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Kathryn B Holroyd,1 Lisa Fosdick,2 Gwenn S Smith,1 Jeannie-Marie Leoutsakos,1 Cynthia A Munro,1 Esther S Oh,1 Kristen E Drake,2 Paul B Rosenberg,1 William S Anderson,1 Stephen Salloway,3–5 J Cara Pendergrass,6 Anna D Burke,7 David A Wolk,8 David F Tang-Wai,9–11 Francisco A Ponce,12 Wael F Asaad,13,14 Marwan N Sabbagh,15 Michael S Okun,16 Gordon Baltuch,17 Kelly D Foote,18 Steven D Targum,2,6 Andres M Lozano,10,11 Constantine G Lyketsos1 1Johns Hopkins University Memory and Alzheimer's Treatment Center, Baltimore, MD, 2Functional Neuromodulation Ltd, Minneapolis, MN, 3Department of Neurology, Butler Hospital, 4Department of Neurology, Rhode Island Hospital, 5Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI, 6Clintara LLC, Boston, MA, 7Banner Alzheimer's Institute, Phoenix, AZ, 8Penn Memory Center, Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA; 9Department of Neurology, 10Department of Neurosurgery, University of Toronto, 11Division of Neurology, University Health Network Memory Clinic, Toronto, ON, Canada; 12Division of Neurological Surgery, Barrow Neurological Institute, St Joseph's Hospital and Medical Center, Phoenix, AZ, 13Department of Neurosurgery, Rhode Island Hospital, 14Department of Neurosurgery, Warren Alpert Medical School of Brown University, Providence, RI, 15Banner Sun Health Research Institute, Sun City, AZ, 16Center for Movement Disorders and Neurorestoration, Department of Neurology, University of Florida – Gainsville, Gainsville, FL, 17Center for Functional and Restorative Neurosurgery, University of Pennsylvania, Philadelphia, PA, 18Department of Neurosurgery, Center for Movement Disorders and Neurorestoration, University of Florida, Gainsville, FL, USA Background: There are currently few available treatments and no cure for Alzheimer disease (AD), a growing public health burden. Animal models and an open-label human trial have indicated that deep brain stimulation (DBS) of memory circuits may improve symptoms and possibly slow disease progression. The ADvance trial was designed to examine DBS of the fornix as a treatment for mild AD. Methods: ADvance is a randomized, double-blind, placebo-controlled, delayed-start, multicenter clinical trial conducted at six sites in the US and one site in Canada. Eighty-five subjects initially consented to be screened for the trial. Of these, 42 subjects who met inclusion and exclusion criteria were implanted with DBS leads anterior to the columns of the fornix bilaterally. They were randomized 1:1 to DBS “off” or DBS “on” groups for the initial 12 months of follow-up. After 1 year, all subjects will have their devices turned “on” for the remainder of the study. Postimplantation, subjects will return for 13 follow-up visits over 48 months for cognitive and psychiatric assessments, brain imaging (up to 12 months), and safety monitoring. The primary outcome measures include Alzheimer's Disease Assessment Scale – cognitive component (ADAS-cog-13), Clinical Dementia Rating sum of boxes (CDR-SB), and cerebral glucose metabolism measured with positron emission tomography. This report details the study methods, baseline subject characteristics of screened and implanted participants, and screen-to-baseline test–retest reliability of the cognitive outcomes. Results: Implanted subjects had a mean age of 68.2 years, were mostly male (55%), and had baseline mean ADAS-cog-13 and CDR-SB scores of 28.9 (SD, 5.2) and 3.9 (SD, 1.6), respectively. There were no significant differences between screened and implanted or nonimplanted subjects on most demographic or clinical assessments. Implanted subjects had significantly lower (better) ADAS-cog-11 (17.5 vs 21.1) scores, but did not differ on CDR-SB. Scores on the major outcome measures for the trial were consistent at screening and baseline. Conclusion: ADvance was successful in enrolling a substantial group of patients for this novel application of DBS, and the study design is strengthened by rigorous subject selection from seven sites, a double-blind placebo-controlled design, and extensive open-label follow-up. Keywords: deep brain stimulation, Alzheimer disease, fornix, methods, clinical trials

