Schaper, Frédéric

Background Deep brain stimulation (DBS) has been investigated for patients with drug-resistant epilepsy who are not candidates for resective surgery. Because different types of epilepsy involve distinct brain networks, numerous DBS targets have been explored, yet a comprehensive synthesis is lacking. Methods To provide a comprehensive overview of this expanding literature, we conducted a systematic review of studies for DBS in epilepsy, including case series, prospective and retrospective studies. We collected data on surgical targets, individual disease characteristics, outcomes and precise electrode placements. DBS electrode coordinates were gathered into a common template space and related to clinical outcomes. Results We included 124 studies, corresponding to 1210 patients and 20 distinct surgical targets. While the anterior (ANT) and centromedian (CM) nuclei of the thalamus remain the most studied, we also review less commonly used targets that show promise for specific forms of epilepsy and may warrant further investigation. Substantial variability in targeting strategies and electrode placement was observed within each of the target regions. Importantly, significant relationships between stimulation location and outcomes were identified for ANT-DBS and CM-DBS. For ANT-DBS, shorter distance to the mammillothalamic tract junction was associated with greater seizure reduction on both study-level and patient-level analyses (r=−0.55, p<0.001 and r=−0.51, p<0.001, respectively). For CM-DBS, localisation effects may be dependent on the form of epilepsy, with stimulation of the parvocellular CM being associated with better outcomes in generalised epilepsy. Conclusions Our results emphasise the importance of accurate targeting in DBS for epilepsy. Our database and atlas of DBS targets are made publicly available, potentially serving further meta-analytical work. PROSPERO registration number CRD420250649304.

Abstract Deep brain stimulation (DBS) of the subthalamic nucleus improves motor symptoms in patients with Parkinson’s disease. Using functional MRI, optimal DBS response networks have been characterized. However, neural activity associated with Parkinsonian symptoms is magnitudes faster than what can be resolved by this method. Although both spatial and temporal domains of these networks appear crucial, no single study has yet investigated both domains simultaneously. Here, we aimed at closing this gap by analysing electrophysiological data from a total of n = 127 hemispheres. Using subthalamic local field potentials that were recorded concurrently alongside whole-brain magnetoencephalography in a multi-centre cohort of patients who underwent subthalamic DBS for the treatment of Parkinson’s disease (n = 100 hemispheres), we analysed the DBS response network in both spatial and temporal domains. In every cortical vertex, cortico-subthalamic coupling was correlated with stimulation outcomes. This network spatially resembled functional MRI-based findings (R = 0.40, P = 0.039) and explained significant amounts of variance in clinical outcomes (βstd = 0.30, P = 0.002), whereas theta–alpha and low beta coupling did not show significant associations with DBS response (theta–alpha: βstd = −0.02, P = 0.805; low beta: βstd = −0.08, P = 0.426). The ‘optimal’ high beta coupling map was robust when subjected to various cross-validation designs (10-fold cross-validation: R = 0.29, P = 0.009; split-half design: R = 0.31, P = 0.026) and was able to predict outcomes across DBS centres [R = 0.74; P(1) = 8.9 × 10−5]. We identified a DBS response network that resembles the previously defined MRI network and operates in the high beta band. Maximal connectivity to this network was associated with optimal DBS outcomes and was able to cross-predict clinical improvements across DBS surgeons and centres.