Basic neurosciences Flashcards

(394 cards)

1
Q

Blood supply to the brain (overview)

A

The body supplies blood to the brain via:

  • the internal carotid arteries
  • the vertebral arteries

These vessels come together to form a ring called the circle of Willis. The function of the circle of Willis is to provide a shunt system should any of the vessels become damaged.

Arising from the circle are the three main vessels that supply the brain with blood:

  • the anterior cerebral artery
  • middle cerebral artery
  • the posterior cerebral artery.
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2
Q

Anterior cerebral artery (ACA) occlusion (associated defects)

A

Hemiparesis of the contralateral foot and leg (more severely than the arm)

Sensory loss of the contralateral foot and leg

Motor dysphasia

(If stroke occurs prior to the anterior communicating artery it is usually well tolerated secondary to collateral circulation)

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3
Q

Middle cerebral artery (MCA) occlusion (associated defects)

A

Hemiparesis of the contralateral face and limbs

Sensory loss of contralateral face and limbs

Dysphasia (when dominant hemisphere affected)

Contralateral neglect

Homonymous hemianopia or quadrantanopia

Dorsolateral prefrontal dysfunction

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4
Q

Posterior cerebral artery (PCA) occlusion (associated defects)

A

Alexia without agraphia (left PCA)

Contralateral loss of pain and temperature sensation

Contralateral hemianopia

Prosopagnosia

Ipsilateral cranial nerve defects (V, VIII, IX, X, & XI)

Horner’s syndrome

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5
Q

Frontal lobe and Parietal lobe are separated by … (aka)

A

The central sulcus

aka fissure of Rolando

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6
Q

Primary motor cortex (region, lobe and Brodmann area)

A

Pre-central gyrus, frontal lobe

Brodmann area 4

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7
Q

Subdivisions of the motor cortex, and their functions (3)

A

Primary motor cortex
- initiating motor movements

Premotor cortex
- planning and initiation of movements on the basis of past experience

Supplementary motor cortex
- regulation of posture

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8
Q

Broca’s area (function, location, and Brodmann areas)

A

Motor speech area

Located in the inferior frontal gyrus on the dominant (usually left) hemisphere

Brodmann areas 44+45

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9
Q

Frontal eye field (function, location, and Brodmann areas)

A

Voluntary saccadic eye movements

Located at the caudal ends of the superior frontal gyrus (Brodmann 8) and middle front gyrus (Brodmann 6)

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10
Q

Primary somatosensory cortex (region, lobe and Brodmann areas)

A

Postcentral gyrus, parietal lobe

Brodmann areas 1, 2, and 3

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11
Q

Primary auditory cortex (region, lobe and Brodmann area)

A

Heschl’s gyrus, aka transverse temporal gyrus, in the temporal lobe

Brodmann areas 41 + 42

It is entirely hidden within the Sylvian fissure (lateral sulcus), with the planum temporale and superior temporal gyrus located lateral to it.

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12
Q

Planum temporale (location and key fact)

A

A triangular region on the upper surface of the superior temporal gyrus (temporal lobe).

It is important for language processing.

The most notable feature is that it displays left-right asymmetry - the left PT is larger than the right in 65% of right-handed individuals.

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13
Q

Wernicke’s area (function, location, and Brodmann areas)

A

Comprehension of written and spoken language.

Superior temporal gyrus in the dominant hemisphere.

Brodmann area 22.

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14
Q

Lateralisation of brain function (summary)

A

Right-handed people

  • Left hemisphere dominant in 90%
  • Right hemisphere dominant in 10%

Left-handed people

  • Left hemisphere dominant in 64%
  • Right hemisphere dominant in 20%
  • Bilateral dominance in 16%
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15
Q

Primary visual cortex (region, lobe and Brodmann area)

A

Striate cortex (calcarine cortex) in the occipital lobe

Brodmann area 17

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16
Q

Which lobe?:

Motor movements
Executive function (e.g. planning, initiation, organisation, set-shifting, reasoning/judgement, abstract thinking)
Decision-making
Working memory; Attention
Language (motor expression of speech)
Inhibition
Personality/emotions/social conduct
Saccadic eye movements
A

Frontal lobe

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17
Q

Motor movements (specific region & lobe)

A

Motor cortex - frontal lobe

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18
Q

Brain region & lobe responsible for:

  • Executive function (e.g. planning, initiation, organisation, set-shifting, reasoning/judgement, abstract thinking)
  • Decision-making
  • Working memory; Attention
A

Premotor cortex - frontal lobe

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19
Q

Brain region + lobe responsible for:

  • Inhibition
  • Personality/emotions/social conduct
A

Orbitofrontal cortex - frontal lobe

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20
Q

Language - motor expression of speech (specific region & lobe)

A

Broca’s area - inferior frontal gyrus on the dominant (usually left) hemisphere; frontal lobe

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21
Q

Saccadic eye movements (specific region & lobe)

A

Frontal eye fields - frontal lobe

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22
Q
Gerstmann syndrome
(brain region deficit, key features)
A

Results from lesions in the left (/dominant) inferior parietal lobe

  • agraphia
  • acalculia
  • finger agnosia (inability to distinguish fingers in the hand)
  • left-right disorientation
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23
Q
Balint syndrome
(brain region deficit, key features)
A

Results from bilateral damage to the posterior parietal lobe

  • ocular apraxia (difficulty keeping the eyes still)
  • optic ataxia (difficulty moving the eyes to a specific position)
  • simultanagnosia (inability to simultaneously perceive the different aspects of a picture and appreciate it as a whole)
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24
Q

Which lobe?:

Perception and processing of sensory information
Visuospatial processing
Praxis
Somatognosia (awareness of one's body)
Calculation ability
Reading
Writing
Naming
Left-right orientation
Visual field processing
A

