Week 10 - Neuroplasticity Flashcards
What was the first evidence of how memory formation results from molecular changes?
Eric Kandel, 1969
Memory formation results from molecular changes
What is long term potentiation?
The persistent strengthening of synapses based on recent patterns of activity
long lasting increases in the signalling between two neurons
Can plasticity be maladaptive?
yes, when associated with negative consequences such as a loss of unction or increased injury
What is metaplasticity?
Interactions between internally generated change and externally induced plasticity
When can maladaptive plasticity occur?
in response to treatment of neuropsychiatric disorders eg. tardive dyskinesia following antipsychotic drugs (dopamine antagonisys)
How does addiction effect plasticity?
maladaptive plasticity in the subcortical reward circuit
prefrontal regulation of subcortical limbic circuits re significantly reduces (loss of inhibitory modulation)
drug seeking/taking is then under control of evolutionarily older brain regions, with little control imposed by neo-cortex
Very resistant to reversal
Behaviours that override the drug seeking are hard to (re)establish
What is neurodegeneration?
Progressive declines in behaviour and neural function, often through a pathogenic process and maladaptive cycle
What does amyloid affect?
Synaptic plasticity and therefore cellular mechanisms for plastic changes in brain circuits
What declines with ageing?
processing speed
working memory
peripheral nervous system function
What are common themes in plasticity that emerge across diverse central nervous system conditions?
Experience dependence
Time sensitivity
Motivation and attention
What is a broad definition of neuroplasticity according to Cramer et al, 2011?
The ability of the nervous system to respond to intrinsic and extrinsic stimuli by reorganising its structure, function and connections
When can neuroplasticity occur?
during development
in response to the environment
in support of learning
in response to disease
in relation to therapy
When can plasticity be viewed as adaptive?
When associated with a gain in function
When can plasticity be viewed as maladaptive?
When associated with negative consequences such as loss of function or injury
What does it mean if there is a shift in inter-hemispheric balance towards the uninjured hemisphere?
Sign of a distressed system
The delayed onset of epilepsy after cerebral trauma suggests that…..?
Progressive changes in the brain, such as axonal sprouting and the formation of new connections, produce alterations in neural signalling and disinhibition that result in the induction of seizures
What are some examples of maladaptive neuroplasticity?
Delayed onset of epilepsy - Progressive changes in the brain, such as axonal sprouting and the formation of new connections, produce alterations in neural signalling and disinhibition that result in the induction of seizures
Chronic pain and allodynia following injury to a limb (eg. amputation) or to CNS
How do mental and addicitive disorders differ from stroke/trauma?
The onset of mental and addictive disorders is usually insidious
Course of the illness tends to be recurring/episodic
Reocvery in most of the disorders is slow when present
relapse rates are high
What areas are particularly noteworthy in relation to the clinical expression of neuropsychiatric disorders?
Prefrontal cortical association areas
What does the kindling model suggest?
Heightened neural sensitivity to specific triggers reflects plasticity in N-Methyl-D-asparate receptor functioning in addiction and other neuropsychiatric disorders
What control mechanisms are hijacked by subcortical reward systems in order to support drug-seeking behaviour?
Prefrontal control
What receptors are critical for long term potentiation?
Perisynaptic metabotropic glutamate receptors
What is cross-modal plasticity?
The ability of sensory maps to reorganise across afferent modalities when normal input is deprived
How may maladaptive neuroplasticity affect a child who has optical problems?
Permanent visual deficits such as amblyopia
What are critical modulators of plasticity?
Salience
Motivation
Attention
What combination therapies have the potential to further drive Hebbian Plasticity?
Concomitant pharamacological
Peripheral nerve stimulation
What interventions have the potential. to increase the efficacy of neuromodulation?
Imagery or behvaioural interventions
The left temporoparietal cortex is one of several regions whose overactivity is associated with the perception of external voices in hallucinating patients. How would you use TMS to treat this?
Low freq stimulation of temporoparietal cortex has been used experimentally to inhibit cortical excitability and thereby quell severe, treatment-resistant auditory hallucinations with some success
What are the two generally hypothesised mechanisms of deep brain stimulations?
Creates a functional lesion via inhibition within the stimulated region and, (immediate effects-meffects on motor function in parkinsons)
alternatively, the deep brain stimulation activates the neuronal network connected to the stimulated region, leading to modulation of pathological network activity (gradual effects - circuit retraining as seen in neuropsychiatric disorders)
What brain areas have shown promise in treating depression with deep brain stimulation?
Subcallosal cortex and its adjacent white matter tracts, suggesting that disruption of the pathological limbic-cortical circuit may ameliorate treatment-resistant depression
Nucleus accumbens
anterior limb of the internal capsule
How has deep brain stimulation shown promise for treating OCD?
Involve the overactivity of cortico-striatal-limbic circuits
Internal capsule extending into the ventral striatum
What is a limitation of molecular mechanisms that support plasticity?
Pharmacological vulnerabilities
Behavioural gains induced by plasticity-promoting pharmacological interventions can be lost
Emerging finctional conncectivity MRI methods provide what information related to neuroplasticity?
Strength of connections across multiple distributed networks such as emotion, motor and cognitive, in parallel
What are some issues in the study of clinical neuroplasticity?
Disease can affect imaging biomarkers
Clinical trial design - crossover studies are not always possible
Selection bias
Impairments and limitations of those enrolled may not be representative of the overall disease population
Plasticity is time sensitive
Variability complicates generalisation
Translating neuroplasticity findings from animals to humans can be difficult
What are the directions for future research regarding neuroplasticity?
Tailoring plasticity-based therapies based on individual patient measurements
High-throughput methods to screen potential plasticity-promoting interventions within specific networks
Examine therapies in combination
Animal models that replicate the complexity of disease mechanisms over time
More understanding of age effects on neuroplasticty
What is EPSP?
Excitatory postsynaptic potential
Size of response, post synaptically
What parts of the hippocampus are involved in long-term potentiation?
CA3 and CA1
Following cerebral trauma, the brain may go through maladaptive changes in conjunction of adaptive changes, what is an example of this?
Epilepsy
Chronic pain causes changes to the structure of the brain as well as causing reductions in cognitive ability. What are the two approaches to treating chronic pain?
Approach 1
Target the injury (bottom-up)
approach 2
Target the pain centrally - address the pain sensation “top down”
Is it effective to treat chronic pain by targeting the injury?
This only addresses the nociceptive signals from the peripheral receptors
Very weak relationship between the extent of musculoskeletal damage and the extent of the pain
What are the two ways to rehabilitate and reverse the abnormal changes to the CNS?
Treat the injury (bottom up)
Target the brain (top down)
What is central sensitisation?
An amplification of neural signalling within the central nervous system eliciting pain hypersensitivity
considered a form on maladaptive plasticity
What can changes in corticospinal excitability demonstrate?
Can reflect reorganisation at the cortical and spinal levels
What happens if an individual modifies their motor strategies to control a joint?
Contribute to chronicity through maladaptive plasticity
What changes cause people to modify their motor strategies to control a joint?
Changes in cortical maps or in the balance between inhibition and excitation may disrupt the facilitation of the muscles needed too execute a motor task, as well as the inhibition of other muscles for fine tuning movement
How may clinicians examine sensorimotor changes in the clinic?
One option would be to evaluate how the joint is controlled by assessing how patients actively move their limb during a motor task
Looking for changes in
movement symmetry
appearance of compensations
Aberrant movements
Also assessment of cognitive-emotional factors
Workplace and sport activities
What has been shown to improve motor performance and reduce clinical symptoms in patients with musculoskeletal disorders?
Sensorimotor or skill training
