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Angela Merkl,1,2 Eva Röck,1 Tanja Schmitz-Hübsch,1,3 Gerd-Helge Schneider,4 Andrea A Kühn1,3,5 1Department of Neurology, Charité – University Medicine Berlin, Campus Virchow Klinikum, 2Department of Psychiatry and Psychotherapy, Charité – University Medicine Berlin, Campus Benjamin Franklin, 3NeuroCure, Charité – University Medicine Berlin, 4Department of Neurosurgery, Charité – University Medicine Berlin, Campus Virchow Klinikum, 5Berlin School of Mind and Brain, Charité – University Medicine Berlin, Berlin, Germany Background: In Parkinson’s disease (PD), cognitive symptoms and mood changes may be even more distressing for the patient than motor symptoms.Objective: Our aim was to determine the effects of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) on working memory (WM) and mood.Methods: Sixteen patients with PD were assessed with STN-DBS switched on (DBS-ON) and with dopaminergic treatment (Med-ON) compared to switched off (DBS-OFF) and without dopaminergic treatment (Med-OFF). The primary outcome measures were a Visual Analog Mood Scale (VAMS) and an emotional 2-back WM task at 12 months after DBS in the optimal DBS-ON/Med-ON setting compared to DBS-OFF/Med-OFF.Results: Comparison of DBS-OFF/Med-OFF to DBS-ON/Med-ON revealed a significant increase in alertness (meanoff/off =51.59±24.54; meanon/on =72.75; P=0.016) and contentedness (meanoff/off =38.73±24.41; meanon/on =79.01±17.66; P=0.001, n=16), and a trend for reduction in sedation (P=0.060), which was related to stimulation as shown in a subgroup of seven patients. The N-back task revealed a significant increase in accuracy with DBS-ON/Med-ON compared to DBS-OFF/Med-OFF (82.0% vs 76.0%, respectively) (P=0.044), regardless of stimulus valence.Conclusion: In line with previous studies, we found that patients rated themselves subjectively as more alert, content, and less sedated during short-term DBS-ON. Accuracy in the WM task increased with the combination of DBS and medication, possibly related to higher alertness of the patients. Our results add to the currently mixed results described for DBS on WM and suggest that there are no deleterious DBS effects on this specific cognitive domain. Keywords: deep brain stimulation, Parkinson’s disease, working memory, neuropsychiatric

Background: Deep brain stimulation of the subthalamic nucleus is an effective treatment for patients with advanced Parkinson's disease. However, affective side effects following subthalamic deep brain stimulation have been reported. Here, we aim to elucidate the influence of affective state on emotional processing as indexed by local field potential activity and to identify neurophysiological markers in patients at risk of developing depressive symptoms during subthalamic deep brain stimulation. Methods: Subthalamic local field potentials were directly recorded via electrodes implanted for deep brain stimulation in 12 Parkinson's disease patients while viewing emotionally salient and neutral pictures. Parkinson's disease patients were assessed for depressive symptoms using the Beck depression inventory at the time of operation and 3 months after continuous subthalamic nucleus deep brain stimulation. Results: We found a significant event-related desynchronization in the local alpha frequency band (8-12 Hz) for emotionally arousing but not neutral pictures. The the event-related desynchronization (ERD) in the alpha frequency band was reduced for pleasant stimuli in patients with mild to moderate depressive symptoms compared with patients without depression. The alpha-ERD to unpleasant stimuli showed the opposite pattern. Consistently, the index of event-related alpha desynchronization (alpha ERD for pleasant stimuli minus alpha ERD for unpleasant stimuli) correlated with the Beck depression inventory at the time of the recordings and at 3 months after continuous deep brain stimulation. The alpha ERD to unpleasant pictures correlated significantly with the Beck depression inventory score at 3 months after chronic deep brain stimulation. Discusion: In conclusion, we found mood-congruent stimulus processing in the subthalamic nucleus of Parkinson's disease patients. Electrophysiological markers such as event-related desynchronization of subthalamic alpha activity reflect state-dependent emotional processing and may potentially be used to predict depressive mood disturbances in Parkinson's disease patients with chronic subthalamic deep brain stimulation at an early stage. © 2011 Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Treatment of patients with Parkinson's disease with levodopa has profound effects on both movement and the pattern of movement-related reactivity in the subthalamic nucleus (STN), as reflected in the local field potential (LFP). The most striking change is the promotion of reactivity in the gamma frequency band, but it remains unclear whether the latter is itself a pathological feature, possibly associated with levodopa induced dyskinesias, or is primarily physiological. Gamma band reactivity in the cerebral cortex of humans without Parkinson's disease occurs contralateral to movement, so we posited that lateralization of subcortical gamma reactivity should