NEUR2020 - QUIZ THREE

how is the motor system structured

motor system goes:

1. spinal motor circuits

2. brainstem motor nuclei

3. primary motor cortex

4. secondary motor cortex

5. association cortex

this system has parallel circuits (there are circuits go upwards and downwards), there are hierarchies of information, it is functionally organised, and sensory feedback is crucially important in modulating the output of the motor system.

muscles and motor system

muscle means muscle fibres with the membrane that is attached to the tendon. This is the lowest level of the hierarchy → motor unit → motor neurone and the muscle fibre(s) it innervates

spinal motor circuits and neuromuscular junction

unipolar neurons carrying information into the system go to the dorsal root ganglion in the spinal nerve and up to the brain. It also goes to the ventral root gives so that information can go into the muscles to act.

the point of the innovation is the neuromuscular junction (this is where acetylcholine acts)

what are the descending motor pathways

from the primary motor cortex, signals descend to the muscles through two dorsolateral regions in the spinal cord and two in the ventromedial region in the spinal cord

what are the two dorsolateral regions signals descend to the muscles through

1. corticospinal dorsolateral tracts

2. corticocorubriospinal tracts

they terminate in contralateral half of one spinal cord segment, and sometimes directly on a motor neuron → responsible for controlling distal limbs (ie. hand, fingers, foot toes (direct and indirect connections). The two different direct and indirect tacts decussate at different points and goes to the opposite side. Contralateral control, one half of the brain controls one half of the body (opposite side).

what do the dorsolateral tracts control

the dorsolateral tracts controlling the limbs

was supported by Lawrence and Kuypers, transected dorsolateral corticospinal tracts in medullary pyramids of monkey. After surgery the monkeys could walk or stand, but could not used limbs for other activities

what are the two ventromedial regions signals descend to the muscles through

1. ventromedial corticospinal tract → direct

2. cortico-brainstem-spinal ventromedial tract → indirect

more diffuse, with axons innervating interneurones in several segments of the spinal cord → responsible for controlling body/trunk muscles (direct and indirect). the tracts. make their way down ipsilaterally, do not decussate

what do the ventromedial tracts control

ventromedial tracts control of posture and whole body movements, and they control the limbs movements involved in these activities.

This was shown by Lawrence and Kuypers (1968) who transected ventromedial tracts, monkeys could use their fingers to pick up foods but had postural abnormalities and impaired walking and sitting.

what is the cerebellum responsible for

responsible for gait, speech, and balance, and learning new motor sequences, coordination. As well as fine-tuning and learning functions, goal-directed navigation within environment, and sensory prediction of motor sequences

cerebellar ataxia

cerebellar ataxia causes unsteady, wide based gait → caused by stroke or alcohol related damage

where does the cerebellum receive input from

receives input from primary and secondary motor cortex. And feedback from motor responses from somatosensory and vestibular systems

what other structure does the cerebellum work with

the cerebellum seems to work in tandem with the hippocampus → hippocampus has place cells that help our navigation in environment (related to cerebellum).

Evidence supports that the left hippocampus and cerebellum work together to navigate environment in a temporal optimised way (cerebellum makes sensory predictions, hippocampus maps environment)

basal ganglia

complex, heterogenous interconnected nuclei that are heavily connected with the frontal lobes

has about 5 circuits

it modulates movement but also has cognitive functions such as habitual responses and implicit learning.

the basal ganglia does not work in isolation, it works with the primary motor cortex, thalamus, and supplementary motor area.

what are the two pathways in the basal ganglia and inputs

1. direct → selection of actions

2. indirect → inhibition of actions

you use both the excitatory and inhibitory nuclei in perfect balance (using appropriate actions and holding back inappropriate actions).

what did Gibson propose about action selection (affordances)

He proposes that there are a whole of actions that elicited by everything that is in-front of us. However, we cannot make actions for everything around us (some are appropriate (released/activated) and some are inappropriate (inhibit/suppress))

how are appropriate actions selected in basal ganglia

the appropriate actions are selected by the direct pathway of the basal ganglia (sub-cortical) and released into the cortex by the supplementary motor area to the cortex

where are the excitatory and inhibitory selection pathways located in basal ganglia and how does it work

within the basal ganglia, the substantia nigra complex contains the excitatory and inhibitory selection pathways. Inhibitory works off of the dopamine 2 receptors, and excitatory works off of the dopamine 1 receptors. There is a fine balance between the activation of these nuclei in the intact system.

