Motor recovery after stroke is related to neural plasticity, which involves developing new neuronal interconnections, acquiring new functions, and compensating for impairment. However, neural plasticity is impaired in the stroke-affected hemisphere. Therefore, it is important that motor recovery therapies facilitate neural plasticity to compensate for functional loss. Stroke rehabilitation programs should include meaningful, repetitive, intensive, and task-specific movement training in an enriched environment to promote neural plasticity and motor recovery. Various novel stroke rehabilitation techniques for motor recovery have been developed based on basic science and clinical studies of neural plasticity. However, the effectiveness of rehabilitative interventions among patients with stroke varies widely because the mechanisms underlying motor recovery are heterogeneous. Neurophysiological and neuroimaging studies have been developed to evaluate the heterogeneity of mechanisms underlying motor recovery for effective rehabilitation interventions after stroke. Here, we review novel stroke rehabilitation techniques associated with neural plasticity and discuss individualized strategies to identify appropriate therapeutic goals, prevent maladaptive plasticity, and maximize functional gain in patients with stroke.

Many studies in human and animal models have shown that neural plasticity compensates for the loss of motor function after stroke. However, neural plasticity concerning compensatory movement, activated ipsilateral motor projections and competitive interaction after stroke contributes to maladaptive plasticity, which negatively affects motor recovery. Compensatory movement on the less-affected side helps to perform self-sustaining activity but also creates an inappropriate movement pattern and ultimately limits the normal motor pattern. The activated ipsilateral motor projections after stroke are unable to sufficiently support the disruption of the corticospinal motor projections and induce the abnormal movement linked to poor motor ability. The competitive interaction between both hemispheres induces abnormal interhemispheric inhibition that weakens motor function in stroke patients. Moreover, widespread disinhibition increases the risk of competitive interaction between the hand and the proximal arm, which results in an incomplete motor recovery. To minimize this maladaptive plasticity, rehabilitation programs should be selected according to the motor impairment of stroke patients. Noninvasive brain stimulation might also be useful for correcting maladaptive plasticity after stroke. Here, we review the underlying mechanisms of maladaptive plasticity after stroke and propose rehabilitation approaches for appropriate cortical reorganization.

The corpus callosum, which is the largest white matter structure in the human brain, connects the 2 cerebral hemispheres. It plays a crucial role in maintaining the independent processing of the hemispheres and in integrating information between both hemispheres. The functional integrity of interhemispheric interactions can be tested electrophysiologically in humans by using transcranial magnetic stimulation, electroencephalography, and functional magnetic resonance imaging. As a brain structural imaging, diffusion tensor imaging has revealed the microstructural connectivity underlying interhemispheric interactions. Sex, age, and motor training in addition to the size of the corpus callosum influence interhemispheric interactions. Several neurological disorders change hemispheric asymmetry directly by impairing the corpus callosum. Moreover, stroke lesions and unilateral peripheral impairments such as amputation alter interhemispheric interactions indirectly. Noninvasive brain stimulation changes the interhemispheric interactions between both motor cortices. Recently, these brain stimulation techniques were applied in the clinical rehabilitation of patients with stroke by ameliorating the deteriorated modulation of interhemispheric interactions. Here, we review the interhemispheric interactions and mechanisms underlying the pathogenesis of these interactions and propose rehabilitative approaches for appropriate cortical reorganization.

Repetitive transcranial magnetic stimulation and transcranial direct current stimulation are noninvasive brain stimulation (NIBS) techniques that can alter excitability of the human cortex. Considering the interhemispheric competition occurring after stroke, improvement in motor deficits can be achieved by increasing the excitability of the affected hemisphere or decreasing the excitability of the unaffected hemisphere. Many reports have shown that NIBS application improves motor function in stroke patients by using their physiological peculiarity. For continuous motor improvement, it is important to impart additional motor training while NIBS modulates the neural network between both hemispheres and remodels the disturbed network in the affected hemisphere. NIBS can be an adjuvant therapy for developed neurorehabilitation strategies for stroke patients. Moreover, recent studies have reported that bilateral NIBS can more effectively facilitate neural plasticity and induce motor recovery after stroke. However, the best NIBS pattern has not been established, and clinicians should select the type of NIBS by considering the NIBS mechanism. Here, we review the underlying mechanisms and future views of NIBS therapy and propose rehabilitation approaches for appropriate cortical reorganization.

Motor recovery after stroke involves developing new neural connections, acquiring new functions, and compensating for impairments. These processes are related to neural plasticity. Various novel stroke rehabilitation techniques based on basic science and clinical studies of neural plasticity have been developed to aid motor recovery. Current research aims to determine whether using combinations of these techniques can synergistically improve motor recovery. When different stroke neurorehabilitation therapies are combined, the timing of each therapeutic program must be considered to enable optimal neural plasticity. Synchronizing stroke rehabilitation with voluntary neural and/or muscle activity can lead to motor recovery by targeting Hebbian plasticity. This reinforces the neural connections between paretic muscles and the residual motor area. Homeostatic metaplasticity, which stabilizes the activity of neurons and neural circuits, can either augment or reduce the synergic effect depending on the timing of combination therapy and types of neurorehabilitation that are used. Moreover, the possibility that the threshold and degree of induced plasticity can be altered after stroke should be noted. This review focuses on the mechanisms underlying combinations of neurorehabilitation approaches and their future clinical applications. We suggest therapeutic approaches for cortical reorganization and maximal functional gain in patients with stroke, based on the processes of Hebbian plasticity and homeostatic metaplasticity. Few of the possible combinations of stroke neurorehabilitation have been tested experimentally; therefore, further studies are required to determine the appropriate combination for motor recovery.