Basic neurosciences Flashcards
Blood supply to the brain (overview)
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.
Anterior cerebral artery (ACA) occlusion (associated defects)
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)
Middle cerebral artery (MCA) occlusion (associated defects)
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
Posterior cerebral artery (PCA) occlusion (associated defects)
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
Frontal lobe and Parietal lobe are separated by … (aka)
The central sulcus
aka fissure of Rolando
Primary motor cortex (region, lobe and Brodmann area)
Pre-central gyrus, frontal lobe
Brodmann area 4
Subdivisions of the motor cortex, and their functions (3)
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
Broca’s area (function, location, and Brodmann areas)
Motor speech area
Located in the inferior frontal gyrus on the dominant (usually left) hemisphere
Brodmann areas 44+45
Frontal eye field (function, location, and Brodmann areas)
Voluntary saccadic eye movements
Located at the caudal ends of the superior frontal gyrus (Brodmann 8) and middle front gyrus (Brodmann 6)
Primary somatosensory cortex (region, lobe and Brodmann areas)
Postcentral gyrus, parietal lobe
Brodmann areas 1, 2, and 3
Primary auditory cortex (region, lobe and Brodmann area)
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.
Planum temporale (location and key fact)
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.
Wernicke’s area (function, location, and Brodmann areas)
Comprehension of written and spoken language.
Superior temporal gyrus in the dominant hemisphere.
Brodmann area 22.
Lateralisation of brain function (summary)
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%
Primary visual cortex (region, lobe and Brodmann area)
Striate cortex (calcarine cortex) in the occipital lobe
Brodmann area 17
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
Frontal lobe
Motor movements (specific region & lobe)
Motor cortex - frontal lobe
Brain region & lobe responsible for:
- Executive function (e.g. planning, initiation, organisation, set-shifting, reasoning/judgement, abstract thinking)
- Decision-making
- Working memory; Attention
Premotor cortex - frontal lobe
Brain region + lobe responsible for:
- Inhibition
- Personality/emotions/social conduct
Orbitofrontal cortex - frontal lobe
Language - motor expression of speech (specific region & lobe)
Broca’s area - inferior frontal gyrus on the dominant (usually left) hemisphere; frontal lobe
Saccadic eye movements (specific region & lobe)
Frontal eye fields - frontal lobe
Gerstmann syndrome (brain region deficit, key features)
Results from lesions in the left (/dominant) inferior parietal lobe
- agraphia
- acalculia
- finger agnosia (inability to distinguish fingers in the hand)
- left-right disorientation
Balint syndrome (brain region deficit, key features)
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)
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
Parietal lobe
Which lobe?:
Memory Deductive reasoning Language comprehension Auditory perception Affective prosody Music comprehension Face recognition Visual field processing (superior) Olfactory perception
Temporal lobe
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
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
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.
Structures in the visual pathway (7)
Eye Optic nerve Optic chiasm Optic tract Lateral geniculate nucleus Optic radiation Primary visual cortex
Limbic system (basic substructure (2) and functions)
- Structures in the cerebral cortex - collectively termed the limbic lobe
- hippocampus
- insular cortex
- orbital frontal cortex
- subcallosal gyrus
- cingulate gyrus
- parahippocampal gyrus - Subcortical structures
- olfactory bulb
- hypothalamus
- amygdala
- septal nuclei
- some thalamic nuclei
Functions:
- Processing of emotions
- Encoding and retrieval of memory
- Autonomic functions
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
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
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)
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)
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
Diencephalon - subdivision (4)
The — is divided into 4 areas, which are interposed between the brain stem and cerebral hemispheres:
- thalamus
- hypothalamus
- epithalamus
- subthalamic nucleus
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
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
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.
