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Background: Deep brain stimulation (DBS) of the globus pallidus interna (GPi) is a highly efficacious treatment for cervical dystonia, but its mechanism of action is not fully understood. Here, we investigate the brain metabolic effects of GPi-DBS in cervical dystonia., Methods: Eleven patients with GPi-DBS underwent brain 18F-fluorodeoxyglucose positron emission tomography imaging during stimulation on and off. Changes in regional brain glucose metabolism were investigated at the active contact location and across the whole brain. Changes in motor symptom severity were quantified using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), executive function using trail making test (TMT) and parkinsonism using Unified Parkinson's Disease Rating Scale (UPDRS)., Results: The mean (SD) best therapeutic response to DBS during the treatment was 81 (22)%. The TWSTRS score was 3.2 (3.9) points lower DBS on compared with off (p=0.02). At the stimulation site, stimulation was associated with increased metabolism, which correlated with DBS stimulation amplitude (r=0.70, p=0.03) but not with changes in motor symptom severity (p>0.9). In the whole brain analysis, stimulation increased metabolism in the GPi, subthalamic nucleus, putamen, primary sensorimotor cortex (P FDR <0.05). Acute improvement in TWSTRS correlated with metabolic activation in the sensorimotor cortex and overall treatment response in the supplementary motor area. Worsening of TMT-B score was associated with activation of the anterior cingulate cortex and parkinsonism with activation in the putamen., Conclusions: GPi-DBS increases metabolic activity at the stimulation site and sensorimotor network. The clinical benefit and adverse effects are mediated by modulation of specific networks., Competing Interests: Competing interests: The authors report no relevant competing interests. EAH was supported by The Finnish Parkinson Foundation, Turku University Foundation, The Finnish Medical Foundation and Turku University Hospital (VTR funds). EP is a member of the MDS Non-Motor Parkinson’s Disease Study Group, is a PI in Finland in International Adroit-study (Abbott DBS Registry of Outcomes for Indications over Time) and has received funding from Government research grant (TYH). HD was supported by the Nündel Foundation. JV reports grants and personal fees from Medtronic, grants and personal fees from Boston Scientific, personal fees from Abbott outside the submitted work. JV was supported by the German Research Foundation (DFG, Project-ID424778381, TRR 295). VK serves as an advisory board member of AbbVie, has received travel expenses from Nordic Infucare AB and research funding from the Finnish Alcohol Research Foundation, the Päivikki and Sakari Sohlberg Foundation, the International Parkinson and Movement Disorder Society, and Finnish governmental research funding (VTR). MMR reports grant support and honoraria for speaking from Medtronic and Boston Scientific, outside the submitted and was supported by the German Research Foundation (DFG, Project-ID424778381, TRR 295). JJ received grants from the Finnish Medical Foundation, Instrumentarium Research Foundation, Finnish Foundation for Alcohol Studies, University of Turku (Sigrid Juselius Foundation, Private Donation) and Turku University Hospital (ERVA funds), a congress travel grant from Abbott and Abbvie, lecturer honoraria from Lundbeck and Novartis, and consulting fees from Summaryx., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Studies have shown that beta band activity is not tonically elevated but comprises exaggerated phasic bursts of varying durations and magnitudes, for Parkinson's disease (PD) patients. Current methods for detecting beta bursts target a single frequency peak in beta band, potentially ignoring bursts in the wider beta band. In this study, we propose a new robust framework for beta burst identification across wide frequency ranges. Chronic local field potential at-rest recordings were obtained from seven PD patients implanted with Medtronic SenSight™ deep brain stimulation (DBS) electrodes. The proposed method uses wavelet decomposition to compute the time-frequency spectrum and identifies bursts spanning multiple frequency bins by thresholding, offering an additional burst measure, ∆f, that captures the width of a burst in the frequency domain. Analysis included calculating burst duration, magnitude, and ∆f and evaluating the distribution and likelihood of bursts between the low beta (13-20 Hz) and high beta (21-35 Hz). Finally, the results of the analysis were correlated to motor impairment (MDS-UPDRS III) med off scores. We found that low beta bursts with longer durations and larger width in the frequency domain (∆f) were positively correlated, while high beta bursts with longer durations and larger ∆f were negatively correlated with motor impairment. The proposed method, finding clear differences between bursting behavior in high and low beta bands, has clearly demonstrated the importance of considering wide frequency bands for beta burst behavior with implications for closed-loop DBS paradigms., (© 2023. The Author(s).)

