The Three Pearls DOSE FUNCTION MOTIVATION

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2 The Three Pearls DOSE FUNCTION MOTIVATION

3 Barriers to Evidence-Based Neurorehabilitation No placebo pill for training therapy Blinded studies often impossible Outcome measures for movement, language, and cognition Large amount of therapist time is expensive Most studies are underpowered

4 Why Does Rehab Work? We should approach this as a scientific experiment Examine why people recover Review the principles of neural repair Identify factors that promote neural repair

5 Normal Development Newborn genes instruct the brain to connect retinal nerve cells with the occipital cortex At birth, each neuron in the cerebral cortex has 25,000 synapses By 2 3 years old: 15,000 synapses/neuron Adult: 7,500/neuron Process of synaptic pruning

6 Synaptic Pruning Which connections will survive? Experience determines which will survive and which will be pruned Use it or lose it Plasticity enables the process of developing and pruning connections

7 Recovery Process Resolution of edema Resolution of diaschisis Behavioral compensation Neuroplasticity Regeneration

8 Neural Plasticity Basis for learning in the intact brain and relearning in the damaged brain that occurs through rehabilitation (Kleim and Jones, 2008) Plasticity provides an opportunity for significant recovery

9 10 Principles Which Affect Neural Plasticity 1 Use it or lose it 2 Use it and improve it 3 Specificity 4 Repetition matters 5 Intensity matters 6 Time matters 7 Salience matters 8 Age matters 9 Transference 10 Interference -Kleim and Jones: J Speech Lang Hearing Res; 51:S , 2008

10 Principles 1& 2 1 Brain circuits not used for task performance for an extended period of time begin to degrade, resulting in further loss of function 2 Training is critical to help induce plasticity

11 Collateral Sprouting Collateral sprouting to reinnervate cells and circuits

12 CUT WIRES BACK TOGETHER

13 Neural Plasticity Unmasking of other neural pathways and synapses (neural plasticity) neural plasticity

14 Cortical Reorganization Nudo Neural bases for motor recovery after stroke By permission of Academic Press, 1997.

15 Principles 3 & 4 3 Training needs to be specific, as it may not generalize 4 Repetition required for lasting change and to maintain learning outside of therapy

16 Principles 5 & 6 5 The intensity of training affects plasticity 6 There appear to be windows in which rehabilitation is especially effective; in general, earlier is better

17 Principles 7 & 8 7 Paying attention to the task at hand is better 8 Healthy old animals clearly benefit from rehabilitation

18 Principles 9 & 10 9 Learn simple tasks first 10 The development of bad habits can impede learning new, more effective habits

19 The Three Pearls DOSE FUNCTION MOTIVATION

20 What Happens without Rehabilitation? Will develop compensatory strategies to attempt to perform daily activities May be adaptive (use unaffected limb)

21 What Happens without Rehabilitation? Often develop maladaptive strategies that interfere with improvements in function that could be obtained in therapy May never learn to use affected limb

22 Without Therapy, Patients Are Self-Limiting People don t do things that are too hard without assistance and prompts

23 Recovery Versus Compensation Rehabilitation is the process of using learning dependent plasticity Rehabilitation takes advantage of previously learned behaviors that may still exist within the neural circuits of the injured nervous system Recovery suggests that function has been restored within the neural tissue, while compensation suggests that residual undamaged neural tissue is taking over the function

24 Learned Non-use

25 Constraint Therapy Mitten or sling on unaffected arm Forced use of affected arm Time and duration May use mechanical devices to facilitate grasping

26 Enriched Environment Hebb, 1940s: Took rats home as pets with improved behavioral outcomes Rosenzweig, 1960s: Environmental stimuli led to biochemical changes, dendritic arborization, and increased learning Physical activity increases adult hippocampal neurogenesis Effect is sustained even after the environment is withdrawn

27 Enriched Environment

28 Examples of Human Plasticity Hand representation in humans increases in people who perform complex finger movements, such as the left hand of string players or the index finger of Braille readers

29 Central Pattern Generator

30 Rossignol Studies Complete transection lowest thoracic segment Within a few weeks, walk on a treadmill Treadmill training important to recovery Higher speed, more consecutive steps, lengthen step cycles, more symmetrical Early training improves rate of recovery

31 Where Is the CPG? Rossignol Lesions at T13 = locomotion 2 nd lesion L2 3 = does not interfere with locomotion 2 nd lesion L3 4= abolishes locomotion Lower lumbar segments probably contain key neural elements that provide crucial input for operation of the CPG (central pattern generator)

32 Future Research: SCI Plasticity Clinically important as to where to target pharmacological stimulation, cell grafts, or electrical stimulators

33 Drug Effects Numerous studies last 40 years Drugs may enhance or inhibit plasticity and recovery Experimental drugs can promote or inhibit axonal sprouting and synaptic plasticity Norepinephrine (+), amphetamines (+), sympathomimetic (+) Phenobarbital ( ) Benzodiazepines ( ), phenytoin ( ) increase GABA

34 Action d-amphetamine Presynaptic release monoamines, noradrenaline, dopamine, serotonin Inhibition of their uptake from the synaptic cleft

35 Action d-amphetamine Decrease remote depression (diaschisis) Facilitate longterm potentiation and memory storage Facilitate reorganization

36 Principles of TMS Stimulation of corticospinal tract Recorded in muscle as motor-evoked potential (MEP) Repetitive stimulation (rtms) can excite the affected hemisphere and inhibit the unaffected side to restore balance Protocols still not clear Corticospinal tract Motoneuron Used to enhance motor performance

37 rtms for Motor Rehabilitation-plus Other uses: Dysphagia Neglect Aphasia Cognition Depression

38 The Three Pearls DOSE FUNCTION MOTIVATION