Deep brain stimulation is a treatment option for patients with drug-resistant epilepsy. The precise mechanism of neuromodulation in epilepsy is unknown, and biomarkers are needed for optimizing treatment. The aim of this study was to describe the neural network associated with deep brain stimulation targets for epilepsy and to explore its potential application as a novel biomarker for neuromodulation. Using seed-to-voxel functional connectivity maps, weighted by seizure outcomes, brain areas associated with stimulation were identified in normative resting state functional scans of 1000 individuals. To pinpoint specific regions in the normative epilepsy deep brain stimulation network, we examined overlapping areas of functional connectivity between the anterior thalamic nucleus, centromedian thalamic nucleus, hippocampus and less studied epilepsy deep brain stimulation targets. Graph network analysis was used to describe the relationship between regions in the identified network. Furthermore, we examined the associations of the epilepsy deep brain stimulation network with disease pathophysiology, canonical resting state networks and findings from a systematic review of resting state functional MRI studies in epilepsy deep brain stimulation patients. Cortical nodes identified in the normative epilepsy deep brain stimulation network were in the anterior and posterior cingulate, medial frontal and sensorimotor cortices, frontal operculum and bilateral insulae. Subcortical nodes of the network were in the basal ganglia, mesencephalon, basal forebrain and cerebellum. Anterior thalamic nucleus was identified as a central hub in the network with the highest betweenness and closeness values, while centromedian thalamic nucleus and hippocampus showed average centrality values. The caudate nucleus and mammillothalamic tract also displayed high centrality values. The anterior cingulate cortex was identified as an important cortical hub associated with the effect of deep brain stimulation in epilepsy. The neural network of deep brain stimulation targets shared hubs with known epileptic networks and brain regions involved in seizure propagation and generalization. Two cortical clusters identified in the epilepsy deep brain stimulation network included regions corresponding to resting state networks, mainly the default mode and salience networks. Our results were concordant with findings from a systematic review of resting state functional MRI studies in patients with deep brain stimulation for epilepsy. Our findings suggest that the various epilepsy deep brain stimulation targets share a common cortico-subcortical network, which might in part underpin the antiseizure effects of stimulation. Interindividual differences in this network functional connectivity could potentially be used as biomarkers in selection of patients, stimulation parameters and neuromodulation targets.

Background: The surgical treatment of insular lesions has been historically associated with high morbidity. Laser interstitial thermal therapy (LITT) has been increasingly used in the treatment of insular lesions, commonly neoplastic or epileptogenic. Stereotaxis is used to guide laser probes to the insula where real-time magnetic resonance thermometry defines lesion creation. There is an absence of previously published reviews on insular LITT, despite a rapid uptake in use, making further study imperative.Methods: Here we present a systematic review of the PubMed and Scopus databases, examining the reported clinical indications, outcomes, and adverse effects of insular LITT.Results: A review of the literature revealed 10 retrospective studies reporting on 53 patients (43 pediatric and 10 adults) that were treated with insular LITT. 87% of cases were for the treatment of epilepsy, with 89% of patients achieving seizure outcomes of Engle I-III following treatment. The other 13% of cases reported on insular tumors and radiological improvement was seen in all cases following treatment. All but one study reported adverse events following LITT with a rate of 37%. The most common adverse events were transient hemiparesis (29%) and transient aphasia (6%). One patient experienced an intracerebral hemorrhage, which required a decompressive hemicraniectomy, with subsequent full recovery.Conclusion: This systematic review highlights the suitability of LITT for the treatment of both insular seizure foci and insular tumors. Despite the growing use of this technique, prospective studies remain absent in the literature. Future work should directly evaluate the efficacy of LITT with randomized and controlled trials.