3 main types of white matter tracts
Commissural fibres
Association fibres
Projection fibres
The largest white matter tract
Corpus callosum
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
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
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
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
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
The longest intrahemispheric white matter tract
The superior longitudinal fasciculus
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
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
Basal ganglia - components (4)
Striatum (caudate, putamen, nucleus accumbens)
Subthalamic nucleus
Substantia nigra (divided into pars compacta and pars reticulate)
Globus pallidus
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
Brainstem - key structures (3)
Medulla oblongata
Pons
Midbrain
Midbrain - 2 major structures
Red nucleus
Substantia nigra
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
Olfactory nerve (I) (fibres, function, test)
Sensory
- Smell
Test smell with clove or coffee
Optic nerve (II) (fibres, function, test)
Sensory
- Vision
Tests:
- snellen chart (acuity)
- ischihara chart (colour vision)
- pupillary reflexes - light and accommodation
- visual fields
- fundoscopy
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
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
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
Abducens nerve (VI) (fibres, function, test)
Motor - Movement of eye muscle: lateral rectus (lateral movement of eye) Test - eye movements with head still
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
Vestibulo-cochlear nerve (VIII)
fibres, function, test
Sensory
- hearing
- proprioception of head and balance
Test - Rhinne and Weber tests
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
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
Accessory nerve (XI) (fibres, function, test)
Motor
- trapezius and sternocleidomastoid muscles
Test - turn head and shrug shoulders against resistance
Hypoglossal nerve (XII) (fibres, function, test)
Motor
- movement of tongue
Test - look for wasting/fasciculation. Stick out tongue and look for deviation.
How many nerve nuclei does the brainstem contain?
10
Olfactory and optic nerves come from the cerebrum
Which side of the body do cerebellar lesions affect?
Ipsilateral
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’
Which white matter tract?:
Connects the orbitofrontal cortex to the anterior temporal lobes. Plays an important role in social cognition and language.
Uncinate fasciculus
2 main types of cells in the nervous system
Neurons
Glial cells
From which primary germ layer do neurons originate?
Ectoderm
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
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
Structural classification of neurons (3)
Unipolar
Bipolar
Multipolar
Most neurons are multipolar - one axon and one or more dendrites
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
(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
(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
(cell)
- small glial cells of mesenchymal origin
- the primary immune cells of the CNS
Microglia
(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
Glial cell
- derived from the neural crest
- only found in the peripheral nervous system
-responsible for the myelination of the PNS
Schwann cells
Glial cell in the PNS, derived from the neural crest
Provides a supportive role
Satellite cells
Cerebral cortex
essence, subdivisions
The outer covering of grey matter over the cerebral hemispheres
- Neocortex (top layer)
- Allocortex
- Paleocortex
- Archicortex
Paleocortex - subdivisions (2)
part of the cerebral cortex
includes the entorhinal cortex (in the medial temporal lobe) and piriform lobe (specialised for olfaction)
Archicortex (function)
consists of the hippocampus, dealing with memory and spatial function
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
Neocortex - 2 main cell types
Pyramidal cells
Stellate cells
Pyramidal cells (location)
- make up 75% of cortical neurons
- the principal output neurons, found in layers II-V of the neocortex
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
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
Other cells in the neocortex (3)
Fusiform cells
Horizontal cells of Cajul
Cells or Martionotti
Cerebellar cortex - layers (3, +cells)
Molecular, outermost layer
Purkinje, middle layer
Granular, innermost layer
Molecular, outermost layer of the cerebellar cortex - cells (4)
Axons of granule cells
Dendrites of Purkinje cells
Stellate and Basket cells
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
Granular, innermost layer of the cerebellar cortex - cells (2)
Granule cells - whose axons extend into the molecular layer
Golgi cells
Cell type?:
- found uniquely in the cerebellum
- only source of output from the cerebellar cortex
- inhibitory (use GABA)
Purkinje cells
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
Stellate, basket and Golgi cells (location, function)
inhibitory interneurons in the cerebellar cortex
Main cell type found in the hippocampus
Pyramidal cell
Main cell type found in the dentate gyrus (within the hippocampus)
Granule cell
Major neurotransmitters (6)
Dopamine Noradrenaline Serotonin Acetylcholine Histamine Glutamate
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
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
Brian regions involved in major neurochemical pathways
Regions involved in motor control (3)
Subtantia nigra (in the brainstem)
Striatum
Cerebellum
Brian region involved in major neurochemical pathways
Regions involved in appetite and hormone release (2)
Hypothalamus
Pituitary
Brian region involved in major neurochemical pathways
Associated with relaying sensory and motor signals to the cortex, as well as sleep and wakefulness
Thalamus
Brian region involved in major neurochemical pathways
… lies in the brainstem and is associated with sleep and respiratory function
Locus coeruleus
Brian region involved in major neurochemical pathways
Regions involved with memory (3)
Amygdala (fear and memory consolidation)
Hippocampus
Nucleus basalis of Meynert
Brian region involved in major neurochemical pathways
… lies in the brainstem and is involved with emotions and behaviour
Ventral tegmental area
==================
in the midbrain
Brian region involved in major neurochemical pathways
… lies in the brainstem and is associated with pain, sleep and wakefulness
Raphe nuclei
4 major dopamine pathways in the brain
Mesolimbic
Mesocortical
Nigrostriatal
Tuberoinfundibular
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
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
Mesocortical pathway (dopamine) - brain regions
Projects from the ventral tegmental area (in the brainstem) to the prefrontal cortex.
