Nucleus Basalis Connectivity Relates to Seizure Freedom Following Epilepsy Surgery: A Potential Target for Neuromodulation

Introduction: Patients with focal epilepsy can suffer from recurrent consciousness-impairing seizures, which substantially affect quality of life. Although resective surgery eliminates seizures in 60-80% of drug-resistant patients[1], not all are surgical candidates. Neuromodulation of subcortical arousal structures may help prevent loss of consciousness in these patients, but it is unclear which structures should be targeted. The nucleus basalis of Meynert (NBM) has been shown to have decreased functional connectivity (FC) in patients before surgery[2], and preliminary evidence suggests FC increases in patients achieving seizure freedom following surgery. However, optimal brain function depends on dynamic network fluctuations[3], thus investigating disease-specific function and recovery necessitates characterizing post-surgical dynamic connectivity changes in addition to static connectivity. We sought to characterize dynamic FC of the NBM in patients before and after achieving seizure freedom compared to healthy controls. We hypothesized dynamic NBM FC in seizure-free patients would more closely resemble controls postoperatively than preoperatively, suggesting recovery of dynamic network activity through neuromodulation of the NBM could prevent loss of consciousness in patients ineligible for resection.

Methods: We performed dynamic FC analyses using a 1-minute sliding window (2-second stride) over 20 minutes of resting-state fMRI collected before and approximately one year following surgery of 17 seizure-free patients and collected once for 20 controls at Vanderbilt University. fMRI data was parcellated using the Desikan-Killiany cortical atlas and patient-specific NBM segmentations[4]. We computed mean strength (sum of all connections) of the ipsilateral and contralateral NBM to the whole-brain. Analyses compared preoperative patients, seizure-free postoperative patients, and controls.

Results: In preoperative patients, mean strength of the NBM ipsilateral to the seizure-onset zone differed significantly from controls for 23.4% of the scanning period, compared with 10.5% of the scanning period for seizure-free postoperative patients (Fig 1A; McNemar test: p< 0.001). Thus, dynamic NBM connectivity was more similar to controls in postoperative patients than preoperative patients. Mean strength of the contralateral NBM differed from controls for 7.0% and 13.5% of the scanning period in preoperative and postoperative patients, respectively (Fig 1B; McNemar test: p< 0.001).

Conclusion: These findings suggest that dynamic NBM connectivity more closely resembles controls following surgery in seizure-free patients, corroborating static connectivity findings. Recovery of the NBM’s “healthy” static and dynamic participation in brain networks may contribute to seizure freedom following surgical resection. As tissue-sparing surgical intervention is hypothesized to induce long-term network reorganization[5], NBM-targeted neuromodulation may aid brain network recovery towards dynamics present in seizure-free patients and alleviate consciousness-impairing seizures in patients ineligible for resection.