Neuroplasticity (Courteney Fisher)

What does neuroplasticity refer to

neurons ability to reorganise and alter their anatomical and functional connectivity in response to the environmental input

What is structural neuroplasticity

• adjust neuronal morphology

• dynamic changes in cellular structures

• structural aspects of neuronal connectivity

What is functional neuroplasticity

• patterns of responsiveness

• activity of synapses, neurones, circuits

• presynaptic neurotransmitter release

• intracellular signalling pathways

• protein synthesis

• gene expression

The brain needs to maintain a dynamic balance between stability and plasticity, what is stability and plasticity

• stability: preserves existing connections and knowledge

• plasticity: allows learning, adaptation, and change

Disrupted balance can contribute to and give examples

psychopathology

• too much stability: rigidity, difficulty adapting or learning

• too much plasticity: instability, possibly linked to disorders like schizophrenia

Both hyperplasticity and hypoplasticity can cause

dysfunction

Why is experience important

it drives brain development and change

What is synaptic stabilisation

repeated activation strengthens circuits

Examples of how repetition builds habitual brain pathways

• negative thinking = stronger negative circuits

• positive thinking = stronger positive circuits

How do gene regulate plasticity

through epigenetic mechanisms

What is an epigenetic mechanism

a way the body changes how genes are expressed without changing the DNA sequence itself

• think of it like dimming or brightening a light - the switch (the gene) stays the same, but its activity level changes

What are some common epigenetic mechanisms

• DNA methylation – adds chemical “tags” that turn genes down or off

• histone modification – loosens or tightens DNA packaging to turn genes on or off

• non-coding RNAs – help regulate which genes are active

What is a sensitive period

defined as a time in development during which the brain is responsive to experiences in the form of patterns of activity

• Daw, 1997

What is a critical period

if the presence or absence of an experience results in irreversible change

What would happen if a critical period occurs too soon or too late

development can be severely disrupted

• skills would develop incorrectly, weak, delayed or may never even develop

• brain might miss important early experiences required to shape a function (late)

• brain may not be ready for certain inputs or experiences (early)

When is the brain at the most plastic point

after birth (first few years of life)

How do cues from the outside world help the brain develop

the cues tell the brain’s molecular machinery how to form circuits needed for survival

• everyones experiences differ so no two brains are the same

How does GABA determine when critical periods begin

• GABA is the brain’s main inhibitory neurotransmitter, working in balance with glutamate

• while glutamate increases neural firing, GABA calms or silences neurones

• this balance between excitation and inhibition signals when the brain is ready to reorganise and learn

How does the infant brain transition from chaotic activity to an organised pattern that opens a critical period

• neurons first fire randomly as they attempt to form connections, during this stage there is no organised pattern of activity

• specialised cells begin to fire and release GABA into the surrounding circuits

• then GABA-releasing inhibitory cells reduce the random activity, allowing circuits to form organised, repeating patterns

• this balance of excitation and inhibition triggers the start of a critical period

What is activity-dependent refinement in brain development

• it’s the process where balanced excitation and inhibition allow the brain to form organised activity patterns

• neurons that fire through experience strengthen their connections, while unused synapses are pruned away

An imbalance in the excitatory-inhibitory balance is hypothesised to be

an underlying mechanism of ASD, schizophrenia, and other neurological disorders

What happens to circuits when there’s too much excitation

circuits become noisy or unstable

What happens to circuits when there’s too much inhibition

signals fail to propagate

The excitation/inhibition of circuits is crucial for …

• perception

• memory

• motor control

• emotional regulation

Describe the excitation/inhibition balance with epilepsy

runaway excitation or insufficient inhibition causes uncontrolled synchronous firing across networks

Describe the excitation/inhibition balance with Alzheimer’s disease

loss of inhibitory interneurones in the hippocampus and cortex leads to hyper excitability and network dysfunction

Describe the excitation/inhibition balance with Parkinson’s disease

abnormal excitation/inhibition regulation in basal ganglia-thalamocortical loops disrupts motor control, alongside dopamine deficits

Describe the excitation/inhibition balance with schizophrenia

deficits in fast spiking GABAergic interneurones destabilise cortical networks and impair working memory and cognition

When do most symptoms of ASD develop

in the first few years of life when synaptic development and maturation are occurring at a rapid rate

One of the most consistent morphological findings that emerged from the structural neuroimaging studies in ASD is …

early brain overgrowth

By the time children with ASD reach 2–4 years of age, overall MRI brain volume is abnormally …

enlarged by about 10% relative to typically developing 2- to 4-year-olds

MRI studies reveal grey matter abnormalities in ASD, suggesting …

an increase in neurone cell bodies

• this reflects structural neuroplasticity (aberrant neuroplasticity) an atypical increase in neurones or synapses

ASD is highly …, so regular patterns may not apply to all individuals on the spectrum

heterogenous

Some forms of ASD might be caused by reduced activity of

GABA

• as a reduction of GABAergic inhibition would impair the suppression of neural noise, leading to a lower signal-to-noise ratio affecting neural processing

What does Transcranial Magnetic Stimulation (TMS) do

TMS uses magnetic pulses to excite or inhibit neural activity

• single pulses briefly activate neurons

• repeated pulses (rTMS) can increase or decrease excitability, with effects lasting beyond the session

What could stabilise cortical hyperplasticity in autism

the ‘mechanism-driven’ rTMS that potentiates inhibitory mechanisms

Describe how researchers studied the auditory cortex of infant rats to understand how experience influences brain development

• control rats raised in normal environments developed organised cortical maps, with neurones clustered by sound frequency

• rats exposed to only a single tone developed distorted maps, over-representing that one frequency

  • demonstrates that experience sculpts the brain, especially during critical periods

What was established in the study of the auditory cortex of infant rats to understand how experience influences brain development

lack of diverse sensory input can dramatically reshape cortical organisation

• highlighting the brain’s sensitivity early in development

What shapes brain development

early experiences

• including emotional and social ones

Rats raised in stressful environments showed

underdeveloped dendrites compared to those in enriched environments

• these findings indicate that stress and adversity in early life can lead to long-lasting changes in neural structure

How do the neurones look like in animals raised in stressful environments

appear stunted, reflecting impaired growth

• these findings indicate that stress and adversity in early life can lead to long-lasting changes in neural structure

In the study of taking Rhesus monkeys from their mothers, how did the Rhesus monkeys reared with their mothers differed to those without

Rhesus monkeys reared with their mother showed different DNA methylation patterns compared to those raised without maternal care

• the differences show that early life experiences can alter gene expression in the brain

The study of Rhesus monkeys showed what

early adversity (stress in early childhood) has lasting developmental effects, as the brain’s high structural plasticity stabilises frequently used circuits, even if they are maladaptive

Child maltreatment is common and associated with different forms of psychopathology such as

• depression

• anxiety

• post-traumatic stress disorder

• disruptive behaviour disorders

Disruptions in emotion regulation (ER) are thought to be what type of mechanism linked to what

transdiagnositc mechanism linking child maltreatment and psychopathology

Patients with anxiety disorders exhibit what

excessive neural reactivity in the amygdala

What is structural plasticity

reductions in amygdala size compared to attention bias modification

What is functional plasticity

reduced amygdala activity during emotional tasks

Describe the brain before pre-treatment to trauma in the amygdala

maltreated youth had greater activation in left amygdala and salience processing regions

Describe the brain after post-treatment to trauma in the amygdala

reduced activation in multiple regions involved in cognitive control