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)
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
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
Tuberoinfundibular pathway (dopamine) - brain regions
Projects from the hypothalamus to the anterior pituitary gland
Tuberoinfundibular pathway (dopamine) - clinical significance
Dopamine in this pathway normally inhibits prolactin secretion.
Hypoactivity (caused by dopamine receptor blockade)-> hyperprolactinaemia
2 major noradrenaline pathways in the brain
Ascending noradrenaline pathway
Descending noradrenaline pathway
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
Descending noradrenaline pathway
brain regions and functions
Projects from the brainstem down the spinal cord
Regulates pain pathways
2 major serotonin pathways in the brain
Ascending serotonin pathway
Descending serotonin pathway
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
Descending serotonin pathway
brain regions and functions
Projects from the brainstem down the spinal cord
Regulates pain pathways
2 major acetylcholine pathways in the brain
Acetylcholine pathway from the brainstem
Acetylcholine pathway from the basal forebrain
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
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
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
5 major glutamate pathways in the brain
Cortical brainstem glutamate pathway
Corticostriatal glutamate pathway
Thalamocortical glutamate pathway
Corticothalamic glutamate pathway
Cortico-cortical glutamate pathway
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
Cortical brainstem glutamate pathway (clinical significance)
The cortical brainstem glutamate pathway normally:
- 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 - acts as an accelerator on the mesocortical dopamine pathway
- Hypoactivity -> decreased mesocortical activity and therefore the negative symptoms of schizophrenia
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
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.
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
Synapse - definition + types (3)
A junction between two nerve cells
- Chemical synapses
- excitatory (depolarisation of the postsynaptic neuron)
- inhibitory (hypoerpolarisation of the postsynaptic neuron) - Electrical synapses
- abundant both in the retina and cerebral cortex - Conjoint synapses (electrical and chemical properties)
The role of the hypothalamus in feeding behaviour (2)
Ventromedial hypothalamus - the satiety centre
Lateral hypothalamus - the feeding centre
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]
Anorexigenic hormones (hormones that decrease appetite) - 2
Leptin
- produced by adipose tissue
Cholecystokinine (CCK)
- produced mainly by the gut
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)
Which primary afferent axons are myelinated?
All of the A axons (alpha, beta, delta) are myelinated
C fibres are unmyelinated
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)
Embryonic brain - divisions (3)
Forebrain (prosencephalon)
- diencephalon
- telencephalon
Midbrain (mesencephalon)
Hindbrain (rhombencephalon)
- metencephalon
- myelencephalon
Forebrain (prosencephalon) - subdivisions
Telencephalon (cerebrum)
- cerebral cortex
- underlying white matter
- basal ganglia.
Diencephalon
- prethalamus
- thalamus
- hypothalamus
- subthalamus
- epithalamus
- pretectum
Midbrain (mesencephalon) - subdivisions
tectum (or corpora quadrigemina)
tegmentum
ventricular mesocoelia
cerebral peduncles
several nuclei and fasciculi.
