July 2014 issue
July 31, 2014 | Five years after the failed Northstar Neuroscience clinical trial of epidural stimulation for stroke rehabilitation stunned the neuromodulation industry and stymied research in that area, investigators are now pressing ahead with new approaches exploiting cortical plasticity and brain stimulation. Two independent teams in Ohio and New Jersey are leading the way to refine the targets and the therapy paradigms/
Recently, a team led by Sergei Adamovich at New Jersey Institute of Technology and Eugene Tunik at Rutgers received a $1.3 million NIH award to investigate fronto-parietal brain networks involved with hand and arm control. Understanding how discrete parts of the brain interact to coordinate hand and arm movements in healthy individuals is a critical starting point for developing better stroke-rehabilitation therapies. Acquiring a solid baseline knowledge of the brain’s fronto-parietal is essential for regaining movement impaired by a stroke-induced brain lesion or traumatic brain injury.
The research will use transcranial magnetic stimulation to induce responses in specific regions of the brain, and robotic/virtual-reality training systems that use the CyberGrasp hand exoskeleton and a library of therapeutic video games developed in Adamovich’s laboratory. Brain and muscle interaction will be mapped during various normal reaching and grasping activities with physical objects and tasks in virtual video environments.
The new research that Adamovich is initiating complements previous efforts that have led to the development of therapeutic stroke interventions now being assessed at a sub-acute rehabilitation facility maintained by the St. Joseph’s Healthcare System in Wayne, NJ. The robotically assisted exercises and game-like physical challenges in virtual reality yielded positive results when initially evaluated with volunteers who were chronically impaired more than six months after a stroke.
Meanwhile, a recently published study in The Neuroscientist by a team of researchers at the Cleveland Clinic advocates for a systematic shift in perspective and suggests that chronically stimulating premotor areas of the brain—as opposed to M1—would strongly promote stroke motor recovery, for example by restoring balance between the stroke and the intact hemispheres while establishing greater widespread connectivity. “Before the therapeutic potential of brain stimulation is missed amidst the enthusiasm for its ability to augment brain activity, it is urgent to systematically understand whom stimulation of the brain may benefit, how, and why,” said study author Ela Plow.
Using a conceptual model, Plow, David Cunningham, Nicole Varnerin, and Andre Machado suggest expanding the scope of stimulation to include other targets, such as premotor and supplementary motor cortices that are more likely to survive damage in humans, offer their independent output, and collaborate with areas in the intact hemisphere to recruit their cooperation towards recovery as well. Rather than propose that these substrates could serve as the be-all-end-all of plasticity, the researchers suggest that their role may be more meaningful in those with greater damage and do not discount the possibility of success for other substrates such as cerebellum, striatum, and parietal cortices.
Plow continued, “Conflicting evidence in stroke has dampened the enthusiasm for brain stimulation witnessed across several hundred early studies in the last decade, limiting the potential of clinical outpatient or even inpatient delivery in the immediate future. Before starting another clinical trial and waiting to see if by chance the new study shows positive effects, we suggest re-evaluating and shifting perspective.”
The researchers outline the previous use of stimulation in stroke rehabilitation from trials with homogeneous animal models, to early clinical studies where patients responded exceptionally well to stimulation of their residual cortex, to larger clinical trials that enrolled more impaired participants in which stimulation of motor cortices failed to uniformly augment outcomes of recovery.
“Our intent here is to create a shift in perspective that forces us to broaden our scope of stimulation from affecting a single target and a single mechanism to imagining how and what may remain to assume the potential for recovery in humans,” Plow said.