occur following levodopa if the latter restores a more physiological pattern in patients with Parkinson's disease. Accordingly, we studied movement-related changes in STN LFP activity in 11 Parkinson's disease patients (age 59 +/- 2.7 years, three females) while they performed ipsi- and contralateral self-paced joystick movements ON and OFF levodopa. A bilaterally symmetrical gamma band power increase occurred around movement onset in the OFF state. Following levodopa this feature became significantly more pronounced in the subthalamic region contralateral to movement. The physiological nature of this asymmetric pattern of gamma reactivity was confirmed in the STN of two tremor patients without Parkinson's disease. Although levodopa treatment in the Parkinson's disease patients did not lead to lateralization of power suppression at lower frequencies (8-30 Hz), it did increase the degree of power suppression. These findings suggest that dopaminergic therapy restores a more physiological pattern of reactivity in the STN of patients with Parkinson's disease. [ABSTRACT FROM AUTHOR]

The ability to initiate volitional action is fundamental to human behaviour. Loss of dopaminergic neurons in Parkinson's disease is associated with impaired action initiation, also termed akinesia. Both dopamine and subthalamic deep brain stimulation (DBS) can alleviate akinesia, but the underlying mechanisms are unknown. An important question is whether dopamine and DBS facilitate de novo build-up of neural dynamics for motor execution or accelerate existing cortical movement initiation signals through shared modulatory circuit effects. Answering these questions can provide the foundation for new closed-loop neurotherapies with adaptive DBS, but the objectification of neural processing delays prior to performance of volitional action remains a significant challenge. To overcome this challenge, we studied readiness potentials and trained brain signal decoders on invasive neurophysiology signals in 25 DBS patients (12 female) with Parkinson's disease during performance of self-initiated movements. Combined sensorimotor cortex electrocorticography and subthalamic local field potential recordings were performed OFF therapy (n = 22), ON dopaminergic medication (n = 18) and on subthalamic deep brain stimulation (n = 8). This allowed us to compare their therapeutic effects on neural latencies between the earliest cortical representation of movement intention as decoded by linear discriminant analysis classifiers and onset of muscle activation recorded with electromyography. In the hypodopaminergic OFF state, we observed long latencies between motor intention and motor execution for readiness potentials and machine learning classifications. Both, dopamine and DBS significantly shortened these latencies, hinting towards a shared therapeutic mechanism for alleviation of akinesia. To investigate this further, we analysed directional cortico-subthalamic oscillatory communication with multivariate granger causality. Strikingly, we found that both therapies independently shifted cortico-subthalamic oscillatory information flow from antikinetic beta (13-35 Hz) to prokinetic theta (4-10 Hz) rhythms, which was correlated with latencies in motor execution. Our study reveals a shared brain network modulation pattern of dopamine and DBS that may underlie the acceleration of neural dynamics for augmentation of movement initiation in Parkinson's disease. Instead of producing or increasing preparatory brain signals, both therapies modulate oscillatory communication. These insights provide a link between the pathophysiology of akinesia and its' therapeutic alleviation with oscillatory network changes in other non-motor and motor domains, e.g. related to hyperkinesia or effort and reward perception. In the future, our study may inspire the development of clinical brain computer interfaces based on brain signal decoders to provide temporally precise support for action initiation in patients with brain disorders., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Dystonia is a hyperkinetic movement disorder that has been associated with an imbalance towards the direct pathway between striatum and internal pallidum, but the neuronal underpinnings of this abnormal basal ganglia pathway activity remain unknown. Here, we report invasive recordings from ten dystonia patients via deep brain stimulation electrodes that allow for parallel recordings of several basal ganglia nuclei, namely the striatum, external and internal pallidum, that all displayed activity in the low frequency band (3-12 Hz). In addition to a correlation with low-frequency activity in the internal pallidum (R = 0.88, P = 0.001), we demonstrate that dystonic symptoms correlate specifically with low-frequency coupling between striatum and internal pallidum (R = 0.75, P = 0.009). This points towards a pathophysiological role of the direct striato-pallidal pathway in dystonia that is conveyed via coupling in the enhanced low-frequency band. Our study provides a mechanistic insight into the pathophysiology of dystonia by revealing a link between symptom severity and frequency-specific coupling of distinct basal ganglia pathways., (© 2024. The Author(s).)

