Lateralized excitation–inhibition rebalance correlates with motor recovery following hemispheric surgery

Abstract Hemispheric epilepsy surgery effectively achieves seizure control, yet postoperative motor recovery remains challenging. Whether motor compensation is linked to the excitation-inhibition balance in the unaffected hemisphere (UH) remains unclear. Using scalp EEG, we quantified the aperiodic exponent of the power spectrum as a noninvasive biomarker of cortical excitation-inhibition ratio (where a flatter spectral slope reflects neural excitation). We retrospectively analyzed 46 patients who underwent hemispheric surgery and 23 age-matched unilateral non-hemispheric controls. Motor function was measured preoperatively and three months postoperatively, with preoperative status classified as preserved or impaired. We assessed preoperative inter-hemispheric asymmetry, postoperative UH modulation, and their linear interaction in predicting motor improvement. Jackknife mapping was used to identify the contribution of specific scalp sensor. Our results show that the hemispheric cohort exhibited a distinct preoperative excitation-inhibition asymmetry (P < 0.0001). Postoperatively, the UH exponent interacted significantly with preoperative status to track the change of motor function (P < 0.0001; R2=0.53). In patients with preoperative deficits, flatter UH slopes (disinhibition) were associated with functional gains (P = 0.0442), while steeper slopes (over-inhibition) correlated with decline (P = 0.0001). Conversely, in patients with preserved function, steeper UH slopes (inhibition) were linked to better outcomes (P = 0.0023), whereas flatter slopes led to deterioration (P = 0.0175). Jackknife mapping localized the primary contribution to sensor overlying the UH centro-parietal region. These findings suggest that state-dependent modulation of UH excitation-inhibition balance is a factor associated with motor recovery after hemispheric surgery—stabilization is beneficial when baseline function is preserved, while facilitation is beneficial when it is impaired. The aperiodic exponent emerges as a practical biomarker to monitor cortical excitation-inhibition dynamics and to guide individualized, precision neurorehabilitation strategies.