Brain + Behaviour Flashcards
what is hypofrontality?
Hypofrontality is a state of decreased cerebral blood flow (CBF) in the prefrontal cortex of the brain. Hypofrontality is symptomatic of several neurological medical conditions, such as schizophrenia, attention deficit hyperactivity disorder (ADHD), bipolar disorder, and major depressive disorder.
Recurring negative thoughts, aka rumination, are a common symptom of depression associated with an imbalance between the activity of key neuronal structures. Which brain area is hypoactive when a patient presents with this symptom?
lateral pre-frontal cortex
Which serotonergic receptor does buspirone bind to
Buspirone binds primarily to the 5-HT1A receptor as a partial agonist
Buspirone also has some affinity for D2 dopamine receptors
What compound is responsible for the ‘cheese-effect’ in patients taking monoamine oxidase inhibitors (MAOIs)
Tyramine
Tyramine is broken down in the gut by enzyme monoamine oxidase (MAO); when someone is taking MAOI (e.g. phenelzine, tranylcypromine) this enzyme is inhibited= excess tyramine in blood
effects of excess tyramine (‘cheese’ effect)
- severe high blood pressure
-headache
-stroke/cardiac events
Patients shld therefore avoid foods w tyramine; aged or fermented food e.g. beer, cheese, cured meats + pickled products
Which receptor does morphine work on?
Morphine works primarily on mu-opioid receptors (MOR). These receptors are located in the brain and are responsible for analgesia, euphoria, sedation
Amyloid precursor protein is cleaved by enzymes to produce Abeta42 amyloidogenic peptide. The activity of which enzyme or combination of enzymes produces this peptide?
beta-secretase + gamma-secretase
Which part of the nervous system controls skeletal muscles?
the somatic nervous system controls skeletal muscles
What is the difference between somatic and autonomic nervous system
Somatic Nervous System: involves things you can consciously sense and do.
Autonomic nervous system works ‘automatically’/ without you thinking about it, (running the behind-the-scenes processes that keep you alive)
Which spinal tract transmits crude touch?
anterior spinothalamic tract (n.b. it also transmits ‘slow pain’ with the c fibres)
Which part of the forebrain relays somatosensory information to the cortex?
thalamus
The thalamus in the brain functions quite similarly to a post office as it acts as a sensory relay station that receives, organizes, and transmits sensory information to various parts of the brain for further processing
Where are the cell bodies of peripheral sensory nerves found?
dorsal root ganglia
Which neurotransmitter is released by preganglionic parasympathetic neurons
Acetylcholine
Which receptor is expressed at the preganglionic synapse in the sympathetic nervous system
nicotinic acetylcholine receptors
Which cranial nerve is activated by tooth pain?
Trigeminal nerve (CN V)
CN V provides most of the face’s sensory innervation and the mastication muscles’ motor stimulation. [1] The nerve’s 3 main branches are the ophthalmic (V1), maxillary (V2), and mandibular (V3) nerves
Which cranial nerve provides motor fibres for the muscles of mastication
Trigeminal (CN V)
The hippocampus is responsible for memory and learning; what lobe of the brain is it part of?
Hippocampus is part of temporal lobe
which parts of the brain do the following arteries supply;
- anterior cerebral artery (ACA)
- middle cerebral artery (MCA)
- posterior cerebral artery (PCA)
anterior cerebral artery (ACA)=
-lateral superior frontal cortex
-medial frontal + parietal lobes
middle cerebral artery (MCA)=
-lateral inferior frontal + parietal cortices
-superior temporal lobes
posterior cerebral artery (PCA)=
-lateral posterior parietal cortex
-occipital cortex
-inferior temporal lobes
which artery supplies each of the following:
- anterior 2/3rds of spinal cord
- posterior 1/3rd of spinal cord
- nerve roots of spinal cord
anterior 2/3rds of spinal cord= anterior spinal artery
posterior 1/3rd of spinal cord= posterior spinal arteries
nerve roots of spinal cord= segmental medullary arteries
what is the role of acetylcholine in the nervous system
acetylcholine= mainly excitatory. Used by spinal cord neurons: controls muscles; in the brain: regulates memory (also involved in motivation, arousal + attention)
what is the role of dopamine in the nervous system
dopamine= Involved in movement regulation; in feelings of pleasure and motivation when released by the brain reward system. Has multiple functions beyond reward, especially in cognition.
what is the role of GABA in the nervous system
GABA= The major inhibitory neurotransmitter in the brain. (chilling neurotransmitter)
what is the role of glutamate in the nervous system
glutamate= the major excitatory neurotransmitter in the brain. Important for memory, cognition, and mood regulation
what is the role of glycine in the nervous system
glycine= It has both inhibitory and excitatory effects (as co-agonist with glutamate).
what is the role of noradrenaline in the nervous system
noradrenaline= Peripheral nervous system – as part of the sympathetic nervous system, it mobilizes the body for action (involved in stress and the flight-or-fight response). CNS – it mobilizes the brain for action (arousal, alertness, attention, readiness for action) and regulates mood.
what is the role of serotonin in the nervous system
Serotonin= Involved in mood and sensory perception regulation, pain modulation, bowel function, and appetite (the gut provides around 95% of total body serotonin).
What is Pabrinex used for?
Pabrinex (replaces vitamin B1/thiamine ,B2,B3, B6, C glucose for energy metabolism) is indicated for rapid treatment of severe depletion or malabsorption of vitamins B and C, particularly in alcoholism, after acute infection occurring post-operatively or in psychiatric settings
the resting potential of a central neurone is due to :
the resting potential of a central neurone is due to :
K+ leaking out through non gated K+ channels
Some of brain regions that belong to the group to which Broca’s area and the frontal eye fields (FEFs) are attached are places where attention is shifted and memories are stored. What group is this referring to?
Association motor areas include a large variety of brain regions (prefrontal, parietal, temporal, and occipital cortices) where, for some, not only different sensory modalities combine and motor planning occurs, but attention is shifted and memories are stored.
Broca’s area
A cortical area of the LEFT hemisphere specialised in the production of speech movements
Broca’s area is no longer activated by the time speech commences, showing that its role is one of planning rather than producing speech
Broca’s area coordinates the linkage between:
the articulatory representations (motor cortex) and the sensory representation of words (temporal cortex)
what kind of aphasia does damage to Broca’s area result in
damage to Broca’s area= motor/expressive aphasia
a nonfluent aphasia that makes it difficult to write or speak thoughts, even when the speaker knows what they want to say
Speak in short (< 4 words) or incomplete sentences
Substitute one word for another or one sound for another
Speak in sentences that don’t make sense
Difficulty writing
Retain the ability to read and understand speech
i.e. comprehension preserved, but expression impaired
what brodmann area are the frontal eye fields
the frontal eye fields are in Brodmann area 8
the FEF are anterior to the motor strip in the frontal lobes= brodmann area 8
this area receives input from the occipital lobes and sends output to the extraocular muscles through the pontine nuclei, reticular formation, superior coliculus, basal ganglia + cerebellum
Explain the role of the frontal eye fields (FEFs) in the initiation of saccades + smooth pursuit
the FEF are important for initiation of SACCADES + SMOOTH PURSUIT; used to locate objects for survival
Saccades:
- small, rapid jerky movements of the eyes
- Speed: Very fast (up to 900°/s)
- Function: Used to quickly reposition the fovea (the central part of the retina responsible for sharp vision) onto objects of interest.
e.g. reading, scanning a crowd, looking at objects in quick succession
Smooth pursuit:
- Slow, continuous eye movements used to track a moving object
-Speed: Much slower than saccades (typically 30–100°/s)
- Function: Keeps a moving object in focus on the fovea, allowing for clear vision while tracking.
e.g. Watching a moving car, tracking a flying bird, following a finger
n.b. smooth pursuit requires a moving target; cannot be performed voluntarily without a stimulus.
what is apraxia?
Apraxia: the loss of ability to execute or carry out skilled movement and gestures despite having the physical ability and desire to perform them (“praxis” = skilled action)
Bilateral damage to the FEFs produces what kind of apraxia
Bilateral damage to the FEFs produces oculomotor apraxia
Patients cannot move their eyes horizontally and move them quick enough to follow a moving object or read a line of text
They automatically turn their head in order to compensate for the lack of eye movement
They often move their head too far and have to move several times to get the desired object on their fovea
if there is a lesion to the following how do the eyes drift?