Research on the mental rotation task has sparked debate regarding the specific processes that underly the capability of humans to mentally rotate objects. The spread of reported brain activations suggests that mental rotation is subserved by a neural network circle. However, no common network has yet been found that uncovers the crucial processes underlying this ability. We aimed to identify the common network crucial for mental rotation by coordinate-based network mapping of previous neuroimaging findings in mental rotation. A meta-analysis revealed 710 peak activation coordinates from 42 fMRI studies in mental rotation, which include a total 844 participants. The coordinates were mapped to a normative functional connectome (n = 1000) to identify a network of connected regions. To account for experimental factors, we examined this network against two control tasks, action imitation and symbolic number processing. A common and crucial network for mental rotation, centring on dorsal premotor, superior parietal and inferior temporal lobes was revealed. This network, separated from other experimental aspects, suggests that the crucial processes underlying mental rotation are motor rotation, visuospatial processing, and higher order visual object recognition., Competing Interests: Conflict of interest MR reports grant support and honoraria for speaking from Medtronic and Boston Scientific, outside the submitted work. J.V. reports grants and personal fees from Medtronic Inc., grants and personal fees from Boston Scientific, personal fees from Abbott, outside the submitted work., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Deep brain stimulation of the internal globus pallidus effectively alleviates dystonia motor symptoms. However, delayed symptom control and a lack of therapeutic biomarkers and a single pallidal sweetspot region complicates optimal programming. Postoperative management is complex, typically requiring multiple, lengthy follow-ups with an experienced physician - an important barrier to widespread adoption in medication-refractory dystonia patients., Objective: Here we prospectively tested the best machine-predicted programming settings in a dystonia cohort treated with GPi-DBS against the settings derived from clinical long-term care in a specialised DBS centre., Methods: Previously, we reconstructed an anatomical map of motor improvement probability across the pallidal region using individual stimulation volumes and clinical outcomes in dystonia patients. We used this to develop an algorithm that tests in silico thousands of putative stimulation settings in de novo patients after reconstructing an individual, image-based anatomical model of electrode positions, and suggests stimulation parameters with the highest likelihood of optimal symptom control. To test real-life application, our prospective study compared results in 10 patients against programming settings derived from long-term care., Results: In this cohort, dystonia symptom reduction was observed at 74.9 ± 15.3% with C-SURF programming as compared to 66.3 ± 16.3% with clinical programming (p < 0.012). The average total electrical energy delivered (TEED) was similar for both the clinical and C-SURF programming (262.0 μJ/s vs. 306.1 μJ/s respectively)., Conclusion: Our findings highlight the clinical potential of machine-based programming in dystonia, which could markedly reduce the programming burden in postoperative management., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: FL reports grants from Boston Scientific not relevant to the submitted manuscript. MMR reports grants and personal fees from Boston Scientific and Medtronic, not relevant to the submitted work. MJR reports grants and personal fees from Boston Scientific, Medtronic and Zambon, not relevant to the submitted work. JV reports grants and personal fees from Medtronic, personal fees from St. Jude, grants and personal fees from Boston Scientific, personal fees from UCB, personal fees from Merz, personal fees from Allergan, personal fees from TEVA, personal fees from Novartis, personal fees from AbbVie and personal fees from Grünenthal, all outside the submitted work. All other authors report no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Deep brain stimulation of the subthalamic nucleus is an effective treatment of Parkinson's disease, yet it is often associated with a general deterioration of speech intelligibility. Clustering the phenotypes of dysarthria has been proposed as a strategy to tackle these stimulation-induced speech problems., Methods: In this study, we examine a cohort of 24 patients to test the real-life application of the proposed clustering and attempt to attribute the clusters to specific brain networks with two different approaches of connectivity analysis., Results: Both our data-driven and hypothesis-driven approaches revealed strong connections of variants of stimulation-induced dysarthria to brain regions that are known actors of motor speech control. We showed a strong connection between the spastic dysarthria type and the precentral gyrus and supplementary motor area, prompting a possible disruption of corticobulbar fibers. The connection between the strained voice dysarthria and more frontal areas hints toward a deeper disruption of the motor programming of speech production., Conclusions: These results provide insights into the mechanism