Rethinking interhemispheric imbalance as a target for stroke neurorehabilitation

Abstract

Objective: Patients with chronic stroke have been shown to have failure to release interhemispheric inhibition (IHI) from the intact to the damaged hemisphere before movement execution (premovement IHI). This inhibitory imbalance was found to correlate with poor motor performance in the chronic stage after stroke and has since become a target for therapeutic interventions. The logic of this approach, however, implies that abnormal premovement IHI is causal to poor behavioral outcome and should therefore be present early after stroke when motor impairment is at its worst. To test this idea, in a longitudinal study, we investigated interhemispheric interactions by tracking patients' premovement IHI for one year following stroke. Methods: We assessed premovement IHI and motor behavior five times over a 1-year period after ischemic stroke in 22 patients and 11 healthy participants. Results: We found that premovement IHI was normal during the acute/subacute period and only became abnormal at the chronic stage; specifically, release of IHI in movement preparation worsened as motor behavior improved. In addition, premovement IHI did not correlate with behavioral measures cross-sectionally, whereas the longitudinal emergence of abnormal premovement IHI from the acute to the chronic stage was inversely correlated with recovery of finger individuation. Interpretation: These results suggest that interhemispheric imbalance is not a cause of poor motor recovery, but instead might be the consequence of underlying recovery processes. These findings call into question the rehabilitation strategy of attempting to rebalance interhemispheric interactions in order to improve motor recovery after stroke. ANN NEUROL 2019;85:502-513 I t has been proposed that one contributor to chronic hemiparesis is an imbalanced inhibitory interaction between the lesioned and intact hemispheres via transcallosal connections. This interhemispheric-competition model proposes that the two hemispheres, which normally exert mutual inhibition in healthy individuals, become imbalanced after stroke, and that unopposed inhibition from the healthy to the damaged side impedes recovery. 1 This framework is largely based on a seminal study that showed persistent premovement interhemispheric inhibition (IHI) from the contra-to ipsilesional motor cortex before movement execution in patients with chronic stroke. 2 This failure to release IHI before movement onset (abnormal premovement IHI) correlated with weakness and impaired finger tapping performance. 2 Influenced by this stroke-recovery View this article online at wileyonlinelibrary.com.

Immediate and long-term effects of BCI-based rehabilitation of the upper extremity after stroke: a systematic review and meta-analysis

“…However, Young et al argued that this result could not be generalized to patients with cortical lesions because they found an ipsilesional lateralization during movements of affected hands at baseline toward a bilaterally distributed activity after receiving BCI training in a group of patients in which cortical lesions were involved [97]. A recent longitudinal observational study showed that the interhemispheric inhibition (IHI) was not associated with motor impairment after stroke and, in particular, the IHI was normal in the acute/ subacute stage and gradually became abnormal at the chronic stage [98]. Moreover, another meta-analysis summarized the way in which there is no clear evidence for the hyper-excitability of the unaffected hemisphere or imbalanced interhemispheric inhibition [92].…”

Electroencephalographic Phase Synchrony Index as a Biomarker of Poststroke Motor Impairment and Recovery

“…52 However, this interaction could vary depending on the time after stroke, lesion location, and measurement conditions. 26,53,54 In fact, a supportive role of the contralesional hemisphere has been suggested, at least in the subacute stage. 27,55 In the current study, the contralesional IntrahC-PSIs (δ and θ) were significantly higher in patients than in controls.…”

The differential roles of contralesional frontoparietal areas in cortical reorganization after stroke

“…Here, particularly contralesional primary motor cortex (M1) has been suggested to exert abnormally high inhibitory influences upon ipsilesional M1, thereby hindering motor performance and recovery [14e16]. However, recent results have suggested that these changes might also constitute a representation of the underlying recovery processes rather than a cause of poor motor recovery, given that abnormal interhemispheric inhibition emerges over time parallel to motor recovery [17]. Inconsistent results concerning the functional role of the contralesional hemisphere have been attributed to differences between subacute and chronic stroke, differences of mild, moderate, and severe motor impairment, lesion size and location, or the functional integrity of corticomotor pathways [1,9,10,18].…”