- FEFs lesion
- pons lesion
FEFs lesion; eyes drift ipsilaterally (towards the lesion side)
Pons lesion= eyes drift contralaterally (away from the lesion side)
The sensory representation of words happens in which cortex
The sensory representation of words happens in the temporal cortex
In the temporal cortex acoustic and visual representations of words are stored
what is aphasia, what is an aphasic patient?
Aphasia is a language disorder caused by damage to the brain, typically in areas responsible for language processing, such as Broca’s area or Wernicke’s area (usually in the left hemisphere). It affects a person’s ability to speak, understand, read, or write but does not impact intelligence.
An aphasic patient (someone who suffers from aphasia)
Where does the pyramidal tract lateral corticospinal tract deccusate and why is this relevant in injury?
pyramidal tract decussates at the spinomedullary junction (spinal cord+medulla junction)
injury above deccusation= effect seen on contralateral (opposite) side
injury below deccusation= effect seen on ipsilateral side
In the ventral horn, the α motor neurons supplying distal extensor muscles are located ___ and _____
In the ventral horn, the α motor neurons supplying proximal flexor muscles are located ____ and _____
In the ventral horn, the α motor neurons supplying distal extensor muscles are located LATERALLY and VENTRALLY
In the ventral horn, the α motor neurons supplying proximal flexor muscles are located MEDIALLY and DORSALLY
where does the ‘small’ anterior/ ventral corticospinal tract terminate?
the ‘small’ anterior/ ventral corticospinal tract terminates at mid-thoracic level
where does the anterior corticospinal tract decussate?
In the spinal level it innervates
what movements does the corticobulbar tract control?
Controls voluntary movements of the head and neck
Corticobulbar tract supplies upper motor neuron innervation to the cranial nerves supplying head and face.
Corticobulbar tract carries upper motor neuron input to motor nuclei of trigeminal, facial, glossopharyngeal, vagus, accessory, and hypoglossal nerves
define:
-spasticity
-clonus
-hypereflexia
- Spasticity
Definition: Spasticity is a condition where muscles are stiff, tight, and resistant to movement due to increased muscle tone (hypertonia).
Cause: It results from damage to the upper motor neurons (UMNs) in the brain or spinal cord, leading to disrupted inhibitory control over reflexes. - Clonus
Definition: Clonus is a rhythmic, involuntary muscle contraction and relaxation (jerky movements) in response to a sudden stretch.
Cause: It occurs due to hyperactive stretch reflexes caused by upper motor neuron lesions. - Hyperreflexia
Definition: Hyperreflexia is an exaggerated reflex response due to loss of normal inhibitory control from the brain.
Cause: It results from upper motor neuron damage, leading to overactive reflex loops in the spinal cord.
when the pyramidal tracts get damaged (e.g. damage to corticospinal tract/CST) what happens to the extrapyramidal system?
When CST is damaged the extrapyramidal system becomes hyperactive = resulting in hyperactive stretch reflexes + spasticity
what is decerebrate posture vs decorticate posture
Decerebrate posture: A rigid extension of the arms and legs, with wrists rotated outward (pronated), legs straight, and toes pointed downward (plantar flexion).
Cause: Damage to the brainstem (below the level of the red nucleus), affecting the midbrain or pons. This disrupts inhibitory control from the cortex, leading to excessive extensor muscle activity.
Decorticate Posture: Abnormal flexion of the arms towards the core (“mummy pose”), with legs extended and toes pointed downward.
Cause: Damage to the corticospinal tract above the brainstem, typically at the level of the cerebral hemispheres, internal capsule, or thalamus. This disrupts motor control but spares brainstem reflexes.
define
- paresis
- paraesthesia
paresis= a condition in which muscle movement has become weakened or impaired.
paraesthesia= an abnormal sensation, typically tingling or pricking (‘pins and needles’), caused chiefly by pressure on or damage to peripheral nerves.
Name role and organisation of the different pyramidal tracts; each of their origin, decussation and travel in spinal cord
Pyramidal tracts:
1. Corticospinal Tract
* Origin: Arises from the primary motor cortex (Brodmann area 4), premotor cortex (area 6), and parts of the somatosensory cortex.
- Decussation:
LATERAL CORTICOSPINAL TRACT (85-90% of CST fibres) cross at the pyramidal decussation in the lower medulla
ANTERIOR CORTICOSPINAL TRACT remaining fibers continue ipsilaterally decussate in the spinal cord
- Spinal Cord Pathway:
- Lateral Corticospinal Tract: Descends in the lateral funiculus, terminating at various spinal levels to control distal limb muscles.
- Anterior Corticospinal Tract: Travels in the anterior funiculus, primarily influencing axial and proximal limb muscles.
anterior CST function: Gross motor and postural control
lateral CST function: Fine motor and precise voluntary movement
- Corticobulbar Tract
- Origin: Similar to the corticospinal tract, it originates from the motor cortex.
- Decussation: Fibers innervate cranial nerve nuclei bilaterally, except for parts of the facial nerve (CN VII) and hypoglossal nerve (CN XII), which receive predominantly contralateral input.
- Pathway: Descends through the genu of the internal capsule to the brainstem, terminating in motor nuclei of cranial nerves.
- Role: Controls muscles of the face, head, and neck, facilitating functions like facial expression, mastication, and swallowing.
Name role and organisation of the different extrapyramidal tracts; each of their origin, decussation and travel in spinal cord
Extrapyramidal Tracts
These tracts originate from subcortical structures and modulate involuntary motor activities, posture, and muscle tone.
- Rubrospinal Tract
- Origin: Red nucleus in the midbrain.
- Decussation: Fibers cross immediately in the midbrain.
- Spinal Cord Pathway: Descends in the lateral funiculus, anterior to the lateral corticospinal tract.
- Role: Facilitates flexor muscle activity in the upper limbs.
- Reticulospinal Tract
- Origin: Reticular formation in the pons and medulla.
- Decussation: Predominantly uncrossed, though some fibers may cross.
- Spinal Cord Pathway: Divided into medial (pontine) and lateral (medullary) tracts, descending in the anterior and lateral funiculi, respectively.
- Role: Regulates muscle tone and reflex activities, influencing both flexor and extensor muscles.
- Vestibulospinal Tract
- Origin: Vestibular nuclei in the pons and medulla.
- Decussation: Primarily uncrossed.
- Spinal Cord Pathway: Descends in the anterior funiculus.
- Role: Maintains balance and posture by facilitating extensor muscle activity in response to vestibular input.
- Tectospinal Tract
- Origin: Superior colliculus in the midbrain.
- Decussation: Fibers cross in the midbrain.
- Spinal Cord Pathway: Descends in the anterior funiculus, terminating primarily in cervical segments.
- Role: Mediates head and neck movements in response to visual and auditory stimuli.
what is the arcuate fasciculus
the arcuate fasciculus (AF; from Latin ‘curved bundle’) is a bundle of axons that generally connects Broca’s area and Wernicke’s area in the brain. It is an association fiber tract connecting caudal temporal lobe and inferior frontal lobe
what happens to behaviour following a lesion to the pre-frontal cortex
pre-frontal syndrome= following the lesion, behaviour becomes automatic habitual, stimulus-driven; loss of ‘goal-orientated behaviour’
- dramatic behavioural + personality changes
what is the function of the orbitofrontal cortex (OFC); what OFC damage can lead to.
OFC function: values + expected values based on knowledge and experience
e.g.