Background: Segmented electrodes for deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD) enable directional current steering leading to expanded programming options., Objective: This retrospective study covering a longitudinal period of up to 7 years compares the efficacy of segmented and non-segmented leads in motor symptom alleviation and reduction of dopaminergic medication in PD patients treated in a specialized center and assesses the long-term use of directional steering in clinical routine., Methods: Demographic data and clinical scores before surgery and at 12-month follow-up (12MFU) as well as stimulation parameters at 12MFU and last follow-up (LFU) were assessed in all patients implanted with segmented leads between 01/2016 and 12/2019 and non-segmented leads in a corresponding time-period. Patients were classified as very good (>60 %), good (30-60 %) and poor (<30 %) responders according to DBS-induced motor improvement., Results: Clinical data at 12MFU was available for 61/96 patients with segmented (SEG) and 42/53 with non-segmented leads (N-SEG). Mean DBS-induced motor improvement and reduction of medication at 12MFU did not differ significantly between SEG and N-SEG groups or in a subgroup analysis of steering modes. There was a lower proportion of poor responders in the SEG compared with the N-SEG group (23% vs. 31%), though not statistically significant. At LFU, the percentage of patients set at directional steering increased from 54% to 70%., Conclusion: Efficacy in reduction of motor symptoms and medication does not differ between electrode types for STN-DBS at 12 months follow-up. The use of directional steering increases over time and may account for a lower proportion of poor responders., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [A.L.A.M., V.H., M.A., B.A. and DKW have no conflicts of interest to declare. PK received speakeŕs honoraria from Stadapharm, AbbVie and MedTronic outside of this work and is in the Advisory Board of Abbvie and MedTronic. G.-H.S. has received honoraria from Medtronic, Boston Scientific, and Abbott unrelated to this work. A.A.K. has served on advisory boards of Medtronic and has received honoraria and travel support from Medtronic, Boston Scientific and Stada Pharm outside of this work]., (© 2024 The Author(s).)

Background: Comprehensive characterization of the metabolome in cerebrospinal fluid (CSF) and serum by Nuclear Magnetic Resonance (NMR) spectroscopy may identify biomarkers and contribute to the understanding of the pathophysiology of neurological diseases., Methods: Metabolites were determined by NMR spectroscopy in stored CSF/serum samples of 20 patients with Parkinson's disease, 25 patients with other neuro-degenerative diseases, 22 patients with cerebral ischemia, 48 patients with multiple sclerosis, and 58 control patients with normal CSF findings. The data set was analysed using descriptive and multivariate statistics, as well as machine learning models., Results: CSF glucose and lactic acid measured by NMR spectroscopy and routine clinical chemistry showed a strong correlation between both methods (glucose, R 2  = 0.87, n = 173; lactic acid, R 2  = 0.74, n = 173). NMR spectroscopy detected a total of 99 metabolites; 51 in both, CSF and serum, 16 in CSF only, and 32 in serum only. CSF concentrations of some metabolites increased with age and/or decreasing blood-brain-barrier function. Metabolite detection rates were overall similar among the different disease groups. However, in two-group comparisons, absolute metabolite levels in CSF and serum discriminated between multiple sclerosis and neurodegenerative diseases (area under the curve (AUC) = 0.96), multiple sclerosis and Parkinson's disease (AUC = 0.89), and Parkinson's disease and control patients (AUC = 0.91), as demonstrated by random forest statistical models. Orthogonal partial least square discriminant analysis using absolute metabolite levels in CSF and serum furthermore permitted separation of Parkinson's disease and neurodegenerative diseases. CSF propionic acid levels were about fourfold lower in Parkinson's disease as compared to neurodegenerative diseases., Conclusions: These findings outline the landscape of the CSF and serum metabolome in different categories of neurological diseases and identify age and blood-brain-barrier function as relevant co-factors for CSF levels of certain metabolites. Metabolome profiles as determined by NMR spectroscopy may potentially aid in differentiating groups of patients with different neurological diseases, including clinically meaningful differentiations, such as Parkinson's disease from other neurodegenerative diseases., (© 2024. The Author(s).)