Parkinson’s disease and basal ganglia

in people with Parkinson’s disease the excitatory connection is knocked out, and so the appropriate action is not being triggered, and the inhibitory connection is overly triggered

positive symptoms of Parkinson’s

1. tremor → resting (disappears when limb is in use or in sleep, contrast with cerebellar intention tremor)

2. rigidity and akinesia → resistance to passive movements, leading to postural problems, loss of righting reflexes → may feel like cogwheel rigidity on passive movement by examiner

3. with/without cognitive dysfunction, dementia, depression, tiredness/fatigue

4. forward leaning/backward leaning

5. postural hypotension (many falls)

negative symptoms of Parkinson’s

1. reduction in spontaneous movement (hypokinesia)

2. slow initiation of movement (akinesia)→ progressive slowing or freezing during movement and reduced range and scale of movement (ie. poor arm swing, slow gait, postural instability, worsening hand-writing)

3. dull weak voice without inflections (hypophonia) and slow speech

4. mask like, unemotional expression

initial treatment for Parkinson’s

treatment for Parkinson’s has come through via L-Dopa, which is artificial dopamine that can get through the blood brain barrier. There are a lot of side effects, however

side effects of L-Dopa

1. disorientation, confusion

2. affect

3. auditory/visual hallucinations

4. poor working memory

5. freezing

6. eventual drug failure

7. on-off cycle with movement problems

recent treatment for Parkinson’s

the more recent kinds of treatment is deep brain stimulation, and works for a longer time that L-Dopa (not forever, though)

Huntington’s disease

Huntington’s disease is the destruction of the basal ganglia/caudate nucleus has shrank.

it is the destruction of the GABAergic (and some cholinergic) neurones in the striatum (caudate and putamen and to some extent the globus pallidus).

There is progressive striatal atrophy (medial caudate first, then putamen, then tail of caudate). Defective metabolism precedes loss of tissue

what are the three peculiarities of Huntington’s disorder

1. hereditary nature → autosomal dominant with complete lifetime penetrance, on chromosome 4

2. manifestation in adulthood

3. tendency to insanity and suicide

what are the first signs of Huntington’s

the first signs are usually affective → depression, anxiety, impulsivity, aggression

followed by:

1. restlessness, clumsiness, personality changes, forgetfulness

2. altered speech and writing, saccadic changes

3. bradyphrenia and bradykinesia

4. poor motor dexterity, unsteadiness, and reduced speed

5. athetosis, chorea

movements often appear to be fragments of normal behaviours, involve multiple joints and thus resemble voluntary action, and they are briefly suppressible, and decrease during sleep but increase with stress

Tourette’s

intermittent tics (motor, verbal), but otherwise normal motor and sensory activity, and normal cognition

they can be caused by genes or the environment, there is an imbalance of GABAergic activity in the basal ganglia

they are involuntary (often echolalia or coprolalia), partly suppressible, anxiety and sleep deprivation increases Tourette’s

before tic onset there seems to be significant activation in the mesial and lateral pre-motor areas (so cortical areas are involved as well as the basal ganglia)

they are a premonitory sensory phenomena

what are treatments for Tourette’s

management when severe involve neuroleptics such as haloperidol and risperidone

Primary Motor cortex

in the precentral gyrus of frontal lobe.

