Interhemispheric Inhibitory Interactions (InHIb)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
University of British Columbia ( Canadian Institutes of Health Research (CIHR) )
ClinicalTrials.gov Identifier:
NCT01371409
First received: June 2, 2011
Last updated: March 25, 2014
Last verified: March 2014
  Purpose

After a stroke the excitability of the brain decreases on the stroke side and increases on the opposite, non-stroke side. These changes make use of the stroke-affected arm difficult and slow recovery. Rehabilitation exercises that increase arm use after stroke help increase brain excitability, but the net effect of this approach is low. New therapies are needed that restore more equal levels of brain excitability between the two sides. Brain stimulation is a noninvasive way to affect activity the excitability of brain cells. Pairing brain stimulation with exercises that require patients to learn new movements may help the brain to learn. Using stimulation that reduces activity in the side opposite to the stroke can increase activity on the stroke -affected side, through connections between the two brain hemispheres. The purpose of this study is to test if brain stimulation on the side opposite to the stroke, paired with arm movement exercises, can help patients learn new arm movements and improve arm function.

In this study people with stroke will receive brain stimulation over two different areas on the side of the brain opposite to the stroke: 1) those areas responsible for movement and 2) those responsible for sensation. These experiments will test both the short and long term effects of brain stimulation on patients' learning and arm function and will allow us to identify which area of the brain best improves learning and arm function. These experiments have the potential to improve the effectiveness of rehabilitation after stroke. The proposed study is among the first to test stimulation over the side of the brain opposite to the stroke damage and at multiple sites. This unique approach may help stimulate the development of new methods for stroke rehabilitation.


Condition Intervention
Stroke
Other: continuous theta burst stimulation

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Interhemispheric Contributions to Neuroplasticity and Motor Learning After Stroke

Further study details as provided by University of British Columbia:

Primary Outcome Measures:
  • Response Time [ Time Frame: change from baseline to day 6 ] [ Designated as safety issue: No ]
    Response time on a custom designed serial tracking program


Secondary Outcome Measures:
  • Wolf Motor [ Time Frame: change from baseline to day 6 ] [ Designated as safety issue: No ]
    standardized measure of upper limb function

  • Limb Position Matching [ Time Frame: change from baseline to day 6 ] [ Designated as safety issue: No ]
    Limb position matching using custom designed software

  • Intracortical Inhibition [ Time Frame: change from baseline to day 6 ] [ Designated as safety issue: No ]
    Intracortical Inhibition as measured by paired pulse transcranial magnetic stimulation

  • Movement Time [ Time Frame: change from baseline to day 6 ] [ Designated as safety issue: No ]
    movement time on custom designed serial tracking program

  • Movement Trajectory [ Time Frame: change from baseline to day 6 ] [ Designated as safety issue: No ]
    Movement trajectory on a custom designed serial tracking program

  • Intracortical facilitation [ Time Frame: change from baseline to day 6 ] [ Designated as safety issue: No ]
    Intracortical facilitation as measured by paired pulse transcranial magnetic stimulation


Enrollment: 49
Study Start Date: April 2011
Estimated Study Completion Date: January 2015
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: active cTBS Other: continuous theta burst stimulation
80% active motor threshold, 600 pulses
Other Name: transcranial magnetic stimulation
Sham Comparator: Sham cTBS Other: continuous theta burst stimulation
80% active motor threshold, 600 pulses
Other Name: transcranial magnetic stimulation

Detailed Description:

The overall objective of this proposal is to examine the efficacy of new approaches to stroke recovery based on recent reports of interhemispheric contributions to neuroplastic change and motor skill learning. After stroke, cortical excitability is decreased in the ipsilesional and increased in the contralesional primary motor cortices (M1). Combined, these changes hamper hemiparetic arm use and impede functional recovery. Increasing hemiparetic arm use elevates the excitability of the ipsilesional cortex and improves function. Importantly, skilled motor practice raises cortical excitability to an even greater extent than merely increasing generalized use. However, the impact of increasing cortical excitability on recovery of function after stroke is limited, perhaps because the rate of change associated with both increasing use and learning new motor skills is low.

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive method of brain stimulation. In humans, rTMS applied at high frequencies can increase cortical excitability; conversely, at low frequencies it can decrease cortical excitability. While rTMS in isolation can change cortical excitability after stroke its impact on neuroplastic change is small, likely reflecting a lack of consolidation in the absence of paired motor behaviour. Modulating the activity in a given neural network with brain stimulation prior to motor skill practice may in essence prime the system and enhance the neuroplastic effects associated with learning new motor skills. Yet to date, few studies have paired rTMS with practice of a novel motor task and assessed changes in motor function or behaviour.

Intuitively, it seems simplest to employ high frequency rTMS in the ipsilesional cortex to enhance cortical excitability. However, because of the difficulty of locating stimulation targets in the damaged hemisphere, low-frequency rTMS applied over the contralesional cortex may be the better approach. Though the direct effect of low-frequency rTMS in the human cortex is to suppress activity in the stimulated region it also indirectly enhances distant activity. Low-frequency rTMS over M1 increases cortical activity in the contralateral M1 homologue. We recently extended this finding to the primary sensory cortex (S1); demonstrating that low-frequency rTMS over left S1 increased excitability in (i.e., disinhibited) right S1. Therefore, suppressing the contralesional cortex to enhance ipsilesional cortical activity may facilitate a neural environment that is conducive for neuroplastic change.

Taken together these data suggest that inhibitory brain stimulation over the contralesional cortex, paired with skilled motor practice, may offer a new approach for stroke rehabilitation. To better understand whether this approach has merit, we propose to test two specific aims in separate experiments.

Specific Aim: To test the cumulative effects of repeated sessions that pair brain stimulation over M1c versus S1c with skilled motor practice in individuals with stroke.

We will assess hemiparetic arm motor and sensory function, motor performance/ motor skill acquisition (repeated sequence response times), cortical excitability, and neuroelectric activity in individuals with chronic sub-cortical stroke. Pre-brain stimulation measures will be compared with those obtained after 5 days of training paired with brain stimulation at a separate no-rTMS retention test to assess the cumulative effects of brain stimulation.

  Eligibility

Ages Eligible for Study:   40 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • aged 40-75
  • single, MCA territory stroke
  • at least 6 months post stroke
  • Fugl-Meyer (upper extremity) score of 15-55

Exclusion Criteria:

  • absence of TMS motor evoked potential
  • score <24 on the Montreal Cognitive Assessment
  • history of seizure/epilepsy, head trauma, major psychiatric diagnosis
  • aphasic (score <13 on Frenchay Aphasia Screen)
  • contraindications to TMS/MRI
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01371409

Locations
Canada, British Columbia
University of British Columbia
Vancouver, British Columbia, Canada, V6T 2B5
Sponsors and Collaborators
Canadian Institutes of Health Research (CIHR)
Investigators
Principal Investigator: Lara A Boyd, PT, PhD University of British Columbia
  More Information

No publications provided

Responsible Party: University of British Columbia ( Canadian Institutes of Health Research (CIHR) )
ClinicalTrials.gov Identifier: NCT01371409     History of Changes
Other Study ID Numbers: H09-00368, CIHR
Study First Received: June 2, 2011
Last Updated: March 25, 2014
Health Authority: Canada: Health Canada

Keywords provided by University of British Columbia:
Stroke
TMS
Paired Pulse
EEG
Motor Learning

Additional relevant MeSH terms:
Stroke
Brain Diseases
Cardiovascular Diseases
Central Nervous System Diseases
Cerebrovascular Disorders
Nervous System Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on October 29, 2014