- Decision-Making & Value-Based Choices
- Emotion & Social Behavior Regulation
- Reward & Punishment Processing
- Impulse Control & Behavioural Flexibility
Damage to the OFC can lead to: Orbitofrontal syndrome:
❌ Impulsivity & Poor Decision-Making (e.g., reckless financial choices)
❌ Lack of persistence/planning
❌ Lack/blunted emotional Regulation/experience (e.g., inappropriate anger or laughter)
❌ Socially Inappropriate Behavior (e.g., rudeness, lack of empathy)
❌ Difficulty Learning from Consequences (e.g., continuing risky behaviour despite negative outcomes)
what is the function of the medial prefrontal cortex (mPFC); what mPFC damage can lead to
-explain the dorso-ventral gradient (dmPFC, rmPFC, vmPFC)
function of the medial prefrontal cortex (mPFC):
- directs the correct emotional or motor response in light of the knowledge acquired from past experience
- regulates fight or flight by working w amygdala
damage to mPFC:
- Social withdrawal, inappropriate behavior
- Risky behavior, stubbornness
- apathy, loss of interest in goals
- Poor self-reflection, lack of insight
dorso-ventral gradient (dmPFC, rmPFC, vmPFC); as we go more:
- dorsal= controls of actions
- ventral= emotional/autonomic responses
what system controls the fight-or-flight response
fight-or-flight response is controlled by the limbic system (amygdala, hippocampus, parahippocampal gyrus, cingulate cortex, septal nuclei, mamillary body, fornix, hypothalamus) particularly the amygdala, which activates the hypothalamus to trigger the body’s stress response
the dorsolateral prefrontal cortex and the frontal pole both support goal-directed behaviour + cognitive flexibility. What are the Brodmann areas of each. What happens if these areas are lesioned?
dorsolateral prefrontal cortex = Brodmann 9 + 46
frontal pole = 10
after lesion to dorsolateral prefrontal cortex + frontal pole=
- lack of ability to plan
- apathetic
- lack of ability to sequence actions or tasks
- poor working memory for spatial info ( RIGHT lesion)
- poor working memory for verbal info (if LEFT lesion)
- personality changes
what is the function of supplementary motor area (SMA); located in medial part of Brodmann area 6
The supplementary motor area (SMA)= organises actions based on internal goals + personal experience
SMA makes an actual plan for purposeful actions (piano playing)
SMA has strong reciprocal connections with medial frontal cortex
The premotor cortex is located just anterior to the primary motor cortex (lateral part of Brodmann area 6). What is the function of the pre motor cortex and what does it have strong reciprocal connections with?
the premotor cortex= organises EXTERNALLY sensory-guided actions; selects movement based on external info from primary sensory cortices
- has strong reciprocal connections w parietal lobe
the primary motor cortex (M1) is what brodmann area + what is its function; consequence of lesion to M1
the primary motor cortex (M1) is Brodmann area 4; and it’s function is the execution of movements
M1 receives input from almost all cortical areas involved in motor control
lesion of the primary motor cortex results in profound paralysis
central sulcus separates which lobes?
The central sulcus separates the frontal and parietal lobes
where is the primary visual cortex located?
occipital lobe
what is the falx cerebri?
Falx cerebri is defined as a sickle-shaped vertical fold of dura mater that separates the two cerebral hemispheres and helps in preventing certain types of brain herniation.
what is the corpus callosum?
The corpus callosum is the largest white matter structure in the brain
Corpus callosum connects the right and left hemispheres of brain; ensures both sides of the brain can communicate and send signals to each other
What is the bereitschaftpotential (BP) aka ‘readiness potential’ and how is it involved in voluntary movement?
The Bereitschaftspotential (BP), or “readiness potential,” is a slow, gradual electrical signal that appears in the brain before a voluntary movement is performed.
N.B.
- early component (BP1) is generated by the pre-SMA/SMA + premotor cortex
- late component (BP2) is when the neural signal leaves the primary motor cortex
The primary sources of BP are:
- Supplementary Motor Area (SMA) → Prepares and plans complex, self-initiated movements.
- Premotor Cortex (PMC) → Helps with motor planning.
- Primary Motor Cortex (M1) → Executes the actual movement.
Basal Ganglia & Thalamus → Modulate movement initiation.
The BP is strongest over the contralateral motor cortex, meaning if you’re moving your right hand, the left hemisphere of your brain shows the most BP activity.
what is visual acuity; what test examines it?
Visual acuity (VA) refers to the sharpness or clarity of vision, specifically how well you can distinguish fine details at a given distance.
Snellen’s test; patient stands at 20ft or 6 meters away and reads letters
i.e. its called 20/20 vision if its perfect because u can see at 20ft
what plates test for colourblindness?
Ishihara plates test for colour blindness
What is the afferent and efferent limbs of the pupillary light reflex
afferent (sensory) limb [CN II]:
1. Retina → Detects light
2. Optic nerve (CN II) → Carries sensory signal
3. Pretectal nucleus (midbrain) → Relays signal to both sides
4. Edinger-Westphal nucleus (EWN, midbrain) → Sends motor output
efferent (motor) limb [CN III]:
1. Edinger-Westphal nucleus (midbrain) → Sends motor signal
2. Oculomotor nerve (CN III) → Carries motor signal
3. Ciliary ganglion (parasympathetic ganglion near the eye) → Relays motor signal
4. Sphincter pupillae muscle (iris) → Constricts the pupil
What is the Marcus Gunn pupil
Marcus Gunn pupil aka relative afferent pupillary defect; is when light is shone in the affected eye and both pupils constrict less (or they dilate (compared to when light is shone in unaffected eye)
what is the difference between conductive and sensorineural hearing loss; compare Rinne and Webbers test in each
Conductive Hearing Loss (CHL) → Problem in sound conduction through the outer or middle ear.
CHL sound perception: Reduced loudness, but clarity remains
CHL causes: Earwax, ear infections, otosclerosis (a form of abnormal bone growth within the middle ear that causes progressive hearing loss)
CHL= hearing aids effecitve
Rinne test in CHL= negative
Weber test in CHL= sound is louder in affected ear
Sensorineural Hearing Loss (SNHL) → Problem in the inner ear (cochlea) or auditory nerve (CN VIII).
SNHL sound perception: Both loudness and clarity are affected
SNHL causes: Aging, noise exposure, nerve damage, ototoxic drugs (e.g. aminoglycoside antibiotics, macrolide antibiotics, loop diuretics)
SNHL= hearing aids less effective; COCHLEAR IMPLANTS needed in severe cases
Rinne test in SNHL= positive/normal
Weber test in SNHL= sound is louder in unaffected ear
which hearing test compares each; explain each test
-air + bone conduction
- differentiates between conductive and sensorineural hearing loss
Tuning Fork Used for both: 512 Hz tuning fork (best for human speech range)
Rinne’s test = air + bone conduction
Normal hearing or SNHL: Air conduction (AC) > Bone conduction (BC) (Rinne positive).
Conductive hearing loss: Bone conduction (BC) > Air conduction (AC) (Rinne negative).
Weber’s test= differentiates between conductive and sensorineural hearing loss
It involves placing a vibrating tuning fork in the middle of the forehead
- in normal hearing/symmetrical hearing loss the sound is perceived equally in both ears
- in conductive hearing loss, sound is louder in affected ear
- in sensorineural hearing loss, sound is louder in unaffected ear
if a patient presents with a ‘weak cough’ what does this indicate?
weak cough= problems with closing glottis= vagus nerve lesion
what basal ganglial pathway is damaged in Parkinson’s disease?
The degeneration of the nigrostriatal pathway and subsequent loss of striatal dopamine contributes to the cardinal clinical motor symptoms: tremor, rigidity, bradykinesia and postural instability
what dopamine receptors are inhibitory and which are excitatory?
Dopamine receptors are G-protein-coupled receptors
excitatory= D1-class receptors (D1 and D5)
inhibitory= D2-class receptors (D2, D3, D4)
Blood supply to basal ganglia + its relevance with stroke
Blood Supply to the Basal Ganglia:
- Lenticulostriate Arteries:
- Origin: Arise from the M1 (horizontal) segment of the Middle Cerebral Artery (MCA).
-Supply: Primarily the putamen, globus pallidus, and parts of the caudate nucleus.
- Clinical Note: These arteries are small and lack significant collateral circulation, making them susceptible to occlusion. Blockage can lead to lacunar infarcts, small, deep strokes within the brain. - Recurrent Artery of Heubner (Distal Medial Striate Artery):
- Origin: Branches from the A1 segment of the Anterior Cerebral Artery (ACA).
- Supply: Anterior portions of the caudate nucleus, putamen, globus pallidus, and the anterior limb of the internal capsule.
- Clinical Note: Infarction in this artery can affect motor pathways, leading to weakness and other motor deficits. - Anterior Choroidal Artery:
- Origin: Typically arises from the internal carotid artery.
- Supply: Parts of the globus pallidus, tail of the caudate nucleus, and the posterior limb of the internal capsule.
- Clinical Note: Occlusion can result in a classic triad of contralateral hemiplegia, hemianaesthesia, and homonymous hemianopia due to its involvement with motor and sensory pathways.