Hindbrain (rhombencephalon) - subdivision
medulla, pons, and cerebellum
Neurotransmitter (definition)
A substance released from presynaptic nerve terminals which produces rapid inhibitory or excitatory effects on the post synaptic cell
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
Amino acid neurotransmitters (2 + 2)
GABA
Glutamate
(also Glycine and Aspartate, but these are less important to psychiatry)
Monoamine neurotransmitters (3 + 3)
Dopamine
Serotonin
Noradrenaline
Adrenaline
Melatonin
Histamine
(less important for psychiatry/less well understood)
Neurotransmitters - Other amine (1)
Acetylcholine
The major excitatory neurotransmitter in the CNS
Glutamate
======
also Aspartate
The major inhibitory neurotransmitter in the CNS
GABA
=======
also Glycine
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)
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
Catecholamines (3)
Dopamine
Adrenaline
Noradrenaline
‘DAN’
Noradrenaline/Dopamine - synthesis pathway (4 molecules, 3 enzymes)
Tyrosine (Tyrosine hydroxylase) - *rate-limiting step* Levodopa (DOPA decarboxylase) Dopamine (Dopamine beta-hydroxylase) Noradrenaline
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
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
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).
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
Noradrenaline - degradation enzymes (2) and product
COMT (catechol-O-methyltransferase)
MAO-A
—————–
MHPG (3-methoxy-4-hydroxyphenylglycoll)
Dopamine - degradation enzymes (3) and product
COMT (catechol-O-methyltransferase) MAO-A MAO-B ------------------- HVA (homovanilic acid)
Serotonin - degradation enzymes (2) and product
Serotonin (MAO-A) Intermediary (Aldehyde dehydrogenase) 5-H1AA
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.
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.
Presynaptic processes occurring at the synapse (3)
Autoreceptors
Heteroreceptors
Reuptake transporter proteins
Autoreceptors (essence)
Presynaptic receptors on the same neuron (e.g. serotonergic receptors on serotonergic terminals)
Inhibit further neurotransmitter release via negative feedback
Heteroreceptors (essence)
Presynaptic receptors that respond to neurochemicals released from other neurons
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
Ionotropic receptors (essence)
Ligand-gated ion channels that open allowing an electrical current to pass through the cell membrane
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
Ionotropic receptors - examples (5)
GABA-A 5HT-3 Nicotinic acetylcholine NMDA (Glutaminergic) Glycine
Metabotropic receptors - examples (6)
GABA-B Serotonin (except 5HT-3) Muscarinic acetylcholine (M1-M3) Noradrenaline (alpha and beta) Mu Opioid Dopamine (D1-D5)
A drug or substance that acts at a cell receptor to produce a response, by activating the receptor
Agonist
A drug or substance that blocks a receptor, preventing activation
Antagonist
A drug that binds to a receptor and produces a submaximal response. May therefore prevent other agonists from producing their full response.
Partial agonist
A drug or substance that has the opposite effect to the agonist at that receptor
Inverse agonist
A drug that can cause neuroregulation of neuroreceptors, leading to down- or up-regulation
Chronic agonist
Neuroreceptor up-regulation
Occurs when an increased concentration of neurotransmitters causes an increase in the number of postsynaptic receptors
Neuroreceptor down-regulation
Occurs when there is a decrease in the number of receptors in response to a long-term increase in neurotransmission
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
A reduction in the effect produced by a drug or substance over time.
Tolerance
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
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
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
Presynaptic downregulation of these receptors is thought to be responsible for the delayed action of SSRIs
5-HT1A
Stimulation of these serotonin receptors has an anti-migraine effect
5-HT1D
These serotonin receptors are the target of atypical antipsychotics.
Stimulation causes anxiety, agitation, insomnia, sexual dysfunction
5-HT2
These serotonin receptors are associated with the propensity of atypical antipsychotics to cause weight gain
5-HT2C
The only ionotropic serotonin receptor.
Stimulation (e.g. by SSRIs) causes nausea, diarrhoea, and headache. Ondansetron is an antagonist.
5-HT3
This serotonin receptor is involved in circadian rhythm regulation.
5-HT7
Acetylcholine receptors (classification)
Nicotinic receptors
- ionotropic
Muscarinic receptors (M1-M5)
- metabotropic
- mediate the effects of anticholinergic drugs
- M1 (peripheral) - tachycardia
- M4 - hypersalivation (in clozapine)
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
Benzodiazepines (mechanism of action)
Bind to the alpha subunit of GABA-A
-> increases the frequency of chloride channel openings
Dysfunction of which lobe?
