Clinical trial NCT03086551: Modulating Interaction of Motor Learning Networks in Rehabilitation of Stroke
Official title: Modulating Interaction of Motor Learning Networks in Rehabilitation of Stroke
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Stroke
Stroke, Chronic
Stroke, Middle Cerebral Artery With Infarction
Keywords: Transcranial Magnetic Stimulation
Motor Impairment
Rehabilitation
Motor Learning
Lead sponsor: University of Michigan
Sponsor class: OTHER
First posted: 2017-03-22
Enrollment: 12
Sex: ALL
Minimum age (years): 50
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: This study uses a form on non-invasive brain stimulation called transcranial magnetic stimulation to understand 1) understand how the brain learns post-stroke and 2) assess non-invasive brain stimulation as an addition to current stroke rehabilitation approaches. In two study arms the investigators will compare the effect of active transcranial magnetic stimulation paired with motor practice with placebo (or sham) transcranial magnetic stimulation paired with the same motor practice.

Detailed description: Stroke is the leading cause of permanent disability in the United States. In the absence of treatments to restore the lost tissue, clinical scientists have focused upon repetitive forced used of the paretic limb to promote neural reorganization in preserved tissue and reduce disability. However, forced use interventions are time intensive and the extent of functional recovery is variable. One potential contributor to this variability is the potential trade-off between compensatory cognitive motor control strategies and the extent of procedural learning that can occur. Compensatory strategies adopted by patients may produce quick short-term increases in performance but retard slower sustained improvements by interfering with development of procedural learning. Consistent with this hypothesis, the investigators' previous work documents an increased reliance upon dorsolateral prefrontal cortex during performance of learned skills post-stoke. However, the investigators' previous work also demonstrates that the effect of increased activity in dorsolateral prefrontal cortex may limit reorganization in important areas involved in the consolidation of practice thereby limiting functional recovery post-stroke.

Transcranial magnetic stimulation offers a unique opportunity to investigate the relationship between dorsolateral prefrontal cortex activity and consolidation of motor practice/rehabilitaion post-stroke. Here the investigators' objective is to determine whether suppression of the contralesional dorsolateral prefrontal cortex, with continuous theta burst transcranial magnetic brain stimulation (cTBS), a form of transcranial magnetic stimulation, prior to motor practice enhances brain reorganization in critical areas and leads to greater sustained improvements in motor ability over time.

The proposed work will enhance the understanding of motor learning post-stroke and provide preliminary evidence for the benefits of dorsolateral prefrontal cTBS as an adjunct to current rehabilitation interventions.

Eligibility criteria: Inclusion Criteria:

1. Age between 50-75 years
2. movement-related deficit associated with first time middle cerebral artery stroke
3. greater than 6-months post-stroke
4. Fugl-Meyer score between 15 and 60
5. ability to elicit a motor evoked potential from the ipsilesional cortex

Exclusion Criteria:

1. a score \<27 on the Mini-Mental Status Exam
2. a score of \<123 on the Mattis Dementia Rating Scale
3. a score of \<13 on the Frenchay Aphasia Screen
4. a history of seizure/epilepsy, head trauma, major psychiatric diagnosis, neurodegenerative disorder or substance abuse
5. a history of congestive heart failure
6. systolic blood pressure above 120 mmHg and/or diastolic pressure above 80 mmHg
7. the taking of any GABAergic, NMDA-receptor antagonist or other drug known to influence the neural receptors that facilitate neural plasticity
8. an infarct resulting from ischemic stroke of anterior or posterior cerebral artery OR an infarct that encroaches within 2cm of the site of cTBS stimulation
9. absence of an MEP in response to single pulse transcranial magnetic stimulation over ipsilesional M1 and 10) any other contraindication to TMS or MRI.

Primary outcomes:
measure: Change From Baseline in Sequential Response Time to Post-Intervention
timeFrame: Baseline and post-intervention
Secondary outcomes:
measure: Change From Baseline in Time to Complete the Jebsen-Taylor Hand Function Test
timeFrame: Baseline and post-intervention
measure: Change in Sequential Response Time Immediately Follow an Individual Bout of Non-invasive Brain Stimulation (e.g. Within Session)
timeFrame: Within session baseline to ~8 minutes post-application of non-invasive stimulation within the same session
measure: Motor Evoked Potential Amplitude (in Microvolts) at Pre-baseline and Post-Intervention
timeFrame: Baseline and post-intervention
measure: Change From Baseline in Cortical Excitability Post-Intervention
timeFrame: Baseline and post-intervention
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: Human Sensorimotor Laboratory, School of Kinesiology, University of Michigan
state: Michigan
Study officials:
affiliation: Sch. of Kinesiology, Univ. of Michigan
name: Sean K Meehan, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Meehan SK, Randhawa B, Wessel B, Boyd LA. Implicit sequence-specific motor learning after subcortical stroke is associated with increased prefrontal brain activations: an fMRI study. Hum Brain Mapp. 2011 Feb;32(2):290-303. doi: 10.1002/hbm.21019.
citation: Meehan SK, Dao E, Linsdell MA, Boyd LA. Continuous theta burst stimulation over the contralesional sensory and motor cortex enhances motor learning post-stroke. Neurosci Lett. 2011 Aug 1;500(1):26-30. doi: 10.1016/j.neulet.2011.05.237. Epub 2011 Jun 12.
citation: Brodie SM, Meehan S, Borich MR, Boyd LA. 5 Hz repetitive transcranial magnetic stimulation over the ipsilesional sensory cortex enhances motor learning after stroke. Front Hum Neurosci. 2014 Mar 21;8:143. doi: 10.3389/fnhum.2014.00143. eCollection 2014.