Abstracts

Rationale: Epilepsy is one of the most common neurological disorders, affecting almost 1% of the population. Approximately one third of patients with epilepsy are refractory to pharmacological treatment and may require surgery. However, resected surgery can fail or lead to cognitive impairment. Recently, SEEG-guided radiofrequency thermocoagulation (SEEG-guided RF-TC) has shown very positive results with minimal risks, aiming to reduce seizure frequency by modifying epileptogenic networks through local thermocoagulative lesions. Although RF-TC has been shown to functionally modify brain networks immediately, the longer-term functional changes after RF-TC and the underlying network mechanism remain unclear.

Methods: We studied 43 epilepsy patients (12 with frontal lobe epilepsy, 16 with temporal lobe epilepsy, and 5 with occipital lobe epilepsy) at two time points; preoperatively and at least six months after RF-TC as well as 22 controls. All participants underwent functional MRI scans. Therapeutic response was defined as a >50% reduction in seizure frequency for at least 6 months after RF-TC. We used lesion network mapping to identify a common brain network, known as the lesion network, with high functional connectivity to thermocoagulative epileptogenic areas at different locations. We assessed connection strength within the lesion network in three groups and then related the changes of connection strength within the lesion network to the functional characteristics of thermocoagulative epileptogenic areas.

Results: The lesion network mapped from different thermocoagulative epileptogenic areas was predominantly distributed in the temporo-limbic circuit, fronto-parietal networks, cerebellum, and brainstem. Compared with the control group, the connection strength within the lesion network in the epilepsy patients was significantly reduced. And after RF-TC, the connection strength within the lesion network of the epilepsy patients was significantly improved compared with that before RF-TC, but there was still a difference compared with the control group. In particular, the connection strength within the lesion network of epilepsy patients in the responder (R) group reached a normal level after RF-TC, while there was no significant change in the non-responder (NR) group. Specifically, the increased connection strength within the lesion network of epilepsy patients after RF-TC was significantly associated with the connectivity of the thermocoagulative brain areas to the lesion network, but not with the local functional activity of the thermocoagulative brain areas.

Conclusions: To our knowledge, this study firstly provides a novel link between focal disconnections in the functional brain network and downstream effects on function in distant brain networks as an underlying mechanism of RF-TC. It is the disconnection of diseased brain connections, rather than the lesion itself, that drives functional reorganization after RF-TC, with implications for epilepsy and wider neuroscience.

Funding: National Natural Science Foundation of China(82072006 and 82372085)