Relevance in Stroke:
The small size and limited collateral circulation of these arteries make the basal ganglia vulnerable to ischemic strokes. Hypertension is a significant risk factor, as it can lead to the narrowing or occlusion of these vessels. Strokes in the basal ganglia can result in various neurological deficits, including motor impairments, sensory disturbances, and cognitive or emotional changes, depending on the specific nuclei and pathways affected
what structure separates caudate nucleus and putamen
The parts of striatum are separated by the internal capsule
what white matter tract covers the most lateral part of the lentiform nucleus (putamen + globus pallidus)
external capsule
what part of the basal ganglia nuclei are completely embedded in white matter, both medially and laterally
Lentiform nucleus
We are two C-shaped nuclei located in the frontal lobe. Our head region curves and extends to form an elongated body tapering at the tail and ending in temporal lobe. Who are we?
caudate nucleus
Define the following words:
- chorea
- athetosis (result of damage to striatum like seen in cerebral palsy)
- ballismus (result in damage to subthalamic nucleus)
Chorea = (greek; to dance) refers to non-rhythmic, jerky, rapid, nonsuppressible involuntary movement, mostly of the distal muscles + face
Athetosis= slow, involuntary, regular writhing movements of the fingers, hands, toes + feet (in some cases arms/legs/neck/tongue) these are movements resulting from lesions to the striatum (often as a result of cerebral palsy
Ballismus= a type of chorea, usually involving violent, involuntary flinging of 1 arm/ or 1 leg (usually one side of body affected: ‘hemiballismus’). The movements are wider + more intense than chorea. Usually as a result of damage to subthalamic nucleus
Parkinson’s disease; causes, symptoms, treatment/management
Parkinson’s disease (PD) is a progressive neurodegenerative disorder primarily affecting motor function.
Pathophysiology: PD is characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta. This neuronal loss leads to a significant reduction in dopamine levels within the striatum, disrupting the balance of motor control.
Pathological Hallmark: The presence of Lewy bodies, which are intracellular aggregates of α-synuclein, is a key pathological feature of PD.
Clinical Features:
Motor Symptoms:
- Bradykinesia: Slowness of movement; a cardinal feature required for diagnosis.
- Resting Tremor: Typically a “pill-rolling” tremor observed at rest.
- Muscle Rigidity: Increased muscle tone leading to stiffness.
- Postural Instability: Impaired balance, often leading to falls.
Non-Motor Symptoms:
- Autonomic Dysfunction: Orthostatic hypotension, constipation.
- Neuropsychiatric Symptoms: - - - Depression, anxiety, cognitive impairment.
- Sleep Disturbances: REM sleep behavior disorder, insomnia.
Management:
Pharmacological Treatment:
- Levodopa: Considered the most effective treatment for motor symptoms. It’s often combined with a dopa-decarboxylase inhibitor to reduce peripheral conversion.
Dopamine Agonists: Such as pramipexole or ropinirole; used in early stages or as adjunct therapy.
MAO-B Inhibitors: Like selegiline or rasagiline; can provide mild symptomatic benefit.
Non-Pharmacological Treatment:
- Physiotherapy: To improve balance and motor function.
- Occupational Therapy: Assists with daily living activities.
- Speech and Language Therapy: Addresses speech and swallowing difficulties.
Advanced Therapies:
- Deep Brain Stimulation (DBS): Considered for patients with advanced PD experiencing motor fluctuations not controlled by medication.
Parkinsonism is defined by 4 symptoms usually observed in patients (multiple causes including Parkinson’s disease, Wilson’s disease, drug induced parkinsonism). What are these 4 symptoms
parkinsonism;
1) resting tremor
2) rigidity
3) slowness of movement (bradykinesia/akinesia)
4) loss of postural reflexes
Prodromal symptoms, are symptoms that occur at very early stages of a medical condition. They are ‘the first’ warning signs of illness. What are the prodromal symptoms of Parkinson’s
- hyposmia (decreased sense of smell)
- RBD (rapid eye movement behavioural disorder)
- EDS (Excessive Daytime Sleepiness)
- Hypotension
- Urinary and erectile dysfunction
these symptoms are prodromal; appearing years before motor symptoms of Parkinson’s manifest
How do we confirm a diagnosis of Parkinson’s via scan?
Monitoring of gradual dopaminergic nigral cell loss through dopamine transporter (DaT) imaging in the striatum
DaTscan involves an injection of a small amount of a radioactive drug and a machine called a single-photon emission computed tomography (SPECT) scanner, similar to an MRI. The drug binds to dopamine transmitters in the brain, showing where in the brain dopaminergic neurons are.
what genes implicated in parkinson’s
About 15 percent of people with Parkinson’s disease genetic markers; LRRK2, PARK2, PARK7, PINK1 or the SNCA (codes for protein alpha-synuclean) gene
What experimental drug (synthetic heroin) caused early Parkinsonism in young ppl?
MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is an organic compound. It is classified as a tetrahydropyridine.
MPTP is a precursor to the monoaminergic neurotoxin MPP+, whic is neurotoxic to dopaminergic neurons in the substantia nigra ; hence causes parkinsonism
In 1982, seven young adults developed severe and irreversible parkinsonism shortly after they injected themselves with a new synthetic heroin
What is the pharmacological management of Parkinson’s disease (NICE) + briefly explain mechanisms
1) if impacts quality of life: Levodopa combined with DOPA decarboxylase inhibitors e.g. carbidopa, benserazide (stop L-dopa breakdown). Usually a preparation e.g. Madopar
1) if little impact on quality of life: Non-ergot derived dopamine agonist e.g. ropinirole, pramipexole, rotigotine (transdermal patch), apomorphine (can be used as infusion for major motor fluctuations) OR a Levodopa preparation OR MAO-B inhibitor e.g. selegiline, rasagiline, safinamide (protects residual dopamine against oxidation)
2) Patients w moto complications despite optimal Levodopa:
- non-ergot derived dopamine agonist
- MAO-B inhibitor
- COMT inhibitor e.g. entacapone, tolcapone (used in combination w L-dopa to enhance its effects)
-Anticholinergic compounds e.g. procyclidine, orphenadrine (as dopamine losee leads to hyperactivity of cholinergic cells)
3) If dykinesia persists DESPITE optimal Levodopa: + Amantidine
4) depression- Citalopram, sertraline or Mirtazapine (if insomniac)
psychosis- quetiapine, if ineffective clozapine
A thalamotomy vs pallidotomy?
A thalamotomy (more effective for tremors) procedure involves creating a lesion in the Vim (ventral intermediate nucelus of the thalamus) areas and this can help with tremor symptoms due to Parkinson’s disease or to essential tremor among disorders
Thalamotomy used for:
- Severe tremors that do not respond to medication.
- Less effective for bradykinesia (slowness) or rigidity.
- Usually performed unilaterally (on one side) to avoid speech and cognitive side effects.
Pallidotomy (more effective for dyskenesia)– lesion made and scar forms on Globus Pallidus internus (or GPi) part of basal ganglia
Used for:
- Reducing dyskinesia (involuntary movements) caused by levodopa.
- Improving rigidity and bradykinesia.
- Can help with some tremor symptoms but is less effective than thalamotomy for tremors.
- Typically performed on one side, but bilateral pallidotomy is risky due to cognitive side effects.
Thalamotomy → Best for tremors.
Pallidotomy → Best for dyskinesia, rigidity, and bradykinesia.
what frequency is used for DBS (Deep brain stimulation)
With 130 Hz as the default stimulation frequency, most patients are treated with DBS pulses between 60 and 200 H
List the 6 symptoms associated with cerebellar injury
To remember the clinical features of cerebellar disease the word DANISH may be helpful:
D=dysdiakdochokinesis (DDK) refers to the inability to perform coordinated, rapid muscle movements
A= Ataxia (Uncoordinated, wide-based gait)
N=nystagmus ( Involuntary eye movements)
I= intention tremor (Tremor during purposeful movements)
S= scanning dysarthria (slurred/scanning speech)
H=heel-shin test; How Is the Test Performed?
The patient is asked to place the heel of one foot on the opposite shin and slide it down in a straight line to the ankle.
The test is repeated on both sides.
2. What Does an Abnormal Heel-Shin Test Indicate?
Cerebellar Ataxia:
Unsteady, jerky, or wavering movements instead of a smooth downward motion.