Contralateral hemiplegia, impaired problem solving, disinhibition, lack of initiative, Broca’s aphasia and agraphia (dominant)
Frontal lobe
Dysfunction of which lobe?
Wernicke’s aphasia (dominant), homonymous upper quadrantanopia, auditory agnosia (non-dominant)
Temporal lobe
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)
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
Dysfunction of which lobe?
Visual agnosia, visual illusions, contralateral homonymous hemianopia
Occipital lobe
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.
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
Fluent (receptive) aphasia - examples (4)
Wernicke’s aphasia
Anomic aphasia
Conduction aphasia
Transcortical sensory aphasia
Non fluent (expressive) aphasia - examples (3)
Broca’s aphasia
Transcortical motor aphasia
Global aphasia
Pure aphasia - example (3)
Pure alexia
pure agraphia
pure word deafness
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.
total population prevalence of dementia among over 65s
7.1%
total population prevalence of dementia in the UK
1.3%
Alzheimer’s disease (% of all dementia cases)
62%
Vascular dementia (% of all dementia cases)
17%
Mixed dementia (% of all dementia cases)
10%
Dementia with Lewy bodies (% of all dementia cases)
4%
Frontotemporal dementia (% of all dementia cases)
2%
Parkinson’s dementia (% of all dementia cases)
2%
Anatomical classification of dementia (3)
Cortical
Subcortical
Mixed
Cortical dementia - areas affected (3)
Frontal lobes
Temporal lobes
Parietal lobes
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)
Cortical dementia - examples (4)
Alzheimer’s disease
Pick’s disease
Creutzfeldt-Jakob disease
Binswanger’s disease
Subcortical dementia - areas affected (3)
Thalamus
Basal ganglia (caudate nucleus, substantia nigra)
Deep white matter
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
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
Mixed dementia - examples (3)
Multi-infarct dementia
Corticobasal degeneration
Frontotemporal dementia (amyotrophic form of motor neurone disease)
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)
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)
Senile plaques (description)
extracellular deposits of beta amyloid in the gray matter of the brain
found in Alzheimer’s disease
Neurofibrillary tangles (description)
intracellular structures made by the hyperphosphorylation of the microtubule-associated tau protein
found in Alzheimer’s disease
In which disease are the following histopathological features seen?:
cerebral amyloid angiopathy (CAA)
granulovacuolar degeneration (GVD)
Hirano bodies
Alzheimer’s disease
Alzheimer’s disease - biochemical pathology
deficit of acetylecholine from damage to an ascending forebrain projection
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
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)
Frontotemporal dementia - common features (4)
Onset before 65
Insidious onset
Personality change and social conduct problems
Relatively preserved memory and visuospatial skills
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
Frontotemporal lobe degeneration (gross anatomical features)
Atrophy of the frontal and temporal lobes
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.
Pick’s Disease - gross anatomical features
‘knife-blade’ atrophy of the frontal and temporal lobes
Pick’s Disease - histopathological features
Pick bodies (spherical aggregations of tau protein) Pick cells Gliosis Neurofibrillary tangles Senile plaques
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
What drugs should be avoided in Lewy body dementia as patients?
Neuroleptics - patients can develop irreversible parkinsonism
Lewy body dementia - macroscopic changes (2)
Pallor of the substantia nigra Cerebral atrophy (but less marked than in Alzheimer's)
Lewy body dementia - microscopic changes (3)
Lewy bodies
- intracellular protein accumulations
- made of alpha synuclein
Neurofibrillary tangles
Senile plaques
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
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
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)
Schizophrenia - microscopic pathological changes (2)
reduction of the size of the dorsolateral prefrontal cortex
reduction of the size of the hippocampus
Pure sensory cranial nerves (3)
Olfactory
Optic
Vestibulocochlear
1 - 2 - 8
Pure motor cranial nerves (5)
Oculomotor Trochlear Abducens Accessory Hypoglossal
3 - 4 - 6 - 11 - 12
Mixed (sensory and motor) cranial nerves (4)
Trigeminal
Facial
Glossopharyngeal
Vagus
5 - 7 - 9 - 10
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.
