Al-Fatly et al. establish predictive connectivity maps of deep brain stimulation in essential tremor. They demonstrate that electrode connectivity to tremor-associated brain areas can predict postoperative improvement and that these maps can be somatotopically segregated according to the tremor-affected body parts.

Objective: Subthalamic nucleus deep brain stimulation (STN‐DBS) in Parkinson's disease (PD) not only stimulates focal target structures but also affects distributed brain networks. The impact this network modulation has on non‐motor DBS effects is not well‐characterized. By focusing on the affective domain, we systematically investigate the impact of electrode placement and associated structural connectivity on changes in depressive symptoms following STN‐DBS, which have been reported to improve, worsen, or remain unchanged.Methods: Depressive symptoms before and after STN‐DBS surgery were documented in 116 patients with PD from 3 DBS centers (Berlin, Queensland, and Cologne). Based on individual electrode reconstructions, the volumes of tissue activated (VTAs) were estimated and combined with normative connectome data to identify structural connections passing through VTAs. Berlin and Queensland cohorts formed a training and cross‐validation dataset used to identify structural connectivity explaining change in depressive symptoms. The Cologne data served as the test‐set for which depressive symptom change was predicted.Results: Structural connectivity was linked to depressive symptom change under STN‐DBS. An optimal connectivity map trained on the Berlin cohort could predict changes in depressive symptoms in Queensland patients and vice versa. Furthermore, the joint training‐set map predicted changes in depressive symptoms in the independent test‐set. Worsening of depressive symptoms was associated with left prefrontal connectivity.Interpretation: Fibers connecting the electrode with left prefrontal areas were associated with worsening of depressive symptoms. Our results suggest that for the left STN‐DBS lead, placement impacting fibers to left prefrontal areas should be avoided to maximize improvement of depressive symptoms. ANN NEUROL 2020;87:962–975

Background: The pattern and role of microglial activation in multiple system atrophy is largely unclear. The objective of this study was to use [¹¹C](R)‐PK11195 PET to determine the extent and correlation of activated microglia with clinical parameters in MSA patients.Methods: Fourteen patients with the parkinsonian phenotype of MSA (MSA‐P) with a mean disease duration of 2.9 years (range 2‐5 years) were examined with [¹¹C](R)‐PK11195 PET and compared with 10 healthy controls.Results: Patients with the parkinsonian phenotype of MSA showed a significant (P ≤ 0.01) mean increase in binding potentials compared with healthy controls in the caudate nucleus, putamen, pallidum, precentral gyrus, orbitofrontal cortex, presubgenual anterior cingulate cortex, and the superior parietal gyrus. No correlations between binding potentials and clinical parameters were found.Conclusions: In early clinical stages of the parkinsonian phenotype of MSA, there is widespread microglial activation as a marker of neuroinflammatory changes without correlation to clinical parameters in our patient population. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Background: Deep brain stimulation of the subthalamic nucleus (STN‐DBS) is an effective and evidence‐based treatment for idiopathic Parkinson's disease (iPD). A minority of patients does not sufficiently benefit from STN‐DBS.Objective: The predictive validity of the levodopa challenge for individual patients is analyzed.Methods: Data from patients assessed with a preoperative Levodopa‐test and a follow‐up examination (mean ± standard deviation: 9.15 months ±3.39) from Kiel (n = 253), Berlin (n = 78) and Toronto (n = 98) were studied. Insufficient DBS outcome was defined as an overall UPDRS‐III reduction <33% compared to UPDRS‐III in med‐off at baseline or alternatively if the minimal clinically important improvement of 5 points was not reached. Single UPDRS‐items and sub‐scores were dichotomized. Following exploratory analysis, we trained supervised regression‐ and classification models for outcome prediction.Results: Data analysis confirmed significant correlation between the absolute UPDRS‐III reduction during Levodopa challenge and after stimulation. But individual improvement was inaccurately predicted with a large range of up to 30 UPDRS III points. Further analysis identified preoperative UPDRS‐III/med‐off‐scores and preoperative Levodopa‐improvement as most influential factors. The models for UPDRS‐III and sub‐scores improvement achieved comparably low accuracy.Conclusions: With large prediction intervals, the Levodopa challenge use for patient counseling is limited, though remains important for excluding non‐responders to Levodopa. Despite these deficiencies, the current practice of patient selection is highly successful and builds not only on the Levodopa challenge. However, more specific motor tasks and further paraclinical tools for prediction need to be developed.

Background: Subthalamic nucleus deep brain stimulation (STN‐DBS) effectively treats motor symptoms and quality of life (QoL) of advanced and fluctuating early Parkinson's disease. Little is known about the relation between electrode position and changes in symptom control and ultimately QoL.Objectives: The relation between the stimulated part of the STN and clinical outcomes, including the motor score of the Unified Parkinson's Disease Rating Scale (UPDRS) and the quality‐of‐life questionnaire, was assessed in a subcohort of the EARLYSTIM study.Methods: Sixty‐nine patients from the EARLYSTIM cohort who underwent DBS, with a comprehensive clinical characterization before and 24 months after surgery, were included. Intercorrelations of clinical outcome changes, correlation between the affected functional parts of the STN, and changes in clinical outcomes were investigated. We further calculated sweet spots for different clinical parameters.Results: Improvements in the UPDRS III and Parkinson's Disease Questionnaire (PDQ‐39) correlated positively with the extent of the overlap with the sensorimotor STN. The sweet spots for the UPDRS III (x = 11.6, y = −13.1, z = −6.3) and the PDQ‐39 differed (x = 14.8, y = −12.4, z = −4.3) ~3.8 mm.Conclusions: The main influence of DBS on QoL is likely mediated through the sensory‐motor basal ganglia loop. The PDQ sweet spot is located in a posteroventral spatial location in the STN territory. For aspects of QoL, however, there was also evidence of improvement through stimulation of the other STN subnuclei. More research is necessary to customize the DBS target to individual symptoms of each patient. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society