It is a major hub of convergence of cortical motor signals and one of major outgoing point of signals

damage causes hemiplegia (weakness in the body part represented by that site)

it is somatotopic

secondary motor cortex

input from association cortex and output to primary motor cortex

it is involved in the programming of specific patterns of movement with input from the dorsolateral prefrontal cortex (with input from cerebellum and basal ganglia)

what does the secondary motor cortex consist of

1. preSMA

2. SMA (supplementary motor area)

3. Dorsal premotor

4. Ventral premotor

5. 3x cingulate motor areas (at least 2 in humans)

sensorimotor association cortex

posterior parietal located

takes input from more than one sensory system:

1. integrates knowledge (and positioning) of objects

2. knowledge of position of body parts

3. directs attention

outputs of sensorimotor association cortex

• output involves:

1. dorsolateral prefrontal association cortex → involved in the decision to make an action based on previous information/experience (not the action itself and not in the processing of the target object)

2. secondary motor cortex

3. frontal eye fields

disorder caused when damage occurs to SAC input areas

deficits after damage include ataxia and impaired body representation

disorder caused when damage occurs to SAC output areas

deficits after damage include apraxia and contralateral neglect

ataxia

inability to use vital information to guide movement of hands to a point in space

deficit is more severe in periphery of visual field, but visual fixation is preserved

there are incorrect/awkward movements and errors in accuracy (over/undershoots)

shown in Milner (2003)

apraxia

inability to act (ie. to move the moveable parts of the body in a purposeful manner)

a disorder of skilled movement resulting from neurologic dysfunction (ability to move is intact, and not due to sensory loss, weakness or ataxia)

intrinsic spatial coding

intrinsic spatial coding is knowing what our own body parts are doing.

intrinsic coding is essential when a body part is going to be obscured from vision at some stage in the movement planning and execution

Wolpert et al (1998)

Wolpert et al (1998) investigated intrinsic spatial coding in a patient who complained that she perceives her right arm and leg to drift and fade unless she is able to see them. In bed she had loss of knowledge in limb position.

they found that the superior parietal lobe is critical for sensorimotor integration by maintaining an internal representation of the body’s state

the basic component of the motor control system (as per Wolpert et al (1998)

1. desired state → what you want to do (goal)

2. estimated actual state → know what muscles etc should feel like

3. predicted state → know what the object should feel like

each of these states talk to each other with comparators and there are a whole system of motor commands (ie. perceiving the goal, movement etc.)

efference copy

an efference copy is a movement to perception (held in the parietal lobe) → tells our body what that object should feel like once it touches our body

affordances

affordances (selection and inhibition of actions) → always are in balance

this also explains why we cannot tickle ourselves → because we predict what it will feel like.

alien hand syndrome

when our motor control system is in disarray we can develop alien/anarchic hand syndrome → we can strangle ourselves (affordances are not suppressed and there is no efference copy) → the system doesn’t know what the hand should feel like → so people with this syndrome grab at everything and anything around them.

action imitation and James (1890)

action imitation is a basis for action comprehension

James (1890) argued that every mental representation of a movement awakens to some degree the actual movement which it is object.

observing, imagining or in any way representing action excites the programmes involved in that action. We understand other people because their actions activate the same motor programmes within us

Rizzolati (1998)

Rizzolatti (1998) showed monkey’s watching humans perform an action (ie. putting a peanut in-front of them) that they have to replicate later on found immense action in their F5 region of brain.

these neurons also activate if the monkey knows that the object is behind a screen (its been shown the object earlier and knows its behind a screen)

the mirror neurone network

similar to monkeys shown in Rizzolati

involves:

1. inferior parietal lobule

2. superior temporal sulcus/middle temporal gyrus

3. premotor area

4. inferior gyrus

mirror neurone system facilitates action understanding, allowing planning of our actions and understanding of others’ actions

what did Rizzolati propose mirror neurones in monkeys respond to

1. to sight of goal directed actions only

2. as long as the goal is achieved, even if it is out of sigh

3. to sound of an action

4. when action is performed by an agent (hand object interactions) → however, this has been disproved.

now what do we propose mirror neurons respond to

1. to action goals, rather than action per se

2. non human models can elicit action observation effects → we can respond to robotic stimuli as well, if we have experienced with those stimuli (ie. robotic carers, distance healthcare)

3. context, experience, and individual differences matter → shown in the Calvo-Merino (2006) study of ballet dancers

neuroplasticity and time dependency

the window of opportunity within which experience can influence development.

