Neuroplasticity After Stroke Overview 1. What is neuroplasticity? 2. - - PowerPoint PPT Presentation

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Neuroplasticity After Stroke Overview 1. What is neuroplasticity? 2. - - PowerPoint PPT Presentation

National Brain Injury Symposium: Complexity and best practice March 13th 2015 Neurorehabilitation and Brain Plasticity NICK WARD, UCL INSTITUTE OF NEUROLOGY, QUEEN SQUARE n.ward@ucl.ac.uk Slides at


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NICK WARD, UCL INSTITUTE OF NEUROLOGY, QUEEN SQUARE n.ward@ucl.ac.uk @WardLab

Neurorehabilitation and Brain Plasticity

Slides ¡at ¡www.ucl.ac.uk/ion/departments/sobell/Research/NWard ¡or ¡look ¡on ¡ ¡

National Brain Injury Symposium: Complexity and best practice March 13th 2015

@WardLab

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Overview

  • 1. What is neuroplasticity?
  • 2. Enhancing potential for neuroplasticity in stroke
  • 3. RCTs? - Barriers to translation
  • 4. Imaging the potential for neuroplasticity in humans

Neuroplasticity After Stroke

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Treatments aimed at reducing impairments (Task-specific) training

drugs

  • ther

cortical stimulation

Neuroplasticity After Stroke

  • 1. When is neuroplasticity relevant in neurorehabilitation?

Rehabilitation is a process of active change by which a person who has become disabled acquires the knowledge and skills needed for optimum physical, psychological and social function

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Neuroplasticity After Stroke

  • 1. What is plasticity?

Changes in strength of a synaptic connection (or at a systems level, network connection) in response to either an environmental stimulus or increase in synaptic activity

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Brain slice Plasticity takes place in the cortex

  • changing strength of existing connections
  • new connections
  • getting rid of unused connections

Cortex Pyramidal cell Neuroplasticity After Stroke

  • 1. What is plasticity?
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Dendritic growth in vivo

Niell et al., Nat Neurosci 2004; 7: 254-260

Axon arborisation in vivo

Hua et al., Nature 2005; 434: 1022-1026

dendrites axon

Neuroplasticity After Stroke

  • 1. What is plasticity?
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A B

infarct

3 months post stroke 17 days post stroke 24 days post stroke 31 days post stroke 10 days post stroke affected side affected side

Neuroplasticity After Stroke

  • 1. Changes in residual functional architecture
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Neuroplasticity After Stroke

  • 2. Enhancing potential for neuroplasticity

Drugs NIBS Enriched Environments

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Murphy & Corbett, Nat Rev Neurosci 2009;10:861-72.

Neuroplasticity After Stroke

  • 2. Spontaneous Biological Recovery?
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Neuroplasticity After Stroke

  • 2. Enriched environments for neuroplasticity
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Biernaskie & Corbett, J Neurosci. 21, 5272–5280 (2001).

Neuroplasticity After Stroke

  • 2. Enriched environments for neuroplasticity
  • Enriched environments plus training leads to significant improvements in skilled reaching
  • Running exercise immediately before reaching practice increases efficacy of training
  • If training started after day 30 it is largely ineffective (day 90 in humans?)
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Kolb B et al., Neurosci Biobehav Rev 1998; 22: 143-59

Neuroplasticity After Stroke

  • 2. Enriched environments for neuroplasticity
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Robotic treadmill training Robotic arm training Home video arm/hand training

Neuroplasticity After Stroke

  • 2. Enriched environments for neuroplasticity
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  • In the cortex GABA is inhibitory,

glutamate is excitatory

  • Reduced activity at GABAergic

interneurons allows plasticity in adults

  • Enhanced glutamatergic

signalling leads to LTP

  • So …altering the balance of

inhibition/excitation is important in reopening new periods of plasticity in adult cortex

Neuroplasticity After Stroke

  • 2. Inhibition-Excitation – a therapeutic target?
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Drugs NIBS Neuroplasticity After Stroke

  • 2. Inhibition-Excitation – a therapeutic target?
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amphetamine

less disability more disability

SSRIs (e.g. FLAME, FOCUS in UK) Acetylcholinesterase inhibitors

Neuroplasticity After Stroke

  • 2. Enhancing potential for neuroplasticity - pharmacological
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chronic administration of fluoxetine (in rats) reopens critical period of plasticity in adulthood

In humans (healthy and stroke), a single dose

  • increases simple motor performance
  • increases motor cortex activity (fMRI)
  • increases motor cortex excitability (TMS)

Neuroplasticity After Stroke

  • 2. Enhancing potential for neuroplasticity – fluoxetine?
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After effects of tDCS

  • Increase in NMDA-dependent intracortical facilitation
  • Reduces GABA-ergic intracortical inhibition
  • Reduces intracortical GABA (MR Spectroscopy)

Neuroplasticity After Stroke

  • 2. Enhancing potential neuroplasticity potential – NIBS?
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Why not perform large RCTs? Neuroplasticity After Stroke

  • 3. Barriers to translation …sources of variability
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Why not perform large RCTs? Neuroplasticity After Stroke

  • 3. Barriers to translation …sources of variability
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Why not perform large RCTs? Neuroplasticity After Stroke

  • 3. Barriers to translation …sources of variability
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Why not perform large RCTs? Neuroplasticity After Stroke

  • 3. Barriers to translation …sources of variability

Hamada M et al. Cereb. Cortex 2013;23:1593-1605

Inhibitory TBS? Excitatory TBS? TBS (and TDCS) is very variable!