Parietal lobe

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Which lobe?: ``` Memory Deductive reasoning Language comprehension Auditory perception Affective prosody Music comprehension Face recognition Visual field processing (superior) Olfactory perception ```
Temporal lobe
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Kluver-Bucy Syndrome | brain region deficit, key features
Rare, neurobehavioural impairment resulting bilateral medial temporal lobe dysfunction (specifically the amygdala) - hyperorality (pica) - hypersexuality - placidity/docility (lack of anger) - visual agnosia - prosopagnosia - psychic blindness (emotional unresponsiveness) - hypermetamorphosis (tendency to react to every visual stimulus which could lead to easy distractibility - objects are repeatedly examined as they were novel) - memory loss - seizures
27
Anton-Babinski syndrome (essence)
Cortical blindness Caused by injury to the occipital lobe Features - Anosognosia - denial of blindness despite objective evidence of visual loss - Confabulation - to fill in the missing sensory input
28
Occipital lobe function
The occipital lobe is responsible for perception of visual sensation. However, having a lesion on any other site in the course of the optic tract (which runs under the frontal lobe and through the temporal and parietal lobes) could also affect vision despite having an intact occipital lobe.
29
Structures in the visual pathway (7)
``` Eye Optic nerve Optic chiasm Optic tract Lateral geniculate nucleus Optic radiation Primary visual cortex ```
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Limbic system (basic substructure (2) and functions)
1. Structures in the cerebral cortex - collectively termed the limbic lobe - hippocampus - insular cortex - orbital frontal cortex - subcallosal gyrus - cingulate gyrus - parahippocampal gyrus 2. Subcortical structures - olfactory bulb - hypothalamus - amygdala - septal nuclei - some thalamic nuclei Functions: - Processing of emotions - Encoding and retrieval of memory - Autonomic functions
31
Limbic lobe (2 major components)
Cingulate gyrus - lies immediately above the corpus callosum - the posterior cingulate cortex has a central function in supporting autobiographical memories, planning for the future and focussing attention Parahippocampal gyrus - lies in the medial temporal lobe and surrounds the hippocampal formation - active in general memory creation/recall, and specific recollection of visual scenes
32
Hippocampus - functions (3)
declarative memory (encoding, retrieval) visuospatial orientation regulation of the HPA axis Impairment is one of the first things to occur in Alzheimer's disease, often leading to confusion and memory loss
33
two almond-shaped clusters of nuclei located deep and medially within the temporal lobes of the brain part of the limbic system associated with processing of emotion and the acquisition and expression of fear conditioning
Amydala(e)
34
a set of structures that lie below the rostrum of the corpus callosum part of the limbic system they receive reciprocal connections from the olfactory bulb, hippocampus, amygdala, hypothalamus, midbrain, habenula, cingulate gyrus, and thalamus
Septal nuclei (medial olfactory area)
35
lies just below the septal nuclei, below the rostrum of the corpus collosum plays a key role in reward and reinforcement, and hence things such as motivation and drug dependency
Nucleus accumbens
36
Diencephalon - subdivision (4)
The --- is divided into 4 areas, which are interposed between the brain stem and cerebral hemispheres: - thalamus - hypothalamus - epithalamus - subthalamic nucleus
37
The --- is like a switchboard regulating and relaying information to and from the brain. Almost all sensory input (with the exception of the olfactory system) goes through the --- and motor output goes via the --- to the rest of the body. It also plays a role in regulating sleep and wakefulness, level of arousal and consciousness - damage can lead to permanent coma.
Thalamus
38
``` Links the nervous system to the endocrine system, through control of the pituitary gland, to release 8 major hormones Temperature regulation Management of food and water intake Sexual behaviour and reproduction Mediation of the emotional response ```
Hypothalamus
39
White matter (essence)
White matter is composed of myelinated axons, which run in bundles called white matter tracts - these tracts connect various grey matter areas of the brain to each other.
40
3 main types of white matter tracts
Commissural fibres Association fibres Projection fibres
41
The largest white matter tract
Corpus callosum
42
Commissural fibres (aka, function, examples)
aka transverse fibres connect the corresponding areas between the two hemispheres of the brain ``` e.g. transverse fibres of the corpus callosum anterior commissure posterior commisure hippocampal commissure habenular commissure ```
43
Which white matter tract?: Transports nociceptive (pain) stimuli to the contralateral side of the brain in the lateral spinothalamic tracts Also contains decussating fibres from the olfactory tracts and connects the two amygdala and other parts of the temporal lobe, thus contributing to olfaction, memory, emotion, speech, and hearing.
Anterior commissure
44
Which white matter tract?: Interconnects the pretectal nuclei, which in turn receive the afferents from the optic tract, mediating the consensual pupillary light reflex and taking the fibres to the Edinger Westphal nuclei of the oculomotor nerve
Posterior commissure
45
Association fibres (function, examples)
Connect regions of within the same hemisphere of the brain e.g. the cingulum the superior longitudinal fasciculus and arcuate fasciculus the inferior longitudinal fasciculus and uncinate fasciculus the fornix of the hippocampi
46
Which white matter tract?: Travels in a C-shape through the frontal, parietal and temporal lobes above the corpus callosum. Hippocampal atrophy in Alzheimer's disease has been linked to disruption of this tract.sy
The cingulum
47
The longest intrahemispheric white matter tract
The superior longitudinal fasciculus
48
Which white matter tract?: - an association tract - one of the subdivisions of the superior longitudinal fasciculus - connects Broca's and Wernicke's areas - plays a major role in language use and comprehension - damage results in conduction aphasia
The arcuate fasciculus
49
Projection fibres (function, key example)
--- connect the cerebral cortex with the lower parts of the brain (brainstem) and the spinal cord, in both directions. These could be afferent to the cerebral cortex (corticopetal) or efferent from the cerebral cortex (corticofugal). e.g. the internal capsule
50
Basal ganglia - components (4)
Striatum (caudate, putamen, nucleus accumbens) Subthalamic nucleus Substantia nigra (divided into pars compacta and pars reticulate) Globus pallidus
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The --- enable practised motor acts, gating the voluntary movements initiated in the motor cortex and suppressing inappropriate motor commands. They also play a role in cognitive function, especially certain forms of implicit memory tasks, through connections to the prefrontal association cortex and limbic cortex.
Basal Ganglia
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Brainstem - key structures (3)
Medulla oblongata Pons Midbrain
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Midbrain - 2 major structures
Red nucleus Substantia nigra
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Substantia nigra - subdivisions (2)
pars compacta - contains mainly dopaminergic neurons pars reticulata - contains mainly GABAnergic neurons Degeneration of dopaminergic neurons in the pars compacta is the main pathological feature of Parkinson's disease, leading to depletion of dopamine in the nigrostriatal pathway
55
``` Olfactory nerve (I) (fibres, function, test) ```
Sensory - Smell Test smell with clove or coffee
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``` Optic nerve (II) (fibres, function, test) ```
Sensory - Vision Tests: - snellen chart (acuity) - ischihara chart (colour vision) - pupillary reflexes - light and accommodation - visual fields - fundoscopy
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``` Oculomotor nerve (III) (fibres, function, test) ```
``` Motor - Movement of eye muscles: - superior/inferior/medial rectus; - inferior oblique - levator palpabrae Test - follow finger with head still ``` Parasympathetic - Pupillary constriction Test - accommodation reflex
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``` Trochlear nerve (IV) (fibres, function, test) ```
Motor - Movement of eye muscle: superior oblique (downward and medial movement of eye) Test - eye movements with head still
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``` Trigeminal nerve (V) (fibres, function, test) ```
Sensory - general sensation of face, scalp, oral and nasal cavities; corneal reflex Test - touch patient on each side of face Motor - muscles of mastication Test - bite down and open mouth against resistance
60
``` Abducens nerve (VI) (fibres, function, test) ```
``` Motor - Movement of eye muscle: lateral rectus (lateral movement of eye) Test - eye movements with head still ```
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``` Facial nerve (VII) (fibres, function, test) ```
Sensory - Taste sensation to anterior 2/3 of tongue Test - taste sensation Motor - Muscles of facial expression Test - make various facial expressions
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Vestibulo-cochlear nerve (VIII) | fibres, function, test
Sensory - hearing - proprioception of head and balance Test - Rhinne and Weber tests
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Glosso-pharyngeal nerve (IX) | fibres, function, test
Sensory - general sensation of middle ear and pharynx - taste of posterior 1/3 of the tongue Motor - swallowing Parasympathetic - salivation
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``` Vagus nerve (X) (fibres, function, test) ```
Sensory - general sensations of pharynx, larynx, oesophagus, external ear and viscera Motor - speech and swallowing Parasympathetic - control of GI, cardiovascular and respiratory systems Test - say 'ahh' and look at uvula
65
``` Accessory nerve (XI) (fibres, function, test) ```
Motor - trapezius and sternocleidomastoid muscles Test - turn head and shrug shoulders against resistance
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``` Hypoglossal nerve (XII) (fibres, function, test) ```
Motor - movement of tongue Test - look for wasting/fasciculation. Stick out tongue and look for deviation.
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How many nerve nuclei does the brainstem contain?
10 Olfactory and optic nerves come from the cerebrum
68
Which side of the body do cerebellar lesions affect?
Ipsilateral
69
Cerebellar dysfunction - clinical features
``` Dysdiadochokinesis / Dysmetria (lack of finger nose co-ordination Ataxia Nystagmus Intention tremor Slurred speech Hypotonia/Heel-shin test Broad based gait ``` 'DANISH - B'