There are critical periods (when it is absolutely essential that an experience occurs within a given time limit, and then other mechanisms follow on, ie. younger people have better neuroplasticity) and there are sensitive periods (when an experience can still have an influence outside the interval, ie children that have not learnt language)

neuroplasticity and experience/use

the Hebbian idea that neurones that fire together wire together. If circuits are established, then not used, they do not survive. They need to be maintained. This is linked with neurogenesis, synapse formation, and myelination.

neocortex and deprivation

There were experiments looking at the layers of primary visual cortex in rats.

They found that during one-week monocular deprivation in critical period in the deprived eye had reduced axonal branching. And if deprivation is longer the changes are not comparable greater

they found that there was something going on that was critical that was causing this external axon branching drop off

enrichment and environment neuroplasticity in rats experiment manipulations

1. deprivation (rearing animals in the dark) → fewer synapses and dendritic spines, poor depth and pattern perception

2. enrichment (they could also run on their spinning wheels however, which also contributed to exercise which seems to be important as well)→ more dendritic spines and synapses

what did they find in these enriched environment studies

they investigated effects of experience on the hippocampus. In adult rats, there was an increase in neurones in the dentate gyrus of the hippocampus and in olfactory bulbs.

Enriched environments had 60% more hippocampal neurones.

They also found that there was an association between increased neurones with exercise interaction with the enriched environment.

does neurogenesis make cognition better and how (via rats)

yes

This was shown in a memory behavioural task, whereby rates were put into different environments (sedentary, enriched, exercise, and combination) and then given different objects. If the rats sniffed an object longer on the second presentation, they remembered it.

The results were that enriched and exercised rats had better memory cognition

how is neurogenesis and better cognition seen in humans (experimentally)

this was done through a cognitive task (list-learning task, same list, 5 repeats, one different (interference) list, delayed recall). Investigated in the dentate gyrus.

Dentate gyrus volume increases with exercise and is thus associated with better memory in letter recall tasks

how does information in the layers in the neocortex flow

layers in the neo-cortex have a vertical flow of information via long axons is the basis of columnar organisation. In visions there is ocular dominance columns

Hubel and Wiesel experiment

Hubel and Wiesel investigated cats and the ocular dominance groups to highlight the critical and sensitive periods. In the visual cortex there are contralateral and ipsilateral representation of the visual fields, and so there is a balance between the two.

They had deprived and non-deprived cats. In the non-deprived cats there was equal representation of the visual fields. However, with deprivation they stopped on eye for 3 months (deprivation) and tested them again and found that the cells were not activated in the contralateral eye.

Hubel and Wiesel conclusions

they argued there is a critical period between 0 and 2.5 months for neuronal development in cats. they did it again in older cats and found not a very big effect in equal representation, but some effects, making it a sensitive period and supporting this theory for critical and sensitive periods

plasticity and myelination

activity-related/dependent (neuronal discharge) myelination (impulses regulate myelination → progenitor cells become oligodendrocytes) → in early neuronal development, ATP is released from axons, the oligodendrocytes have receptors to accept the ATP and this triggers the oligodendrocyte to proliferate its dendrites and its processes to become a myelinating oligodendrocyte.

in early neuronal development, ATP is released from axons, degraded to adenosine, which in turn activates P1 purinergic receptors on oligodendrocyte progenitor cells, promoting differentiation, increasing their extension and thus the number of axons they myelinate

why does myelination need to be considered neuroplasticity

Its a dynamic process (the neurons communicate and start the process of differentiation of oligodendrocytes, and this increases their extensions and the number of axons that they myelinate).

if the neurons stops firing, myelination of oligodendrocytes retreat.

impulses and myelination regulation

impulses regulate myelination → myelination enhances neuronal firing. After the progenitors have differentiated into oligodendrocytes, action potentials increase myelination through signalling the astrocytes.

adhesions of myeline to the axon. Rate of neuronal firing modulates expression of L1-CAM cell adhesion molecule which is needed for induction of myeline by oligodendrocytes and Schwann cells → a protein coding gene that is also associated with disorders such as agenesis of corpus callosum (lack of communication between two hemispheres)

so when neurones fire, there is a cascade of events that promotes myelination, and therefore establishment of enhanced neuronal activity (and neuronal circuits)

plasticity and re-wiring of sensory cortex maps

involves multi-sensory map involvement and the idea of competition between sensations.

reorganisation of cortical maps (plasticity here refers to neuronal level changes but also to dynamic nature of these sensory maps of the environment)

Knudsen and Brainard (1991) experiment

the effect of experience on topographic sensory cortex maps was explored by Knudsen and Brainard (1991). They raised barn owls with prisms over their eyes, the prisms displace visual field X degrees to the left or right.

