved) - Dorsolateral prefrontal dysfunction

Answer 89

Middle Cerebral Artery occlusion

Question 90

Localise the lesion: - *Alexia without agraphia* (left side) - can't read, can still write - Contralateral loss of pain and temperature sensation - Contralateral hemianopia (with macular sparing) - Prosopagnosia - Ipsilateral cranial nerve defects (V, VIII, IX, X, & XI) - Horner's syndrome

Answer 90

Posterior Cerebral Artery occlusion - suspect if visual field issues

Question 91

What type of stroke? - presents with either isolated hemiparesis, hemisensory loss or hemiparesis with limb ataxia - strong association with hypertension - common sites include the basal ganglia, thalamus and internal capsule

Answer 91

Lacunar Stroke Note: Internal capsule is innervated by the Circle of Willis

Question 92

Syndrome and blood supply? Ipsilateral CN III palsy Contralateral weakness of upper and lower extremity

Answer 92

Weber's syndrome (branches of the posterior cerebral artery that supply the midbrain)

Question 93

Syndrome and blood supply? Ipsilateral: facial pain and temperature loss Contralateral: limb/torso pain and temperature loss Ataxia, nystagmus Note: if have ipsilateral facial paralysis and deafness...?

Answer 93

Posterior inferior cerebellar artery (lateral medullary syndrome, Wallenberg syndrome) POST a MEDal to Wallenberg) If have ipsilateral facial paralysis and deafness - Anterior inferior cerebellar artery (lateral pontine syndrome) ANTs in the PONd are DEAF

Question 94

Locked In Syndrome is caused by a lesion in which artery?

Answer 94

Basilar artery/ lesion in the pons or medulla

Question 95

Amaurosis fugax is caused by a lesion in which artery?

Answer 95

Retinal/ ophthalmic artery

Question 96

Codons:

Answer 96

Three base nucleotides together Code for amino acids 64 possible codons (triplet sequences)

Question 97

The 3 trisomies that survive to birth are:

Answer 97

Trisomy 21 (Down's syndrome) - 1 in 800 births Trisomy 18 (Edwards syndrome) - 1 in 6000 births (E for EIGHTEEN) - severe intellectual disability, babies often die soon after birth. Kidney malformations, upturned nose, webbing of second and third toes, and clubbed feet (rocker bottom). Trisomy 13 (Patau syndrome) - 1 in 10,000 births - Severe intellectual disability, babies often die soon after birth. Most have congenital heart malformations, anophthalmia and a cleft palate.

Question 98

SYNDROME: short stature (usually apparent by age 5), webbed neck, widely spaced nipples. Absent periods and incomplete breast development are common. Most affected are infertile (although assisted reproduction is an option). Intelligence tends to be normal although rates of intellectual disability are increased.

Answer 98

Turner Syndrome - 1/5000 female births 45X, or 45XO

Question 99

SYNDROME: Considerable variability but most able to live independently and form normal adult relationships. Although intellectual disability is not the norm, some degree of speech and language / educational issue is not uncommon. May be taller than expected. Normal sexual development and fertility is expected (although infertility can occur). Low set ears are associated.

Answer 99

Kleinfelter's Syndrome (XXY) - 1-2/1000 male births

Question 100

4 conditions to know that result from a structural abnormality in the chromosomes (deletions):

Answer 100

- 22q11 Deletion Syndrome (DiGeorge Syndrome/Velocardiofacial Syndrome) - a deletion in the long arm of chromosome 22 (22q11.2) - Cri-du-Chat Syndrome - caused by a deletion in the short arm of chromosome 5 - Prader-Willi Syndrome - typically caused by a deletion in the long arm of chromosome 15 inherited by father - Angelman Syndrome - typically caused by a deletion in the long arm of chromosome 15 inherited by mother

Question 101

Classic Hakim's triad of normal pressure hydrocephalus (communicating hydrocephalus):

Answer 101

Gait instability Urinary incontinence Dementia (wet, wobbly, wacky)

Question 102

Which syndrome: Bilateral posterior parietal/ occipital lobe dysfunction - triad of: 1) optic ataxia 2) occulomotor apraxia 3) simultanagnosia

Answer 102

Balint's syndrome (BILATERAL - B)

Question 103

How does the amygdala function in the context of fear?

Answer 103

It acts to enhance the fight-or-flight response through its connections with the hypothalamus and periaqueductal grey matter.

Question 104

Which term describes heritable phenotype changes that do not involve alterations in the DNA sequence?

Answer 104

Epigenetic Note: Epigenetics involves genetic control by factors other than an individual's DNA sequence. Epigenetic changes can switch genes on or off and determine which proteins are transcribed.

Question 105

1) The nearer two loci are on a chromosome the less likely they are to be separated by crossing over. The measure of the distance between loci is called the: 2) A measure of the likelihood of two loci being within a measurable distance of each other is called the:

Answer 105

1) Recombination fraction - can vary from 0-50% 2) LOD score - >3 is considered evidence for linkage, and a LOD score of <-2 excludes linkage.

Question 106

2 types of gene mapping:

Answer 106

1) Genetic linkage mapping - uses techniques such as pedigree analysis. 2) Physical mapping - a technique used to find the order and physical distance between DNA base pairs by DNA markers

Question 107

A phenomenon whereby the symptoms of a genetic disorder become apparent at an earlier age as it is passed on to the next generation.

Answer 107

Anticipation

Question 108

5 main structures of the Papez circuit:

Answer 108

1) Hippocampus 2) Mamillary Bodies (part of hypothalamus. Involved in memory and spatial orientation) 3) Anterior Nucleus of the Thalamus (relay station) 4) Cingulate Cortex (Associated with decision-making, empathy, and emotion.) 5) Enthorinal Cortex (in the parahippocampal gyrus - Functions as an interface between the hippocampus and neocortex and is involved in memory and navigation.)

Question 109

What is Gerstmann's Syndrome?

Answer 109

Dominant Parietal Lobe dysfunction: agraphia, acalculia, finger agnosia, and RL disorientation

Question 110

What percent of Caucasians are estimated to be homozygous for the isoform alcohol dehydrogenase ADH1B*1?

Answer 110

85-95% i.e slow metabolisers of alcohol - no flushing reaction

Question 111

Which gene is considered to have the greatest impact on the risk of alcohol dependency?

Answer 111

ADH1B (also ALDH2)

Question 112

What is the most common cause of genetic LD?

Answer 112

Fragile X syndrome - trinucleotide repeat disorder CGG a genetic syndrome characterised by mental retardation, an elongated face, macrocephaly large protruding ears, and large testicles (in men), "cluttered" speech They tend to be shy, avoid eye contact, and have difficulties reading facial expressions. They often display stereotypic movements such as hand flapping. Abnormal speech It is an X-linked dominant disorder caused by the amplification of a CGG repeat in the 5 untranslated region of the fragile X mental retardation 1 gene (FMR1). MORE REPEATS = MORE SEVERE Males = affected more severely as only have 1 X chromosome

Question 113

Planum Temporale (in Sylvian Fissure) Asymmetry is reduced in which 2 conditions: (Bonus: what is the anterior border of the Planum Temporale called?)

Answer 113

Schizophrenia and Dyslexia Involved in complex auditory processing, contains Wernicke's area Heschl's gyrus (transverse temporal gyrus) is the anterior border of the planum temporale - contains Broadmann's 41

Question 114

Which Syndrome: Elfin like features, social disinhibition, and abnormal friendliness towards strangers. Very sensitive hearing is also seen (hyperaccusis). Advanced verbal skills, speech is articulate but superficial (referred to as cocktail party speech). Cardiac issues (most common being supravalvular Aortic Stenosis)

Answer 114

William's Syndrome - 7q11 deletion Can be detected by FISH Deletion takes place during meiosis 1/20000

Question 115

Where are the following synthesised: 1) GABA 2) serotonin 3) Norepinephrine

Answer 115

1) Nucleus Accumbens 2) Raphae nucleus (brainstem) and endochromaffin cells (GI tract) 3) Locus Ceruleus

Question 116

2 main measures of twin concordance rates:

Answer 116

1) Pairwise - This rate represents the proportion of twin pairs in which both individuals express a particular trait or condition. Especially useful when comparing MZ and DZ twins to gauge genetic component of a condition (calculated by number of twin pairs where both twins have the trait/ total number of twin pairs) 2) Probandwise - This rate considers only those twin pairs where at least one twin manifests the trait. It's essentially the likelihood that the second twin will also have the trait if the first one does. Can be more useful in rare conditions

Question 117

What is Nissl Substance?