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Which white matter tract?: Connects the orbitofrontal cortex to the anterior temporal lobes. Plays an important role in social cognition and language.
Uncinate fasciculus
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2 main types of cells in the nervous system
Neurons | Glial cells
72
From which primary germ layer do neurons originate?
Ectoderm
73
Neuron - basic components (3)
Cell body (soma) - the major site of metabolic activity Dendrites - outward extensions of the cell body, receiving signals from other neurons Axon - conducts nerve impulses (action potentials) away from the cell body
74
Functional classification of neurons (3)
Sensory Motor Interneurons (aka association neurons) Interneurons are found entirely within the CNS - their function is to enable communication between the CNS and other neurons
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Structural classification of neurons (3)
Unipolar Bipolar Multipolar Most neurons are multipolar - one axon and one or more dendrites
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Glial cell (essence)
They are not directly involved in electrical signalling, but rather provide a supportive function to help maintain the action of neurons More numerous (10-50 times more) than neurons Lack axons and dendrites
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(cell) - derived from neural tube ectoderm - star shaped - the largest type of glial cell - aid formation of the blood-brain barrier - provide structural support and repair processes, regulating oxidised potassium concentration in the extracellular fluid - form a 'glial scar' in response to brain tissue damage (process called astrocytosis/gliosis)
Astrocyte
78
(cell) Glial cell - derived from neural tube ectoderm - found mainly in white matter -responsible for the formation and maintenance of the myelin sheath around an axon in the CNS
Oligodendrocyte
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(cell) - small glial cells of mesenchymal origin - the primary immune cells of the CNS
Microglia
80
(cell) - type of glial cell - make up the lining of the ventricles of the brain and central canal of the spinal cord - they do this by forming the specialised choroid plexus epithelium that secretes CSF
Columnar epithelial cells
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Glial cell - derived from the neural crest - only found in the peripheral nervous system -responsible for the myelination of the PNS
Schwann cells
82
Glial cell in the PNS, derived from the neural crest Provides a supportive role
Satellite cells
83
Cerebral cortex | essence, subdivisions
The outer covering of grey matter over the cerebral hemispheres - Neocortex (top layer) - Allocortex - Paleocortex - Archicortex
84
Paleocortex - subdivisions (2)
part of the cerebral cortex includes the entorhinal cortex (in the medial temporal lobe) and piriform lobe (specialised for olfaction)
85
Archicortex (function)
consists of the hippocampus, dealing with memory and spatial function
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Neocortex - layers (6)
``` I - Molecular (plexiform) layer II - Outer granular III - Outer pyramidal IV - Inner granular V - Inner pyramidal VI - Multiform ``` Neocortex covers more than 90% of the cerebral cortex
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Neocortex - 2 main cell types
Pyramidal cells | Stellate cells
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Pyramidal cells (location)
- make up 75% of cortical neurons | - the principal output neurons, found in layers II-V of the neocortex
89
Betz cells
Giant pyramidal cells located within layer V of the grey matter in the primary motor cortex. They are the largest neurons in the nervous system
90
Stellate cells (aka, location, function)
aka Granular cells small multipolar neurons with a star-like shape - spiny --- cells (excitatory) - smooth --- cells (inhibitory) most prominent in layer IV of the neocortex the main interneurons of the neocortex - their short axons do not leave the cortex ----------------- they are the most common cells in the cerebral cortex
91
Other cells in the neocortex (3)
Fusiform cells Horizontal cells of Cajul Cells or Martionotti
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Cerebellar cortex - layers (3, +cells)
Molecular, outermost layer Purkinje, middle layer Granular, innermost layer
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Molecular, outermost layer of the cerebellar cortex - cells (4)
Axons of granule cells Dendrites of Purkinje cells Stellate and Basket cells
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Purkinje, middle layer of the cerebellar cortex - cells (1)
A single layer of Purkinje cell bodies Their axons extend deep into the cerebellum, and their multiple dendrites extend into the molecular level
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Granular, innermost layer of the cerebellar cortex - cells (2)
Granule cells - whose axons extend into the molecular layer Golgi cells
96
Cell type?: - found uniquely in the cerebellum - only source of output from the cerebellar cortex - inhibitory (use GABA)
Purkinje cells
97
Cell type?: - most numerous type of cell in the cerebellum - excitatory (use glutamate) - excite the Purkinje cells via axonal branches called 'mossy fibres'
Granule cells
98
Stellate, basket and Golgi cells (location, function)
inhibitory interneurons in the cerebellar cortex
99
Main cell type found in the hippocampus
Pyramidal cell
100
Main cell type found in the dentate gyrus (within the hippocampus)
Granule cell
101
Major neurotransmitters (6)
``` Dopamine Noradrenaline Serotonin Acetylcholine Histamine Glutamate ```
102
Brian region involved in major neurochemical pathways Lying within the striatum, this is associated with motivation, pleasure, and reward/reinforcement. Conditions affecting this area can cause delusions and hallucinations
Nucleus accumbens
103
Brian region involved in major neurochemical pathways Associated with executive function (working memory, judgement, decision-making, reasoning, problem-solving, planning), emotional regulation, social behaviour, impulse control and motor control. Conditions affecting this area can cause obsessions and compulsions.
Prefrontal cortex
104
Brian regions involved in major neurochemical pathways Regions involved in motor control (3)
Subtantia nigra (in the brainstem) Striatum Cerebellum
105
Brian region involved in major neurochemical pathways Regions involved in appetite and hormone release (2)
Hypothalamus | Pituitary
106
Brian region involved in major neurochemical pathways Associated with relaying sensory and motor signals to the cortex, as well as sleep and wakefulness
Thalamus
107
Brian region involved in major neurochemical pathways ... lies in the brainstem and is associated with sleep and respiratory function
Locus coeruleus
108
Brian region involved in major neurochemical pathways Regions involved with memory (3)
Amygdala (fear and memory consolidation) Hippocampus Nucleus basalis of Meynert
109
Brian region involved in major neurochemical pathways ... lies in the brainstem and is involved with emotions and behaviour
Ventral tegmental area ================== in the midbrain
110
Brian region involved in major neurochemical pathways ... lies in the brainstem and is associated with pain, sleep and wakefulness
Raphe nuclei
111
4 major dopamine pathways in the brain
Mesolimbic Mesocortical Nigrostriatal Tuberoinfundibular
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Mesolimbic pathway (dopamine) - brain regions
Projects from the ventral tegmental area (in the brainstem) to the nucleus accumbens (in the striatum) which is part of the limbic system
113
Mesolimbic pathway (dopamine) - clinical significance
Overactivity of this pathway (increased dopamine) mediates the positive symptoms of psychosis. The pathway is also associated with motivation/pleasure/reward/reinforcement - this explain the worsening of negative symptoms after treatment with typical antipsychotics - it also has a role in the neurobiology of addiction
114
Mesocortical pathway (dopamine) - brain regions
Projects from the ventral tegmental area (in the brainstem) to the prefrontal cortex.
115
Mesocortical pathway (dopamine) - clinical significance
Hypoactivity of this pathway (e.g. by dopamine blockade) mediates the negative, cognitive and affective symptoms of schizophrenia (alogia, anhedonia, avolition, blunted affect)
116
Nigrostriatal pathway (dopamine) - brain regions
Projects from the substantia nigra (in the brainstem) to the striatum (caudate nucleus and putamen) This pathway is part of the extrapyramidal system and is associated with motor control
117
Nigrostriatal pathway (dopamine) - clinical significance
Hypoactivity of this pathway (e.g. deficiency of dopamine in Parkinson's disease, or antipsychotic dopamine receptor blockade) -> EPSEs: parkinsonism (rigidity, tremor, bradykinesia), akathisia, dystonia Chronic dopamine blockade in this pathway -> tardive dyskinesia
118
Tuberoinfundibular pathway (dopamine) - brain regions
Projects from the hypothalamus to the anterior pituitary gland
119
Tuberoinfundibular pathway (dopamine) - clinical significance
Dopamine in this pathway normally inhibits prolactin secretion. Hypoactivity (caused by dopamine receptor blockade)-> hyperprolactinaemia
120
2 major noradrenaline pathways in the brain
Ascending noradrenaline pathway | Descending noradrenaline pathway
121
Ascending noradrenaline pathway | brain regions and functions
Projects from the locus coeruleus (in the brainstem) to multiple brain regions: - prefrontal cortex - thalamus + hypothalamus - amygdala + hippocampus - cerebellum Regulates multiple functions: - mood - arousal - cognition - sexual behaviour
122
Descending noradrenaline pathway | brain regions and functions
Projects from the brainstem down the spinal cord Regulates pain pathways
123
2 major serotonin pathways in the brain
Ascending serotonin pathway Descending serotonin pathway
124
Ascending serotonin pathway | brain regions and functions
Projects from the raphe nuclei (in the brainstem) to multiple brain regions: - prefrontal cortex - thalamus + hypothalamus - amygdala + hippocampus - nucleus accumbens (in the striatum) - cerebellum Regulates multiple functions: - mood, anxiety - sleep, wakefulness
125
Descending serotonin pathway | brain regions and functions
Projects from the brainstem down the spinal cord Regulates pain pathways
126
2 major acetylcholine pathways in the brain
Acetylcholine pathway from the brainstem Acetylcholine pathway from the basal forebrain
127
Acetylcholine pathway from the brainstem | brain regions and functions
Projects from the brainstem to multiple brain regions: - prefrontal cortex - thalamus + hypothalamus - amygdala + hippocampus Regulates arousal, cognition and other functions
128
Acetylcholine pathway from the basal forebrain | brain regions and functions
Projects from the nucleus basalis of Meynert (in the basal forebrain) to: - prefrontal cortex - amygdala + hippocampus It regulates memory and is implicated in the pathophysiology of Alzheimer's disease
129
The major histamine pathway in the brain | brain regions and functions
