The Role of MER Processing Pipelines for STN Functional Identification During DBS Surgery: A Feature-Based Machine Learning Approach Vincenzo Levi, Stefania Coelli, Chiara Gorlini, Federica Forzanini, Sara Rinaldo, et al. Bioengineering, 2025 Microelectrode recording (MER) is commonly used to validate preoperative targeting during subthalamic nucleus (STN) deep brain stimulation (DBS) surgery for Parkinson’s Disease (PD). Although machine learning (ML) has been used to improve STN localization using MER data, the impact of preprocessing steps on the accuracy of classifiers has received little attention. We evaluated 24 distinct preprocessing pipelines combining four artifact removal strategies, three outlier handling methods, and optional feature normalization. The effect of each data processing procedure’s component of interest was evaluated in function of the performance obtained using three ML models. Artifact rejection methods (i.e., unsupervised variance-based algorithm (COV) and background noise estimation (BCK)), combined with optimized outlier management (i.e., statistical outlier identification per hemisphere (ORH)) consistently improved classification performance. In contrast, applying hemisphere-specific feature normalization prior to classification led to performance degradation across all metrics. SHAP (SHapley Additive exPlanations) analysis, performed to determine feature importance across pipelines, revealed stable agreement with regard to influential features across diverse preprocessing configurations. In conclusion, optimal artifact rejection and outlier treatment are essential in preprocessing MER for STN identification in DBS, whereas preliminary feature normalization strategies may impair model performance. Overall, the best classification performance was obtained by applying the Random Forest model to the dataset treated using COV artifact rejection and ORH outlier management (accuracy = 0.945). SHAP-based interpretability offers valuable guidance for refining ML pipelines. These insights can inform robust protocol development for MER-guided DBS targeting.
Simultaneous MEG-LFP Recordings to Assess In Vivo Dystonic Neurophysiological Networks: A Feasibility Study Elisa Visani, Lorenzo Bergamini, Chiara Gorlini, Dunja Duran, Nico Golfrè Andreasi, et al. Brain Sciences, 2025 Background/Objectives: Subcortical local field potentials (LFPs) provide a valuable in vivo window into the neurophysiology of the dystonia network. These signals can be recorded through Deep Brain Stimulation (DBS) devices and combined with whole-head techniques such as magnetoencephalography (MEG) to study cortical–subcortical interactions. However, simultaneous LFP-MEG acquisition poses challenges, including interference from the DBS device and synchronization issues. We present preliminary data on the feasibility and signal quality of concurrent LFP and MEG recordings in dystonia patients. Methods: We assessed simultaneous MEG-LFP recordings in 11 patients with inherited or idiopathic dystonia who underwent bilateral DBS lead implantation in the Globus Pallidus Internus (GPi). Two synchronization strategies were tested: (1) the Tapping method, using an accelerometer placed on the DBS device, and (2) the Stimulation method, which generated detectable artifacts during sham stimulation. Results: Both methods successfully aligned MEG and LFP signals with a mean temporal delay of 91 ± 22 ms for the Tapping method and 288 ± 166 ms for the Stimulation method. Post-implantation signal-to-noise ratio analysis revealed slight degradation but no significant impact on MEG quality (gradiometers: −0.12 ± 1.85 dB; magnetometers: −0.47 ± 2.03 dB). Conclusions: Simultaneous MEG-LFP recordings in dystonic patients are feasible, yielding high-quality signals, and reliable synchronization. Temporal alignment improved with practice, suggesting a short learning curve. This method opens new opportunities to study cortical-subcortical dynamics and strengthens the potential of combining MEG-LFP approaches for investigating dystonia.