Although deep brain stimulation of the subthalamic nucleus (STN-DBS) induces motor benefits in people with Parkinson's disease (PwPD), the size and duration of the effects of STN-DBS on motor axial (e.g., postural instability, trunk posture alterations) and gait impairments (e.g., freezing of gait - FOG) are still ambiguous. Physical therapy (PT) effectively complements pharmacological treatment to improve postural stability, gait performance, and other dopamine-resistant symptoms (e.g. festination, hesitation, axial motor dysfunctions, and FOG) in PwPD who are non-surgically treated. Despite the potential for positive adjuvant effects of PT following STN-DBS surgery, there is a paucity of science available on the topic. In such a scenario, gathering the opinion and expertise of leading investigators worldwide was pursued to study motor rehabilitation in PwPD following STN-DBS. After summarizing the few available findings through a systematic review, we identified clinical and academically experienced DBS clinicians (n=21) to discuss the challenges related to PT following STN-DBS. A 5-point Likert scale questionnaire was used and based on the results of the systematic review along with a Delphi method. Thirty-nine questions were submitted to the panel - half related to general considerations on PT following STN-DBS, half related to PT treatments. Despite the low-to-moderate quality, the few available rehabilitative studies suggested that PT could improve dynamic and static balance, gait performance and posture. Similarly, panellists strongly agreed that PT might help in improving motor symptoms and quality of life, and it may be possibly prescribed to maximize the effects of the stimulation. The experts agreed that physical therapists could be part of the multidisciplinary team taking care of the patients. Also, they agreed on prescribing of conventional PT, but not massage or manual therapy. Our results will inform the rehabilitation and the DBS community to engage, publish and deepen this area of research. Such efforts may spark guidelines for PT following STN-DBS., Competing Interests: A.F. has received payments as consultant and/or speaker from Abbott, Boston Scientific, Ceregate, Inbrain Neuroelectronics, Medtronic, Iota and has received research support from Boston Scientific, Medtronic. K.D.F. reports receiving research support and fellowship support from Medtronic and Boston Scientific and research support from Functional Neuromodulation. CRB has received support from the NIH (UH3 NS119844) and has served as a consultant for NeuraModix. J.K.K. is a consultant to Medtronic, Boston Scientific, aleva and Inomed. A.A.K. is a consultant to Medtronic, Boston Scientific and Teva. A.M.L. is a consultant to Abbott, Boston Scientific, Insightec, Medtronic and Functional Neuromodulation (Scientific Director). EM has received an educational grant from Boston Scientific and honoraria from Medtronic and Newronika. M.S.O. serves as Medical Advisor in the Parkinson’s Foundation, and has received research grants from NIH, Parkinson’s Foundation, the Michael J. Fox Foundation, the Parkinson Alliance, Smallwood Foundation, the Bachmann-Strauss Foundation, the Tourette Syndrome Association, and the UF Foundation. M.S.O. ‘s research is supported by: R01 NS131342 NIH R01 NR014852, R01NS096008, UH3NS119844, U01NS119562. M.S.O. is PI of the NIH R25NS108939 Training Grant. M.S.O. has received royalties for publications with Hachette Book Group, Demos, Manson, Amazon, Smashwords, Books4Patients, Perseus, Robert Rose, Oxford and Cambridge (movement disorders books). M.S.O. is an associate editor for New England Journal of Medicine Journal Watch Neurology and JAMA Neurology. M.S.O. has participated in CME and educational activities (past 12–24 months) on movement disorders sponsored by WebMD/Medscape, RMEI Medical Education, American Academy of Neurology, Movement Disorders Society, Mediflix and by Vanderbilt University. The institution and not M.S.O. receives grants from industry. M.S.O. has participated as a site PI and/or co-PI for several NIH, foundation, and industry sponsored trials over the years but has not received honoraria. Research projects at the University of Florida receive device and drug donations. A.S. received consulting fees from Abbott, Zambon, and Abbvie, and speaker honoraria from bsh medical communication, Abbott, Kyowa Kirin, Novartis, Abbvie, and Alexion, GE Healtcare. The institution of AS, not AS personally, received funding by the Deutsche Forschungsgemeinschaft, the Brunhilde Moll Foundation, and Abbott. L.T. received occasional payments as a consultant for Boston Scientific, L.T. received honoraria as a speaker on symposia sponsored by Boston Scientific, AbbVIE, Novartis, Neuraxpharm, Teva, the Movement Disorders Society und DIAPLAN. The institution of L.T., not L.T. personally, received funding by Boston Scientific, the German Research Foundation, the German Ministry of Education and Research, the Otto-Loewi-Foundation and the Deutsche Parkinson Vereinigung. Neither L.T. nor any member of his family holds stocks, stock options, patents or financial interests in any of the above-mentioned companies or their competitors. L.T. serves as the president of the German Neurological Society without any payment or any income. V.V.V. received occasional payments as a consultant or speaker on symposia from Boston Scientific and Medtronic. J.V. reports grants and personal fees from Medtronic, grants and personal fees from Boston Scientific, personal fees from Abbott outside the submitted work. J.V. was supported by the German Research Foundation (DFG, Project-ID424778381, TRR 295) – J.V. received consulting and lecture fees from Boston Scientific, Medtronic and Newronika, research grants from the German Research Foundation, the German Ministry of Research and Education, Boston Scientific and Medtronic, lecture Honoraria from UCB, Zambon, Abbott. A.P. and S.M. are founders and shareholders of Newronika Spa, Italy. All other authors declare no competing interests.