Projects from the tuberomammiliary nucleus (in the hypothalamus) to multiple brain regions: - prefrontal cortex - thalamus - amygdala + hippocampus - striatum Regulates arousal, sleep and wakefulness
130
5 major glutamate pathways in the brain
Cortical brainstem glutamate pathway Corticostriatal glutamate pathway Thalamocortical glutamate pathway Corticothalamic glutamate pathway Cortico-cortical glutamate pathway
131
Cortical brainstem glutamate pathway (brain regions)
A descending pathway projecting from the prefrontal cortex to the brainstem neurotransmitter centres: - substantia nigra - ventral tegmental area - locus coeruleus - raphe nucleus This pathway communicates with the mesolimbic and mesocortical dopamine pathways
132
Cortical brainstem glutamate pathway (clinical significance)
The cortical brainstem glutamate pathway normally: 1. acts a brake on the mesolimbic dopamine pathway (glutamate -> GABA release -> dopamine release inhibited) - Hypoactivity -> increased mesolimbic activity and therefore the positive symptoms of schizophrenia 2. acts as an accelerator on the mesocortical dopamine pathway - Hypoactivity -> decreased mesocortical activity and therefore the negative symptoms of schizophrenia
133
Which white matter tract? - a major (association) frontotemporal tract - connects the orbitofrontal cortex to the anterior temporal lobes - plays an important role in social cognition and language
Uncinate fasciculus
134
Neuronal resting membrane potential (voltage + reason)
When a cell is not stimulated, it is in a resting state and the inside of the cell is negatively charged with respect to the outside. The membrane potential of the resting state is -70mV. - This negative charge is due to a high concentration of Na+ outside compared to the K+ inside the cell. - This ionic gradient is maintained by the Na/K pump.
135
Action potential (process)
- Neurotransmitter binds to the post-synaptic neuron -> ion channel opening - The membrane potential is raised from -70mV to -55mV (threshold potential) - This causes influx of Na+ -> depolarisation - Membrane potential reaches +40mV - Na+ channels close - Voltage-gated K+ channels open -> repolarisation
136
Synapse - definition + types (3)
A junction between two nerve cells 1. Chemical synapses - excitatory (depolarisation of the postsynaptic neuron) - inhibitory (hypoerpolarisation of the postsynaptic neuron) 2. Electrical synapses - abundant both in the retina and cerebral cortex 3. Conjoint synapses (electrical and chemical properties)
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The role of the hypothalamus in feeding behaviour (2)
Ventromedial hypothalamus - the satiety centre Lateral hypothalamus - the feeding centre
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Orexigenic hormones (hormones that increase appetite) - 2
Neuropeptide Y - produced by the hypothalamus Ghrelin - produces in the gastric mucosa (only orexigenic hormone produced outside the CNS) [think 'NG' (tube) which is used for feeding]
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Anorexigenic hormones (hormones that decrease appetite) - 2
Leptin - produced by adipose tissue Cholecystokinine (CCK) - produced mainly by the gut
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Primary afferent axons (4)
convey information about touch and pain from the surface of the body to the spinal cord and brain. A-alpha (proprioception) A-beta (touch) A-delta (pain and temperature) C (pain, temperature, and itch)
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Which primary afferent axons are myelinated?
All of the A axons (alpha, beta, delta) are myelinated C fibres are unmyelinated
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Primary afferent axons involved in pain (2)
A-delta fibres are responsible for sharp initial pain C fibres are responsible for slow, dull, longer lasting, second pain (both carry pain sensations to the dorsal horn of the spinal cord)
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Embryonic brain - divisions (3)
Forebrain (prosencephalon) - diencephalon - telencephalon Midbrain (mesencephalon) Hindbrain (rhombencephalon) - metencephalon - myelencephalon
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Forebrain (prosencephalon) - subdivisions
Telencephalon (cerebrum) - cerebral cortex - underlying white matter - basal ganglia. Diencephalon - prethalamus - thalamus - hypothalamus - subthalamus - epithalamus - pretectum
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Midbrain (mesencephalon) - subdivisions
tectum (or corpora quadrigemina) tegmentum ventricular mesocoelia cerebral peduncles several nuclei and fasciculi.
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Hindbrain (rhombencephalon) - subdivision
medulla, pons, and cerebellum
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Neurotransmitter (definition)
A substance released from presynaptic nerve terminals which produces rapid inhibitory or excitatory effects on the post synaptic cell
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Neurotrophic factor (definition)
A substance which influences gene expression and neuronal growth. Predominantly released by glia. ------------------------------------------------- Brain-derived neurotrophic factor (BDNF) - increased in cortical areas - decreased in the hippocampus in patients with schizophrenia
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Amino acid neurotransmitters (2 + 2)
GABA Glutamate (also Glycine and Aspartate, but these are less important to psychiatry)
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Monoamine neurotransmitters (3 + 3)
Dopamine Serotonin Noradrenaline -------------------------------- Adrenaline Melatonin Histamine (less important for psychiatry/less well understood)
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Neurotransmitters - Other amine (1)
Acetylcholine
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The major excitatory neurotransmitter in the CNS
Glutamate ====== also Aspartate
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The major inhibitory neurotransmitter in the CNS
GABA ======= also Glycine
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Neurotransmitter release (process)
- Action potential travels down the neuron (depolarising the membrane by sequential opening of Na channels) - > Influx of calcium through voltage dependent calcium selective ion channels - > Vesicles packed with neurotransmitters fuse with the synaptic membrane and release the neurotransmitter into the synaptic cleft (exocytosis)
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Glutamate and GABA | precursors, degradation
Precursors: both derived either from - glucose (transported to the CSF from the peripher) - glutamine (synthesised by glial cells) "Glucose -> Glutamate -> GABA" Termination: They have their actions terminated mainly by being transported out of the synaptic terminal - Glutamate - degraded by glutamine synthase - GABA - degraded by GABA transaminase
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Catecholamines (3)
Dopamine Adrenaline Noradrenaline 'DAN'
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Noradrenaline/Dopamine - synthesis pathway (4 molecules, 3 enzymes)
``` Tyrosine (Tyrosine hydroxylase) - *rate-limiting step* Levodopa (DOPA decarboxylase) Dopamine (Dopamine beta-hydroxylase) Noradrenaline ```
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Serotonin - synthesis pathway (3 molecules, 2 enzymes)
Tryptophan (Tryptophan hydroxylase) - *rate-limiting step* 5-Hydroxytryptophan (DOPA decarboxylase)* 5-Hydroxytryptamine (5-HT) i.e. Serotonin ======================== * aka L-aromatic amino acid decarboxylase
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Serotonin - location of synthesis
``` CNS in the raphe nuclei (in the brainstem) GI tract (enterochromaffin cells) ``` It is synthesised from the amino acid L-tryptophan which is obtained from the diet. L-tryptophan can cross the blood brain barrier, whereas serotonin cannot
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Degradation of noradrenaline, dopamine, and serotonin (summary of enzymes involved)
COMT (catechol-O-methyltransferase) only breaks down the catecholamines (noradrenaline and dopamine) Monamine oxidase A degrades all three (noradrenaline, dopamine, serotonin) Monamine oxidase B degrades dopamine only (hence use of MAO-Bi's in parkinson's) ----------------------------------------------------------------------- Aldehyde dehydrogenase is involved in the degradation of serotonin's breakdown product to 5-Hydroxyindoleacetic acid (5-HIAA).
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Cheese reaction (mechanism)
- Tyramine is an amine in the diet which triggers release of noradrenaline - Usually this noradrenaline is degraded by MAO in the gut - If MAO is inhibited, then the excess noradrenaline leads to rise in blood pressure and hypertensive crisis
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Noradrenaline - degradation enzymes (2) and product
COMT (catechol-O-methyltransferase) MAO-A ----------------- MHPG (3-methoxy-4-hydroxyphenylglycoll)
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Dopamine - degradation enzymes (3) and product
``` COMT (catechol-O-methyltransferase) MAO-A MAO-B ------------------- HVA (homovanilic acid) ```
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Serotonin - degradation enzymes (2) and product
``` Serotonin (MAO-A) Intermediary (Aldehyde dehydrogenase) 5-H1AA ```
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Acetylcholine - synthesis
Choline + acetyl coenzyme-A (Choline acetyltransferase) Acetylcholine ---------------------- Choline is a nutrient present in a wide range of foods. It is taken up by neurons via specific transporters.
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Acetylcholine - degradation
Acetylcholine (Acetylcholinesterase) (Butyrylcholinesterase) Choline and Acetate ------------------------------------- Acetylcholinesterase is found predominantly at synapses Butyrylcholinesterase is made by the liver and circulates in the blood. It is also found in the brain. Its role at synapses is unclear.
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Presynaptic processes occurring at the synapse (3)
Autoreceptors Heteroreceptors Reuptake transporter proteins
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Autoreceptors (essence)
Presynaptic receptors on the same neuron (e.g. serotonergic receptors on serotonergic terminals) Inhibit further neurotransmitter release via negative feedback
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Heteroreceptors (essence)
Presynaptic receptors that respond to neurochemicals released from other neurons
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Reuptake transporter proteins (essence)
Proteins located on the presynaptic membrane that return the neurotransmitters to the axon terminal, where they are stored in a vesicle or degraded by catabolic enzymes
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Ionotropic receptors (essence)
Ligand-gated ion channels that open allowing an electrical current to pass through the cell membrane
