Non-invasive Cerebellar Stimulation: a Promising Approach for Stroke Recovery?

Non-invasive brain stimulation (NIBS) combined with behavioral training is a promising strategy to augment recovery after stroke. Current research efforts have been mainly focusing on primary motor cortex (M1) stimulation. However, the translation from proof-of-principle to clinical applications is not yet satisfactory. Possible reasons are the heterogeneous properties of stroke, generalization of the stimulation protocols, and hence the lack of patient stratification. One strategy to overcome these limitations could be the evaluation of alternative stimulation targets, like the cerebellum. In this regard, first studies provided evidence that non-invasive cerebellar stimulation can modulate cerebellar processing and linked behavior in healthy subjects. The cerebellum provides unique plasticity mechanisms and has vast connections to interact with neocortical areas. Moreover, the cerebellum could serve as a non-lesioned entry to the motor or cognitive system in supratentorial stroke. In the current article, we review mechanisms of plasticity in the cortico-cerebellar system after stroke, methods for non-invasive cerebellar stimulation, and possible target symptoms in stroke, like fine motor deficits, gait disturbance, or cognitive impairments, and discuss strategies for multi-focal stimulation.

Non-invasive brain stimulation: an interventional tool for enhancing behavioral training after stroke

Friedhelm Christoph Hummel, Maximilian Jonas Wessel

Stroke is the leading cause of disability among adults. Motor deficit is the most common impairment after stroke. Especially, deficits in fine motor skills impair numerous activities of daily life. Re-acquisition of motor skills resulting in improved or more accurate motor performance is paramount to regain function, and is the basis of behavioral motor therapy after stroke. Within the past years, there has been a rapid technological and methodological development in neuroimaging leading to a significant progress in the understanding of the neural substrates that underlie motor skill acquisition and functional recovery in stroke patients. Based on this and the development of novel non-invasive brain stimulation (NIBS) techniques, new adjuvant interventional approaches that augment the response to behavioral training have been proposed. Transcranial direct current, transcranial magnetic, and paired associative (PAS) stimulation are NIBS techniques that can modulate cortical excitability, neuronal plasticity and interact with learning and memory in both healthy individuals and stroke patients. These techniques can enhance the effect of practice and facilitate the retention of tasks that mimic daily life activities. The purpose of the present review is to provide a comprehensive overview of neuroplastic phenomena in the motor system during learning of a motor skill, recovery after brain injury, and of interventional strategies to enhance the beneficial effects of customarily used neurorehabilitation after stroke.

Frontiers Research Foundation2015

Reorganization of the human ipsilesional premotor cortex after stroke

Friedhelm Christoph Hummel

The substrates that mediate recovery of motor function after stroke are incompletely understood. Several primate and human studies proposed the involvement of the premotor cortex of the lesioned hemisphere. Here, we studied four chronic stroke patients with focal subcortical lesions affecting the corticospinal outflow originating in the primary motor cortex (M1) and good motor recovery. We tested the hypothesis that, in these patients, disruption of activity in the premotor cortex of the lesioned hemisphere by transcranial magnetic stimulation (TMS) would result in degraded behaviour in the paretic hand. TMS was applied to the primary motor cortex, dorsal premotor cortex (PMd) and ventral premotor cortex (PMv) of the affected (M1AH, PMdAH, PMvAH) and intact (M1IH, PMdIH, PMvIH) hemispheres of patients and healthy controls in the setting of a simple reaction time (SRT) paradigm performed with the hand contralateral to the stimulated hemisphere. TMS applied to M1 led to substantial contralateral SRT delays in both groups. TMS applied to PMdAH of patients elicited clear delays in contralateral SRT in the paretic hand, whereas TMS applied to PMdIH of patients or healthy volunteers did not. Motor evoked potentials after stimulation of PMdAH were, on average, larger and had, on average, shorter latency than after stimulation of M1AH. These results indicate that PMdAH participates as a substrate mediating functional recovery of executive motor function in patients with focal lesions of corticospinal outflow originating in M1 and good motor recovery. Our results are consistent with the hypothesis that the dorsal premotor cortex of the affected hemisphere can reorganize to control basic parameters of movement usually assigned to M1 function.

Oxford University Press2004

Combined rehabilitation promotes recovery of motor functionality in a mouse model of stroke

Silvestro Micera, Maria Pasquini

Neuro-rehabilitative research is developing novel strategies to enhance the effectiveness of therapies after stroke by using a combination of physical and plasticizing treatments 1-3. Previous studies have shown that repeated optogenetics stimulation of neurons in the peri-lesioned area induces a significant improvement in cerebral blood flow and neurovascular coupling response 4-6. Up to now the mechanisms underneath the reshaping of brain circuitry induced by rehabilitation after stroke are widely unknown. To investigate how rehabilitative therapies shape new cortical maps in the peri-infarct region, we induce a photothrombotic stroke in the primary motor cortex and the expression of Channelrhodopsine 2 (ChR2) in the peri-infarct area on Thyl-GCaMP6f mice. To promote functional recovery after stroke we use both an optogenetic strategy to stimulate targeted excitatory neurons in the peri-lesional region and motor training on a robotic platform (M-Platform) 7. A 473 nm laser repeatedly stimulates ChR2-transfected neurons; the optostimulation is performed five days a week. The motor rehabilitation consists in a pulling task: after the forelimb is passively extended by the linear actuator of the M-platform, the animal has to pull back up to the resting position. By analysing the spatio-temporal calcium dynamic and the reshaping of cortical activation area during the movement throughout the treatment period, we found that the combined treatment restores cortical activation profiles during the forelimb movement. Through behavioural experiments, using Schallert test, we also evaluate changes of forelimb functionality during rehabilitation. Our combination of techniques allows obtaining unprecedented views on cortical plasticity induced by rehabilitative therapies.

SPIE-INT SOC OPTICAL ENGINEERING2019