Answer 117

A Nissl body is a large granular body found ONLY in neurons. They consist of rough endoplasmic reticulum (with free ribosomes) and are the SITE OF PROTEIN SYNTHESIS

Question 118

Concordance of autism in MZ and DZ twins:

Answer 118

Monozygotic concordance = 60-90% (Castelbaum, 2020) Dizygotic concordance = closer to 30% (Frazier, 2014)

Question 119

Which street drugs block SERT?

Answer 119

SERT = monoamine transporter that takes up serotonin Blocked by MDMA, amphetamine, cocaine MAC is SERTain

Question 120

The most well known ATP-driven transporter at the BBB is:

Answer 120

P-glycoprotein

Question 121

DAT vs SPECT scans:

Answer 121

A DAT scan specifically focuses on measuring the density and integrity of dopamine transporters in the brain. SPECT, on the other hand, is a broader imaging technique that measures cerebral blood flow, metabolism, and neuroreceptor activity in the brain.

Question 122

Low levels of which metabolite are seen in depression, aggression and suicidality?

Answer 122

5-hydroxyindoleactic acid (5-HIAA) - a metabolite of serotonin

Question 123

Utilisation behaviours result from damage to which brain area?

Answer 123

Frontal lobe: 'Utilization behaviour' (UB) refers to the automatic elicitation of instrumentally correct, yet highly exaggerated and or inappropriate motor responses to environmental cues and objects i.e loss of normal inhibitory control

Question 124

3 cardinal features of Multi-System Atrophy: 3 ways it presents:

Answer 124

MSA is a Parkinsons-Plus Syndrome. 3 features: 1) Parkinsonism 2) Autonomic failure 3) Cerebellar ataxia PAC 3 presentations: 1) Striatonigral degeneration (mainly Parkinson features) - responds poorly to Levodopa 2) Shy-Drager Syndrome (mainly autonomic features) 3) Olivopontocerebellar atrophy (mainly cerebellar features) Microscopic findings: - Pappp-Lantos Bodies (alpha-synuclein inclusions in oligodendrocytes found in the substantia nigra, cerebellum, and basal ganglia). Macroscopic features: - greenish discolouration and atrophy of the putamen - pallor of substantia nigra - cerebellar atrophy

Question 125

EEG frequencies between 1-12Hz (3 types)

Answer 125

DTA: (DTs caused by Alcohol) 1-4Hz - Delta 4-8Hz - Theta 8-12Hz - Alpha Delta - slow wave sleep (s.III), babies. If present in awake adults = pathology (D - DON'T want when awake, D for Deep sleep) Theta - Drowsy/ sleeping adults (s.I), meditation, young children. If ++ when awake = pathology Alpha - meditation, when relaxed and when eyes closed but awake. They disappear with drowsiness, concentration, stimulation, visual fixation.

Question 126

EEG frequencies between 12-100Hz (3 types)

Answer 126

SBG: 12-14Hz - sigma 12-30Hz - Beta (OVERLAP 12-14) 30-100 - Gamma Sigma - (SLEEP SPINDLES) - Sleep (s.II), seen along with k-complexes Beta - busy, concentrating Gamma - very advanced meditation

Question 127

EEG: Reduced Alpha and Beta, increased delta and theta

Answer 127

Alzheimer's

Question 128

EEG: diffuse slowing

Answer 128

Encephalopathy Normal ageing (focal/ diffuse - if focal, left temporal region) Delirium - along with reduced alpha, increased theta and delta END

Question 129

EEG: low voltage, no alpha (flattening)

Answer 129

Huntington's

Question 130

EEG: Hyperactive trace, fast

Answer 130

DTs

Question 131

EEG: early on there is non specific slowing, later periodic biphasic and triphasic synchronous sharp wave complexes superimposed on a slow background rhythm

Answer 131

CJD (sporadic only!) - S for Slowing and Sporadic and Synchronius Sharp waves

Question 132

6 Types of epilepsy and their EEG findings: West Syndrome:

Answer 132

1) TYPICAL absence (petit mal) - generalized 3Hz spike wave 2) ATYPICAL absence - slow (<2.5Hz ) generalized spike-and-wave (A for absence, low loltage. A before T - Atypical = lower Hz) 3) Focal (Partial) - focal spikes 4) Myoclonic - Generalized 3-6 Hz polyspike and wave discharge 5) Generalised Tonic-Clonic - EEG often obscured by artifact (movement). Generalized fast rhythmic spikes are seen in the tonic stage. Bursts of spikes and after-coming slow waves are synchronous with clonic jerks. A postictal period of irregular slow activity follows 6) Atonic (drop attack) - Generalized spike-and-wave is typical, with atonia at the time of the slow wave West Syndrome: Infantile spasms Hypsarrythmia on EEG, chaotic high amplitude polyspike waves

Question 133

Thre recognisable clinical syndromes under the umbrella of FTD:

Answer 133

1) Behavioural-Variant Frontotemporal Dementia (bvFTD) (Pick's disease) 2) Semantic-variant PPA (svPPA) - anterior temporal lobe affected 3) Non-fluent-variant PPA (nfvPPA) PPA - primary progressive aphasia

Question 134

3 neurodegenerative diseases that overlap clinically with FTD:

Answer 134

1) corticobasal degeneration (CBD) 2) progressive supranuclear palsy (PSP) 3) amyotrophic lateral sclerosis (ALS)

Question 135

What is corticobasal degeneration (CBD)?

Answer 135

Rare progressive neurodegenerative disease that overlaps with FTD Involves cerebral cortex and basal ganglia Movement symptoms are ASYMMETRIC and include apraxia, aphasia, parkinsonism and alien hand syndrome

Question 136

3 main proteins associated with FTD:

Answer 136

1) TAU (MAPT gene - c.17) 2) TDP-43 (genes: GRN, C9orf72, VCP, TARDBP) 3) FUS

Question 138

What is Hardy-Weinberg Equilibrium? The 5 assumptions of HW equilibrium:

Answer 138

The genetic variation in a population will remain constant from one generation to the next in the absence of disturbing factors 1) No mutations 2) No gene flow/ migration 3) Random (chance) mating 4) No genetic drift (i.e large enough pop prevents chance mutations causing mass change) 5) no natural selection (i.e differences in alleles have no evolutionary advantages or disadvantages)

Question 139

Define endophenotype Who introduced the concept of endophenotypes?

Answer 139

Measurable components, unseen by the unaided eye, along the pathway between disease and distal genotype, representing simpler clues to genetic underpinnings than the disease syndrome itself Gottesman and Shields (1973)

Question 140

5 types of single-gene (monogenic/ Mendelian) inheritance:

Answer 140

AD AR X-linked dom X-linked rec Y linked

Question 141

Which cell component: Modifies, sorts, and packages macromolecules for cell secretion (exocytosis) or use within the cell

Answer 141

Golgi Apparatus

Question 142

Which cell component: Consists of rough endoplasmic reticulum (with free ribosomes) and is the site of protein synthesis

Answer 142

Nissl Substance

Question 143

Which cell component: Contains the nucleolus and chromosomes, responsible for maintaining the integrity of genes and controlling the activities of the neuron by regulating gene expression

Answer 143

Nucleus

Question 144

Which cell component: Is involved in lipid synthesis, metabolism of carbohydrates, regulation of calcium concentration, drug detoxification, and attachment of receptors on cell membrane proteins

Answer 144

Smooth endoplasmic reticulum

Question 145

Which Cell component: Powerhouses of the cell involved in energy production through the process of oxidative phosphorylation

Answer 145

Mitochondria

Question 146

Which Cell Component: Provide structural support, involved in cell movement and transportation of organelles within the cell cytoplasm

Answer 146

Microfilaments and microtubules

Question 147

Which component of the cell: Contain hydrolytic enzymes for digestion of macromolecules and are involved in breaking down cellular waste and pathogens

Answer 147

Lysosomes

Question 148

A gap in the myelin sheath of a nerve, between adjacent Schwann cells, which facilitates the rapid conduction of nerve impulses is known as:

Answer 148

Node of Ranvier

Question 149

What method is particularly useful for detecting submicroscopic deletions that may not be visible on a standard karyotype.?