Knudsen and Brainard (1991) findings

1. vision mapping shifted in the direction of the prism

2. auditory map also shifted in the tectum in the corresponding direction and by a corresponding extent

this is plasticity as the synapses are withdrawing. The visual and auditory synapses are unwiring themselves and rewiring themselves.

evidence for competition in neuronal development

has evidence from vision:

1. ocular dominance columns (layer IV) in many species are developed at birth. Deprivation of input in one eye during sensitive periods leads to reduced activation of layer IV of the corresponding visual cortex. But the activation of the other cortex by the intact eye is increased.

2. this is not just a single process, it involves shifting and re-balancing

brain plasticity and guided recovery in clinic

• Involves reorganisation of cortical maps and modification by experience:

1. cutting nerves, sewing together fingers of on hand, altering demands of system by increased use. This changes somatosensory map (change cortically)

2. relevant part of the cortex no longer responds to the touch of that finger. but that now defunct area soon starts to respond to stimulation of the adjacent finger, it fills in the silent areas and takes over.

3. so the adult cortex is a dynamic area, where changes can still happen

Merzenich and Jenkins (1995)

Mapping of the somatosensory hand area in the normal monkey cortex (individual digit representations revealed by single unit recordings)

if the two fingers of one hand are sewn together, months later the cortical maps change so that the sharp border once present between the two fingers is now blurred

Ungerleider et al.

investigated sensory cortex changes due to plasticity in adults by completing a motor task and trained people to play these sequences.

They found increased activation for trained movements compared to untrained movements that lasted up to 8 weeks, even when no training ensued on the task in the interim. Thus, in a normal brain, training can induced rapid changes in organisation that reflect plasticity, so there is a degree of functional plasticity in the cortex.

phantom limb phenomena

reorganisation of cortical maps is also shown in the phantom limb phenomena → after amputation, patients can still feel as though they have the limb and can feel pain and other sensations in or over it. After time elapses, they still feel as though it exists, it reduced in size. If the amputate part is hurt, the limb can feel enlarged again.

Ramachandran (1993) found when the patients cheek was stroked, he reported sensations in his left hand which was missing (this is because the face region in the brain has expanded into the hand region)

what happens when the axon of a neuron is cut off

When this happens, the forward-going (anterograde) degeneration will take place. So the distal portion/forward going portion of the axon breaks down and thus, the backward portion of the axon has nothing to communicate to, and that then breaks down (retrograde degeneration). And when there is nothing on either end communicating, the middle portion breaks down (trans-neuronal degeneration), the whole circuit will break down

concussions

concussions are close and penetrating head injuries. They are a blow to the head. You can experience extremely brief loss of consciousness, or may have no loss at all. There is temporary confusion and behavioural, affective, and cognitive problems. There is no evidence of structural (neuronal) damage) → but microtubules fracture (neurotransmitter transport affected)

the cumulative effect of concussion → internal bleeds and linear and rotational forces can lead to cell death

cognitive and behavioural consequences of concussion

1. punch-drunk syndrome in boxers → general cognitive deterioration and eventual scarring after repeated concussions. Effects are summative

2. Lavoie et al (2003) → EEG recordings (P300 amplitude) of footballers were altered even after two years of sustaining a concussion (P300 attenuation to rare stimuli). Symptomatic concussion footballers did quite poorly on the oddball targets task.

shell shock and head injury link

shell shock in military personnel (reported symptoms as affective, similar to traumatic)→ WW1 soldiers in the trenches, undergoing unrelenting artillery bombardment, suffered from similar symptoms, designated at the time as shell shock. Investigation into a possible organic cause for these symptoms was discontinued.

