Edwards Research

Stroke is a leading cause of adult disability, but the pathophysiology of stroke remains poorly understood. The prevailing consensus is that neurophysiological and cognitive damage post-stroke is associated with unilateral cortical/subcortical damage, and that the corticospinal excitability of the affected hemisphere is reduced, while that of the unaffected hemisphere is elevated. Prior studies show targeted neuromodulation to ameliorate this imbalance can reduce impairment and improve function, and our research demonstrated how transcranial magnetic stimulation (TMS) can be effectively used as a quantitative probe of excitability and reported how it fits in with other clinical outcomes. Our findings have provided important insights into the pathophysiology of stroke, and this work is critical for identifying new therapeutic targets and improving treatment approaches. Our work to date serves as a foundation for future studies investigating the use of TMS-detected excitability levels to better personalize stroke therapies, as well as use of high-definition DC stimulation to target specific stroke symptoms such as verticality misperception 

Prior studies suggest motor pathways may be spared in spinal cord injury, but patients may not be able to functionally engage them. These spared pathways could serve as a biological substrate for motor recovery, and strategies to facilitate voluntary muscle activation could include both increasing the responsiveness of spinal motoneurons to weak descending commands, and increasing output from the brain. Our research has investigated the spared (non-used) descending fibers, their relationship to dysfunction, and how these fibers could be leveraged in rehabilitation. We found that TMS could identify residual pathways despite weak or no voluntary movement in some muscles. We developed and tested a non-invasive stimulation method (Spinal Associative Stimulation), to raise spinal excitability in humans, and this method has potential as a novel approach to facilitate motor recovery in people with spinal cord injury. In addition, we evaluated the effectiveness of upper and lower extremity robotics as a dose-defined therapy in SCI that might be ultimately combined with non-invasive stimulation techniques to promote recovery. Recently, we showed that high-frequency repetitive TMS activated genetic pathways that led to corticospinal tract axon regeneration and sprouting as well as functional recovery in an animal model. We are beginning a clinical trial in humans to determine if this approach may be an effective, non-invasive treatment for spinal cord injury.

As with non-invasive brain stimulation (NIBS), rehabilitation robotics represents both a quantitative assessment tool and an emerging neuro-rehabilitation method. The reliability of upper-extremity robotics has been established, and strong evidence supports its efficacy in stroke. Our work expands on prior studies by further investigating the combination of robotic training methods and transcranial direct current stimulation (tDCS), including the impacts of the parameters of these therapeutic interventions, such as the sequence of the delivery of the intervention components (e.g. tDCS preceding robotic training) and the temporal relationship of tDCS to synaptic activity. Our research was the first to examine the effect of combining conventional tDCS with robotic training in chronic stroke, and our ongoing work in this area has the potential to change clinical practices for motor neurorehabilitation for stroke. 

TMS and tDCS have potential applications for treating neuropsychiatric disorders, as well as neurorehabilitation for conditions such as stroke. For TMS, mapping cortical representations of limb muscles via TMS-motor evoked potentials provides insight into how motor maps are reorganized during recovery after stroke. However, map calculations and quantification methods vary, limiting the spatial specificity of motor maps and data interpretation. Compared to TMS, tools to deliver tDCS are less refined, and the ability to precisely target the location and spread of stimulation is limited. We are creating and refining innovative tools and methodological approaches to address widespread methodological issues in order to advance the translation of TMS and tDCS for use in the clinic. Because of the potential for diverse clinical applications, the development of advanced tools for delivering targeted non-invasive brain stimulation and for evaluating NIBS-derived data, such as changes in motor maps, may have major impacts both on future research and clinical practice.

After a stroke, barriers such as time, cost, accessibility, and clinical silos may limit the rehabilitation services a patient receives (and the extent of recovery). There is increasing evidence of reciprocity between cortical hand-arm and speech-language networks in adults with stroke that could be leveraged to develop more comprehensive, integrated rehabilitation approaches. The findings from this relatively new line of research in the lab are promising. We have now demonstrated in multiple studies, including a multi-national aphasia trial led by McGill University (NORTHSTAR-CA), that synergies between motor and language networks can be leveraged to enhance recovery, emphasizing the need for a more multi-modal approach to stroke rehabilitation. The well-understood and reproducible upper extremity robotic training regimen has proven an ideal strategy to test the effects of supplementary brain stimulation. This line of research will address a pressing clinical need by informing the development of new time- and cost-efficient aphasia treatments that target hand-arm and speech-language deficits collectively by combining traditional speech therapy with RA-arm and/or NIBS.