Answer 149

FISH - Fluorescence In Situ Hybridization It is ideal for confirming suspected microdeletion syndromes, such as 22q11.2 deletion syndrome, because it can target specific genomic regions known to be associated with the clinical presentation.

Question 150

What is the name given to "punch drunk syndrome" or dementia often suffered by those who have experienced head injuries?

Answer 150

Dementia Pugilistica - now generally referred to as chronic traumatic encephalopathy (CTE) Abnormal accumulation of Tau in neurons and glia in an irregular, focal, perivascular distribution and at the depths of cortical sulci (tau tangles seen) - specifically at the SEPTUM PELLUCIDUM which separates the lateral ventricles

Question 151

Autotopagnosia:

Answer 151

Inability to orient parts of the body Left Parietal lobe lesion

Question 152

Anosognosia

Answer 152

Inability to recognise own condition/ illness Right hemisphere lesion

Question 153

Phonagnosia

Answer 153

Inability to recognize familiar voices R Temporal lobe or sulcus lesion PHONe WERNICKE - Temporal

Question 154

Simultanagnosia (subtype of visual agnosia)

Answer 154

Inability to appreciate two objects in the visual field at the same time BILATERAL occipital-parietal lesions (Balint's)

Question 155

Prosopagnosia (subtype of visual agnosia)

Answer 155

Inability to recognise familiar faces, often referred to as 'face blindness' Typically associated with damage to the fusiform gyrus, a region in the brain's occipital and temporal lobes that plays a crucial role in face perception F for Fusiform, F for Faces.

Question 156

Astereoagnosia:

Answer 156

Inability to recognize objects by touch Typically arises from damage to the somatosensory cortex, particularly in the parietal lobe, which is responsible for processing tactile information from the body. (you can't TOUCH an ASTEROID)

Question 157

Greek Warrior-Helmet Appearance is associated with:

Answer 157

Wolf-Hirschhorn syndrome 4p Deletion syndrome (WOLF (4 letters) = WARRIOR)

Question 158

Dopamine breakdown is by which enzymes?

Answer 158

COMT and MAO

Question 159

Heritability is:

Answer 159

the proportion of phenotypic (phenotype is the set of observable characteristics or traits of an organism) variance attributable to genetic variance. This means that if a condition has a heritability of 0.80 then 80% of the variance of that condition seen in a population is attributable to genetic variation. The remaining 20% is attributable to environmental factors. It tells us nothing about individuals

Question 160

Where is the Entorhinal cortex?

Answer 160

A subregion within the parahippocampal gyrus

Question 161

Myelination:

Answer 161

Myelin - fat and water, Produced by glial cells (oligodendrocytes in CNS) Begins at 14 weeks gestation Last area to myelinate is frontal lobe

Question 162

Progressive supranuclear palsy pathology:

Answer 162

Macroscopic changes include:- - Pallor of substantia nigra (with sparing of the locus coeruleus) N.B ALSO SEEN IN PD - Mild midbrain atrophy "hummingbird sign" seen on structural imaging - Atrophy of the superior cerebellar peduncles - Discolouration of the dentate nucleus Microscopic changes include:- - Gliosis - Neurofibrillary tangles and tau inclusions in both astrocytes and oligodendrocytes (coiled bodies), particularly in the substantia nigra, subthalamic nucleus and globus pallidus.

Question 163

Hoover's Sign is:

Answer 163

When a patient with suspected functional (non-organic) paralysis is asked to lift the unaffected leg, the examiner's hand placed under the affected leg feels pressure as the patient unconsciously uses the affected leg to help lift the healthy one. This sign indicates that the strength in the affected leg is essentially normal, suggesting that the paralysis may not be due to a physical cause.

Question 164

Kernig's sign is:

Answer 164

a clinical sign that is positive when a patient lying flat has pain and resistance on passive knee extension when the hip is flexed at a 90-degree angle. It is associated with meningitis and is not demonstrated in the scenario provided.

Question 165

Ideational vs Ideomotor apraxia:

Answer 165

Ideational: An inability to follow a sequence of actions in the correct order. Ideomotor: An inability to carry out learned tasks when given the necessary objects; the patient cannot use an object correctly on command due to a disruption in the ability to plan or execute motor functions, despite understanding the use of the object and having the physical ability to perform the action (may use object for wrong task)

Question 166

In order of frequency the most common brain tumours in adults are:

Answer 166

1) Metastatic tumours 2) Glioblastoma multiforme 3) Anaplastic astrocytoma 4) Meningioma

Question 167

In order of frequency the most common brain tumours in children are:

Answer 167

1) Astrocytoma 2) Medulloblastoma 3) Ependymoma

Question 168

Purines vs Pyramidines:

Answer 168

2x purines = AG (PURe As Gold) 3x pyramidines = CUT (longer word, more of them)

Question 169

What are the areas situated around the Sylvian fissure (lateral sulcus) known as?

Answer 169

perisylvian language area

Question 170

What divides the frontal and parietal lobes above from the temporal lobe below?

Answer 170

Sylvian Fissure (Lateral sulcus)

Question 171

What separates the frontal from the parietal lobe

Answer 171

The central sulcus (the fissure of Rolando)

Question 172

Which bundle of association fibres provides a connection between the frontal and temporal lobes and plays a central role in the repetition of language?

Answer 172

Arcuate Fasciculus - note: lesion here causes conduction aphasia

Question 173

3 foramen of Middle cranial fossa and what do they transmit?

Answer 173

1) Foramen spinosum - middle meningeal artery 2) Foramen ovale - Mandibular division of trigeminal nerve 3) Foramen lacerum - the small meningeal branches of the ascending pharyngeal artery and emissary veins from the cavernous sinus

Question 174

2 foramen in the posterior cranial fossa and what do they transmit:

Answer 174

Foramen Magnum - spinal cord Jugular foramen - CN 9, 10, 11

Question 175

4 hormones that control appetite:

Answer 175

1) Neuropeptide Y is produced by the hypothalamus and increases appetite (hYpothalamus - Y) 2) Ghrelin is produced mainly by the gut and increases appetite (G = Growling stomach) 3) Leptin is produced by adipose tissue and reduces appetite (L = LESS hungry) 4) Cholecystokinin (CCK) is produced mainly by the gut and reduces appetite

Question 176

During stress, which 2 hormones are released from the paraventricular nucleus of the hypothalamus?

Answer 176

Corticotropin-releasing hormone (CRH) Arginine vasopressin (AVP).

Question 177

What does the DEX suppression test measure?

Answer 177

The response of the adrenal glands to ACTH.

Question 178

Fluent speech + impaired repetition + intact comprehension = which type of aphasia?

Answer 178

Conduction aphasia Defining feature: repetition Considered a disconnection syndrome caused by a lesion in the acruate fasciculus

Question 179

Cerebrospinal fluid passes from the subarachnoid space back to the vascular system via:

Answer 179

The subarachnoid villi

Question 180

CSF vs Plasma. CSF has:

Answer 180

Reduced: Protein content Glucose Cholesterol pH Calcium Potassium Same: Sodium More: Chloride Magnesium pCO2

Question 181

Which syndrome: bilateral dysfunction or damage to the medial temporal lobes of the brain

Answer 181

Kluver-Bucy Syndrome (assoc with Alzheimer's, FTD, trauma, herpes, bilateral temporal lobe infarction) The medial temporal regions, particularly the **amygdala** and hippocampus, play a pivotal role in emotion, memory, and behaviour, and their bilateral malfunction can lead to a distinctive clinical presentation: Hyperorality Docility Visual Agnosia Hyperphagia Altered sexuality

Question 182

Where is the lesion: Language Disturbances: Since the dominant temporal lobe typically houses Wernicke's area, its dysfunction can lead to problems with language comprehension (Wernicke’s aphasia). Memory Difficulties: Can specifically affect verbal memory and the ability to remember and understand language-based information. Auditory Verbal Agnosia: Difficulty recognizing spoken words.

Answer 182

Dominant temporal lobe

Question 183

Where is the lesion: Broca's aphasia, executive dysfunction, impaired working memory, mood changes, motor apraxia

Answer 183

Dominant frontal lobe

Question 184

Where is the lesion: Impaired Recognition of Non-Verbal Sounds: Such as music or environmental sounds (auditory agnosia). Emotional Recognition Issues: Trouble interpreting emotional cues in spoken language, like tone of voice. Visual Memory Deficits: Problems may arise with non-verbal memory, such as remembering faces or places.