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Metabotropic receptors (essence)
Receptors that are linked to membrane-bound G proteins which either open up ion channels or initiate a range of second messenger systems
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Ionotropic receptors - examples (5)
``` GABA-A 5HT-3 Nicotinic acetylcholine NMDA (Glutaminergic) Glycine ```
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Metabotropic receptors - examples (6)
``` GABA-B Serotonin (except 5HT-3) Muscarinic acetylcholine (M1-M3) Noradrenaline (alpha and beta) Mu Opioid Dopamine (D1-D5) ```
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A drug or substance that acts at a cell receptor to produce a response, by activating the receptor
Agonist
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A drug or substance that blocks a receptor, preventing activation
Antagonist
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A drug that binds to a receptor and produces a submaximal response. May therefore prevent other agonists from producing their full response.
Partial agonist
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A drug or substance that has the opposite effect to the agonist at that receptor
Inverse agonist
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A drug that can cause neuroregulation of neuroreceptors, leading to down- or up-regulation
Chronic agonist
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Neuroreceptor up-regulation
Occurs when an increased concentration of neurotransmitters causes an increase in the number of postsynaptic receptors
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Neuroreceptor down-regulation
Occurs when there is a decrease in the number of receptors in response to a long-term increase in neurotransmission
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A sudden decrease in the effects produced by a drug or substance that may occur during continuous use or repeated administration. Increasing the dose of the drug may restore the original response.
Tachyphylaxis
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A reduction in the effect produced by a drug or substance over time.
Tolerance
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Dopamine receptors (classification)
D1-like receptors - D1 - D5 D2-like receptors - D2 - D3 - D4 -------------------------------- They are all metabotropic D1-like receptors activate adenylyl cyclase D2-like receptors inhibit adenylyl cyclase
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Noradrenaline receptors (classification)
alpha 1 - postsynaptic - antagonism causes hypotension, sedation, and sexual dysfunction alpha 2 - pre and post synaptic - the presynaptic receptors act as autoreceptors (and are blocked by mirtazepine) - the postsynaptic receptors affect the release of growth hormone, arousal and blood pressure - linked with hypersalivation beta 1 - found mainly in neurons and heart - increases heart rate and cardiac contraction beta 2 - dense in the cerebellum and found in glia and blood vessels ----------------- all are metabotropic
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Serotonin receptors (summary)
~14 5-HT receptor subtypes All are metabotropic except 5-HT3 which is ionotropic -------------------- 5-HT1A - presynaptic downregulation is thought to be responsible for the delayed action of SSRIs 5HT1D - stimulation causes anti-migraine action 5-HT2 - post-synaptic, the target of atypical antipsychotics. Stimulation causes anxiety, agitation, insomnia, sexual dysfunction 5-HT2C - post-synaptic, atypical antipsychotics are associated with weight gain 5-HT3 - stimulation causes nausea, diarrhoea, headache. Ondansetron is antagonist 5-HT7 - involved in circadian rhythm regulation
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Presynaptic downregulation of these receptors is thought to be responsible for the delayed action of SSRIs
5-HT1A
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Stimulation of these serotonin receptors has an anti-migraine effect
5-HT1D
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These serotonin receptors are the target of atypical antipsychotics. Stimulation causes anxiety, agitation, insomnia, sexual dysfunction
5-HT2
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These serotonin receptors are associated with the propensity of atypical antipsychotics to cause weight gain
5-HT2C
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The only ionotropic serotonin receptor. Stimulation (e.g. by SSRIs) causes nausea, diarrhoea, and headache. Ondansetron is an antagonist.
5-HT3
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This serotonin receptor is involved in circadian rhythm regulation.
5-HT7
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Acetylcholine receptors (classification)
Nicotinic receptors - ionotropic Muscarinic receptors (M1-M5) - metabotropic - mediate the effects of anticholinergic drugs - --------------------------------------------------- - M1 (peripheral) - tachycardia - M4 - hypersalivation (in clozapine)
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GABA receptors (classification)
GABA-A - ionotropic - composed of 5 subunits - agonists: ethanol, benzodiazepines, z-drugs, barbiturates GABA-B - metabotropic - agonists: baclofen, GHB GABA-C - mainly found in the retina
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Benzodiazepines (mechanism of action)
Bind to the alpha subunit of GABA-A -> increases the frequency of chloride channel openings
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Dysfunction of which lobe? Contralateral hemiplegia, impaired problem solving, disinhibition, lack of initiative, Broca's aphasia and agraphia (dominant)
Frontal lobe
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Dysfunction of which lobe? Wernicke's aphasia (dominant), homonymous upper quadrantanopia, auditory agnosia (non-dominant)
Temporal lobe
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Dysfunction of which lobe? ``` anosognosia (lack of awareness of a disability or disease) dressing apraxia (difficulty in getting dressed) spatial neglect (lack of awareness of one side of the body) constructional apraxia (inability to copy pictures or combine parts of something into a meaningful whole) ```
Parietal lobe (non-dominant)
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Dysfunction of which lobe? finger agnosia (loss in ability to name or recognise specific fingers on the patient's own or on others hands) dyscalculia (an impaired ability to perform mental arithmetic) dysgraphia (inability to write) right-left disorientation (inability to carry out instructions that involve an appreciation of the right and left)
Parietal lobe (dominant) this is known as Gerstmann's syndrome
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Dysfunction of which lobe? Visual agnosia, visual illusions, contralateral homonymous hemianopia
Occipital lobe
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Alexia without agraphia | essence and pathology
The patient cannot read but is able to write. Understanding spoken language and conversation are intact. Usually due to a lesion destroying the left visual cortex, as well as the connections to the right visual cortex in the corpus callosum. It is typically caused by an occlusion of a branch of the PCA.
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Aphasia - definition and classification (3)
inability to comprehend or formulate language because of damage to specific brain regions - Fluent (receptive) aphasia - Non-fluent (expressive aphasia) - Pure aphasia
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Fluent (receptive) aphasia - examples (4)
Wernicke's aphasia Anomic aphasia Conduction aphasia Transcortical sensory aphasia
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Non fluent (expressive) aphasia - examples (3)
Broca's aphasia Transcortical motor aphasia Global aphasia
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Pure aphasia - example (3)
Pure alexia pure agraphia pure word deafness
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Dementia (essence)
an acquired syndrome of decline in memory and at least one other cognitive domain (e.g. Language, visuospatial or executive dysfunction) that is sufficient to interfere with social and occupational function in an alert person. The ICD-10 requires the following for a diagnosis:- - Disturbed higher cortical function (memory, thinking, orientation) - Consciousness is not clouded (to differentiate from delirium) It also adds that this may be accompanied by affective, motivational, emotional, perceptual, and motor changes.
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total population prevalence of dementia among over 65s
7.1%
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total population prevalence of dementia in the UK
1.3%
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Alzheimer's disease (% of all dementia cases)
62%
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Vascular dementia (% of all dementia cases)
17%
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Mixed dementia (% of all dementia cases)
10%
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Dementia with Lewy bodies (% of all dementia cases)
4%
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Frontotemporal dementia (% of all dementia cases)
2%
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Parkinson's dementia (% of all dementia cases)
2%
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Anatomical classification of dementia (3)
Cortical Subcortical Mixed
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Cortical dementia - areas affected (3)
Frontal lobes Temporal lobes Parietal lobes
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Cortical dementia - clinical features (4)
Amnesia (memory loss) Aphasia (inability to understand/express language) Apraxia (inability to coordinate skilled, purposeful motor tasks e.g. dressing/brushing teeth) Agnosia (inability to recognise familiar people/objects)
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Cortical dementia - examples (4)
Alzheimer's disease Pick's disease Creutzfeldt-Jakob disease Binswanger's disease
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Subcortical dementia - areas affected (3)
Thalamus Basal ganglia (caudate nucleus, substantia nigra) Deep white matter
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Subcortical dementia - clinical features (3)
Bradyphrenia (slowing in cognition), frequently a/w perseveration Frontal executive dysfunction (planning, organisation, problem-solving, multitasking, motivation, controlling emotion) Personality/mood changes
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Subcortical dementia - examples (6)
Vascular dementia Dementia associated Huntington's disease Dementia associated AIDS Dementia associated with Parkinson's disease Dementia associated with Wilson's disease Dementia associated with progressive supranuclear palsy
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Mixed dementia - examples (3)