Background: Despite considerable heritability, previous smaller genome-wide association studies (GWASs) have not identified any robust genetic risk factors for isolated dystonia., Objective: The objective of this study was to perform a large-scale GWAS in a well-characterized, multicenter sample of >6000 individuals to identify genetic risk factors for isolated dystonia., Methods: Array-based GWASs were performed on autosomes for 4303 dystonia participants and 2362 healthy control subjects of European ancestry with subgroup analysis based on age at onset, affected body regions, and a newly developed clinical score. Another 736 individuals were used for validation., Results: This GWAS identified no common genome-wide significant loci that could be replicated despite sufficient power to detect meaningful effects. Power analyses imply that the effects of individual variants are likely very small., Conclusions: Moderate single-nucleotide polymorphism-based heritability indicates that common variants do not contribute to isolated dystonia in this cohort. Sequence-based GWASs (eg, by whole-genome sequencing) might help to better understand the genetic basis. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Objective: The Progressive Supranuclear Palsy quality of life scale (PSP-QoL) has been shown to be a useful tool for capturing health-related quality of life of patients in "everyday life" and in progressive supranuclear palsy (PSP) research. However, at 45 items in length, the questionnaire can take a long time, exhausting PSP patients, in particular if cognitive impaired, which can have a negative impact on the assessment. The aim of this study was to establish a condensed version of the PSP-QoL for research and routine clinical care., Methods: In this retrospective study, data originating from a German cohort of PSP patients was analyzed. Data from 245 PSP patients were included in this study. The short PSP-QoL questionnaire was created using a two-factor solution and item-total and inter-item correlations for mental and physical aspects of daily living of the PSP-QoL followed by confirmatory factor analysis., Results: The final scale included 12 items representing mental (five items) and physical symptoms (seven items). The specified two-factor model displayed an excellent fit in the confirmatory factor analysis. The short Progressive Supranuclear Palsy Quality of Life scale (PSP-ShoQoL) correlated moderately with the PSP Rating Scale (r [243] = 0.514, P < 0.001) and Geriatric depression scale (r [231] = 0.548, P < 0.001). Sensitivity to change confirmed a significant decrease in QoL after 12 months., Discussion: In this study, we created a 12-item PSP-ShoQoL designed to "facilitate" daily clinical work that correlated strongly with the PSP-QoL and was sensitive to change. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background: The dichotomy between the hypo- versus hyperkinetic nature of Parkinson's disease (PD) and dystonia, respectively, is thought to be reflected in the underlying basal ganglia pathophysiology. In this study, we investigated differences in globus pallidus internus (GPi) neuronal activity, and short- and long-term plasticity of direct pathway projections., Methods: Using microelectrode recording data collected from the GPi during deep brain stimulation surgery, we compared neuronal spiketrain features between people with PD and those with dystonia, as well as correlated neuronal features with respective clinical scores. Additionally, we characterized and compared readouts of short- and long-term synaptic plasticity using measures of inhibitory evoked field potentials., Results: GPi neurons were slower, bustier, and less regular in dystonia. In PD, symptom severity positively correlated with the power of low-beta frequency spiketrain oscillations. In dystonia, symptom severity negatively correlated with firing rate and positively correlated with neuronal variability and the power of theta frequency spiketrain oscillations. Dystonia was moreover associated with less long-term plasticity and slower synaptic depression., Conclusions: We substantiated claims of hyper- versus hypofunctional GPi output in PD versus dystonia, and provided cellular-level validation of the pathological nature of theta and low-beta oscillations in respective disorders. Such circuit changes may be underlain by disease-related differences in plasticity of striato-pallidal synapses., Funding: This project was made possible with the financial support of Health Canada through the Canada Brain Research Fund, an innovative partnership between the Government of Canada (through Health Canada) and Brain Canada, and of the Azrieli Foundation (LM), as well as a grant from the Banting Research Foundation in partnership with the Dystonia Medical Research Foundation (LM)., Competing Interests: SS, KS, LS, CF, EH, AK, MH, SK, AL, AF, WH, LM No competing interests declared, (© 2023, Sumarac, Spencer, Steiner et al.)