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Getting plasticity enhancement into clinical practice in stroke

Neuroplasticity After Stroke

  • 3. Biomarkers of potential for plasticity?

Biomarker Behaviour

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ctDCS to contralesional M1 reduced SICI (less inhibition) in ipsilesional M1 tDCS-induced enhancement of skill acquisition

Reduced intracortical inhibition re-opens periods of plasticity in chronic stroke?

Neuroplasticity After Stroke

  • 3. Biomarkers of potential for plasticity?
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Large scale networks Task related networks Intracortical networks

MESOSCOPIC MACROSCOPIC Neuroplasticity After Stroke

  • 4. Biomarkers at a range of scales of brain architecture

A mechanistic approach to studying recovery requires an appropriate level of description

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“…the spectral characteristics of MEG recordings provide a marker of cortical GABAergic activity”

BASELINE BETA-BAND POWER

  • Greater baseline beta-power =

more GABA inhibition?

  • Increased by diazepam

(GABAA effect?)

  • Increased with ageing

Rossiter et al., Neuroimage 2014

Neuroplasticity After Stroke

  • 4. Enhancing Neuroplasticity – mesoscopic scale?

MOVEMENT RELATED BETA-DECREASE

  • Greater decrease in beta-power with

grip = more GABA inhibition?

  • Increased by diazepam and tiagabine

(GABAA effect?)

  • Less MRBD in chronic stroke patients

(particularly those with more impairment)

Rossiter et al., J Neurophysiol 2014

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Network connectivity with DCM for fMRI

Neuroplasticity After Stroke

  • 4. Enhancing Neuroplasticity – macroscopic scale?
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Network connectivity with Graph Theory for fMRI/MEG graph ¡metrics ¡-­‑ ¡efficiency ¡

Neuroplasticity After Stroke

  • 4. Enhancing Neuroplasticity – macroscopic scale?
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Bridge the gap ...

mesoscopic macroscopic

Mechanistic framework ... motor language cognitive Platform for stratification ...

+

behaviour

Predictions

biomarkers patients interventions

biomarkers stratification

Neuroplasticity After Stroke

  • 4. Putting it all together
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  • Neuroscience can help advances in neurorehabilitation
  • The dose of treatment is critical - more is generally better
  • Increasing the potential for experience dependent plasticity

appears possible

  • Neuroimaging should help in stratification
  • Understanding the mechanisms of recovery and treatment

might allow targeted or individualised therapy in future

Neuroplasticity After Stroke

Summary

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FIL:

Karl Friston Rosalyn Moran Gareth Barnes Richard Frackowiak Will Penny Jennie Newton

SOBELL DEPARTMENT :

Holly Rossiter Muddy Bhatt Stephanie Bowen Ella Clark Svenja Espenhahn Marie-Helene Boudrias Chang-hyun Park Sven Bestman John Rothwell Penny Talelli

Acknowledgements

ABIU/NRU:

Fran Brander Kate Kelly Diane Playford Alan Thompson

FUNDING: Neuroplasticity After Stroke

Slides at www.ucl.ac.uk/ion/departments/sobell/Research/NWard

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  • 1. Murphy TH, Corbett D. Plasticity during stroke recovery: from synapse to behaviour.

Nat Rev Neurosci 2009;10:861-72.

  • 2. Carmichael ST. Targets for neural repair therapies after stroke. Stroke 2010;41(10

Suppl):S124-6

  • 3. Philips JP, Devier DJ, Feeney DM. Rehabilitation pharmacology: bridging laboratory

work to clinical application. J Head Trauma Rehabil 2003 Jul-Aug;18(4):342-56.

  • 4. Stagg CJ, Nitsche MA. Physiological basis of transcranial direct current stimulation.

Neuroscientist 2011;17:37-53

  • 5. Stinear CM, Ward NS. How useful is imaging in predicting outcomes in stroke

rehabilitation? Int J Stroke. 2013;8(1):33-7.

  • 6. Ward NS. Assessment of cortical reorganisation for hand function after stroke. J
  • Physiol. 2011;589(Pt 23):5625-32.

Recovery after stroke: Neurorehabilitation

Additional References

Neuroplasticity After Stroke

Additional References