Multi-infarct dementia Corticobasal degeneration Frontotemporal dementia (amyotrophic form of motor neurone disease)
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Alzheimer's disease - gross anatomical (macroscopic) features (3)
Generalised brain atrophy (shrivelling of the cerebral cortex) Focal atrophy of the medial temporal lobes - hippocampus - entorhinal cortex Dilatation of the lateral ventricles (aka hydrocephalus ex vacuo)
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Alzheimer's disease - main histopathological lesions (2)
Senile plaques (extracellular deposits of beta amyloid in the gray matter of the brain) ``` Neurofibrillary tangles (intracellular structures made by the hyperphosphorylation of the microtubule-associated tau protein) ```
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Senile plaques (description)
extracellular deposits of beta amyloid in the gray matter of the brain found in Alzheimer's disease
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Neurofibrillary tangles (description)
intracellular structures made by the hyperphosphorylation of the microtubule-associated tau protein found in Alzheimer's disease
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In which disease are the following histopathological features seen?: cerebral amyloid angiopathy (CAA) granulovacuolar degeneration (GVD) Hirano bodies
Alzheimer's disease
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Alzheimer's disease - biochemical pathology
deficit of acetylecholine from damage to an ascending forebrain projection
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Alzheimer's disease - management (4 drugs)
NICE now recommend the three acetylcholinesterase inhibitors (donepezil, galantamine and rivastigmine) as options for managing mild to moderate Alzheimer's disease memantine (a NMDA receptor antagonist) is reserved for patients with moderate - severe Alzheimer's
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Frontotemporal dementia - essence, subtypes (3)
FTD refers to a clinical syndrome, of which there are 3 types: - behavioural variant (BVFTD) - progressive non-fluent aphasia (PNFA) - semantic dementia (SD)
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Frontotemporal dementia - common features (4)
Onset before 65 Insidious onset Personality change and social conduct problems Relatively preserved memory and visuospatial skills
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Frontotemporal lobe degeneration (FTLD) - essence, subtypes (2)
FTLD refers to a pathological diagnosis, of which there are 2 types: Tauopathies (FTLD-tau) - Pick's disease - Corticobasal degeneration (CBD) - Progressive supranuclear palsy (PSP) - aka Steele-Richardson-Olszewski syndrome) - FTDP-17 - Multisystem atrophy (MSA) Ubiquitinopathies (FTLD-U) - FTLD-TDP - FTDP-17 (PGRN) - FTLD-FUS
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Frontotemporal lobe degeneration (gross anatomical features)
Atrophy of the frontal and temporal lobes
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Pick's Disease - presentation
behavioural-variant frontotemporal dementia personality change and impaired social conduct. Other common features include hyperorality, disinhibition, increased appetite, and perseveration behaviours.
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Pick's Disease - gross anatomical features
'knife-blade' atrophy of the frontal and temporal lobes
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Pick's Disease - histopathological features
``` Pick bodies (spherical aggregations of tau protein) Pick cells Gliosis Neurofibrillary tangles Senile plaques ```
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Lewy body disorders - classification
Parkinson's disease without dementia (PD) Lewy body dementia (LBD) - Dementia with Lewy Bodies (DLB) - Parkinson's disease dementia (PDD) ------------------------------------------------------------------- DLB - PD symptoms develop >1yr after the onset of memory problems PDD - PD symptoms develop within a year of memory problems; or PD symptoms develop first
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What drugs should be avoided in Lewy body dementia as patients?
Neuroleptics - patients can develop irreversible parkinsonism
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Lewy body dementia - macroscopic changes (2)
``` Pallor of the substantia nigra Cerebral atrophy (but less marked than in Alzheimer's) ```
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Lewy body dementia - microscopic changes (3)
Lewy bodies - intracellular protein accumulations - made of alpha synuclein Neurofibrillary tangles Senile plaques
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Classic (sporadic) Creutzfeldt-Jakob disease (CJD) - age of onset - cause - duration to death - symptoms - MRI - EEG
``` Age 55-65 Caused by Genetic mutation 5 month duration to death Early neurological signs and dementia MRI - Bilateral anterior basal ganglia high signal EEG - triphasic waves ```
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Variant Creutzfeldt-Jakob disease (vCJD) - age of onset - cause - duration to death - symptoms - MRI - EEG
``` Age 25-30 Caused by infected meat products ~1 year duration to death psychological symptoms such as anxiety, withdrawal and dysphonia are the most common presenting features MRI - pulvinar sign EEG - generalised slowing ```
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Schizophrenia - macroscopic pathological changes (3)
Ventricular enlargement Reduced brain volume (up to 5%) Reduced left planum temporale gray matter, and reversed planum temporale surface area asymmetry (normally left larger than right in a right handed person)
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Schizophrenia - microscopic pathological changes (2)
reduction of the size of the dorsolateral prefrontal cortex reduction of the size of the hippocampus
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Pure sensory cranial nerves (3)
Olfactory Optic Vestibulocochlear 1 - 2 - 8
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Pure motor cranial nerves (5)
``` Oculomotor Trochlear Abducens Accessory Hypoglossal ``` 3 - 4 - 6 - 11 - 12
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Mixed (sensory and motor) cranial nerves (4)
Trigeminal Facial Glossopharyngeal Vagus 5 - 7 - 9 - 10
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Neuronal cells (key characteristics) - Golgi type 1 - Golgi type 2 - Amacrine neurons
- Golgi type 1 - Long axon; - Golgi type 2 - Short axon terminating near the parent cell; - Amacrine neurons - No axon.
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``` Angular gyrus (location, function, Brodman area) ```
Inferior parietal lobe Processing of auditory and visual input Comprehension of language Number processing Brodmann area 39
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Dementia pugilistica | aka, common presentation
aka 'punch drunk syndrome' a form of dementia usually seen in people who experience repeated head injuries, such as boxers. Symptoms may appear immediately after a single traumatic brain injury, but are typically described following the cessation of exposure to chronic brain injury.
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Which white matter tract + type Efferent projection fibers that connect motor cortex to the brain stem and spinal cord (2)
Corticospinal Corticobulbar both are projection tracts
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Which white matter tract + type Fibers to and from virtually all cortical areas fan out superolaterally from the internal capsule
Corona Radiata Projection tract
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Which white matter tract + type Major conduit of fibers to and from the cerebral cortex
Internal capsule Projection tract
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Which white matter tract + type Connects the lateral geniculate nucleus to occipital (primary visual) cortex
Geniculocalcarine Tract (optic radiation) Projection tract
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Which white matter tract + type The largest white matter fiber bundle, the corpus callosum is a massive accumulation of fibers connecting corresponding areas of cortex between the hemispheres
Corpus Callosum Commissural tract
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Which white matter tract + type --- crosses through the lamina terminalis. Its anterior fibers connect the olfactory bulbs and nuclei; its posterior fibers connect middle and inferior temporal gyri
Anterior Commissure Commissural tract
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Which white matter tract + type Interconnects portions of the frontal, parietal, and temporal lobes
Cingulum Association tract
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Which white matter tract + type Connects occipital and frontal lobes (2)
Superior Occipitofrontal Fasciculus Inferior Occipitofrontal Fasciculus Association tracts
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Which white matter tract + type Connects the orbital and inferior frontal gyri of the frontal lobe to the anterior temporal lobe
Uncinate Fasciculus Association tract
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Which white matter tract + type Connects the frontal lobe cortex to parietal, temporal, and occipital lobe cortices (the largest association bundle)
Superior Longitudinal Fasciculus Association tract
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Which white matter tract + type Connects temporal and occipital lobe cortices
Inferior Longitudinal (occipitotemporal) Fasciculus
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Cerebrospinal fluid - formed by which cells - where - how much
formed by ependymal cells in the choroid plexus of the lateral, third and fourth ventricles approx 500ml/day the fluid is constantly reabsorbed, so that only 100-160ml is present at any one time. It occupies the space between the arachnoid and pia matter.
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Cerebrospinal fluid - transport
Lateral ventricles (foramen of Munro) Third ventricle (aqueduct of Sylvius aka cerebral aqueduct) Fourth ventricle (foramen of Magendie + foramen of Lushka) Subarachnoid space and spinal cord (arachnoid villi) Dural venous sinuses -> return to the vascular system
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CSF | composition compared with plasma
CSF has a composition identical to that of the brain ECF. Major differences with plasma: Reduced - protein content - glucose - cholesterol - pH - calcium - potassium Unchanged - sodium Increased - chloride - magnesium
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Blood brain barrier | essence
a semi permeable membrane formed by the tight junctions of endothelial cells in the capillaries of the brain separates the blood from the CSF
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Blood brain barrier | fenestrations - 6