Inability to keep the heel on the shin or overshooting the target.
Seen in cerebellar lesions, particularly affecting the spinocerebellar pathways.
Sensory Ataxia (due to proprioceptive loss, e.g., peripheral neuropathy):
The test worsens when eyes are closed, as the patient relies on vision to compensate for lost proprioception.
n.b. not to be confused with babinski test; Babinski sign is typically negative because the cerebellum does not directly control motor pathways but affects coordination and tone.
explain the 3 types of tremor
- Resting Tremor; (i.e. tremor at rest) occurs when muscles at rest; disappears with voluntary movement.
-Most noticeable when the limb is fully supported (e.g., resting hands on a lap).
-“Pill-rolling” tremor (thumb and fingers move rhythmically).
-Typically asymmetrical (starts on one side).
Causes:
Parkinson’s disease
- Postural Tremor;(i.e. tremor arm up) occurs when holding a position against gravity, such as keeping arms outstretched.
- Tremor appears when maintaining a posture but not at rest.
- Fine, rapid shaking (6-12 Hz frequency).
Causes:
- Essential Tremor (most common cause; familial, improves with alcohol).
- Physiological tremor (normal response to stress, anxiety, caffeine, or fatigue).
-Hyperthyroidism, medication-induced tremors (e.g., beta-agonists, lithium).
- Intention Tremor (aka Cerebellar Tremor); (i.e. tremor writing) occurs during voluntary movement, especially as the limb approaches a target.
- Absent at rest but worsens near the end of movement (e.g., finger-to-nose test).
- Slow, low-frequency tremor (2-4 Hz).
-Often accompanied by ataxia, dysmetria, and slurred speech (cerebellar dysfunction signs).
Causes:
Cerebellar disorders (stroke, multiple sclerosis, tumor, alcohol-induced ataxia).
Brainstem lesions affecting cerebellar output.
what 3 parts of the brain does deep brain stimulation (DBS) target for Parkinson’s disease and what symptom is each targetting?
What type of Parkinson’s patients will DBS not work on?
-zona incerta (targets tremor)
- subthalamic nucleus (targets tremor)
- globus pallidus interna (targets dystonia + tremor)
n.b. DBS will not work in ‘burnt out’ patient with no dopamine neurones left to act one; so you need to do it whilst they’re still levodopa responsive
what is vascular parkinsonism?
Vascular Parkinsonism (VP) is parkinsonism caused by cerebrovascular disease, particularly small vessel ischemic damage to the basal ganglia and subcortical white matter. It mimics idiopathic Parkinson’s disease (PD) but has distinct clinical and radiological features.
onset:
- sudden or stepwise worsening after strokes unlike in Parkinson’s disease where it’s a gradual progression
tremor:
-rare or mild
gait:
-early gait disturbance
response to levodopa: poor or minimal response
- Caused by multiple small strokes or chronic ischemia affecting the nigrostriatal pathway (dopamine pathways involved in movement).
- Hypertension, diabetes, smoking, hyperlipidemia, atrial fibrillation
- Previous stroke or transient ischemic attacks (TIAs)
A man sits down with his hands resting still on his lap. When he tries to grab a glass of water he begins to tremor. What is his diagnosis?
intentional tremor
Why are patients with Parkinson’s told to stop taking medication for DBS procedure?
- accurate symptom assessment
- so electrodes are placed correctly as medications mask tremors
- reduces risk of dyskinesia (involuntary movements; side effect of long-term levodopa use) as obvi this could jolt the patient move electrode
what symptom of Parkinson’s is Levodopa bad at treating? What treatment is good?
Tremor; levodopa is not good with treating tremor.
DBS is good for treating tremor
Other diseases are experimentally being treated with DBS, what regions would be targeted in each of the following:
- Tourette Syndrome
- Treatment Resistant Depression (TRD)
- Anorexia
- Addiction
- Alzheimer’s disease
- Therapy refractory obsessive compulsive disorder (OCD)
- Obesity
Tourette Syndrome= thalamic centromedian/ parafascicular complex
Treatment Resistant Depression (TRD)= Brodmann area 25 (Subcallosal cingulate white matter, nucleus accumbens)
Anorexia= hypothalamus
Addiction= nucleus accumbens
Alzheimer’s disease= anterior of the fornix
OCD= nucleus accumbens, ventral striatum
Obesity= hypothalamus, nucleus accumbens
Where is cerebellum/ ‘little brain’ found?
cerebellum is found in the posterior cranial fossa
what type of co-ordination is the cerebellum involved in, what does this mean
The cerebellum is involved in sensorimotor co-ordination
- does NOT initiate movement but detects ‘motor errors’
- ‘fine tunes’ motor commands
The cerebellum coordinates movement, posture, balance, eye control, and speech
what does damage to the cerebellum result in?
cerebellar damage produces
-instability + errors in voluntary movement
- extraocular muscles affected causing nystagmus
- gait change ; they open legs to compensate deficit in balance (cerebellar ataxia)
N.B. cerebellar cortex exhibits neuronal plasticity; so partial recovery of function after injury is possible
HOWEVER damage to deep nuclei causes persisting disability
Ataxia medical meaning
Ataxia is a loss of muscle control
what is the vestibulocerebellum made up of
the vestibulocerebellum is made up of nodulus + flocculus
What is the function of each functional division of the cerebellum; what symptoms would result if area damaged?
- cerebrocerebellum aka neocerebllum
- spinocerebellum
- vestibulocerebellum
cerebrocerebellum/ neocerebellum= planning + execution of high skilled movements, temporal sequences + speech
injury to cerebrocerebellum/
neocerebellum= dysmetria (inability to judge distances), INTENTION TREMOR, dysarthria (slurred, slow speech as a result of impaired muscle control), dysdiadochokinesis (inability to perform rapid, coordinated movements)
spinocerebellum= coordination of distal movements (lateral + paramedian) + proximal movements + eye movements (vermis)
injury to spinocerebellum= ataxic gait, hypotonia, pendular reflexes
vestibulocerebellum= vestibulo-ocular reflex, posture + equilibrium
injury to vestibulocerebellum= vertigo (‘spinning feeling’ of dizziness), nystagmus, ataxic gait
what dural septa is the cerebellum separated from the cerebrum by?
Tentorium Cerebelli;
A fold of dura mater that forms a horizontal partition between the cerebellum (below) and the occipital lobes of the cerebrum (above)
what fissure separates each of the following
- the anterior lobe of cerebellum from the posterior lobe
- the posterior lobe of cerebellum from the floculo-nodular lobe
the anterior lobe of cerebellum is separated from the posterior lobe by the PRIMARY FISSURE
the posterior lobe of cerebellum is separated from the floculo-nodular lobe by the POSTERIOR LATERAL FISSURE
In the cerebellum the what parts of the homunculus correspond to the
- vermis
- intermediate zones
vermis= head, neck + trunk (axial)
intermediate zones (aka paravermal areas)= upper and lower limbs
where is the dentate nucleus found?
dentate nucleus is found in the lateral hemispheres in the posterior lobe of the cerebellum
The dentate nucleus is the largest and most lateral of the 4 deep cerebellar nuclei (Fig 2). The emboliform and globose nuclei, collectively referred to as the interposed nuclei, are positioned more medially, and the fastigial nucleus lies adjacent to the midline.
what is hemiballismus
hemiballismus describes wild, flinging limb movements usually caused by a small infarct in the sub-thalamic nucleus
Explain the course the facial nerve (CN VII) takes
This facial nerve has a course that goes from the pons, through the internal acoustic meatus of the temporal bone together with vestibulocochlear nerve (B), and then exits the skull via the stylomastoid foramen.
what is the main blood supply to basal ganglia?
The main blood supply to the basal ganglia comes from lenticulostriate arteries which are branches of the middle cerebral artery (MCA), which is a continuation of the internal carotid artery.
Describe how the vestibular system detects angular + linear acceleration
The vestibular system detects head movements through specialized structures in the inner ear:
* Angular Acceleration: Detected by the semicircular canals. Each canal is oriented perpendicularly to the others, corresponding to the three spatial planes. When the head rotates, endolymph fluid within these canals moves, causing deflection of the cupula and bending of hair cells. This mechanical deformation transduces angular motion into neural signals.