Deep Brain Stimulation for VPS16-Related Dystonia: A Multicenter Study Tatiana Svorenova, Luigi M. Romito, Ahmet Kaymak, Eoin Mulroy, Laura Cif, et al. Annals of Neurology, 2025 ObjectiveThe objective was to evaluate the effects of deep brain stimulation (DBS) in an international cohort of patients with VPS16‐related dystonia.MethodsThis observational study collected preoperative and postoperative demographic, clinical, stimulation, genetic, neuroimaging, and neurophysiological data of medically refractory DYT‐VPS16 patients with implanted DBS in 10 international centers. Motor symptoms and disability outcomes were assessed using the Burke‐Fahn‐Marsden Dystonia Rating Scale Motor (BFMDRS‐M) and Disability (BFMDRS‐D) scales. A cut‐off threshold for considering response to DBS was set at 25% of BFMDRS‐M improvement at the last follow‐up (FU) compared to baseline.ResultsThe cohort consisted of 26 participants (17 men, 65.4%). Age at dystonia onset and surgery was 17.8 ± 10.9 and 35.3 ± 14.8 years, respectively. At the last FU, 102.5 ± 57.3 months (range, 2–216), the mean BFMDRS‐M improvement was 41.6 ± 37.3% (26/26 patients) and 34.8 ± 42.6% for the BFMDRS‐D (23/26 patients). Most patients (19/26, 73%) were considered responders. Higher motor improvement was associated with stimulation of the ventroposterior portion of the internal globus pallidus. A significant inverse relationship was observed between improvement in BFMDRS‐M at last FU, and the presence of spasticity (p = 0.027) and fixed skeletal deformities (p = 0.001) before surgery. Non‐responders had a younger age at disease onset and at implantation, shorter disease duration at DBS surgery, and higher baseline BFMDRS scores.InterpretationDBS was an effective treatment for three‐quarters of patients with pathogenic VPS16 variants in our cohort. Mean motor improvement was most pronounced at the 1‐year FU, but persisted at the last FU despite disease progression. ANN NEUROL 2025
Quantitative Tractography-Based Evaluations in Essential Tremor Patients after MRgFUS Thalamotomy Francesco Ghielmetti, Domenico Aquino, Nico Golfrè Andreasi, Federica Mazzi, Elena Greco, et al. Movement Disorders Clinical Practice, 2024 BackgroundMagnetic resonance‐guided focused ultrasound (MRgFUS) targeting the thalamic ventral intermediate nucleus (VIM) is an innovative treatment for drug‐refractory essential tremor (ET). The relationship between lesion characteristics, dentate‐rubro‐thalamic‐tract (DRTT) involvement and clinical benefit remains unclear.ObjectivesTo investigate whether clinical outcome is related to lesion volume and/or its overlap with the DRTT. To compare the reliability of probabilistic versus deterministic tractography in reconstructing the DRTT and improving VIM targeting.MethodsForty ET patients who underwent MRgFUS thalamotomy between 2019 and 2022 were retrospectively analyzed. Clinical outcomes and adverse effects were recorded at 1/6/12 months after the procedure. The DRTT was generated using deterministic and probabilistic tractography on preoperative diffusion‐tensor 3 T‐images and location and volume of the lesion were calculated.ResultsProbabilistic tractography identified both decussating (d‐DRTT) and non‐decussating (nd‐DRTT) components of the DRTT, whereas the deterministic approach only identified one component overlapping with the nd‐DRTT. Despite the lesions predominantly intersecting the medial portion of the d‐DRTT, with a significantly greater overlap in responder patients, we observed only a non‐significant correlation between tremor improvement and increased d‐DRTT‐lesion overlap (r = 0.22, P = 0.20). The lesion volume demonstrated a significant positive correlation with clinical improvement at 1‐day MRI (r = 0.42, P < 0.01).ConclusionVariability in the reconstructed DRTT position relative to the lesion center of mass, even among good responders, suggests that this fiber bundle is unlikely to be considered the sole target for a successful MRgFUS thalamotomy in ET. Indirect individualized targeting allows for more precise and reproducible identification of actual treatment coordinates than the direct method.