Angular gyrus (location, function, Brodman area)
Inferior parietal lobe
Processing of auditory and visual input
Comprehension of language
Number processing
Brodmann area 39
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.
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
Which white matter tract + type
Fibers to and from virtually all cortical areas fan out superolaterally from the internal capsule
Corona Radiata
Projection tract
Which white matter tract + type
Major conduit of fibers to and from the cerebral cortex
Internal capsule
Projection tract
Which white matter tract + type
Connects the lateral geniculate nucleus to occipital (primary visual) cortex
Geniculocalcarine Tract (optic radiation)
Projection tract
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
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
Which white matter tract + type
Interconnects portions of the frontal, parietal, and temporal lobes
Cingulum
Association tract
Which white matter tract + type
Connects occipital and frontal lobes (2)
Superior Occipitofrontal Fasciculus
Inferior Occipitofrontal Fasciculus
Association tracts
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
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
Which white matter tract + type
Connects temporal and occipital lobe cortices
Inferior Longitudinal (occipitotemporal) Fasciculus
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.
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
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
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
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
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)
Hydrocephalus
essence, classification
an abnormal accumulation of CSF in the ventricles of the brain
COMMUNICATING - i.e. normal pressure hydocephalus
NON-COMMUNICATING
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’)
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
Anterior cranial fossa
- bones (3)
- contents (of the brain)
Frontal bones
Ethmoid bones
Lesser wing of sphenoid
Frontal lobes
Middle cranial fossa
- bones (3)
- contents (of the brain)
Greater wing of the sphenoid
Sella turcica
Majority of temporal bones
Temporal lobes
Posterior cranial fossa
- bones
- contents (of the brain) - 3
Occipital bone
occipital lobes
cerebellum
medulla
Foramen spinosum
- location (fossa)
- allows passage of…
Middle fossa
Middle meningeal artery
Foramen ovale
- location (fossa)
- allows passage of…
Middle fossa
Mandibular division of trigeminal nerve
Foramen lacerum
- location (fossa)
- allows passage of…
Middle fossa
Internal carotid artery
Foramen magnum
- location (fossa)
- allows passage of…
Posterior fossa
Spinal cord
Jugular foramen
- location (fossa)
- allows passage of…
Posterior fossa
Cranial nerves IX, X, and XI
Angular gyrus
- location (lobe)
- functions
Parietal lobe
Language, mathematics and cognition
Cingulate gyrus
- location
- functions
Adjacent to the corpus callosum
Emotion, learning, and memory
Fusiform gyrus
- location (lobe)
- functions
Temporal lobe
Face and body recognition (damage -> prosopagnosia)
word and number recognition (visual)
Precentral gyrus
- location (lobe)
- functions
Frontal lobe
Voluntary movement control
Postcentral gyrus
- location (lobe)
- functions
Parietal lobe
Touch
Lingual gyrus
- location (lobe)
- functions
Occipital lobe
Dreaming, word recognition (visual)
Superior frontal gyrus
- location (lobe)
- functions
Frontal lobe
Laughter and self awareness
Superior temporal gyrus
- location (lobe)
- functions
Temporal lobe
Language (Wernicke’s area)
Sensation of sound
Parahippocampal gyrus
- location
- functions
Surrounds the hippocampus
Memory
also asymmetry has been observed in schizophrenia
Dentate gyrus
- location
- functions
Hippocampus
Formation of episodic memory
Papp-Lantos bodies
- associated condition
- description
Multisystem atrophy
alpha-synuclein inclusions in oligodendrocytes found in the substantia nigra, cerebellum, and basal ganglia
Pick bodies
- associated condition
- description
Frontotemporal dementia
Large, dark-staining aggregates of proteins in neurological tissue
Lewy bodies
- associated conditions (2)
- description
Parkinson’s disease
Lewy Body dementia
Round, concentrically laminated, pale eosinophilic cytoplasmic inclusions (aggregates of alpha-synuclein)
Asteroid bodies
- associated conditions (2)
Sarcoidosis
Berylliosis
Barr bodies