Answer 184

Non-dominant temporal lobe

Question 185

Types of serotonin receptors: All G-protein receptors, bar one.

Answer 185

5-HT1A - play a role in inhibiting serotonin release, can enhance sexual behaviours as dopamine can act freely 5-HT1B - autoregulatory function. They modulate 5-HT reuptake and modulate 5-HT synthesis and release 5-HT2 (A and C): 5-HT2C - linked to anorgasmia (drugs can target this receptor in an attempt to mitigate SSRI-induced anorgasmia) 5-HT2A - also linked to above by inhibiting dopamine release 5-HT3 - the ONLY ligand-gated serotonin receptor. Most associated with nausea 5-HT7 - assoc with circadian rhythms

Question 186

3 Catecholamines present in the body:

Answer 186

Dopamine Adrenaline Noradrenaline All derive from amino acid TYROSINE

Question 187

When would you use WGS (whole genome sequencing)?

Answer 187

This is the most comprehensive method for detecting both known and unknown genetic variations across the entire genome.

Question 188

When would you use karyotyping?

Answer 188

For identifying large chromosomal abnormalities but lacks the resolution to detect small genetic changes or novel mutations at the nucleotide level.

Question 189

Which disease primarily affects the small blood vessels in the white matter of the brain which become blocked by thickening of blood vessel walls? It is characterized by migraine headaches and multiple strokes, which progresses to dementia - what are the genetics?

Answer 189

CADASIL (c.19, NOTCH 3 gene Autosomal Dominant) cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

Question 190

Genetics of Dementia with Lewy Bodies and PD:

Answer 190

Dementia with LB: SNCA - c.4 - AD (codes for alpha synuclein) GBA and APOEe4 increase risk but not direct causes Most cases are sporadic PD: Most cases are idiopathic SNCA - c.4 - AD (codes for alpha synuclein) - found in several families with PD Parkin gene - c.6 Also LRRK2, and PINK1

Question 191

Genetics of Familial frontotemporal dementia

Answer 191

AD C9orf72 - (c.9) most common mutation Also, PGRN (*progranulin*) and MAPT (both c.17) Between 20-50% of cases of FTD are familial

Question 192

Genetics of Late Onset Alzheimer's

Answer 192

APOE4 - c.19- involved in breakdown of amyloid plaques This is called a risk-factor gene because it increases a person's risk of developing the disease. However, inheriting an APOE4 allele does not mean that a person will definitely develop Alzheimer's. Some people with an APOE4 allele never get the disease, and others who develop Alzheimer's do not have any APOE4 alleles. Less involves is another gene - SORL1 (c.11)

Question 193

How does APOE affect Alzheimer's risk (>65)

Answer 193

APOE2 - protective APOE3 - neutral APOE4 - increases risk Homozygotes for APOE4 - 10-30x risk Heterozygotes = 3 x risk Each allele lowers age of onset by 10 years

Question 194

Aneuploidy refers to:

Answer 194

Abnormal number of chromosomes e.g trisomies (21, 13, 18) Monosomies (Turners - XO) Kleinfelters (XXY) Triple Mostly result from the nondisjunction of chromosomes during meisosis 1

Question 195

Sleep stages:

Answer 195

1-3 = non-REM 4 = REM

Question 196

Sleep Stage 1:

Answer 196

Non-REM Approx 5%, 1-7 mins EEG: Theta waves 4-7Hz "dozing off", hypnic jerks

Question 197

Sleep Stage 2:

Answer 197

Non-REM Approx 45%, 10-25 mins - longest stage EEG: Theta waves, K complexes and sleep spindles (short bursts of 12-14Hz activity) Everything slows down, body temp drops, K complexes play role in memory consolidation

Question 198

Sleep Stage 3:

Answer 198

Non-REM Approx 15% (20-40 mins) Deepest stage of sleep - high waking threshold. Growth, repair, immune system strengthening, night terrors (stage 3 into 4), sleepwalking, bed wetting EEG: Delta waves (0-4Hz) - "3D"

Question 199

Sleep Stage 4:

Answer 199

REM sleep Approx 15% (10-60mins) EEG: mixed, but mostly Beta, sawtooth pattern seen High dream activity. When nightmares happen. The percentage of REM sleep decreases with age. REM increases through the night, and Non-REM decreases

Question 200

Which enzyme cleaves APP to produce non-toxic protein fragments

Answer 200

Alpha-secretase N.B: Gamma and Beta secretase also cleave APP but into shorter, stickier fragments called B-amyloid, which form insoluble plaques

Question 201

Which syndrome: Normal for the first 12 months. Regression and loss of skills from around 18 months onwards. Hand-wringing movements are the most common feature. Associated learning disability is profound. Affects girls almost exclusively

Answer 201

Rett Syndrome Xq28 (Mutation in the MECP2 gene) X-linked Dominant Mostly sporadic

Question 202

Which syndrome: Abdominal swelling, cherry red spot, feeding difficulties

Answer 202

Niemann Pick Disease (A and B) 11p15

Question 203

Which Syndrome: Tend to be tall and strong but with no increase in testosterone, . Sexual development is normal. Tend to have lower mean intelligence. Early links with criminality have not been supported, often asympromatic, increased ADHD/ Autism

Answer 203

Jacob's Syndrome 47 XYY

Question 204

Which condition: Hamartomatous tumours affect various organs including the brain. 80% suffer with epilepsy. Autism, ADHD, and

Answer 204

Tuberous Sclerosis Genetically heterogeneous, linkage to 9q and 16p

Question 205

Which Syndrome: Pronounced self injurious behaviour, self hugging, and a hoarse voice

Answer 205

Smith-Magenis syndrome 17p11

Question 206

Which syndrome: Self mutilation, dystonia and writhing movements and results from a disturbance in the metabolism of purines? There is also intellectual disability, behavioural problems and it exclusively affects males (X-linked recessive)

Answer 206

Lesch-Nyhan Syndrome Xq26-27 - mutations in the HPRT1 gene there is an overproduction and accumulation of uric acid resulting in hyperuricemia, nephrolithiasis, gouty arthritis, and subcutaneous tophi.

Question 207

Which Syndrome: Cleft palate, cardiac problems, and learning disabilities. A higher rate of psychiatric disorders is also seen

Answer 207

Velocardiofacial syndrome (Di George syndrome) 22q (deletion)

Question 208

Which condition: Characteristic cry like a meowing kitten, hypotonia, hypertelorism, a down-turned mouth, and microcephaly

Answer 208

Cri du chat 5p deletion

Question 209

Three types of glial cell (4 altogether)

Answer 209

Macroglia (astrocytes and oligodendrocytes) Ependymal cells Microglia Astrocytes have numerous functions including structural support, repair of nervous tissue, providing nourishment to neurons, contributing to the blood brain barrier, neurotransmission, and vasomodulation. There are two main types, protoplasmic and fibrous. Oligodendrocytes are responsible for the formation of myelin sheaths. Ependymal cells line the ventricular system and are involved with CSF circulation and fluid homestasis in the brain. Specialised ependymal cells call choroid plexus cells are responsible for CSF production. Microglia are the immune cells of the CNS. NB a gitter cell is a microglial cell that has engulfed infectious material.

Question 210

In the cerebrum, what is the: 1) fornix 2) insula

Answer 210

1) Bridge of white matter inferior to the corpus callosum; links regions of the limbic system ('emotional' brain) together. Major output tract of the hippocampus (to mamilliary bodies - Papez Circuit) 2) Region of the cerebrum deep within the lateral sulcus; processes information associated with hearing and equilibrium

Question 211

What is the embryonic origin of the thalamus, hypothalamus, optic nerves and third ventricle?

Answer 211

Diencephalon THO-N 3 Note: the largest structure is the thalamus

Question 212

What is the embryonic origin of the pons, cerebellum and sup part of 4th ventricle?

Answer 212

Metencephalon PC Sup4

Question 213

What is the embryonic origin of the medulla and inf part of 4th ventricle?

Answer 213

Myencephalon (My My My Myx4 Medulla Lower 4th V)

Question 214

What is the embryonic origin of the midbrain and cerebral aqueduct?