Importance: If history teaches, as cardiac pacing moved from fixed-rate to on-demand delivery in in 80s of the last century, there are high probabilities that closed-loop and adaptive approaches will become, in the next decade, the natural evolution of conventional Deep Brain Stimulation (cDBS). However, while devices for aDBS are already available for clinical use, few data on their clinical application and technological limitations are available so far. In such scenario, gathering the opinion and expertise of leading investigators worldwide would boost and guide practice and research, thus grounding the clinical development of aDBS., Observations: We identified clinical and academically experienced DBS clinicians (n=21) to discuss the challenges related to aDBS. A 5-point Likert scale questionnaire along with a Delphi method was employed. 42 questions were submitted to the panel, half of them being related to technical aspects while the other half to clinical aspects of aDBS. Experts agreed that aDBS will become clinical practice in 10 years. In the present scenario, although the panel agreed that aDBS applications require skilled clinicians and that algorithms need to be further optimized to manage complex PD symptoms, consensus was reached on aDBS safety and its ability to provide a faster and more stable treatment response than cDBS, also for tremor-dominant Parkinson's disease patients and for those with motor fluctuations and dyskinesias., Conclusions and Relevance: Despite the need of further research, the panel concluded that aDBS is safe, promises to be maximally effective in PD patients with motor fluctuation and dyskinesias and therefore will enter into the clinical practice in the next years, with further research focused on algorithms and markers for complex symptoms., Competing Interests: Declaration of interest M.G., N.V.M., S.O., T.B., E.S., Y.T., C.H., P.L. declare no conflict of interest. M.A.P is a consultant for Boston Scientific, Insightec, Medtronic and Abbott. She has received reimbursement of travel expenses to attend scientific meetings by Palex, Boston Scientific and Medtronic. She has received speaker honoraria from Palex. G. Deuschl G.D. has served as a consultant for Boston Scientific and Cavion and as DSMB member for Functional Neuromodulation. He has received royalties from Thieme Publishers and funding from the German Research Council (SFB 1261, T1). A.F. has received payments as consultant and/or speaker from Abbott, Boston Scientific, Ceregate, Inbrain Neuroelectronics, Medtronic, Iota and has received research support from Boston Scientific, Medtronic. R.M.F. has received speaker honoraria from the Spanish Neurological Society research foundation, Insightec, Palex, Bial and Zambon; has a consulting agreement with Treefrog Therapeutics; has received Reimbursement of travel expenses to attend scientific meetings by Palex, Zambon, the International Parkinson and Movement Disorder Society, the IAPDRD and the World Parkinson Congress; and has received research funding from Instituto de Salud Carlos III, Madrid, Spain for health research projects (PI21 Proyectos de investigacion en salud, AES 2021). C.G.S. has received lecture honoraria from Exeltis, Zambon, Palex, Insightec, Fundacion ACE, Societa Italiana Parkinson e Disordini del Movimento and Asociacion Madrilena de Neurologia, and reimbursement of travel expenses to attend scientific conferences from Boston Scientific and Esteve. J.K.K. is a consultant to Medtronic, Boston Scientific, aleva and Inomed A.A.K. is a consultant to Medtronic, Boston Scientific and Teva. S.L. is a consultant for Iota Biosciences and has previously received honorarium from Medtronic. S. L. research is support by NINDS NIH grants R01NS131405, K23NS120037 and Wellcome discovery award 226645/Z/22/Z A.M.L. is a consultant to Abbott, Boston Scientific, Insightec, Medtronic and Functional Neuromodulation (Scientific Director). M.S.O. serves as Medical Advisor in the Parkinson Foundation, and has received research grants from NIH, Parkinson Foundation, the Michael J. Fox Foundation, the Parkinson Alliance, Smallwood Foundation, the Bachmann-Strauss Foundation, the Tourette Syndrome Association, and the UF Foundation. M.S.O. ‘s research is supported by: R01 NS131342 NIH R01 NR014852, R01NS096008, UH3NS119844, U01NS119562. M.S.O. is PI of the NIH R25NS108939 Training Grant. M.S.O. has received royalties for publications