essence
Stains of inactivated X chromosomes
Mallory bodies
- associated conditions (4)
alcoholic hepatitis
alcoholic cirrhosis
Wilson’s disease
primary-biliary cirrhosis
Schaumann bodies
- associated conditions (2)
Sarcoidosis
Berylliosis
Zebra bodies
- associated conditions (3)
Niemann-Pick disease
Tay-Sachs disease
Any of the mucopolysaccharidoses
LE bodies (AKA hematoxylin bodies)
- associated condition
SLE (lupus)
Hirano bodies
- associated conditions (2)
- description
Normal ageing
but more numerous in Alzheimers disease
Eosinophilic, football shaped inclusion seen in neurons of the brain
Neurofibrillary Tangles
- associated condition
- description
Alzheimer’s disease
Microtubule-associated proteins and neurofilaments
Kayser-Fleischer rings
- associated condition
- description
Wilson’s disease
Rings of discoloration on cornea
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
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
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)
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
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
EEG Alpha Waves
- Frequency
- Brain region
- Normally seen in
8-12 Hz
Posteriorly
When relaxed and when the eyes are closed (whilst awake)
EEG Beta Waves
- Frequency
- Brain region
- Normally seen in
12-30 Hz
Frontally
When busy or concentrating
=================
‘Beta’ - B for ‘busy’
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
EEG Gamma Waves
- Frequency
- Brain region
- Normally seen in
30-100 Hz
No specific areas
Meditation
sporadic CJD
- EEG findings (2)
Early - non specific slowing
Later - periodic biphasic and triphasic synchronous sharp wave complexes, superimposed on a slow background rhythm
Huntingdon’s disease
- EEG findings
Low voltage EEG,
Flattened trace (in particular no alpha)
Delirium
- EEG findings (3)
Diffuse slowing
Decreased alpha
Increased theta and delta
Delirium tremens
- EEG findings
Hyperactive trace, fast
Alzheimer’s disease
- EEG findings (2)
Reduced alpha and beta
Increased delta and theta
Petit mal epilepsy (absence seizure)
- EEG findings
Generalised, bilateral, synchronous, 3Hz (3 waves per second) spike and wave pattern
Generalised epilepsy
- EEG findings
Sharp spikes, 25-30Hz
Partial epilepsy
- EEG findings
Focal spikes
Myoclonic epilepsy
- EEG findings
Generalised spike and wave activity
Encephalopathy
- EEG findings
Diffuse slowing
Normal aging
- EEG findings
Diffuse slowing, which can be focal or diffuse,
if focal most commonly seen in the left temporal region
Typical antipsychotics
- effect on EEG (2)
Decreased beta
Increased alpha and delta,
====================
haloperidol least effect
Which atypical antipsychotic has most significant effect on the EEG?
Clozapine
Antidepressants
- effect on EEG (2)
Reduce beta
Increase in all other wave forms
Anticonvulsants
- effect on EEG
None
Lithium
- effect on EEG
Slowing
Benzodiazepines
- effect on EEG (2)
Increase beta
Decrease alpha
Barbiturates
- effect on EEG
Increase beta
Stimulants (cocaine, nicotine)
- effect on EEG
Increase alpha
Depressants (alcohol, opioids)
- effect on EEG
Decrease alpha
Cannabis
- effect on EEG
Increase alpha
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.
HPA axis (summary)
Hypothalamus (CRH) Anterior pituitary (ACTH) Adrenal cortex (Cortisol)
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
NREM Sleep Stage I
- % of time spent in stage
- EEG findings
5%
Theta waves
NREM Sleep Stage II
- % of time spent in stage
- EEG findings
45%
Sleep spindles
K complexes
NREM Sleep Stage III
- % of time spent in stage
- EEG findings
12%
<50% Delta waves
NREM Sleep Stage IV
- % of time spent in stage
- EEG findings
13%
> 50% Delta waves
Sleep latency
- definition
- average time
Time taken to fall asleep (onset of NREM Stage I)
15-20mins
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
Wernicke and Korsakoff syndrome
- specific brain region affected
Medial thalamus and mammillary bodies of the hypothalamus
Hemiballism
- specific brain region affected
Subthalamic nucleus of the basal ganglia
Huntington chorea
- specific brain region affected
Striatum (caudate nucleus) of the basal ganglia
Parkinson’s disease
- specific brain region affected
Substantia nigra of the basal ganglia
Kluver-Bucy syndrome
(hypersexuality, hyperorality, hyperphagia, visual agnosia)
- specific brain region affected
Amygdala
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.
