Upper limb rehabilitation poststroke: making the science and technology work for patients

Jane Burridge

Overview
Some very basic neuroscience that underpins neuroplasticity Modulation of neuroplasticity Behavioural influences on neuroplasticity How neuroscience can be applied to rehabilitation and in particular FES Potential for combined approaches

The synapse transmission of a signal between two nerves

Chemical (neurotransmitters released on the arrival of an action potential) or Electrical (ions flow between the cells so that they are electrically coupled) Excitatory or Inhibitory

Anterior horn cell connections

What determines whether a cell fires?

Hebbian learning rule (1949): Repetitive activation of a presynaptic neuron together with simultaneous activation of a neighbouring postsynaptic neuron leads to an increase in synaptic strength between them. Substantiated by experimental evidence and underpins LTP and LTD

Hebbian learning hypothesis applied to motor learning associated with voluntary drive and peripheral electrical neuromuscular stimulation

Brain

Pyramidal tracts

AHC

Propriospinal connections Muscle

Hebbian learning hypothesis applied to motor learning associated with voluntary drive and peripheral electrical neuromuscular stimulation
Brain

Pyramidal tracts Lesion

AHC

Propriospinal connections Transmission fails Hebb synapse residual connectivity reduces Muscle

Hebbian learning hypothesis applied to motor learning associated with voluntary drive and peripheral electrical neuromuscular stimulation
Brain

Voluntary effort must coincide with stimulation Lesion

AHC Hebb synapse conductivity increases

Propriospinal connections Motor axon fires backwards and forwards

Muscle

Neuroplasticity
Synaptic connections are continually being modified (reorganisation of circuitry) In response to demand learning, memory, disuse (learnt non-use) After damage to the CNS LTP and LTD: alteration of the structure of the synapse Cellular level Increased sensitivity to neural transmitters Increase number and branches of dendrites Increase and strengthening of synaptic connections (Hebbe) Axon sprouting

Voluntary motor control - classical and current view of motor connections

A X 1 B Y 2 C Z 3
M1
Spinal motoneuron pools

A X 1

B Y 2

C Z 3

Muscles

A single MI neuron can influence the motor neuron pools of many muscles Spinal neuron pools receive input from broad overlapping cortical territories Motor cortex does not map area to muscle and may relate more to patterns of movement primitive patterns or laid down through use The overlapping and flexible structure underpins the ability of the system to adapt and therefore potentially recover following damage

Cortical maps use it or lose it

Topology of the sensory and motor cortex is not fixed but flexible and adapts to learning and experience (Donoghue 1996).

Areas with more connections (fine motor control or more acute sensation) have larger representation Factors that promote change:
1. 2. 3. Enriched environment Lack of sensory input (e.g. amputation) Immobilising a limb

Increase in size relates to increased skill

Flexibility of the motor cortex: implications for rehabilitation

Areas have the ability to adapt their function rather than acquiring new functions Intensive training of one cortical area may be at the expense of other surrounding areas Rapid changes in cortical activity intensive vs. extensive training Identify damaged regions and apply targeted therapy

Modulation of neuroplasticity

Changes in excitability in response to electrical nerve stimulation

TMS evokes a motor potential detected by EMG Relationship between level of TMS and EMG amplitude Following a period of electrical stimulation the relationship changes i.e. the same Level of TMS results in a higher EMG amplitude

See: M.C. Ridding et al, Changes in muscle responses to stimulation of the motor cortex induced by peripheral nerve stimulation in human subjects Exp Brain Res (2000) 131:135143

Paired Associative Stimulation

For a comprehensive review refer to Ziemann et al. (2008)

Electrical and Magnetic stimulation (cranial and peripheral)

Repetitive transcranial magnetic stimulation (rTMS) Transcranial direct current stimulation (tDCS) Paired associative stimulation (PAS) Functional electrical stimulation (FES)

Evidence for rTMS and tDCS

Up-regulation of excitability in the affected hemisphere
Anodal tDCS (1Hummel) sham vs. tDCS) Rapid rate TMS (2Khedr)

Down-regulation of excitability in the intact hemisphere

Cathodal tDCS (4Fregni) Low frequency rTMS (1Hz) to M1 (4Schambra; 5Mansur)

Hummel et al Brain 2Khedr et al neurology 2005 65; 466-68; 3Fregni et al Neuroreport 2005 16:155155; 4Schambra et al, Clin Neurophysiology 2003;114:130-33 5Mansur et al, Neurology 2005 64:1802-04

Paired Associated Stimuli

Pre-measures TMS alone
16

Intervention peripheral nerve stimulus + TMS

Post-measures TMS alone

16

Influencing neuroplastic changes

Anti Nogo A1 Amphetamines and Dopaminergic stimulation Stem cell therapy It is likely that if any are effective they will need to accompanied by intensive physical therapy to drive appropriate neuroplastic changes

Weissner & Schwab Journal of cerebral blood flow & metabolism 23: 154-165 2003

MCA lesion Anti-Nogo-A antibody infusion at 24 hours

A: MRI scan at 24 hours and 9 weeks

B: baited staircase test rat retrieves pellets with affected forepaw C: Grasped and eaten pellets as % of pre-lesion D: Successful attempts (eaten pellets X 100/ eaten pellets + displaced pellets Statistically significant difference treatment vs. control p+0.05 (both C and D)

Summing-up - neuroplasticity
Changes in CNS structure, excitability and connectivity occur in response to environmental and behavioural conditions Neuroplasticity enables people to recover following lesions and for healthy people to learn new skills Interventions may have considerable impact: Modulating cortical excitability Enhancing corticospinal plasticity Neuroscience can explain the mechanisms associated with recovery and potentially drive: Effective rehabilitation approaches Identify who will respond best to what approach Evaluate the effect of interventions at the impairment as well as the functional level