Answer 214

Mesencephalon (The Middle of the Aqueduct could get MESsy)

Question 215

What is the embryonic origin of the cerebral cortex, basal ganglia and lateral ventricles?

Answer 215

Telencephalon CC, BG, LV =TEL-E

Question 216

In the diencephalon, what are the: 1) Mammillary bodies 2) Pineal gland 3) thalamus

Answer 216

1) A relay point most notably involved in memory. When damaged people tend to get a 'diencephalic amnesia' characterised by anterograde amnesia. The mamillary bodies are atrophied in Korsakoff's syndrome (reduced activity of transketolase). The mamillary bodies also contain cells which note the direction of the head and function like a compass to aid navigation 2) Unpaired structure (only one per brain). Main function is secretion of melatonin which regulates circadian rhythms 3) 80% of the diencephalon. Major relay point and processing centre for all sensory impulses (excluding olfaction). Comprised of numerous nuclei and is involved in most functional areas (motor, emotional, memory, visual, auditory)

Question 217

Damage to which area causes Wernicke and Korsakoff Syndrome?

Answer 217

Medial thalamus and mammillary bodies of the hypothalamus

Question 218

Which Syndrome? Affected individuals are cortically blind but are unaware of this and deny they have a problem (anosognosia). It often presents as the patient starts falling over furniture as they can't see. Affected individuals believe they can still see and describe their environments in detail but are wrong in their description (confabulation).

Answer 218

Anton's syndrome (aka Anton-Babinski syndrome). Damage to the Occipital Lobe

Question 219

What does Ubiquitin do?

Answer 219

Proteins are tagged for degradation with a small protein called ubiquitin. They will then be degraded by the proteasome.

Question 220

1) Agonists 2) Antagonists of GABA-A, GABA-B

Answer 220

GABA-A - Agonists: ethanol benzodiazepines z-drugs barbiturates Antagonists: Flumazanil GABA-B - Agonists: baclofen GHB

Question 221

6 cranial nerve reflexes:

Answer 221

1) Pupilliary light reflex S: 2 M:3 2) Accommodation reflex S: 2 M:3 3) Jaw jerk S: 5 M:5 4) Corneal reflex S: 5 M:7 5) Vestibulocochlear S: 8 M: 3, 4, 6 6) Gag reflex S: 11 M: 10

Question 222

How many autosomes do we have?

Answer 222

44 - 22 pairs 23rd pair = sex chromosomes

Question 223

Synthesis, take-up and breakdown of serotonin:

Answer 223

1) Starts with L-tryptophan (can cross BBB, unlike serotonin) 2) Hydroxylation to 5-hydroxytryptophan catalysed by tryptophan hydroxylase 3) Decarboxylation of 5-hydroxytryptophan to serotonin (5-hydroxytryptamine) by L-aromatic amino acid decarboxylase Taken up by SERT Broken down by MAO and then **aldehyde dehydogenase** to 5-Hydroxyindoleacetic acid (5-HIAA).

Question 224

Which mutation: charactarised by a single nucleotide substitution in the DNA sequence that converts an amino-acid-encoding codon into a stop codon. This mutation truncates the protein, often resulting in loss of function due to the early termination of translation.

Answer 224

Nonsense mutation

Question 225

3 types of stop Codons:

Answer 225

TAA/ UAA TAG/ UAG TGA/ UGA (note: T becomes U in RNA)

Question 226

Strychnine is an antagonist of which inhibitory neurotransmitter?

Answer 226

Glycine. Glycine acts to hyperpolarise neurons and thus inhibit their activity. By blocking this action, strychnine leads to an overactivity of the CNS, resulting in the symptoms of strychnine poisoning such as muscle spasms, convulsions and potentially death due to respiratory failure.

Question 227

3 occular features of MS: 3 types and prevelance:

Answer 227

1) Optic neuritis (unilateral visual loss) 2) Internuclear ophthalmoplegia (diplopia and/or nystagmus due to a problem arising from the midbrain) 3) Ocular motor cranial neuropathy (e.g. sixth nerve palsy) 1) Prim Prog: 5-10% 2) relaps-remitt: 20-30% 3) sec. prog (most common): 60%

Question 228

The resting membrane potential of a neuron is due to the high concentration of which extracellular ion? And what is the threshold for an action potential?

Answer 228

Sodium (-70mV - high Na outside cell compared to K inside cell) AP - at -55mV

Question 229

3 types of point mutation: 4 types of chromosomal mutation:

Answer 229

POINT: Insertion Deletion Substitution CHROMOSOMAL: Inversion Deletion Duplication Translocation

Question 230

Histamine production and metabolism

Answer 230

Histamine is produced from the amino acid histidine by a histidine decarboxylase and is metabolised by the combined actions of histamine methyltransferase and MAO.

Question 231

4 types of histamine receptors (where found and function)

Answer 231

H1 CNS tissue, smooth muscle, and endothelium Vasodilation, bronchoconstriction, pain and itching from stings H2 Parietal cells in stomach Stimulates gastric acid secretion H3 Central and peripheral nervous tissue Decreases the release of other neurotransmitters (serotonin, noradrenaline, acetylcholine) H4 Basophils Chemotaxis (cellular movement)

Question 232

3 conditions associated with Copy Number variations:

Answer 232

Schizophrenia, autism, ideopathic LD

Question 233

4 cranial nerves that arise from the medulla:

Answer 233

9, 10, 11,12

Question 234

4 cranial nerves that arise from the pons:

Answer 234

5, 6, 7, 8

Question 235

2 cranial nerves that arise from the midbrain:

Answer 235

3, 4

Question 236

What are the origins of CN 1 and 2?

Answer 236

1) Olfactory - telencephalon 2) Optic - diencephalon (Optic = di = 2 eyes Offactory = what is that TErrible Smell = Tel)

Question 237

Brushfield spots are associated with which syndrome?

Answer 237

Down Syndrome - small white/grey spots in periphery of iris When seen in normal children they are referred to as Kunkmann-Wolffian bodies. They occur in 35-78% of newborn infants with Down syndrome.

Question 238

Hepatolenticular degeneration is better known as:

Answer 238

Wilson's Disease

Question 239

4 major tauopathies are:

Answer 239

Alzheimer's Pick's (frontotemporal dementia) Progressive supranuclear palsy Cortiocobasal degeneration

Question 240

5 trinucleotide repeat disorders to know:

Answer 240

Fragile X - CGG c.12 (X-dom) Myotonic dystrophy - CTG c.19(AD) Huntington's - CAG c.4 (AD) Friedrich's Ataxia - GAA c.9 (AR) Spinocerebellar ataxia - also CAG (AD) NB: known as DYNAMIC mutations

Question 241

In schizophrenia, what causes: 1) psychosis 2) negative symptoms

Answer 241

1) increased dopaminergic activity in the striatum 2) decreased dopaminergic activity in the frontal lobe

Question 242

2 main observations of the dopamine hypothesis:

Answer 242

it is possible to induce a psychotic episode in healthy subjects with pharmacological dopamine agonist all effective antipsychotic drugs provide at least some degree of D2-type dopamine receptor blockade.

Question 243

3 structures in the BG that make up the striatum:

Answer 243

Putamen Caudate Nucleus Accumbens

Question 244

2 structures in the BG that make up the lentiform nucleus:

Answer 244

Globus Pallidus and Putamen

Question 245

Which hormone inhibits the secretion of thyroid-stimulating hormone and growth hormone in the brain, and is produced in both the pancreas and the hypothalamus?

Answer 245

Somatostatin

Question 246

Cerebellar Ataxia, Hunter's Syndrome and Lesch-Nyann syndrome demonstrate which type of inheritance?

Answer 246

X-linked recessive

Question 247

Vitamin D resistant rickets, Rett syndrome, Fragile X syndrome demonstrate which type of inheritance?

Answer 247

X-linked dominant

Question 248

Phenylketonuria, homocystinuria, Hurler's syndrome, galactosaemia, Tay-Sach's disease, Friedrich's ataxia, Wilson's disease, cystic fibrosis demonstrate which type of inheritance?

Answer 248

Autosomal Recessive

Question 249

Conditions where there are a variety of genetic defects all causing the same condition are said to demonstrate:

Answer 249

Heterogeneity

Question 250

What is the significance of a mutation in the Promoter Region?