with Hachette Book Group, Demos, Manson, Amazon, Smashwords, Books4Patients, Perseus, Robert Rose, Oxford and Cambridge (movement disorders books). M.S.O. is an associate editor for New England Journal of Medicine Journal Watch Neurology and JAMA Neurology. M.S.O. has participated in CME and educational activities (past 12–24 months) on movement disorders sponsored by WebMD/Medscape, RMEI Medical Education, American Academy of Neurology, Movement Disorders Society, Mediflix and by Vanderbilt University. The institution and not M.S.O. receives grants from industry. M.S.O. has participated as a site PI and/or co-I for several NIH, foundation, and industry sponsored trials over the years but has not received honoraria. Research projects at the University of Florida receive device and drug donations. J.L.O. received consulting payments from Abbott, Acorda, Jazz, Adamas, AcureX and Aspen as well as research or training grants from Biogen, Boston scientific, Medtronic, Neuroderm, Runelabs, Abbvie, Merz, Amneal and Acadia. A.S. received consulting fees from Abbott, Zambon, and Abbvie, and speaker honoraria from bsh medical communication, Abbott, Kyowa Kirin, Novartis, Abbvie, and Alexion, GE Healtcare. The institution of AS, not AS personally, received funding by the Deutsche Forschungsgemeinschaft, the Brunhilde Moll Foundation, and Abbott. P.A.S. is compensated for time spent on the data safety and monitoring board for Neuralink, Inc. L.T. received occasional payments as a consultant for Boston Scientific, L.T. received honoraria as a speaker on symposia sponsored by Boston Scientific, AbbVIE, Novartis, Neuraxpharm, Teva, the Movement Disorders Society und DIAPLAN. The institution of L.T., not L.T. personally received funding by Boston Scientific, the German Research Foundation, the German Ministry of Education and Research, the Otto-Loewi-Foundation and the Deutsche Parkinson Vereinigung. Neither L.T. nor any member of his family holds stocks, stock options, patents or financial interests in any of the above-mentioned companies or their competitors. Lars Timmermann serves as the president of the German Neurological Society without any payment or any income. G.T. received financial support from Boston Scientific and Medtronic; Research agreement with RuneLabs and Medtronic not related to the present work V.V.V. received occasional payments as a consultant or speaker on symposia from Boston Scientific and Medtronic. J. Volkmann 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) - JV received consulting and lecture fees from Boston Scientific, Medtronic and Newronika. Research grants from the German Research Foundation, the German Ministry of Research and Education, Boston Scientific and Medtronic. Lecture Honoraria from UCB, Zambon, Abbott. A.P. and S.M. are founders and shareholders of Newronika Spa, Italy.

Magnetoencephalography (MEG) allows the non-invasive measurement of brain activity at millisecond precision combined with localization of the underlying generators. So far, MEG-systems consisted of superconducting quantum interference devices (SQUIDS), which suffer from several limitations. Recent technological advances, however, have enabled the development of novel MEG-systems based on optically pumped magnetometers (OPMs), offering several advantages over conventional SQUID-MEG systems. Considering potential improvements in the measurement of neuronal signals as well as reduced operating costs, the application of OPM-MEG systems for clinical neuroscience and diagnostic settings is highly promising. Here we provide an overview of the current state-of-the art of OPM-MEG and its unique potential for translational neuroscience. First, we discuss the technological features of OPMs and benchmark OPM-MEG against SQUID-MEG and electroencephalography (EEG), followed by a summary of pioneering studies of OPMs in healthy populations. Key applications of OPM-MEG for the investigation of psychiatric and neurological conditions are then reviewed. Specifically, we suggest novel applications of OPM-MEG for the identification of biomarkers and circuit deficits in schizophrenia, dementias, movement disorders, epilepsy, and neurodevelopmental syndromes (autism spectrum disorder and attention deficit hyperactivity disorder). Finally, we give an outlook of OPM-MEG for translational neuroscience with a focus on remaining methodological and technical challenges., (© 2024. The Author(s).)