Behavioural influences on neuroplasticity

Facilitation of sensorimotor re-learning

Neuromusculoskeletal factors: Improved motor control Muscle strengthening and increased range of movement Modulation of spasticity Sensory input Intrinsic - direct stimulation of sensory fibres or secondary, tactile / proprioceptive feedback Extrinsic - feedback from the experience of movement or the observed achievement of a goal Repetition - goal orientated Motivation - Increased attention

Practice Simple repetition is not enough Challenging - at the limit of performance

Med 2003; 41: 7-10) (Nudo RJ, J Rehabil

Context: goal orientated, relevant, real vs. imagined (Ching-yi Wu Arch Phys med 2000) or simulated (Hu-ing Ma. Am J OT
1999)

Varied - Random vs. block Feedback: encouragement

(Hanlon RE, Arch Phys Med Aug 96)

Ericsson KA et al. The role of deliberate practice in the acquisition of expert performance. Psych rev 1993 Vol 100; 3; 363-406

What can we learn from the principles of motor learning?

Rehabilitation is boring: how can we motivate patients? Need for intensity - home use portable Allow the patient take charge Encourage patients to try harder practice more - using games or relevant activities Can we use technology to adapt the task presented? Optimise performance and learning Provide feedback to engage and motivate Design systems that have a personalised content Measure progress

Can we combine modulation of the CNS with technology based practice?

How does this relate to Neurorehabilitation technologies?

The potential influence of rehabilitation technology on performance

Robotics or Functional Electrical Stimulation Movement Movement & & Sensory Sensory input input Stiffness Stiffness // ROM ROM Spasticity Spasticity Muscle Muscle strength strength

Unable to perform task

Reduce support

Repetition Varied Varied repetition repetition Goal orientated practice Goal orientated practice at of at limit limit of performance performance Feedback Feedback from Feedback from Feedback from from successful performance successful successful performance successful performance performance
Neuroplasticity Neuroplasticity Motor Motor Learning Learning

Repetition

Improved Improved Performance Performance

Inertial sensor triggered stimulation for reach and grasp

Voluntary drive - attention Paired Associated Stimuli Goal orientated and functional Feedback of performance Muscle strengthening Possible reduction in spasticity

Implanted microstimulators (Bions) for closed loop upper limb rehabilitation post-stroke
Microstimulators implanted into elbow, wrist and finger/thumb extensors Independent control of each device
Sensors initiate stimulation and transfer between activity sequences

Stimulation is responsive to participants speed of movement Therapeutic effect of 12 weeks home exercise and 12 week follow-up

Robot Therapy

Theoretical benefit of Rehabilitation Robots

Robot will allow the patient to achieve a task Repetitive goal orientated practice requiring attention Tasks can be adjusted to provide success at the limit of performance Motivating and varied VR / games Allows intensive and safe training could be used in conjunction with FES or CIMT (shaping) therapy at home Appropriate for all levels of ability

Evidence for Robot Therapy

Strong evidence for improved motor control (impairment) and some evidence for improved function [Kwakkel 2008, EBRSR & Prange 2006] Proximal training = proximal benefit Possibly people with moderate impairment respond better Better understanding of how therapy should be applied dose, activities, bilateral, resisted / assisted Include hand and wrist Potential for combining functional training with robot training Potential for combining with modulation of neuroplasticity

Systematic review Kwakkel (2008)

Designing a Smart Armeo

Including the wrist and hand Initial work to model normal hand opening in the specific tasks Mechanical opening ES to open the hand Providing feedback

Using iterative learning control to modulate electrical stimulation (ES) in a robot workstation tracking task

2D pursuit tracking task Using ES rather than mechanical error correction ILC to ensure that minimal ES is applied to correct tracking error

Iterative Learning Control mediated by FES with chronic stroke subjects - Workstation

Elliptical projected trajectory

Learning Control (ILC) using a Robot & FES - ILC algorithm applies during extension phase only

Tracking results
Fig 1 Fig 2

Fig 1 shows the UNSTIMULTED error as each session for each subject Fig 2a shows the mean corrected error in one task at each session for all subjects Fig 2b shows the % max stimulation used

CIMT, FUT and the Southampton Mitt

Learnt non-use supported by neurophysiology and animal studies Inhibition of the unaffected hemisphere excitation of the contralateral (affected) hemisphere? Large and growing body of literature multiple methodologies Beneficial in early recovery for patients with proximal control and some wrist and hand function particularly those with neglect

CIMT: outcome of the EXCITE trial

Single-blind multi-centre RCT 3-9 months post-stroke (all had >10 active wrist extension) Compared two-weeks CIMT with conventional care (Treatment N=106: Control N=116) CIMT: Constraint of the non-affected hand for 90% of the waking day AND received task training (shaping) for up to 6 hours/day Primary outcome measures: WMFT and MAL Between baseline and Post-treatment assessments there was a greater improvement in the CIMT group compared with controls which was statistically significant (p<0.05) in all outcome measures At 12 months, except for the weight and grip components of the WMFT, between group differences were maintained Issues is this a practical treatment?

Summing-up
Without neuroplasticity we would not be able to learn or to recover from CNS lesions Many factors influence neuroplasticity that can be divided into: Neurophysiological factors influencing the excitability of the CNS or the release of neurotransmitters Behavioural factors Rehabilitation technologies can be designed to capitalise on this knowledge