Answer 250

Promoter regions are crucial for the initiation of transcription, which involves the synthesis of RNA from a DNA template. Mutations in this area can significantly impact gene expression and can contribute to various diseases, including Alzheimer's. A mutation in the promoter region could affect the binding of transcription factors or RNA polymerase, thus altering gene expression.

Question 251

3 divisions of the embryonic brain (5 subdivisions):

Answer 251

1) Forebrain (Prosencephalon) subdivided into: - telencephalon (forms cerebrum) - diencephalon 2) Midbrain - mesencephalon 3) Hindbrain (rhombencephalon) (includes medulla, pons, cerebellum) - metencephalon - myencephalon

Question 252

What is the name given to an autonomously replicating, extrachromosomal circular DNA molecule, distinct from the normal bacterial genome and nonessential for cell survival under nonselective conditions?

Answer 252

Plasmid

Question 253

What is the term given to the spherical embryonic mass of blastomeres formed before the blastula and resulting from cleavage of the fertilized ovum.

Answer 253

Morula

Question 254

What is the difference between mosaics and chimeras?

Answer 254

Mosaics and chimeras are animals that have more than one genetically-distinct population of cells. The distinction between these two forms is quite clearly defined, although at times ignored or misused. In mosaics, the genetically different cell types all arise from a single zygote, whereas chimeras originate from more than one zygote. Mosaics = single zygote Chimeras = Couple of zygotes

Question 255

What sort of agonists have been shown in animals to increase striatal dopamine release?

Answer 255

Cannabinoid

Question 256

A modest (10-20%) elevation in which receptor density is seen in schizophrenia independent of the effects of antipsychotic drugs?

Answer 256

Striatal D2/3 receptor density

Question 257

Right vs Left frontal lobe lesions:

Answer 257

Left: more likely to be associated with depression, particularly if the lesion involves the dorsolateral portion of prefrontal cortex. Right: associated with impulsivity, disinhibition, and aggression.

Question 258

Which molecule, when elevated, has been implicated in BBB breakdown in Alzheimer's disease?

Answer 258

Beta-Amyloid

Question 259

Hypermetabolism of the orbitofrontal area is associated with:

Answer 259

OCD Also seen in caudate, thalamus, prefrontal cortex, and anterior cingulate Hence this is the area targeted by transcranial magnetic stimulation in OCD

Question 260

What has been the most consistent EEG finding associated with clozapine use?

Answer 260

Decreased alpha, increased theta, increased delta

Question 261

Lithium vs Lamotrigine EEG findings:

Answer 261

Lithium = increased x4 (A, B, D, T) Lamotrigine = decreased x 4

Question 262

1) Horizontal transmission is seen in: 2) Vertical transmission is seen in:

Answer 262

1) AR conditions 2) AD conditions

Question 263

What is horizontal inheritance pattern?

Answer 263

A horizontal inheritance pattern is one where a trait or disorder is seen in siblings but not in their parents or offspring. This pattern is typically indicative of an autosomal recessive mode of inheritance.

Question 264

What is Locus Heterogeneity?

Answer 264

Locus heterogeneity refers to the situation when a disorder or trait is caused by mutations in genes at different chromosomal loci. E.G Alzheimer's - Presenilin 1, 2 and APP

Question 265

What is genomic imprinting?

Answer 265

Genomic imprinting refers to a situation where a piece of DNA can behave differently depending on whether it is inherited from the mother or the father.

Question 266

What component of the BBB actively transports certain drugs and potential toxins out of the brain and back into the bloodstream, thereby playing a protective role and influencing drug pharmacokinetics in the brain?

Answer 266

P-glycoprotein

Question 267

Which Dopamine receptors are referred to as D1-like receptors? What is activated by these receptors?

Answer 267

D1 and D5 (all g-protein coupled) Activation of this family of receptors activates adenylyl cyclase (aka adenylate cyclase), increasing the intracellular concentration of the second messenger cyclic adenosine monophosphate (cAMP). D1 is the most abundant

Question 268

Which dopamine receptors are referred to as D2-like receptors? What is activated by these receptors?

Answer 268

D2, D3, D4 (all g-protein coupled) Activation of this family of receptors inhibits the formation of cAMP by inhibiting the enzyme adenylyl cyclase.

Question 269

Monozygotic vs Dizygotic concordance of autism:

Answer 269

Monozygotic concordance = 60-90% Dizygotic concordance = closer to 30% (Frazier, 2014) The molecular genetics is still poorly understood. Copy number variations (CNVs) are implicated along with a number of candidate genes.

Question 270

Monozygotic vs Dizygotic Concordance of schizophrenia:

Answer 270

Schizophrenia demonstrates incomplete penetrance which is evidenced by: monozygotic concordance of approximately 50% dizygotic concordance of 17% (Gottesman, 1972).

Question 271

5 Macroscopic pathological features of schizophrenia:

Answer 271

Ventricular enlargement Subtle reductions in total gray matter volume Reduced brain volume (up to 5%) Reductions in gray matter volume Reduced asymmetry (planum temporale)

Question 272

2 functional findings in the brain of those with schizophrenia:

Answer 272

Decreased activation of prefrontal cortex (hypofrontality) Increased activation of temporal regions during hallucinations

Question 273

Which syndrome? Hyperphagia (excessive eating) and obesity Short stature Delayed puberty, hypogonadism, infertility Learning difficulties Compulsive behaviour (e.g. skin picking)

Answer 273

Prader-Willi Syndrome

Question 274

GABA is synthesised from:

Answer 274

Glutamate

Question 275

Which spinal cord lesion: bilateral spastic paresis, loss of proprioception and vibration sensation and limb ataxia

Answer 275

Subacute combined degeneration of the spinal cord

Question 276

Which spinal cord lesion: flacid paresis of the intrinsic hand muscles with loss of pain and temperature sensation

Answer 276

Syringomyelia

Question 277

A lesion where will cause superior homonymous quadrantanopia?

Answer 277

Contralateral parts of visual pathway - inferior optic radiation (Temporal Meyers Loop)

Question 278

Where is the lesion: Spatial attention defIcits, disinhibition, poor judgement of time and sequence, Expressive Deficits in Non-verbal Communication, Prosody Changes i.e problems with the rhythm and inflection of speech, which may make verbal communication seem monotone or inappropriate to the context.

Answer 278

Non-dom frontal lobe

Question 279

Toxoplasmosis vs Progressive multifocal leukoencephalopathy

Answer 279

Both: HIV, neuro symptoms T: multiple brain lesions with ring enhancement P: widespread demyelination

Question 280

Which condition: accounts for around 30% of cerebral lesions associated with the Epstein-Barr virus CT: single or multiple homogenous enhancing lesions

Answer 280

Primary CNS lymphoma

Question 281

Toxoplasmosis vs lymphoma

Answer 281

T: multiple lesions L: single lesions T: Ring/ nodular enhancement L: solid/ homogenous enhancement T: Thalium SPECT negative L: Thallium SPECT positive

Question 282

Which condition: most common fungal infection of CNS - headache, fever, malaise, nausea/vomiting, seizures, focal neurological deficit CSF: high opening pressure, India ink test positive CT: meningeal enhancement, cerebral oedema meningitis is typical presentation but may occasionally cause a space occupying lesion

Answer 282

Cryptococcus

Question 283

Which condition is the most common HIV related brain disease?

Answer 283

Toxoplasmosis

Question 284

How does HIV spread to the brain?

