Combining Neural and Behavioral Therapies to Advance Stroke Recovery - PowerPoint PPT Presentation

Title: Combining Neural and Behavioral Therapies to Advance Stroke Recovery


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Combining Neural and Behavioral Therapies to
Advance Stroke Recovery
Dorian Rose, PhD, PT K12 Mentor Carolynn Patten,
PhD, PT University of Florida Rehabilitation
Research Career Development (K12) Annual Advisory
Meeting May 19, 2009
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Professional Background

• B.S. Physical Therapy, Daemen College
• Clinical Service in Neurologic Rehabilitation
  (SCI, TBI, Stroke)
• M.S. Human Movement Science, University of North
  Carolina Chapel Hill
• Research/Clinical Service in Neurologic
  Rehabilitation (SCI, Stroke)
• -Therapist for PPG R01 (Edgerton, PI)
• Ph.D. Biokinesiology, University of Southern
  California
• - Coordinator for R03 (Winstein, PI) Evaluator
  for R01 (Wolf, PI, EXCITe)
• Research Assistant Professor, University of
  Florida
• - Coordinator for R01 (Duncan, PI, LEAPS)

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Background

• Over 775,000 people experience a new or
  recurrent stroke each year in the United States
• Leading cause of serious long-term disability
• Although most patients regain some walking
  ability, restoration of normal motor function in
  the paretic upper extremity occurs in fewer than
  15 of stroke survivors
• Limited limb use leads to compromised skin
  integrity, contracture, pain, further leading to
  social isolation and depression

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Background
Limited progress in the demonstration of
substantive UE motor recovery post-stroke

• Sensorimotor training (Volpe et al., 2000)
• Imagery (Page et al., 2001)
• Electrical Stimulation (Powell et al., 1999)
• Electrical Stimulation/Biofeedback (Francisco et
  al., 1998)
• Constraint-Induced Movement Therapy (Wolf, et
  al., 2006)

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Background
Motor control dependent on mutual transcallosal
inhibition

• In health, the two cortical hemispheres maintain
  a balance of excitability via interhemispheric
  inhibition
• Interhemispheric balance is critical to the
  normal motor control required for skilled
  movements

-
-
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Interhemispheric Balance Disrupted following
Stroke
Contralesional hemisphere
Ipsilesional hemisphere
Disinhibition of the contralesional M1 post-stroke
x
-
-
Contralateral paretic UE
Pathologically exaggerated inhibition of the
lesioned hemisphere by the disinhibited
contralesional hemisphere
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Goal Reestablish balance of transcallosal
inhibition
Contralesional hemisphere
Ipsilesional hemisphere
x
-
Decrease activity in contralesional hemisphere
Increase activity in ipsilesional hemisphere
-
Contralateral paretic UE
Pathologically exaggerated inhibition of the
lesioned hemisphere by the disinhibited
contralesional hemisphere
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Overall Aim
To examine two rehabilitation approaches that
represent potential drivers of cortical
excitability in the lesioned hemisphere 1)
Behavioral approach engagement of the
non-lesioned hemisphere via bilateral,
symmetrical UE movements 2) Neurobiological
approach stimulation (excitatory) of the
lesioned hemisphere via repetitive Transcranial
Magnetic Stimulation (rTMS).
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Specific Aims
x
Contralesional paretic UE
Ipsilesional UE
SA 1 Behavioral approach Bilateral UE training
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Bilateral Upper Extremity Training influences
Cortical Excitability

• Activation of similar neural networks in both
  hemispheres
• Identical motor commands generated in each
  hemisphere may modulate transcallosal inhibition
  to re-balance the two hemispheres
• Decrease in contralesional map volume with
  improved paretic UE motor control (Fugl-Meyer
  assessment) compared to a unilateral (paretic UE
  only) training