* Linear Acceleration: Detected by the otolith organs (utricle and saccule). These structures contain hair cells embedded in a gelatinous matrix with calcium carbonate crystals (otoconia) on top. Linear movements or gravitational forces cause displacement of the otoconia, leading to bending of the hair cells and conversion of linear acceleration into neural signals.
Describe the vestibulo-ocular reflex (physiological nystagmus) + explain how pathological nystagmus can occur
Vestibulo-Ocular Reflex/VOR; Head turn → Vestibular nuclei → MLF → CN VI (lateral rectus) + CN III (medial rectus) → Eyes move opposite to head turn.
VOR ensures gaze stabilisation for clear vision during movement.
nystagmus: involuntary, rhythmic eye movements, typically comprising a slow phase (drift) in one direction followed by a quick, corrective phase in the opposite direction. It can occur physiologically (as a response to sustained rotation) or pathologically due to VOR dysfunction.
List the clinical signs of vestibular system dysfunction
Vestibular dysfunction can manifest through various symptoms, including:
- Vertigo: A sensation of spinning or motion
- Nystagmus: Involuntary eye movements
- Postural Instability: Unsteady gait and balance issues
- Nausea and Vomiting: Often accompanying vertigo
- Intolerance to Head Movements: Discomfort or dizziness with head motion
These symptoms can result from peripheral causes (e.g., benign paroxysmal positional vertigo) or central causes (e.g., ischemic stroke in the posterior fossa
Describe tests for balance disorders
- Head Impulse Test: Assesses the VOR by observing the ability to maintain gaze on a target during rapid head movements.
- Dix-Hallpike Maneuver: Diagnoses benign paroxysmal positional vertigo by observing nystagmus and vertigo in response to specific head positions.
- Romberg Test: Evaluates postural stability by having the patient stand with feet together, eyes closed, and assessing for swaying or imbalance.
- Caloric Testing: Stimulates the vestibular system using warm or cold water or air in the ear canal to induce nystagmus, assessing unilateral vestibular function. Head turn to the right will increasing firing of the right horizontal canal and decrease firing of the left to compensate.
(n.b. COWS acronym; Cold water= eyes deviate to ipsilateral ear, nystagmus beats away to Opposite ear.
Warm water= eyes deviate to contralateral ear + nystagmus beats towards Same ear. - Electronystagmography (ENG) or Videonystagmography (VNG): Record eye movements to evaluate vestibular function and identify nystagmus patterns.
What are the functions of the vestibular system
The vestibular system is a sensory system that maintains balance, posture + orientation
The vestibular system detects motion, head position + spatial orientation via the eyes, general proprioceptive (muscles,joints) + cutaneous receptors, and vestibular receptors in the inner ear (vestibular apparatus)
Where is endolymph produced? Where is perilymph produced? What’s the difference?
Perilymph = Extracellular-like, surrounds labyrinth, absorbs vibrations.
Endolymph = Intracellular-like, inside labyrinth, activates hair cells.
Perilymph:
Where? Scala tympani & scala vestibuli (surrounds membranous labyrinth).
Ions? High Na⁺, Low K⁺ (like CSF/plasma).
Function? Cushions & transmits sound to cochlea.
Made by? CSF & blood plasma (via cochlear aqueduct).
Endolymph:
Where? Scala media & membranous labyrinth (inside semicircular canals, utricle, saccule).
Ions? High K⁺, Low Na⁺ (like intracellular fluid).
Function? Drives hair cell activation for hearing & balance.
Made by? Stria vascularis (cochlea) & dark cells (vestibular system).
what structure joins the auditory labyrinth to the vestibular labyrinth?
Ductus Reuniens is the structure that joins the auditory labyrinth (cochlea) to the vestibular labyrinth.
Ductus Reuniens:
Function: Connects the scala media (cochlear duct) of the cochlea to the saccule in the vestibular system.
Location: A narrow membranous duct within the endolymphatic system.
Role: Allows endolymph to flow between the cochlea and vestibular system, maintaining the ionic balance necessary for both hearing and balance.
which neurotransmitter is released when hair cells depolarise in the ampullae of the semicircular ducts
GLUTAMATE is released when hair cells depolarise in ampullae of semicircular ducts
The main symptom of vestibular lesion is vertigo; a spinning sensation towards the side of the lesion; often accompanied with vomit + balance difficulties. Vestibular lesions are treated with antiemetics, antihistamines + benzodiazepines. Why are benzodiazepines used?
Benzodiazepines (e.g., diazepam, lorazepam, clonazepam) are prescribed for vestibular lesions because they suppress vestibular activity= reducing symptoms like vertigo, dizziness, and nystagmus.
Benzodiazepines (BZDs) are GABA-A receptor agonists (bind to BZD site on GABA-A receptor). Increased GABA activity dampens abnormal vestibular signals, reducing the hyperactivity caused by vestibular imbalance
What brain regions make up the vestibular cortex
Parieto-Insular Vestibular Cortex (PIVC) (core vestibular processing)
Retroinsular Cortex (Ri) (integrates otolith & semicircular canal signals)
Parietal Operculum (OP2) (human vestibular area, visual-vestibular integration)
Posterior Insular Cortex (PIC) (vestibular and visual input processing)
Temporo-Parietal Junction (TPJ) (multisensory integration)
Cingulate Sulcus Visual Area (CSv) (self-motion perception)
Precuneus Motion Area (PcM) (visual-vestibular coordination)
V6 Complex (visual motion & spatial awareness)
Describe the physiological mechanism of pain (4 processes)
- Transduction(ion channels): noxious (potentially harmful) stimuli translated into electrical activity at sensory nerve endings
- Transmission (neurones): propagation of impulses along pain pathways
- Perception (brain pain matrix): discrimination/ affect/ motivation
- Modulation: Positive + negative modulation occurs
Nociceptors are pain receptors on an organ that detect tissue damage; what do the following detect?
-TRPV1 channel
- TRPM8 channel
- Acid-sensing ion channel (ASIC)
- Capsaicin receptor TRPV1 channel is a non-selective cation channel that is activated by temperature, acid, capsaicin + mustard/wasabi
- TRPM8 ion channel (cold and menthol receptor 1) is activated by cold temperature + cooling agents (menthol)
- Acid-sensing ion channel (ASIC) is a cation channel activated by pH changes
Remember as:
She’s hot, she’s V1 (the one) (TRPV1)
Are cool (8), m8? (TRPM8)
What primary afferent axon is unmyelinated i.e. transmits slowest pain. List afferent axons from most to least to unmyelinated
- A beta (most myelinated)
- A delta (less myelinated)
- C fibres (unmyelinated)
what fibres transmit ‘1st pain’ a sharp, stinging, pricking
vs
which fibres transmit ‘2nd pain’, a diffuse + persistent burning pain
Myelinated A delta fibres carry ‘1st pain’ a sharp, stinging, pricking
vs
Unmyelinated C fibres carry ‘2nd pain’, a diffuse + persistent burning pain
N.B. speed of transmission is dependent on myelination + axon diameter (faster if myelinated + wider diameter cuz less resistance to flow)
Describe the following conditions + their mutation/ alteration in nociceptor (due to mutation)
- Congenital insensitivity to pain (CIP)
- Inherited erythromelalgia (IE)
- Congenital insensitivity to pain (CIP)= caused by loss of function mutations in Nav1.7 (sodium channel subunit) THEY FEEL NO PAIN rare condition in which individual cannot feel pain so often have wounds, broken bones, health issues not detected
- Inherited erythromelalgia (IE)= caused by gain of function mutations in Nav1.7 channel (sodium channel subunit) HYPERSENSITIVE TO PAIN; it’s a painful neuropathy involving severe chronic burning pain sensations in hands + feet
Describe the cause of pathology in the following neuropathies (loss of sensory fibres)
- Congenital insensitivity to pain with anhidrosis (CIPA)
- Diabetic neuropathy
- Congenital insensitivity to pain with anhidrosis (CIPA)= mutation in TRKA gene encodes neurotrophic receptor tyrosine kinase 1 (TrkA receptor) for nerve growth factor (NGF); NGF support survival of nociceptive sensory neurones in DRG so these patients lack NGF-dependent A delta + C fibres
- Diabetic neuropathy= high blood glucose damages the nerve fibres especially in legs + feet (ex. painful)
What role do each of the following play in the perception of pain
- limbic system
- intralaminar (reticular) nuclei of thalamus
- periaqueductal grey (PAG)
- reticular formation
- limbic system= subjective sensations of pain + pleasure
- intralaminar (reticular) nuclei of thalamus= induced arousal + descending control of nociceptor input
- periaqueductal grey (PAG)= descending pain modulation
- reticular formation= alerting cerebral cortex + focus of attention on pain
What role do each of the following play in the perception of pain
- anterior cingulate cortex (ACC)
- pre-frontal cortex
- insula
- primary sensory cortex
- amygdala
processes underlying pain perception involve primarily the thalamus and cortex, however the others also play roles
- anterior cingulate cortex (ACC)= emotional reaction/ motivation
- pre-frontal cortex= evaluation/ cognition
- insula= ‘pain’ map, interoception, homeostatic adjustment, emotion
- primary sensory cortex= somatosensory, discrimination-location intensity
- amygdala= aversion; emotional memory + response
Define the following:
- allodynia
- hyperalgesia
- peripheral sensitisation
- central sensitisation
- allodynia= a condition where pain is caused by a non-noxious (non-painful) stimulus (e.g. tickle with a feather)
- hyperalgesia= a condition where an abnormal increased pain sensitivity is caused by noxious (painful) stimulus (e.g. hot water on sunburn)
- peripheral sensitisation= an increased sensitivity to afferent nerve stimuli at the peripheral site
- central sensitisation= an increased sensitivity to an afferent nerve stimuli at the CNS site
Which area of the frontal lobes organizes sensory externally-guided actions?
