W8 - Neuroplasticity

neuroplasticity

the capacity for neuronal change

• happens in intact nervous system and after injuring it

types of neuroplastic changes

structural

• anatomical changes

• eg. to neuronal connections/size of cortical areas

functional

• structures deviating from the initial function

phantom limb syndrome

Lotze et al. (2001)

participants:

• phantom limb with pain

• phantom limb without pain

• healthy controls

participants imagined a movement:

• patients with phantom limb pain showed activity in the face area (corresponding to the mouth) when imagining hand movements

participants pursed their lips:

• patients with phantom limb pain showed activity patterns extending to the hand areas in S1 (and M1)

what does Lotze et al. (2001)’s phantom limb study show

there is selective coactivation of the cortical hand and mouth areas in patients with phantom limb pain

• this reorganizational change may be the neural correlate of phantom limb pain

aka phantom limb pain is closely linked to cortical reorganization

what causes brain damage

tumours

strokes

infections

neurological diseases

injuries

neuroplastic responses to nervous system damage

degeneration/deterioration

regeneration/regrowth of damaged neurons

reorganisation

recovery

• Pinel and Barnes (2017)

degeneration/deterioration

important aspect of brain development

• observed in a healthy nervous system in early development

but also a characteristic of disease and neuron death

synaptic pruning during childhood

3 types:

• anterograde

• retrograde

  • these 2 from axotomy (a cut in an axon)

• transneuronal

synaptic pruning

process of removing weak/unused neural connections (synapses) to strengthen the most used ones

• maximises the efficacy of mature neural circuits

occurs most at 4-6 years old

• before this is just synapse formation

  • 2 years has the highest amount of synapses

anterograde degeneration

distal segment swells up and degenerates

occurs within days following axotomy

retrograde degeneration

proximal segment degenerates

• typically leads to entire neuron death

occurs after anterograde degeneration

transneuronal degeneration

when degeneration spreads from site of damage to adjacent neurons

anterograde transneuronal degeneration

• spreads from damaged neuron to ones they’re synapsed onto

retrograde transneuronal degeneration

• spreads to neurons synapsing on the damaged cell

regeneration

regrowth of damaged neurons

less accurate in mammals and higher vertebrates

• but can take place during the early stages of development, before adulthood is reached

• CNS neurons do not regenerate in adult mammals

  • but there is possibility for PNS neurons to regenerate

regeneration of PNS neurons

due to Schwann cells

• these are glial cells that produce myelin sheath in the PNS

  • they produce neurotrophic factors that stimulate growth of new axons

cell-adhesion molecules provide a pathway for axonal growth

why can’t CNS neurons regenerate in adult mammals

due to oligodendroglia - Silver et al. (2015)

• these are glial cells that produce myeline sheath in the CNS (remyelination)

• which actively blocks axon regeneration, following injury

  • leads to permanent functional deficits like strokes and spinal cord injuries

instead of regenerating damaged CNS cells, the brain relies on plasticity/reorganisation to take over lost/damaged functions

reorganisation mechanisms

strengthening of existing connections through the release of inhibition of adjacent nerves

collateral sprouting

• vacant synapses become occupied and establish new functional pathways and connections

synaptic plasticity

• strengthening/weakening existing synapses based on activity

  • long-term potentiation/depression

• differs to pruning, which is eliminating synapses to increase brain efficiency

collateral sprouting

the formation of new axon branches in neighbouring neurons which then synapse at vacant sites left by degenerated axons

• forms new functional pathways

evidence for cortical reorganisation in lab animals

Sanes et al. (1990)

• cut the motor neurons which controlled muscles of rats’ whiskers

a few weeks later

• stimulating regions of the motor cortex now activated muscles of the face rather than whisker movement

• evidence that other areas of brain take over, potentially strengthening, their functions

there is rapid reorganisation of the mammalian motor cortex following peripheral nerve lesions

• within 4 hours

• the motor cortex is dynamically organised

evidence for cortical reorganisation in humans - Amedi et al. (2005)

visual areas of the brain activated when blind participants perform somatosensory discrimination tasks

where reorganisation can occur

after strokes

after nerve damage

in amputees

in blind people

recovery

recovery of functions following CNS damage is poorly understood due to:

• biological limitations of regeneration

• complexity of the nervous system

• individual differences in injuries = hard to compare results

• poor ability to distinguish recovery from compensatory mechanisms (plasticity, reorganisation)

treatment of nervous system damage

blocking neurodegeneration

neurotransplantation

rehabilitative training

blocking neurodegeneration - Xu et al. (1999) rat study

damaged hippocampus in rats

• apoptosis of neurons in this area

  • programmed cell death

• deficits in performing spatial learning task

introduction of a neuronal apoptosis inhibitor protein (NAIP) via a virus:

• reduced neuron loss

• better task performance

blocking neurodegeneration - Samantaray et al. (2011)

examined the effectiveness of low doses of estrogen following spinal cord injury in rats

• estrogen administration found to reduce apoptosis/cell death and inflammation following injury

estrogen serves as a neuroprotective agent

• study did not focus on behavioural outcomes however

suggests estrogen as potential factor in spinal cord injury treatment

neurotransplantation - Cheng et al. (1996)

transected the spinal cord of rats, making them paraplegic

• implanted small sections of myelinated peripheral nerves (MPN) which bridged the gaps in the spinal cord

  • from Schwann cells

lead to regeneration of spinal cord neurons

• this improved hind limb function in the rats

rehabilitative training - strokes

Nudo et al. (1996)

• induced leisons in the hand area of monkeys’ motor cortex

those who went through intensive therapy on the affected limb showed greater functional recovery and reduced cortical damage in M1

shows neurotransplantation treatments might be more effective if accompanied by appropriate training

rehabilitative training - constraint-induced therapy

Kwakkel et al. (2015)

• involves reducing the functioning of the intact limb and training the impaired one

leads to:

• improved performance of the affected limb

• cortical reorganisation favouring representation of the affected limb

rehabilitative training - facilitated walking

supporting spinal cord injury patients with a harness improves locomotion by producing greater speed and - coordination

• results in patients being able to walk independently gradually