But studies have recently revealed that athletes with repeated head trauma can develop a neurodegenerative diseases, chronic traumatic encephalopathy, can present with similar clinical features as shell shock.

key mechanical factors involved in head injury

the key mechanical factors associated with brain injury are an increase in intracranial pressure and the brain’s motion relative to the skull. Overpressure affects the brain immediately upon impact with the skull.

closed head injury

does not penetrate the skull

what can closed head injury cause

1. contusions are bruises caused when the brain slams against the skull. These are coup (bruise on the same side as blow) and contra-coup (bruise on the opposite side of where the blow was).

2. Haematomas (bleeds due to the shearing of blood vessels). Alcohol is an anti-coagulant. So much bleeding can cause a midline shift.

3. oedema → swelling due to fluid → actually protective mechanisms but damages the brain due to pressure

4. loss of consciousness → downward pressure on the brain stem, but also when brain moves forward, it tends to twist in the skull, disrupting brain stem functions including consciousness

5. epilepsy → disrupted tissue can start to produce impaired neural activity

penetrating head injuries

penetrating head injuries you get all of the same as closed head injuries and can cause infections, scarring, and thus, epilepsy

skull fractures can be

1. linear

2. depressed → more complicated because impact drives fragments into dura and brain → infection and focus for epileptic activity

post-traumatic epilepsy

post-traumatic epilepsy is due to presence of scar tissue (changes in membrane structure and function). Here patients typically receive anticonvulsants prophylactically

biomechanics of TBI (at neuronal level)

with either anterograde or retrograde degeneration, the neuron is not activated by the post-synaptic neuron (causes a domino effect of metabolic changes)

neurones that are not completely ruptured may re-sprout axonal projections (called restoration). But they may also form unwanted connections → causing behavioural disturbance (as neurones that fire together, wire together)

cerebrovascular accidents (stroke)

stroke is a sudden disruption to the brain’s blood circulation

it is any abnormality of the brain resulting from pathology of the blood vessels

causes of stroke

1. lesion of vessel wall

2. occlusion of lumen due to thrombus/embolus

3. rupture, altered permeability

4. increased viscosity or other change of the blood (ie. medicine a patient is taking that thins out the blood)

the brain receives 15% of the resting cardiac output and accounts for 20% of the oxygen consumption. It needs oxygen.

what does stroke cause

1. haemorrhage → bleed into the brain when the blood vessel ruptures → may happen because of congenital weakness in blood vessel wall or because of an aneurysm

2. Ischaemia → disruption in blood supply (to thrombus, embolus, arteriosclerosis), build up of blood, like a clot. The consequences of ischaemia typically take a few days to develop

3. Infarcts → areas of dead tissue. This is surrounded by the penumbra, which is alive but dysfunctional, which may recover depending on treatment and the thickness of one’s blood vessel walls

mitochondria and cerebral hypoxia

mitochondria are really sensitive to hypoxia.

cerebral hypoxia leads to mitochondrial dysfunction. On re-perfusion, dysfunction is partially and transiently reversed. It then causes neurotransmitter dysfunction and neurone death

you also get an ongoing inflammation process (microglia). It is not only at the site of the stroke but also in distant regions for up to 6 months

neuronal regeneration after damage in mammals

1. the capacity is higher in early development, but drops off with maturity (as we age)

2. there is a distinction between CNS and PNS regeneration → PNS is more capable due to Schwann cells being able to produce neurotrophic factors to stimulate growth. Whereas in the CNS the oligodendrocytes do not have these qualities and release factors which inhibit growth

when does neuronal regeneration after damage start

neuronal regeneration from the proximal stump of the nerve start ~2 to 3 days after damage

three points of neuronal regeneration

1. if the Schwann cells are not damaged, the axon can regrow through and get to its original target

2. if there is complete but small separation (including the Schwann cells), the axons may regrow into the wrong sheaths → wrong destination → poor coordination

3. if there is complete but large separation, there may be no regeneration, and the regrowing axons become a tangle, with no destination. When an axon degenerates, axons from neighbouring intact neurones may grow to synapse as the vacated sites (causing collateral sprouting)

why does regeneration not occur in intact neurons

the reason this does not happen in intact neurons is to do with boundaries. At the point of boundaries there is inhibition neuronal connection and the other one.