At several areas the BBB is fenestrated to allow neurosecretory products to enter the blood. These areas are known as circumventricular organs and include:- - Pineal body - Posterior pituitary - Area postrema - Subfornical organ - Vascular organ of the lamina terminalis - Median eminence
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Blood brain barrier | permeability - key facts
- Lipid soluble molecules pass through relatively easily whereas water soluble ones do not. - Large molecules do not pass through the BBB easily - Molecules that are highly charged struggle to pass through - The permeability of the BBB increases when it is inflamed - Nasally administered drugs can theoretically bypass the BBB - The BBB is fenestrated at the circumventricular organs (make an effort to remember the posterior pituitary and the area postrema)
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Hydrocephalus | essence, classification
an abnormal accumulation of CSF in the ventricles of the brain COMMUNICATING - i.e. normal pressure hydocephalus NON-COMMUNICATING
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Normal pressure hydrocephalus - cause - classic triad (aka)
impaired re-absorption of CSF by the arachnoid villi The CSF pressure is typically high but still within the normal range, for this reason it does not present with features of high ICP such as headache and nausea Hakim's triad: - Incontinence - Gait ataxia - Dementia ('wet, wobbly, wacky')
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Non-communicating hydrocephalus - cause - features (6)
obstruction to the flow of CSF in the third or fourth ventricle signs of raised intracranial pressure:- - Headache - Vomiting - Hypertension - Bradycardia - Altered consciousness - Papilledema
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Anterior cranial fossa - bones (3) - contents (of the brain)
Frontal bones Ethmoid bones Lesser wing of sphenoid Frontal lobes
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Middle cranial fossa - bones (3) - contents (of the brain)
Greater wing of the sphenoid Sella turcica Majority of temporal bones Temporal lobes
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Posterior cranial fossa - bones - contents (of the brain) - 3
Occipital bone occipital lobes cerebellum medulla
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Foramen spinosum - location (fossa) - allows passage of...
Middle fossa Middle meningeal artery
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Foramen ovale - location (fossa) - allows passage of...
Middle fossa Mandibular division of trigeminal nerve
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Foramen lacerum - location (fossa) - allows passage of...
Middle fossa Internal carotid artery
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Foramen magnum - location (fossa) - allows passage of...
Posterior fossa Spinal cord
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Jugular foramen - location (fossa) - allows passage of...
Posterior fossa Cranial nerves IX, X, and XI
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Angular gyrus - location (lobe) - functions
Parietal lobe Language, mathematics and cognition
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Cingulate gyrus - location - functions
Adjacent to the corpus callosum Emotion, learning, and memory
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Fusiform gyrus - location (lobe) - functions
Temporal lobe Face and body recognition (damage -> prosopagnosia) word and number recognition (visual)
282
Precentral gyrus - location (lobe) - functions
Frontal lobe Voluntary movement control
283
Postcentral gyrus - location (lobe) - functions
Parietal lobe Touch
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Lingual gyrus - location (lobe) - functions
Occipital lobe Dreaming, word recognition (visual)
285
Superior frontal gyrus - location (lobe) - functions
Frontal lobe Laughter and self awareness
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Superior temporal gyrus - location (lobe) - functions
Temporal lobe Language (Wernicke's area) Sensation of sound
287
Parahippocampal gyrus - location - functions
Surrounds the hippocampus | Memory also asymmetry has been observed in schizophrenia
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Dentate gyrus - location - functions
Hippocampus Formation of episodic memory
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Papp-Lantos bodies - associated condition - description
Multisystem atrophy alpha-synuclein inclusions in oligodendrocytes found in the substantia nigra, cerebellum, and basal ganglia
290
Pick bodies - associated condition - description
Frontotemporal dementia Large, dark-staining aggregates of proteins in neurological tissue
291
Lewy bodies - associated conditions (2) - description
Parkinson's disease Lewy Body dementia Round, concentrically laminated, pale eosinophilic cytoplasmic inclusions (aggregates of alpha-synuclein)
292
Asteroid bodies - associated conditions (2)
Sarcoidosis | Berylliosis
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Barr bodies | essence
Stains of inactivated X chromosomes
294
Mallory bodies - associated conditions (4)
alcoholic hepatitis alcoholic cirrhosis Wilson's disease primary-biliary cirrhosis
295
Schaumann bodies - associated conditions (2)
Sarcoidosis | Berylliosis
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Zebra bodies - associated conditions (3)
Niemann-Pick disease Tay-Sachs disease Any of the mucopolysaccharidoses
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LE bodies (AKA hematoxylin bodies) - associated condition
SLE (lupus)
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Hirano bodies - associated conditions (2) - description
Normal ageing but more numerous in Alzheimers disease Eosinophilic, football shaped inclusion seen in neurons of the brain
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Neurofibrillary Tangles - associated condition - description
Alzheimer's disease Microtubule-associated proteins and neurofilaments
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Kayser-Fleischer rings - associated condition - description
Wilson's disease Rings of discoloration on cornea
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Kuru plaques - associated condition - description
Kuru and Gerstmann-Sträussler syndrome sometimes present in Creutzfeldt-Jakob disease (CJD) composed partly of a host-encoded prion protein
302
Papez circuit | essence
a neural pathway in the brain that mediates the process of emotion it was one of the first descriptions of the limbic system bilateral, symmetrical and located on the medial surface of the brain. llinks the cortex to the hypothalamus
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Papez circuit - components (8)
``` Hippocampus fornix (its major output tract) Mamillary bodies of the hypothalamus mamillothalamic tract Anterior nucleus of the thalamus Cingulate gyrus Parahippocampal gyrus Entorhinal cortex (-> returns to hippocampus) ```
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EEG Delta Waves - Frequency - Brain region - Normally seen in
1-4 Hz Frontally in adults and posteriorly in children Slow wave sleep and in babies. If present when awake this strongly suggests pathology
305
EEG Theta Waves - Frequency - Brain region - Normally seen in
4-8 Hz Generalised Young children, drowsy and sleeping adults, with certain medications, meditation. Small amount seen in awake adults, excessive amount when awake may indicate pathology
306
EEG Alpha Waves - Frequency - Brain region - Normally seen in
8-12 Hz Posteriorly When relaxed and when the eyes are closed (whilst awake)
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EEG Beta Waves - Frequency - Brain region - Normally seen in
12-30 Hz Frontally When busy or concentrating ================= 'Beta' - B for 'busy'
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EEG Sigma Waves (aka) - Frequency - Brain region - Normally seen in
(aka sleep spindles) 12-14 Hz Frontal and central regions Stage 2 sleep. =================== Along with k-complexes they are the defining characteristic of stage 2 sleep
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EEG Gamma Waves - Frequency - Brain region - Normally seen in
30-100 Hz No specific areas Meditation
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sporadic CJD - EEG findings (2)
Early - non specific slowing Later - periodic biphasic and triphasic synchronous sharp wave complexes, superimposed on a slow background rhythm
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Huntingdon's disease - EEG findings
Low voltage EEG, Flattened trace (in particular no alpha)
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Delirium - EEG findings (3)
Diffuse slowing Decreased alpha Increased theta and delta
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Delirium tremens - EEG findings
Hyperactive trace, fast
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Alzheimer's disease - EEG findings (2)
Reduced alpha and beta Increased delta and theta
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Petit mal epilepsy (absence seizure) - EEG findings
Generalised, bilateral, synchronous, 3Hz (3 waves per second) spike and wave pattern
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Generalised epilepsy - EEG findings
Sharp spikes, 25-30Hz
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Partial epilepsy - EEG findings
Focal spikes
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Myoclonic epilepsy - EEG findings
Generalised spike and wave activity
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Encephalopathy - EEG findings
Diffuse slowing
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Normal aging - EEG findings
Diffuse slowing, which can be focal or diffuse, if focal most commonly seen in the left temporal region
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Typical antipsychotics - effect on EEG (2)
Decreased beta Increased alpha and delta, ==================== haloperidol least effect
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Which atypical antipsychotic has most significant effect on the EEG?
Clozapine
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Antidepressants - effect on EEG (2)
Reduce beta | Increase in all other wave forms
324
Anticonvulsants - effect on EEG
None
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Lithium - effect on EEG
Slowing
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Benzodiazepines - effect on EEG (2)
Increase beta Decrease alpha
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Barbiturates - effect on EEG
Increase beta
328
Stimulants (cocaine, nicotine) - effect on EEG
Increase alpha
329
Depressants (alcohol, opioids) - effect on EEG
Decrease alpha
330
Cannabis - effect on EEG
Increase alpha
331
Which stage of sleep predominates in a neonate?
REM sleep ========================= Newborns sleep about 16 hours a day. They spend more than 50% of sleep time in REM sleep. Sleep-onset REM is also seen in neonates.
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HPA axis (summary)
``` Hypothalamus (CRH) Anterior pituitary (ACTH) Adrenal cortex (Cortisol) ```
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HPA axis dysfunction in depression