of stimulation-induced dysarthria in deep brain stimulation of the subthalamic nucleus and may guide reprogramming attempts for individual Parkinson's patients based on pathophysiological understanding of the affected networks., Competing Interests: Declaration of competing interest FL reports grants from Boston Scientific not relevant to the submitted work. MMR reports grants and personal fees from Boston Scientific and Medtronic, not relevant to the submitted work. JV reports grants and personal fees from Medtronic, personal fees from St. Jude, grants and personal fees from Boston Scientific, personal fees from UCB, personal fees from Merz, personal fees from Allergan, personal fees from TEVA, personal fees from Novartis, personal fees from AbbVie and personal fees from Grünenthal, all outside the submitted work., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Purpose: The aim was to characterize a combined vestibular, ocular motor and postural syndrome induced by deep brain stimulation (DBS) of the subthalamic nucleus in a patient with Parkinson's disease., Methods: In a systematic DBS programming session, eye, head and trunk position in roll and pitch plane were documented as a function of stimulation amplitude and field direction. Repeat ocular coherence tomography was used to estimate ocular torsion. The interstitial nucleus of Cajal (INC), zona incerta (ZI) and ascending vestibular fibre tracts were segmented on magnetic resonance imaging using both individual and normative structural connectomic data. Thresholded symptom-associated volumes of tissue activated (VTA) were calculated based on documented stimulation parameters., Results: Ipsilateral ocular tilt reaction and body lateropulsion as well as contralateral torsional nystagmus were elicited by the right electrode in a current-dependent manner and subsided after DBS deactivation. With increasing currents, binocular tonic upgaze and body retropulsion were observed. Symptoms were consistent with an irritative effect on the INC. Symptom-associated VTA was found to overlap with the dorsal ZI and the ipsilateral vestibulothalamic tract, while lying rather distant to the INC proper. A ZI-to-INC 'incerto-interstitial' tract with contact to the medial-uppermost portion of the VTA could be traced., Conclusion: Unilateral stimulation of INC-related circuitry induces an ipsilateral vestibular, ocular motor and postural roll-plane syndrome, which converts into a pitch-plane syndrome when functional activation expands bilaterally. In this case, tractography points to an incerto-interstitial pathway, a tract previously only characterized in non-human primates. Directional current steering proved useful in managing this rare side effect., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Deep brain stimulation (DBS) is an established therapy for patients with Parkinson's disease. In silico computer models for DBS hold the potential to inform a selection of stimulation parameters. In recent years, the focus has shifted towards DBS-induced firing in myelinated axons, deemed particularly relevant for the external modulation of neural activity., Objective: The aim of this project was to investigate correlations between patient-specific pathway activation profiles and clinical motor improvement., Methods: We used the concept of pathway activation modeling, which incorporates advanced volume conductor models and anatomically authentic fiber trajectories to estimate DBS-induced action potential initiation in anatomically plausible pathways that traverse in close proximity to targeted nuclei. We applied the method on two retrospective datasets of DBS patients, whose clinical improvement had been evaluated according to the motor part of the Unified Parkinson's Disease Rating Scale. Based on differences in outcome and activation levels for intrapatient DBS protocols in a training cohort, we derived a pathway activation profile that theoretically induces a complete alleviation of symptoms described by UPDRS-III. The profile was further enhanced by analyzing the importance of matching activation levels for individual pathways., Results: The obtained profile emphasized the importance of activation in pathways descending from the motor-relevant cortical regions as well as the pallidothalamic pathways. The degree of similarity of patient-specific profiles to the optimal profile significantly correlated with clinical motor improvement in a test cohort., Conclusion: Pathway activation modeling has a translational utility in the context of motor symptom alleviation in Parkinson's patients treated with DBS., Competing Interests: Declaration of Competing Interest J.V. have business relationships with Medtronic, Abbott, and Boston Scientific, which are makers of DBS devices, outside the submitted work. A.A.K. reports personal fees and non-financial support from Medtronic, personal fees from Boston Scientific, grants and personal fees from Abbott, outside the submitted work. M.R. reports grant support and honoraria for speaking from Medtronic and Boston Scientific, outside the submitted work. A.H. reports lecture fees for Medtronic and Boston Scientific and is a consultant for AlphaOmega. G.R.W received travel expenses and attendance fees by Boston Scientific and Ipsen Pharma. K.B., N.L., C.N., J.R., H.E. and U.v.R. have nothing to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)