mechanisms of CNS reorganisation

1. establishment of new connections by collateral sprouting → long term reorganisation can be too great to be explained by changes to existing connections only

2. strengthening of existing connections due to release from inhibition (by original connections) → reorganisation can be so rapid but also restricted, it cannot be explained by normal growth, rather a change in the balance of maintenance. As shown in the hand injury study (no longer boundary separation between the three fingers)

what are mis-referrals

mis-referrals are errors in verbal reports of touch consistent with exchanged nerve positions

factors in neuronal recovery

1. age

2. rehabilitative training

3. growth hormones

age/pregnancy and neuronal recovery

during pregnancy, if the cerebral cortex of the baby is damaged while neurogenesis is still ongoing, the brain is able to compensate by making neurons and there is a better functional outcome than if the injury is in adulthood.

If there is damage during the time of neural migration (when neurogenesis has stopped and neurons have to connect to their endpoint), there is poor functional outcome. Injury during the peak time of synaptogenesis allows for compensatory synaptogenesis and correlated functional improvement

thus an injury during the 3rd trimester and birth will lead to poor functional outcome because this is the time of maximum migration, whereas injury during the next 18 months will allow a better outcome because this is the peak time of synaptogenesis

rehabilitative training and neuronal recovery

reducing the extent of lesions. Shown in Nudo et al (1996) → ischaemic lesions in the hand area of the motor cortex in monkeys, they got them to pick up pellets, and they found the penumbra reduced. In humans, this is the same and is due to sensory competition

Phineas Gage

Phineas Gage endured an accident where a steel rod shot through the front of his skull. He cam away with a significant part of his frontal lobe destroyed. He underwent a dramatic personality shift. He is an example of a dys-executive patient.

he became very fitful, irreverent, and grossly profane. He was also impatient and obstinate yet capricious and vacillating, unable to settle on any of the plans he devised for future actions. He was unable to perform the duties that made him a successful foreman. But he did work as a coach-and-six driver in Chile for six years.

Arnold Pick

described a man who had presented in life with progressive loss of speech and dementia. When this patient died his brain was found to be atrophied.

This shrinkage had been caused by brain cells dying in localised areas. This feature of localisation is very different to Alzheimer’s disease where the atrophy is more generalised.

Pick’s disease

fronto-temporal atrophy with knife-life thinning of the gyri in frontal and temporal lobes. The ventricles are really dilated, and there are swollen brain cells (Pick cells) with abnormal tau protein inclusions.

Pick’s disease symptoms

• these patients were found to have abnormal spontaneous behaviours during examination:

1. inappropriate jocularity

2. echolalia and echopraxia

3. disinhibited approach or utilisation behaviours

4. unkempt, depressed in early stages

5. primitive reflexes such as grasp, suck, and snout, toes

progression of Pick’s disease (fronto-temporal dementia)

during the first 2 years of Pick’s disease (frontotemporal demeia, psychiatric abnormalities related to the classic frontal lobe syndromes → aggressive and social inappropriateness, apathy and disinhibition, decreased spontaneity

speech and language abnormalities often begin early and progress fast. Memory impairment relatively less severe than speech/language and behavioural changes. Verbal output that is often non-fluent, with poor naming of objects

movements disorders often involve akinesia, plastic rigidity, or paratonia on motor examination, and perseveration.

three types of Pick’s disease (fronto-temporal dementia)

1. behavioural variant → disinhibition and inappropriate behaviours, emotional unconcern, together with cognitive changes

2. semantic variant → involving semantic memory loss (meaning and recognition of words and objects, linked to temporal lobe)

3. progressive non-fluent aphasia (language disorder) → understanding of language maintained but language output is disrupted

two types of lobotomies

1. leucotome → inserted six times into the patients brain and the cutting wire was extruded after each insertion and rotated to cut out a core of the tissue. The rough positioning of the cuts were near the front of the brain (frontal lobes)

2. transorbital sectioning (used by Walter Freeman) → inserted into the eyeball and leucotome was switched from side to side to cut the tissue.