Answer 284

Infected macrophages

Question 285

Which condition: AD, neurocutaneous condition - Ash-leaf spots - Shagreen patches - angiofibromas - *retinal* haemartomas - subungal fibromata - polycystic kidneys - developmental delay and LD - epilepsy

Answer 285

Tuberous sclerosis

Question 286

Which condition: AD neurocutaneous condition - Cafe-au-lait spots - axillary/groin freckles - acoustic neuromas and other CNS tumours* - Iris haemartomas

Answer 286

Neurofibromatosis * NF2 only

Question 287

Which artery causes the lesion: ipsilateral oculomotor palsy and contralateral weakness of the upper and lower extremity

Answer 287

Branches of the posterior cerebral artery that supply the midbrain

Question 288

Friedrich's Ataxia vs Subacute Combined Degeneration of the Spinal Cord (Vit B12 and Vit E deficiency):

Answer 288

Same 3 tracts affected: Lateral corticospinal tracts Dorsal columns Spinocerebellar tracts Same 3 main symptoms (motor and sensory): 1. Bilateral spastic paresis 2. Bilateral loss of proprioception and vibration sensation 3. Bilateral limb ataxia Friedrich's Ataxia also has cerebellar ataxia → other features e.g. intention tremor

Question 289

Which condition? 1. Ipsilateral spastic paresis below lesion 2. Ipsilateral loss of proprioception and vibration sensation 3. Contralateral loss of pain and temperature sensation

Answer 289

Brown-Sequard syndrome (spinal cord hemisection) 1. Lateral corticospinal tract 2. Dorsal columns 3. Lateral spinothalamic tract

Question 290

Which condition: 1. Flacid paresis (typically affecting the intrinsic hand muscles) 2. Loss of pain and temperature sensation

Answer 290

Syringomyelia 1. Ventral horns 2. Lateral spinothalamic tract

Question 291

Which condition: 1. Bilateral spastic paresis 2. Bilateral loss of pain and temperature sensation

Answer 291

Anterior spinal artery occlusion 1. Lateral corticospinal tracts 2. Lateral spinothalamic tracts

Question 292

2 spinal cord lesions that result in motor lesions only:

Answer 292

Amyotrophic lateral sclerosis (motor neuron disease) - affects both upper (corticospinal tracts) and lower motor neurons and results in a combination of upper and lower motor neuron signs Poliomyelitis affects anterior horns resulting in lower motor neuron signs

Question 293

What are the motor (efferent) tracts in the spinal cord?

Answer 293

Pyramidal: lateral corticospinal, anterior corticospinal Extrapyramidal

Question 294

Which lobe is commonly affected in Herpes Simplex Encephalitis?

Answer 294

Temporal (and inferior frontal)

Question 295

Which condition: fever, headache, psychiatric symptoms, seizures, vomiting, focal features e.g. aphasia

Answer 295

HSV encephalitis (Note: HSV-1 is responsible for 95% of cases)

Question 296

What 5 investigations should be done and what would they show in HSV encephalitis?

Answer 296

LP: CSF - lymphocytosis, elevated protein PCR for HSV CT: medial temporal and inferior frontal changes (e.g. petechial haemorrhages) - normal in one-third of patients MRI is better EEG pattern: lateralised periodic discharges at 2 Hz

Question 297

Treatment and prognosis of HSV encephalitis:

Answer 297

Treatment: intravenous aciclovir The prognosis is dependent on whether aciclovir is commenced early. If treatment is started promptly the mortality is 10-20%. Left untreated the mortality approaches 80%

Question 298

In the context of Hebbian theory, what outcome is expected when there is repetitive simultaneous activation of connected neurons?

Answer 298

The synaptic connection between the neurons strengthens

Question 299

4 things that define narcolepsy:

Answer 299

- Excessive sleepiness - Cataplexy (a sudden loss of muscle tone triggered by emotions) - Hypnagogic hallucinations - Sleep paralysis

Question 300

How does prion disease work?

Answer 300

Normal PrP (Prion protein) = PrPC (alpha-helical structure) Abnormal PrP = PrPSc (much of the alpha-helical structure is replaced by a beta-sheet structure) PrPSc can change adjacent normal Prion proteins into PrPSc's = how it spreads PrPSc is resistant to protease and therefore cannot be broken down in the body.

Question 301

4 tests done in diagnosing narcolepsy: What neuropeptide hormone is often deficient in patients with narcolepsy?

Answer 301

- Multiple sleep latency test - Polysomnogram - Sleep deprived EEG - Cerebrospinal fluid analysis Narcolepsy has been associated with hypocretin deficiency (AKA orexin)

Question 302

Which mineral causes vesicles packed with neurotransmitter to fuse with the synaptic membrane and release the neurotransmitter into the synaptic cleft?

Answer 302

Calcium

Question 303

What is Diffusor Tensor Imaging?

Answer 303

A type of MRI which is a method for estimating the paths water takes as it diffuses through white matter, and so showing white matter tracts

Question 304

What is fMRI?

Answer 304

It examines changes in blood oxygen level dependent signal (i.e deoxygenation of Hb) as a proxy measure of neural activity

Question 305

In which part of the brain would you find medium spiny neurones?

Answer 305

Striatum These neurons play a critical role in the processing of movement-related and reward-related signals, making them essential for understanding conditions like Parkinson's disease and Huntington's disease. Clinically, insights into the function and dysfunction of medium spiny neurons in the striatum can aid in the development of treatments for these and other neurological disorders.

Question 306

In which part of the brain would you find Purkinje cells?

Answer 306

Cerebellum - these cells coordinate voluntary movements

Question 307

What type of cells mainly make up the hippocampus?

Answer 307

Pyramidal cells

Question 308

What type of cell makes up 60-70% of all neurones in the cortex?

Answer 308

Pyramidal cells The rest are non-pyramidal cells (granular/stellate cells). There are two types of non-pyramidal cell, one excitatory (glutamate), and one inhibitory (GABA).

Question 309

The statistical method used to determine the pattern of inheritance of a particular trait within a family is known as:

Answer 309

Segregation Analysis

Question 310

What study method is used in genetics to test for a non-random association between a specific allele and a trait or disease?

Answer 310

Association Studies

Question 311

CB1 and CB2 are what kind of receptor? Which is more common in the CNS?

Answer 311

G-Protein coupled, primarily coupling to inhibitory G proteins CB1 - more in CNS - particularly abundant in cortex, basal ganglia, hippocampus, and cerebellum. CB2 - less in CNS - primarily present in microglia and vascular elements.

Question 312

What are the 2 main endocannabinoids and what receptors do they have effects at?

Answer 312

1) anandamide (arachidonoyl ethanolamide) - partial agonist at CB1 and CB2 (low efficacy agonist at CB1 receptors and a very low efficacy agonist at CB2 receptors). 2) 2-arachidonoyl glycerol (2-AG) - high efficacy agonist for both CB1 and CB2 receptors.

Question 313

What type of molecule is THC (delta-9-tetrahydrocannabinol)?

Answer 313

Exogenous cannabinoid

Question 314

What is the estimated heritability for: 1) ADHD 2) Autism 3) Schizophrenia 4) Bipolar

Answer 314

1) 70-80% 2) 80-90% 3) 80% 4) 60-80%

Question 315

What gene is most consistently implicated in ADHD?

Answer 315

DRD4 - Dopamine D4

Question 316

What is the estimated heritability for: 5) Anorexia 6) Alcohol dependence 7) OCD 8) Major depression

Answer 316

5) 35% 6) 40-60% 7) 40-60% 8) 30-40%

Question 317

Name the 10 main hypothalamic nuclei - 3 main categories

Answer 317

Suprachiasmatic Preoptic Arcuate Paraventricular and Supraoptic (ABOVE 5 all = endocrine function) Anterior and Posterior Lateral (3x limbic) Dorsomedial and Ventromedial (2 x autonomic)

Question 318

What is the function of the following hypothalamic nuclei: - Dorsomedial and Ventromedial - Lateral

Answer 318

LIMBIC function - body-weight regulation Lateral - hunger centre - stimulation = increased appetite, lesions = anorexia Dorsomedial - (stimulates appetite and sensitive to leptin, stimulates GI tract), emotion (rage), libido, circadian activity. Stimulation = obesity, savage behaviour Ventromedial - Body-weight regulation (satiety centre), sexual behaviour, insulin regulation. Lesions = hyperphagia

Question 319

What is the function of the following hypothalamic nuclei: Anterior and Posterior

Answer 319

THERMOREGULATION i.e AUTONOMIC function Anterior - keeps you cool, therefore lesions = hyperthermia Posterior = opposite

Question 320

What is the function of the following hypothalamic nuclei: Paraventricular and Supraoptic

Answer 320

Endocrine function: WATER BALANCE - lesions here can cause DI OXYTOCIN REGULATION - PV ADH release - SO They send these hormones to the POSTERIOR PITUITARY

Question 321

What is the function of the following hypothalamic nuclei: Arcuate Preoptic Suprachiasmatic

Answer 321

Arcuate = DOPAMINE RELEASE Contains DOPA-ergic neurones that inhibit prolactin release. Lesions = galactorrhoea, amenorrhoea. Note: also sensitive to LEPTIN Preoptic - Regulates the release of gonadotropic hormones Lesions pre-puberty = arrested sexual development. Lesions post-puberty = impotence, amenorrhoea. Also, thermoregulation. Suprachiasmatic = SLEEP/ RHYTHM REGULATION - receives input from the retina. Sends hormones to the pineal gland to stimulate melatonin release

Question 322

Which brain area is associated with moral judgement?