Stinear Byblow, 2004 Summer et al., 2007
Specific Aim 1
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Spatially Asymmetric Task
?
?
?
target
home
target
home
Rose Winstein, 2005
Specific Aim 1
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Rose Winstein, 2005
Specific Aim 1
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LED target
P
NP
Rose Winstein, 2005
Specific Aim 1
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Specific Aims
SA 2 Neurobiological approach repetitive
Transcranial Magnetic Stimulation (rTMS)
r TMS gt 1 Hz
x
Contralesional paretic UE
Ipsilesional UE
SA 1 Behavioral approach
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rTMS as a therapeutic modality can alter cortical
excitability
x
r TMS gt 1 Hz
-

• Demonstrated utility in individuals with
  depression, Parkinsons Disease, epilepsy

• Previous applications in those with stroke
• Increase in grip strength, Purdue Pegboard, UE
  Fugl-Meyer (Yozbatiran et al., 2009)
• Reduction in resting motor threshold (Malcolm et
  al., 2007)
• Increase in peak MEP, increase in movement
  accuracy decrease in movement time (Kim et al.,
  2006)
• Increase in frequency of MEP (Pomeroy et al.,
  2007)

Specific Aim 2
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METHODS
Participants n36

• Inclusion Criteria
• Dx of 1st stroke gt 6 months
• PROM bilateral shoulder/elbow WFL
• UE Fugl-Meyer shoulder/elbow subcomponent
  score15-25
• 18-80 years of age

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Procedure
Pre-Test 1
16 intervention sessions
Retention Test
Immediate Post-Test
Pre-Test 2
2 days
30 days
1 week
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Behavioral Intervention Unimanual (paretic only)
or Bimanual
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Neurobiological Intervention
rTMS

• Applied to the ipsilesional hemisphere
• 2000 stimulations (50 trains of 40 stimuli)
• Stimulus rate 20 Hz
• Stimulus train duration 2 seconds
• Inter-train interval 28 seconds
• Stimulus intensity 90 of motor threshold

Malcom et al., 2007 Yozbatiran et al., 2009
Sham rTMS

• Applied to the ipsilesional hemisphere
• Applied perpendicular to the scalp
• Same TMS parameters used as for real rTMS

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Behavioral Outcome Measures
Clinical Wolf Motor Function Test
Kinesiologic Reach to Point _at_ 90 arms length
Kinematic Measures Primary Reach Path
Ratio Secondary MT, PRV
EMG Measures Muscle Onset relative to movement
initiation Maximum Voluntary Isometric
Contraction
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Neurophysiologic Outcome Measures

• Motor Evoked Potential resting motor threshold
• Input/Output recruitment curve slope

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Neurophysiologic Outcome Measures

• Ipsilateral Silent Period

• Intracortical Facilitation/Inhibition

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Data Analysis Specific Aim 1
2 (group) x 4 (time) repeated measures ANOVA
Hypothesis 1. Bilateral training will produce
greater improvements in behavioral/neurobiological
measures than Unilateral training
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Data Analysis Specific Aim 2a
2 (group) x 4 (time) repeated measures ANOVA
Hypothesis 2a. rTMS will produce greater
improvements in behavioral/neurobiological
measures than sham rTMS condition
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Data Analysis Specific Aim 2b
Wilcoxon-matched rank sign test
Hypothesis 2b. Application of rTMS as an adjuvant
to bilateral UE training will enhance
behavioral/neurobiological changes to a greater
degree than application as an adjuvant to
unilateral training.
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Future Work

• Results from this initial work will inform future
  studies concerning
• Subject characteristics
• Sample size
• Study design
• Outcome measures
• Intervention parameters (behavioral and
  neurobiological)

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Future Work
Goal Reestablish balance of transcallosal
inhibition
Contralesional hemisphere
Ipsilesional hemisphere
r TMS lt 1 Hz
x
Decrease activity in contralesional hemisphere
-
-
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Acknowledgements
K12/VA-CDA2 Lead Mentor Carolynn Patten, PhD,
PT VA-CDA2 Mentoring team William Triggs,
MD Steve Kautz, PhD Jeff Kleim, PhD Neural
Control of Movement Lab Members Chetan Phadke,
PhD, PT David Clark, ScD Manuela Corti, PT VA
Brain Rehabilitation Research Center Leslie
Gonzalez-Rothi, PhD - Program Director Steve
Nadeau, MD Medical Director