Alien hand sign
the experience of bizarre hands movements for which the patient feels no sense of control
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.).
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.
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)
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)
Cranial nerve reflexes:
Pupillary light reflex
- Sensory component
- Motor component
Sensory: Optic
Motor: Oculomotor
Cranial nerve reflexes:
Accommodation reflex
- Sensory component
- Motor component
Sensory: Optic
Motor: Oculomotor
Cranial nerve reflexes:
Jaw jerk
- Sensory component
- Motor component
Sensory: Trigeminal
Motor: Trigeminal
Cranial nerve reflexes:
Corneal reflex
- Sensory component
- Motor component
Sensory: Trigeminal
Motor: Facial
Cranial nerve reflexes:
Vestibulo-ocular reflex
- Sensory component
- Motor component
Sensory: Vestibulocochlear
Motor: Oculomotor, trochlear, abducent
Cranial nerve reflexes:
Gag reflex
- Sensory component
- Motor component
Sensory: Glossopharyngeal
Motor: Vagus
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.
an inability to make fine/delicate movements
Limb kinetic apraxia
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
an inability to copy a picture or combine parts of something to form a whole
Constructional apraxia
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
an inability to control eye movements
Oculomotor apraxia
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
Homonymous quadrantanopia (location of lesions)
- superior
- inferior
superior: lesion of temporal lobe
inferior: lesion of parietal lobe
mnemonic = PITS (Parietal-Inferior, Temporal-Superior)
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
Illicit drugs (mechanism of action)
- drugs that interefere with ionotropic receptors or ion channels (4)
Alcohol
nicotine
benzodiazepines
ketamine
Illicit drugs (mechanism of action)
- Drugs which interfere with G coupled receptors (3)
Opioids
cannabinoids
y-hydroxybutyrate (GHB)
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.
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)
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.
Which cranial nerves exit through the Cribiform plate?
Olfactory (I)
Which cranial nerves exit through the Optic foramen?
Optic nerve (II)
Which cranial nerves exit through the Superior orbital fissure?
Oculomotor (III)
Trochlear (IV)
Trigeminal (ophthalmic V1)
Abducens (VI)
Which cranial nerves exit through the Round foramen?
Trigeminal (maxillary V2)
Which cranial nerves exit through the Oval foramen (Foramen Ovale)?
Trigeminal (mandibular V3)
Which cranial nerves exit through the Internal auditory canal?
Facial (VII)
Vestibulocochlear (VIII)
Which cranial nerves exit through the Jugular foramen?
Glossopharyngeal (IX)
Vagus (X)
Accessory (XI)
Which cranial nerves exit through the Hypoglossal canal?
Hypoglossal (XII)
Autotopagnosia
Inability to orient parts of the body
Phonagnosia
Inability to recognize familiar voices
Astereoagnosia
Inability to recognize objects by touch
Lentiform nucleus
- components (2)
Putamen
Globus pallidus
Hypothalamic nucleus responsible for:
Circadian rhythm
Suprachiasmatic
Hypothalamic nucleus responsible for:
Secretes GnRH to stimulate LH and FSH in the anterior pituitary
Regulates body temperature
Preoptic
Hypothalamic nucleus responsible for:
Synthesizes oxytocin
Paraventricular
Hypothalamic nucleus responsible for:
Regulates parasympathetics to keep cool
Anterior
Hypothalamic nucleus responsible for:
Regulates sympathetics to keep warm
Posterior
Hypothalamic nucleus responsible for:
Synthesizes ADH
Supraoptic
Hypothalamic nucleus responsible for:
Releases dopamine
GHRH to anterior pituitary
Hunger & satiety
Arcuate
Hypothalamic nucleus responsible for:
Stimulate gastrointestinal system, hunger
Triggers shivering
Dorsomedial
Hypothalamic nucleus responsible for:
Satiety
Ventromedial
Hypothalamic nucleus responsible for:
Hunger and thirst
Lateral
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
What brain region is responsible for executive functions such as planning, judgement, and decision-making?
Dorsolateral prefrontal cortex