Premotor cortex
Which brain region releases dopamine to facilitate movement?
Substantia nigra pars compacta
Dopaminergic neurons in the SNpc project to the striatum, forming the nigrostriatal pathway, which plays a critical role in the modulation of voluntary movements
Which drugs are used in dopamine replacement therapy in Parkinson’s disease as a DOPA decarboxylase inhibitor combined with L-DOPA?
+ name some common formulations with levodopa/L-DOPA
DOPA decarboxylase inhibitors= Benserazide, Carbidopa,
work by inhibiting the enzyme aromatic L-amino acid decarboxylase (DOPA decarboxylase), which is responsible for converting L-DOPA into dopamine in peripheral tissues (you want the dopamine in brain not peripheral tissues; hence this reduces bad side effects and means u can lose the L-DOPA at lower dose)
Common formulations with Levodopa:
Carbidopa/Levodopa (Sinemet)
Benserazide/Levodopa (Madopar
For the management of Huntington’s disease, which drug can be used as mood stabilizer?
Carbamazepine (anticonvulsant + mood stabiliser)
mechanism of action:
- Sodium Channel Blockade: Carbamazepine stabilizes sodium channels in neurons, reducing excessive neuronal firing. This action may help control movement abnormalities in HD
-Neurotransmitter Modulation: It affects neurotransmitter systems, including dopamine and glutamate, which are involved in HD. This modulation may help alleviate symptoms related to dopamine dysregulation and limit excitotoxicity.
What is the name of the fluid contained within the inner ear?
endolymph
Which cell type is found within the middle layer of the cerebellum?
Purkinje cells
Which brainstem region that contains noradrenergic neurons produces analgesia in a fight-or-flight situation?
locus coeruleus in the brainstem region that contains noradrenergic neurons producing analgesia in a fight-or-flight situation
Which opioid with a short half-life can rapidly reverse opioid overdose?
Naloxone
Which type of drug can be used for the management of a complex type of pain?
pregabalin
What are the first-line drugs for neuropathic pain
The first-line drugs for neuropathic pain are:
- SNRIs (Duloxetine, Venlafaxine)
- TCAs (Amitriptyline, Nortriptyline)
- Ca2+ channel ligands (Gabapentin, Pregabalin)
What route of drug administration has the highest bioavailability?
Intravenous
What pharmacological term defines the concentration of a drug that is required to occupy 50% of the drug target at equilibrium?
Affinity
Which antiepileptic drug inhibits the GABA transporter GAT-1?
Tiagabine
Which cerebral artery supplies the corpus callosum?
anterior cerebral artery supplies corpus callosum
Which artery supplies the pons?
basilar artery supplies the pons
What type of stroke occurs when an artery supplying the basal ganglia is blocked?
lacunar stroke
What is the name of a contusion that occurs on the side of the brain opposite to the original impact?
Contrecoup
What brain area is damaged in expressive aphasia?
Broca’s area
What neuropeptide can be blocked to prevent migraine?
CGRP
Which 3 domains are measured by the Glasgow coma scale?
Eyeopening, verbal and motor responses
The Papez circuit was described as a circuit for the feeling of emotion, but is now thought to be involved in memory. Which type of memory?
Episodic memory= a type of long-term memory that involves conscious recollection of previous experiences together with their context in terms of time, place, associated emotions, etc.
Limbic regions contribute to emotions. Which brain region is associated with sadness?
Subgenual cingulate cortex is associated with sadness
Which term describes the process by which an association forms between a behaviour and its consequence
Operant conditioning
What psychological process accounts for a relapse triggered by the sight of a syringe?
Classical conditioning
At which level of the synapse do antidepressants selective serotonin reuptake inhibitors (SSRI) act to modulate serotonergic transmission?
Transporter
Which brain region that becomes hypoactive is responsible for psychomotor retardation in depression?
Dorsolateral prefrontal cortex
whats the difference between an endogenous + exogenous agent (when talking about receptors)
endogenous agent= respond to neurotransmitters, hormones and cytokines
exogenous agent= respond to drugs
Define the following terms:
- seizures
- epileptogenesis
- epilepsy
Seizures = Abnormal, paroxysmal changes in the electrical activity of the brain; they reflect large-scale synchronous discharges of neuronal networks
Epileptogenesis = The process by which normal brain function progresses towards generation of abnormal electrical activity
Epilepsy = A neurological disorder that represents a brain state that supports recurrent, unprovoked seizures – it has neurobiological, cognitive, psychological, and social consequences
Define status epilepticus; then tell me the 3 main categories of epileptic seizure.
Status Epilepticus = A form of epilepsy which is a life-threatening medical emergency. Seizures which last more than 5 minutes (or more than 1 seizure in 5 minutes without regaining consciousness).
3 types:
Generalized Onset = They affect both sides of the brain from the onset. The networks affected can be cortical or subcortical.
Focal Onset = They start in an area or network in one of the brain hemispheres. The networks affected can be cortical or subcortical. They can remain localized or spread to large areas. They can also be described with the term partial seizures.
Unknown Onset = Seizures are classified in this category if the beginning of the seizure is uncertain. During clinical evaluation, it may become possible to change the classification into either generalized or focal onset seizure.
name the structural changes seen in epileptic brain
- reorganisation of hippocampal tissue in temporal lobe epilepsy
- loss of chandelier cells (increases the risk of abnormal excitatory activity); a specific population of interneurons which are GABAergic cells that control the activity of cortical pyramidal cells; they synase on the axon initial segment of pyramidal cells
name the 3 main cellular mechanisms linked to the development of epilepsy; mention other causes too
1) abnormal neuronal excitability (ion channels)
2) decreased neuronal inhibition (GABA-dependent)
3) Increased neuronal excitation (glutamate-dependent)
n.b. neurones in an epileptic focus have burst firing profiles, which reflect abnormal fluctuations in membrane voltage; the ‘paroxysmal depolarising shift’ phenomenon; a particular role for NMDA glutamate receptors in the depolarising plateau
other causes:
- glial abnormalities
There is a new paper on the mechanism of epileptogenesis; it describes epilepsy as a ‘interneuronopathy’ + a disorder of intracellular signalling. Epilepsy may involve activation of the mTOR pathway or the REST pathway. What role does each pathway play?
mTOR pathway is a major regulator of growth + homeostasis
REST pathway leads to negative regulation of the expression of many genes in CNS
Define generalised tonic-clonic seizures (grand mal) vs absence seizures (petit mal) + their treatment according to NICE
- Generalised Tonic-Clonic Seizures (formerly known as Grand Mal Seizures):
Description: These seizures involve a loss of consciousness and violent muscle contractions, affecting the entire body
Tonic- stiffness (muscle rigidity)
Clonic- rhythmic jerking movements (repetitive muscle contractions)
First-Line: Lamotrigine as monotherapy.
Alternative Options: If lamotrigine is unsuitable/not tolerated, consider carbamazepine or oxcarbazepine.
