Individual contralesional recruitment in the context of structural reserve in early motor reorganization after stroke

The concept of structural reserve in stroke reorganization assumes that the functional role of the contralesional hemisphere strongly depends on the brain tissue spared by the lesion in the affected hemisphere. Recent studies, however, have indicated that the impact of the contralesional hemisphere exhibits region-specific variability with concurrently existing maladaptive and supportive influences exerted by distinct contralesional regions. These findings challenge the concept of structural reserve’s uniform deduction of the contralesional relevance and call for a more differentiated investigation of the interactions between contralesional motor regions and ipsilesional network structures.

We here explored the relationship between the behavioral role of key areas of the contralesional motor system and lesion-induced connectome disruption early after stroke. Accordingly, we analyzed online TMS interference data of twenty-five stroke patients pooled from two previous studies to disentangle interindividual differences in the functional roles of contralesional primary motor cortex (M1), contralesional dorsal premotor cortex (dPMC), and contralesional anterior interparietal sulcus (aIPS) for motor function early after stroke. Connectome-based lesion symptom mapping (CLSM) as well as lesion quantification of the corticospinal tract (CST) were used to investigate how rTMS effects depend on structural network properties of the ipsilesional hemisphere, i.e., the structural reserve.

At group and individual levels, online TMS interference with contralesional M1 and aIPS but not dPMC led to improved motor performance early after stroke, indicating a detrimental influence of both regions. Performance improvement following M1 interference was positively linked to ipsilesional CST lesion load, indicating a more detrimental influence of contralesional M1 on motor function early after stroke the higher the CST lesion load.

At the connectome level, a more disturbing role of contralesional M1 was related to a more severe disruption of the structural integrity of ipsilesional M1 in the affected motor network. In stark contrast, a detrimental influence of contralesional aIPS was particularly found in case of less disruption of the ipsilesional M1 connectivity.

In summary, our findings indicate that contralesional areas distinctively interfere with motor performance early after stroke depending on ipsilesional structural integrity, extending the concept of structural reserve to regional specificity in recovery of function following brain lesions.