Hypersecretion of CRH, ACTH, and Cortisol Adrenocoritcal enlargement CRH elevated in the CSF About 50% of depressed inpatients do not show the normal suppression of cortisol on dexamethasone suppression test
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NREM Sleep Stage I - % of time spent in stage - EEG findings
5% Theta waves
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NREM Sleep Stage II - % of time spent in stage - EEG findings
45% Sleep spindles K complexes
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NREM Sleep Stage III - % of time spent in stage - EEG findings
12% <50% Delta waves
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NREM Sleep Stage IV - % of time spent in stage - EEG findings
13% >50% Delta waves
338
Sleep latency - definition - average time
Time taken to fall asleep (onset of NREM Stage I) 15-20mins
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Mirror neuron - location - function
a particular class of visuomotor neurons, originally discovered in area F5 of the monkey PREMOTOR CORTEX they discharge both when the monkey does a particular action and when it observes another individual (monkey or human) doing a similar action. They offer a model for understanding imitation learning
340
Wernicke and Korsakoff syndrome - specific brain region affected
Medial thalamus and mammillary bodies of the hypothalamus
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Hemiballism - specific brain region affected
Subthalamic nucleus of the basal ganglia
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Huntington chorea - specific brain region affected
Striatum (caudate nucleus) of the basal ganglia
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Parkinson's disease - specific brain region affected
Substantia nigra of the basal ganglia
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Kluver-Bucy syndrome (hypersexuality, hyperorality, hyperphagia, visual agnosia) - specific brain region affected
Amygdala
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Utilization behaviour - description - caused by dysfunction to which lobe?
reaching out and automatically using objects in the environment in an object-appropriate manner that is inappropriate for the particular context. e.g. a patient may pick up a toothbrush and begin to brush his teeth, in response to a toothbrush being placed in front of him, but in a context or setting in which brushing teeth would not normally be expected or done, such as in an appointment with a doctor. results from lesions of the orbitofrontal lobe whereby there is a loss of normal inhibitory control.
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Alien hand sign
the experience of bizarre hands movements for which the patient feels no sense of control
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Manual groping behaviour - description
refers to situations where the hand (and often the eyes as well) follow an object under examination, in a somewhat magnetic fashion. Following tactile stimulation, automatic manual manipulation is observed. The patients may, for example, hold, rub, or manipulate objects placed in front of them or on their own person (e.g., buttons, the fabric of collars, etc.).
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Environmental Dependency Syndrome
the deficits in personal control of action and a striking overreliance on social and physical environmental stimuli for guiding ones behaviour in a more elaborate social context. e.g. one patient, upon being told that the examiners office was an art gallery, began staring and commenting on pictures as if they were on display.
349
Multisystem atrophy - essence - presentations/cardinal features (3)
one of the Parkinson plus syndromes, three presentations: Triad of symptoms: - Cerebellar Ataxia - Autonomic failure - Parkinsonism ``` Shy-Drager Syndrome (mainly autonomic failure) Striatonigral degeneration (mainly Parkinsonism) Olivopontocerebellar atrophy (mainly cerebellar ataxia) ```
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Multisystem atrophy - macroscopic features (3) - microscopic features (1)
Macroscopic features - Pallor of substantia nigra - Greenish discolouration and atrophy of the putamen - Cerebellar atrophy Micrscopic features: - Papp-Lantos bodies (alpha-synuclein inclusions in oligodendrocytes found in the substantia nigra, cerebellum, and basal ganglia)
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Cranial nerve reflexes: Pupillary light reflex - Sensory component - Motor component
Sensory: Optic Motor: Oculomotor
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Cranial nerve reflexes: Accommodation reflex - Sensory component - Motor component
Sensory: Optic Motor: Oculomotor
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Cranial nerve reflexes: Jaw jerk - Sensory component - Motor component
Sensory: Trigeminal Motor: Trigeminal
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Cranial nerve reflexes: Corneal reflex - Sensory component - Motor component
Sensory: Trigeminal Motor: Facial
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Cranial nerve reflexes: Vestibulo-ocular reflex - Sensory component - Motor component
Sensory: Vestibulocochlear Motor: Oculomotor, trochlear, abducent
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Cranial nerve reflexes: Gag reflex - Sensory component - Motor component
Sensory: Glossopharyngeal Motor: Vagus
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Apraxia | essence
a motor disorder caused by damage to the brain (specifically the posterior parietal cortex) in which the individual has difficulty with the motor planning to perform tasks or movements when asked, provided that the request or command is understood and the individual is willing to perform the task.
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an inability to make fine/delicate movements
Limb kinetic apraxia
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an inability to follow out learned tasks when given the necessary objects e.g. if given a hairbrush they try to write with it
Ideomotor apraxia
360
an inability to copy a picture or combine parts of something to form a whole
Constructional apraxia
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an inability to follow a sequence of actions in the correct order e.g. Take a match out a box and strike it with your left hand
Ideational apraxia
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an inability to control eye movements
Oculomotor apraxia
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Homonymous hemianopia (location of lesions) - incongruous (asymmetrical) - congruous (symmetrical) - macula sparing
- incongruous (asymmetrical) - optic tract - congruous (symmetrical) - optic radiation or occipital cortex - macula sparing - occipital cortex
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Homonymous quadrantanopia (location of lesions) - superior - inferior
superior: lesion of temporal lobe inferior: lesion of parietal lobe ----------------------------------------------------- mnemonic = PITS (Parietal-Inferior, Temporal-Superior)
365
Bitemporal hemianopia (location of lesions) - upper quadrant defect > lower quadrant defect - lower quadrant defect > upper quadrant defect
optic chiasm upper quadrant defect > lower quadrant defect: - inferior chiasmal compression - commonly a pituitary tumour lower quadrant defect > upper quadrant defect - superior chiasmal compression - commonly a craniopharyngioma
366
Illicit drugs (mechanism of action) - drugs that interefere with ionotropic receptors or ion channels (4)
Alcohol nicotine benzodiazepines ketamine
367
Illicit drugs (mechanism of action) - Drugs which interfere with G coupled receptors (3)
Opioids cannabinoids y-hydroxybutyrate (GHB)
368
Illicit drugs (mechanism of action) Drugs that target monoamine transporters (3)
Amphetamine ecstasy cocaine ===================== The main mechanism by which cocaine and amphetamine act is by increasing levels of dopamine in the synaptic cleft. They do this however in slightly different ways.
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Wilson's disease - aka - pathophysiology - brain regions affected
hepatolenticular degeneration failure to excrete copper results in very high levels in the liver and brain degeneration of the lenticular nucleus (putamen and globus pallidus)
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Wilson's disease - biochemistry findings - clinical features
low levels of both ceruloplasmin and total serum copper. The condition presents with movement disorders such as dystonia, parkinsonian tremor, and rigidity combined with behavioural problems and a degree of dementia is often seen. A Kayser-Fleischer ring is the term given to the brown ring seen around the iris in people with Wilson's disease.
371
Which cranial nerves exit through the Cribiform plate?
Olfactory (I)
372
Which cranial nerves exit through the Optic foramen?
Optic nerve (II)
373
Which cranial nerves exit through the Superior orbital fissure?
Oculomotor (III) Trochlear (IV) Trigeminal (ophthalmic V1) Abducens (VI)
374
Which cranial nerves exit through the Round foramen?
Trigeminal (maxillary V2)
375
Which cranial nerves exit through the Oval foramen (Foramen Ovale)?
Trigeminal (mandibular V3)
376
Which cranial nerves exit through the Internal auditory canal?
Facial (VII) | Vestibulocochlear (VIII)
377
Which cranial nerves exit through the Jugular foramen?
Glossopharyngeal (IX) Vagus (X) Accessory (XI)
378
Which cranial nerves exit through the Hypoglossal canal?
Hypoglossal (XII)
379
Autotopagnosia
Inability to orient parts of the body
380
Phonagnosia
Inability to recognize familiar voices
381
Astereoagnosia
Inability to recognize objects by touch
382
Lentiform nucleus - components (2)
Putamen Globus pallidus
383
Hypothalamic nucleus responsible for: Circadian rhythm
Suprachiasmatic
384
Hypothalamic nucleus responsible for: Secretes GnRH to stimulate LH and FSH in the anterior pituitary Regulates body temperature
Preoptic
385
Hypothalamic nucleus responsible for: Synthesizes oxytocin
Paraventricular
386
Hypothalamic nucleus responsible for: Regulates parasympathetics to keep cool
Anterior
387
Hypothalamic nucleus responsible for: Regulates sympathetics to keep warm
Posterior
388
Hypothalamic nucleus responsible for: Synthesizes ADH
Supraoptic
389
Hypothalamic nucleus responsible for: Releases dopamine GHRH to anterior pituitary Hunger & satiety
Arcuate
390
Hypothalamic nucleus responsible for: Stimulate gastrointestinal system, hunger Triggers shivering
Dorsomedial
391
Hypothalamic nucleus responsible for: Satiety
Ventromedial
392
Hypothalamic nucleus responsible for: Hunger and thirst
Lateral
393
5-HIAA - what is it - association with depression
serotonin metabolite (5-hydroxyindoleacetic acid) low CSF levels in a third of people with depression low CSF levels also associated with: - higher likelihood of suicide - increased levels of aggression
394
What brain region is responsible for executive functions such as planning, judgement, and decision-making?
Dorsolateral prefrontal cortex