Background: There remains high variability in clinical outcomes when the same magnetic resonance image‐guided focused ultrasound (MRgFUS) thalamotomy target is used for both essential tremor (ET) and tremor‐dominant Parkinson's disease (TDPD).Objective: Our goal is to refine the MRgFUS thalamotomy target for TDPD versus ET.Methods: We retrospectively performed voxel‐wise efficacy and structural connectivity mapping using 3‐12‐month post‐procedure hand tremor scores for a multicenter cohort of 32 TDPD patients and a previously published cohort of 79 ET patients, and 24‐hour T1‐weighted post‐MRgFUS brain images. We validated our findings using Unified Parkinson's Disease Rating Scale part III scores for an independent cohort of nine TDPD patients.Results: The post‐MRgFUS clinical improvements were 45.9% ± 35.9%, 55.5% ± 36%, and 46.1% ± 18.6% for ET, multicenter TDPD and validation TDPD cohorts, respectively. The TDPD and ET efficacy maps differed significantly (p_permute < 0.05), with peak TDPD improvement (87%) at x = −13.5; y = −15.0; z = 1.5, ~3.5 mm anterior and 3 mm dorsal to the ET target. Discriminative connectivity projections were to the motor and premotor regions in TDPD, and to the motor and somatosensory regions in ET. The disorder‐specific voxel‐wise efficacy map could be used to estimate outcome in TDPD patients with high accuracy (R = 0.8; R² = 0.64; P < 0.0001). The model was validated using the independent cohort of nine TDPD patients (R = 0.73; R² = 0.53; P = 0.025—voxel analysis).Conclusion: We demonstrated that the most effective MRgFUS thalamotomy target in TDPD is in the ventral intermediate nucleus/ventralis oralis posterior border region. This finding offers new insights into the thalamic regions instrumental in tremor control, with pivotal implications for improving treatment outcomes. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background: The efficacy and adverse events (AEs) of bilateral magnetic resonance‐guided focused ultrasound (MRgFUS) thalamotomies for essential tremor (ET) have not been compared to those of deep brain stimulation (DBS). Furthermore, it is uncertain whether second‐side thalamotomies can be positioned differently from the first without compromising effectiveness.Objective: We aimed to indirectly compare bilateral MRgFUS and DBS, while identifying optimal lesion/stimulation locations.Methods: We retrospectively examined 41 ET patients who received either bilateral thalamic DBS (n = 22) or MRgFUS (n = 19) surgery. The primary outcome was the comparison of modalities for change in Clinical Rating Scale for Tremor (CRST) from baseline to post second surgery. We characterized AEs, generated probabilistic maps, and tracked streamlines intersecting lesions. First‐side lesions were always intentionally placed ventrally (z = 0/+2 mm above the intercommissural plane [ICP]), and second‐side lesions were placed dorsally (z = +3 mm above ICP).Results: Tremor scores improved significantly after second surgeries (MRgFUS: 56.3 ± 7.1 to 24.2 ± 10.4, P < 0.001; DBS: 58.8 ± 11.6 to 25.0 ± 13, P < 0.05, mean follow‐up: 23/26 months), with no differences between modalities. Following first surgeries, scores were MRgFUS: 37.9 ± 7.9 and DBS: 35.2 ± 13.6, with significant improvement from baseline (P < 0.001, mean follow‐up: 40/73 months). All AEs were grade 1–2, with AE‐free rates of 41% for DBS and 32% for MRgFUS. First‐side lesions exhibited maximal efficacy in the ventral Vim, extending to posterior subthalamic area (PSA), whereas second‐side lesions demonstrated maximal efficacy in the dorsomedial Vim‐Vop border. DBS maps corroborated this finding and confined to Vim‐Vop border. Lesions intersecting with networks interconnected with the supplementary motor area, in addition to M1, were associated with improved outcomes.Conclusions: The efficacies of bilateral MRgFUS and DBS appear comparable. MRgFUS probabilistic maps vary with different targeting methods, revealing two distinct sweet spots: dorsal Vim‐Vop border and ventral Vim/PSA. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background: Deep brain stimulation (DBS) is an established treatment for movement disorders such as Parkinson's disease (PD) and essential tremor (ET). However, the decision between unilateral, staged bilateral, or simultaneous bilateral DBS remains controversial, influenced by clinical presentation, patient preferences, and economic factors. Objective: The aim was to compare motor score improvements, adverse events (AE), incremental benefits, and progression with unilateral to bilateral procedures and the rationale for second‐side surgery. Methods: This systematic review examined studies on patients treated with unilateral or bilateral (simultaneous or staged) DBS from 1999 to 2025, focusing on outcomes, safety, and efficacy. Results: In PD, unilateral DBS targeting the subthalamic nucleus (STN) or globus pallidus internus (GPi) improves motor scores by up to 37%, whereas bilateral DBS yields improvements of up to 66%. Unilateral DBS provides up to 75% improvement in contralateral symptoms but only up to 28% in ipsilateral symptoms. More than half of PD patients eventually opt for second‐side surgery due to worsening symptoms. In ET, unilateral ventral intermediate nucleus (VIM) DBS improves hand tremor by up to 89%, with staged bilateral procedures offering an additional 77% to 89% improvement contralaterally. Axial tremor improves by up to 60% with unilateral VIM DBS and a further 60% after bilateral surgery. Bilateral VIM DBS is linked to more AEs, such as gait disorders and dysarthria, whereas STN and GPi DBS have comparable risks. Staged surgeries are associated with longer surgical times and increased revisions and programming. Conclusions: Individualized treatment decisions are essential, with bilateral DBS providing superior long‐term outcomes for both PD and ET.