- Absence Seizures (formerly known as Petit Mal Seizures):
Description: Characterised by brief, sudden lapses in attention and activity, often mistaken for daydreaming.
First-Line: Ethosuximide as monotherapy.
Alternative Options: If ethosuximide is unsuitable or not tolerated, consider lamotrigine.
(Memory tip: absence seizures u ‘lose ur ethos’ - 1st line is ethosuximide’
Define focal seizures and myoclonic seizure + their treatment according to NICE
- Focal Seizures:
Description: Seizures originating in a specific area of the brain, with symptoms varying depending on the affected region.
First-Line Treatment: Offer carbamazepine or lamotrigine as monotherapy.
Alternative Options: If the first choice is unsuitable or not tolerated, consider levetiracetam, oxcarbazepine, or sodium valproate.
- Myoclonic Seizures:
Description: Involve sudden, brief jerks or twitches of a muscle or group of muscles.
First-Line Treatment: Offer sodium valproate as monotherapy.
Alternative Options: If sodium valproate is unsuitable or not tolerated, consider levetiracetam or topiramate.
Define tonic vs atonic seizures + their treatment according to NICE
- Tonic or Atonic Seizures:
Description: Tonic seizures involve sudden muscle stiffening, while atonic seizures involve sudden loss of muscle tone, often leading to falls.
n.b. both treated the same
First-Line Treatment: Offer sodium valproate as monotherapy.
Alternative Options: If sodium valproate is unsuitable or not tolerated, consider lamotrigine.
why is carbamazepine not used in absence or myoclonic seizures
How carbamazepine can worsen absence seizures:
Absence seizures are primarily caused by abnormal activity in T-type calcium channels in the thalamus.
Drugs like ethosuximide and sodium valproate work by blocking these calcium channels.
Carbamazepine does not inhibit T-type calcium channels and can actually increase burst firing in the thalamus, leading to worsening of absence seizures.
How carbamazepine worsens myoclonic seizures:
Myoclonic seizures involve sudden muscle jerks due to cortical hyperexcitability.
Carbamazepine can paradoxically increase excitability in certain neuronal circuits, leading to increased myoclonic jerks.
definition of chronic pain
chronic pain is pain that has been present for more than 12 wks (3 months), and that lasts beyond tissue healing
function + location of raphe nuclei
(function) The raphe nuclei of the brainstem provide the major source of serotonergic neurons in the central nervous system
(location) The raphe nuclei are positioned midline in the brainstem throughout the midbrain, pons, and medulla
what is the difference between pain + nociception; what are the 4 stages of nociception
pain= subjective experience
nociception= bodies ability to detect changes in environment (noxious stimuli i.e. potentially harmful stimuli)
1) transduction
2) transmission
3) perception
4) pain modulation
What patient groups are contraindicated for NSAID use (e.g. ibuprofen, naproxen, diclofenac.
celecoxib, mefenamic acid, etoricoxib.
indomethacin.
N.B. PARACETAMOL IS NOT AN NSAID
Non-steroidal anti-inflammatory drugs inappropriate in patients with
- asthma
- renal impairment
- heart disease
- uncontrolled hypertension
- peptic ulcers
What class of drug is often prescribed with NSAIDs to reduce risk of gastrointestinal side effect (e.g. acid reflux, gastritis, peptic ulcers)?
proton pump inhibitors e.g. omeprazole, lansoprazole
Opioid side effects
- constipation
- skin itching (PRURITIS)
- nausea
- altered mental status
- respiratory depression
what does damage to the corpus callosum result in
Damage to the corpus callosum severs communication between the cerebral hemispheres
mammillary bodies function in memory
The mammillary bodies are involved in recollective memory/ storage of episodic daily memory (memories associated with daily events).
Chronic primary pain is pain without known physical cause. Chronic secondary pain is pain with known physical cause. What would you treat chronic primary pain with and what would you avoid
chronic primary pain;
- ANTIDEPRESSANTS
- DO NOT GIVE ANALGESIA unless its an antidepressant
The DN4 questionnaire is used to assess neuropathic pain; what do the numbers mean? And then outline the 1st line for treating neuropathic pain
scored out of 10
4 or more= it’s neuropathic pain
first-line:
- amitriptyline (TCA)
- duloxetine (SNRI)
- gabapentin (anticonvulsant)
- pregabalin (anticonvulsant)
N.B. ONLY 1 MED CAN BE USED AT A TIME
other options:
- tramadol (short term relief)
- capsaicin cream (localised areas)
- physiotherapy
- psychotherapy
What is trigeminal neuralgia (symptoms + causes and what is the first-line treatment?
trigeminal neuralgia= (type of extreme pain) sudden, paroxysmal attacks of pain: electric shock-like, sharp, stabbing, usually unilateral (lasts few secs to few min)
site: cheekbone, nose, upper lip, upper teeth, sometimes extended to lower lip, teeth, chin
most common cause: compression, distortion or stretching of the nerve V root fibres by a branch of anterior or posterior inferior cerebellar artery
first-line: carbamazepine (blocks sodium channels)
What is cachexia (they use heroin to treat this)
Cachexia is a complex metabolic syndrome characterized by involuntary weight loss, muscle atrophy, and systemic inflammation often seen in people chronic illnesses. (doesn’t improve with nutrition)
Most common in diseases like cancer, congestive heart failure, chronic obstructive pulmonary disease, chronic kidney disease, and AIDS
How much of cardiac output, total body o2 and total body glucose does the brain use?
av. brain blood flow in mL/g?
The brain receives 15% of cardiac output + used 20% of o2 + 25% of total glucose
av. brain blood flow= 46mL/100 grams
How many seconds of anoxia will render you unconscious and how many minutes with lead to permanent unconsciousness + neuron death?
20 secs of anoxia leads to unconcsciousness
> 5min permanent unconsciousness + neuron death
CN III (oculomotor) palsy presentation?
Presentation of Third Nerve Palsy:
- ‘Down & Out’ Eye Position → due to unopposed actions of the lateral rectus and superior oblique.
- Ptosis (Drooping Eyelid) → due to loss of innervation to levator palpebrae superioris.
- Mydriasis (Pupillary Dilatation) → due to loss of parasympathetic innervation to sphincter pupillae.
n.b. Occulomotor (CN III)
Origin: oculomotor nucleus in the midbrain of the brainstem.
Course:
Emerges from the anterior aspect of the midbrain.
Travels through the cavernous sinus before entering the orbit via the superior orbital fissure.
Motor Supply:
Extraocular muscles:
Superior rectus
Medial rectus
Inferior rectus
Inferior oblique
Levator palpebrae superioris (raises the upper eyelid).
Parasympathetic Supply:
Preganglionic fibres originate in the Edinger-Westphal nucleus.
Postganglionic fibres arise from the ciliary ganglion to innervate:
Sphincter pupillae → causing pupillary constriction (miosis)
Ciliary muscles → for lens accommodation
define hemiparesis
Hemiparesis is one-sided muscle weakness
left middle cerebral artery infarctions result in what kind of losses/symptoms?
Left middle cerebral artery infarctions typically result in contralateral hemiparesis, contralateral hemisensory deficit, and aphasia. Infarcts that involve Broca’s area result in expressive aphasia.
arachnoid granulations allow CSF to flow into venous blood of sinuses but prevent backflow of blood into ______ ____
arachnoid granulations allow CSF to flow into venous blood of sinuses but prevent backflow of blood into SUB-ARACHNOID SPACE
most ppl have a dominant transverse sinus on which side
58% population have RIGHT dominant transverse sinus
Ischaemic strokes are far more common (80%) than haemorrhagic strokes. Name some major causes of haemorrhagic stroke
major causes of haemorrhagic stroke:
- hypertension
- aneurysm
- elderly
- head injury (trauma)
- alcoholics
- arteriovenous malformation
Transient Ischaemic attacks (TIAs) are a warning sign of heart attack or stroke; what is TIA + symptoms if anterior vs posterior circulation affected
TIA= a transient episode of neurologic dysfunction caused by focal brain, spinal cord, or retina ischemia, without acute infarction
symptoms if anterior circulation:
- motor weakness
- hemi-sensory loss
- dysarthria
- transient monocular blindness
symptoms if posterior circulation:
- vertigo
- diplopia
- ataxia
- amnesia