Answer 322

The ventromedial prefrontal cortex (vmPFC) is a part of the brain that has been implicated in the processing of risk, fear, decision-making and moral judgements.

Question 323

Which area of the brain is associated with working memory?

Answer 323

Working memory is primarily associated with the dorsolateral prefrontal cortex (dlPFC),

Question 324

What are the 3 layers of the cerebral cortex?

Answer 324

- Archicortex - oldest part of the cortex, connects the limbic system to the cortex - Paleocortex - associated with the olfactory system - Neocortex - accounts for 90% of the cortex (associated with higher functions like thought and language)

Question 325

Crossing over takes place in which phase of Meiotic division?

Answer 325

Prophase I

Question 326

In which stage of mitosis do the chromosomes become aligned at the middle of the cell?

Answer 326

Metaphase (They MET in the MIDDLE)

Question 327

DNA replication occurs during which stage of the cell cycle?

Answer 327

Interphase

Question 328

At which stage of mitotic division do paired chromosomes separate and begin moving to opposite ends of the cell?

Answer 328

Anaphase - they move Apart (A)

Question 329

What are the 6 stages of mitosis in order?

Answer 329

Prophase Prometaphase Metaphase Anaphase Telophase Cytokinesis

Question 330

At which stage in mitotit division do chromatids arrive at opposite poles of the cell and new nuclear membranes begin to form around them?

Answer 330

Telophase - they;re now far away and have to TELePHone each other

Question 331

What happens in Prophase and Prometaphase in mitosis?

Answer 331

Prophase - Chromatin condenses and becomes visible as chromosomes Prometaphase - The nuclear membrane dissolves and microtubules become attached to the centromeres

Question 332

What is the blood supply of the caudate nucleus?

Answer 332

Anterior and Middle cerebral arteries

Question 333

Which neuroplastic effect is most reliably observed in patients undergoing ECT?

Answer 333

Increased hippocampal volume (Increased hippocampal brain-derived neurotrophic factor (BDNF) levels)

Question 334

What is the falx cerebri?

Answer 334

A layer of dura matter that separates the two cerebral hemispheres

Question 335

Secreted by the stomach, this hormone has a paracrine effect and inhibits the release of hydrochloric acid.

Answer 335

Somatostatin

Question 336

This hormone is secreted by the cells in the duodenum when they are exposed to the acidic contents of the emptying stomach

Answer 336

Secretin

Question 337

This hormone stimulates the exocrine cells of the stomach to secrete gastric juice

Answer 337

Gastrin

Question 338

3 types of MS and their relative percentages:

Answer 338

Primary Progressive - least common - 5-10% Relapsing-remitting - 20-30% Secondary progressive - most common - 60%

Question 339

3 occular features of MS:

Answer 339

- Optic neuritis (unilateral visual loss) - Internuclear ophthalmoplegia (diplopia and/or nystagmus due to a problem arising from the midbrain) - Ocular motor cranial neuropathy (e.g. sixth nerve palsy)

Question 340

Cortical thinning in which area is the most characteristic finding in bipolar disorder?

Answer 340

Ventrolateral prefrontal cortex.

Question 341

Which gait abnormality is seen in Parkinson's?

Answer 341

Festinating gait - short, jerky steps

Question 342

What do fractional anisotropy results in individuals with bipolar disorder indicate? (DTI scan)

Answer 342

Reduced white matter integrity in the white matter tracks of the corpus callosum (and cingulum)

Question 343

What structural changes can be seen in the grey matter of patients with bipolar?

Answer 343

Higher:bilateral ventricular volumes Lower: (HAT) hippocampal volumes amygdala volumes thalamic volumes

Question 344

What genetic testing method allows for the screening of thousands of genes at once, and screens for copy number variations, gene expression levels, and SNPs i.e a variety of genetic abnormalities at one time e.g in early onset schizophrenia

Answer 344

Microarray analysis

Question 345

Which neural circuit is considered to be most relevant to the pathology of OCD?

Answer 345

Cortico-striato-thalamo-cortical (CSTC) Circuit.

Question 346

What does the proteosome do?

Answer 346

The proteosome function is to degrade endogenous proteins (i.e. proteins manufactured by the cell). Proteins are tagged for degredation by ubiquitin

Question 347

How does the nucleus accumbens play a role in drug addiction?

Answer 347

The nucleus accumbens plays a central role in the neural circuitry of drug addiction by integrating highly specific information about the environment and past experience. Important component of the brain's reward circuit

Question 348

What is absent on EEG in Fatal Familial Insomnia?

Answer 348

Sigma waves (normally seen in Stage 2 sleep)

Question 349

When does somnambulism happen?

Answer 349

Somnambulism = sleepwalking It happens during deep nREM sleep, typically during the first half of the night

Question 350

Cataplexy vs Catalepsy:

Answer 350

Cataplexy is a sudden, brief loss of voluntary muscle tone triggered by strong emotions, such as laughter, surprise, or anger. In some cases, sudden loud noises could also trigger an episode. It is a characteristic symptom of narcolepsy, a sleep disorder. 'Catalepsy': Catalepsy is a condition where a person maintains body positions for long periods, it is not the sudden collapse due to a stimulus.

Question 351

Which type of sensory information projects straight to the cortex without passing through the thalamus?

Answer 351

Olfactory This is clinically relevant as olfactory pathways have a direct link to limbic structures, which are involved in emotion and memory.

Question 352

4 types of Primary Afferent axons:

Answer 352

A-alpha - proprioception A-beta - touch A-delta - pain and temp (A's are myelinated) C - pain, temp, itch (C = unmyelinated so slow, dull, longer lasting, second pain.)

Question 353

What is the MAIN blood supply of the corpus callosum?

Answer 353

Anterior Cerebral Artery (Also others)

Question 354

What is the only extraoccular muscle innervated by the trochlear nerve? What movements?

Answer 354

Superior Oblique - depression (and rotation)

Question 355

What is the only extraoccular muscle innervated by the abducens nerve? What movements?

Answer 355

Lateral rectus - Abduction

Question 356

In PTSD, what findings are there on EEG during sleep? x3

Answer 356

1) increase in S1 NREM sleep 2) decreased slow wave sleep 3) increased eye movements during REM

Question 357

What area of the brain is targeted during transcranial magnetic stimulation in: 1) OCD 2) major depression

Answer 357

1) orbitofrontal 2) left frontal

Question 358

In what condition are the following areas stimulated in DBS? 1) Internal globus pallidus and subthalamic nucleus 2) internal capsule (and subthalamic nucleus) 3) subcallosal cingulate 4) ventromedial thalamus

Answer 358

1) Parkinsons 2) OCD (treatment resistant) 3) treatment resistant depression 4) tourettes

Question 359

How is GABA formed?

Answer 359

Glutamate is catalysed by glutamase decarboxtlase (GAD)

Question 360

Activation of microglia, reduced CSF 5-HIAA and Tryptophan Hydroxylase polymorphism are seen in:

Answer 360

Suicidality

Question 361

Anterior insula activation is seen in:

Answer 361

Substance Use Disorders

Question 362

Re: animal models of psychiatric disorders, in what condition are the following seen: 1) BDNF haploinsufficient mice 2) Circadian rhythm disruption and 3) ERK knockout

Answer 362

Bipolar Disorder

Question 363

Re: animal models of psychiatric disorders, in what condition are the following seen: 1) maternal separation 2) Social defeat 3) chronic defeat and 4) olfactory bylbectomised rat

Answer 363

Depressive Disorder

Question 364

Mutations in the SHANK3 gene on c.22 are associated with which condition?

Answer 364

Autism spectrum

Question 365

What area of the brain has increased blood flow in depression?

Answer 365

Anterior Cingulate Cortex - area implicated in modulation of emotional behaviour

Question 366

Changes to the medial temporal lobe, midline diencephalon and hippocampus are likely to relate to what?

Answer 366

Amnesia