Targeted Neuromodulation of Abnormal Interhemispheric Connectivity to Promote Neural Plasticity and Recovery of Arm Function after Stroke: A Randomized Crossover Clinical Trial Study Protocol.

Michael R Borich,Jacqueline A Palmer,Steven L Wolf,Andrew Q Tan

doi:10.1155/2018/9875326

Abstract

Background Despite intensive rehabilitation efforts, most stroke survivors have persistent functional disability of the paretic arm and hand. These motor impairments may be due in part to maladaptive changes in structural and functional connections between brain regions. The following early stage clinical trial study protocol describes a noninvasive brain stimulation approach to target transcallosally mediated interhemispheric connections between the ipsi- and contralesional motor cortices (iM1 and cM1) using corticocortical paired associative stimulation (ihPAS). This clinical trial aims to characterize ihPAS-induced modulation of interhemispheric connectivity and the effect on motor skill performance and learning in chronic stroke survivors. Methods/Design A repeated-measures, cross-over design study will recruit 20 individuals post-stroke with chronic mild–moderate paretic arm impairment. Each participant will complete an active ihPAS and control ihPAS session. Assessments of cortical excitability and motor skill performance will be conducted prior to and at four time points following the ihPAS intervention. The primary outcome measures will be: TMS-evoked interhemispheric motor connectivity, corticomotor excitability, and response time on a modified serial reaction time task. Discussion/Conclusion The findings from this single-site early stage clinical trial will provide foundational results to inform the design of larger-scale, multisite clinical trials to evaluate the therapeutic potential of ihPAS-based neuromodulation for upper limb recovery after stroke. This trial is registered with NCT02465034.

Highlights

Despite intensive rehabilitation efforts, most stroke survivors have persistent functional disability of the paretic arm and hand
In this early-stage clinical trial protocol, we will explore ihPAS as a novel noninvasive brain stimulation approach to induce spike-timingdependent plasticity (STDP) in interhemispheric motor connections to transiently modify IHI and ipsilesional cortical excitability targeting cortical pathways implicated in mediating chronic stroke-related arm motor impairment
Exclusion criteria of the participants were as follows: (1) if they are outside the age range of 40– 85; (2) if they show signs of dementia [21]; (3) if they have aphasia [22]; (4) if they have a history of head trauma, a major psychiatric diagnosis, a neurodegenerative disorder, or substance abuse; or (5) if they report contraindications to TMS or magnetic resonance imaging(MRI)

Summary

Background

Most individuals have persistent functional impairments that diminish quality of life, increase morbidity, and raise health care costs [1]. Neural Plasticity activity between iM1 and cM1 via transcallosal pathways influenced by GABA-receptor activity is seen in stroke survivors [11] and associated with greater motor impairment [5] This exaggerated interhemispheric inhibition (IHI) results in an abnormal activity imbalance between brain hemispheres. STDP induction with ihPAS has not been investigated in stroke and its potential impact on neuroplasticity, arm motor skill performance, and learning in individuals with chronic stroke-related arm impairment is unknown In this early-stage clinical trial protocol, we will explore ihPAS as a novel noninvasive brain stimulation approach to induce STDP in interhemispheric motor connections to transiently modify IHI and ipsilesional cortical excitability targeting cortical pathways implicated in mediating chronic stroke-related arm motor impairment. We hypothesize that ihPAS of transcallosal connections between M1HAND representations will: (1) induce STDP that increases cortical excitability of the targeted region (iM1HAND) and reduces abnormal IHI from cM1HAND to iM1HAND and (2) enhance motor skill performance and learning of a modified serial reaction time task (SRTT) after STDP induction

Methods

Findings

Discussion