Background: Recently, anterior limb of the internal capsule and nucleus accumbens deep brain stimulation (DBS) has been used in the treatment of medication-refractory obsessive-compulsive disorder (OCD). This region has been previously explored with lesion therapy, but with the advent of DBS there exists the possibility of monitoring the acute and chronic effects of electrical stimulation. The stimulation-induced benefits and side effects can be reversibly and blindly applied to a variety of locations in this region.Objective: To explore the acute effects of DBS in the anterior limb of the internal capsule and nucleus accumbens region.Methods: Ten total DBS leads in five patients with chronic and severe treatment-refractory OCD were tested. Patients were examined 30 days after DBS placement and received either "sham" testing or actual testing of the acute effects of DBS (the alternative condition tested 30 days later).Results: Pooled responses were reviewed for comparability of distribution using standard descriptive methods, and relationships between the variables of interest were sought using chi2 analysis. A total of 845 stimulation trials across the five patients were recorded and pooled. Of these 16% were elicited from sham stimulation and 17% from placebo (0 V stimulation). A comparison of active to sham trials showed that sham stimulation was not associated with significant side effects or responses from patients. Non-mood-related responses were found to be significantly associated with the ventral lead contacts (0 and 1) (p = 0.001). Responses such as taste, smell and smile were strongly associated with the most ventral lead positions. Similarly, physiological responses--for example, autonomic changes, increased breathing rate, sweating, nausea, cold sensation, heat sensation, fear, panic and panic episodes--were significantly associated with ventral stimulation (p = 0.001). Fear and panic responses appeared clustered around the most ventral electrode (0). Acute stimulation resulted in either improved or worsened mood responses in both the dorsal and ventral regions of the anterior limb of the internal capsule.Conclusion: The acute effects of DBS in the region of the anterior limb of the internal capsule and nucleus accumbens, particularly when obtained in a blinded fashion, provide a unique opportunity to localise brain regions and explore circuitry. [ABSTRACT FROM AUTHOR]

Objectives: To describe feeding patterns and mothers' perceptions of desirable feeding practices in low-birth-weight (LBW) infants after hospital discharge in England and to test for the association of inappropriate practices/perceptions with identifiable demographics.Design: Postal questionnaires from 198 mothers of LBW infants in London, Liverpool and Winchester were analysed regarding infant demographics, mothers' demographics, infant milks used, solid feeding practices and mothers' perceptions of infant feeding practices.Results: At birth, the median weight, independent of gestational age, was 1.80 kg (range 0.6-2.50 kg) and 37.1% of infants received breast milk exclusively; 83.7% were breast-fed at some stage, a practice favoured more by first-time mothers (90.2%) than multiparous mothers (73.4%) (P = 0.004) as well as by mothers of higher social groups (P = 0.019). The median age of solid food introduction was 17 postnatal weeks (range 8-36 weeks); the timing correlated strongly with infant birth weight (P < 0.001). A high-fibre diet and a low-fat diet were incorrectly considered important for their infants by 67.1% and 51.6% of mothers, respectively. Regarding a high-fibre diet as important was associated with being a multiparous mother (P = 0.006), while regarding a low-fat diet as important was associated with low social group (P = 0.018). A quarter of mothers did not consider 'plenty of calories' to be important for their infants, reflecting similar attitudes in 1990 for mothers of term infants; this incorrect attitude exhibited an association with being a first-time mother (P = 0.047).Conclusions: Infant feeding practices were very variable, showing poor concordance with national and international recommendations for term infants. In selecting foods for their infants, many mothers appeared to be applying principles more appropriate to planning a healthy diet for adults. There is an urgent need to develop and implement evidence-based guidelines for feeding LBW infants after hospital discharge, with special attention given to multiparous mothers as well as mothers from lower social groups. [ABSTRACT FROM AUTHOR]

Background: Mood, cognitive, and behavioural changes have been reported with deep brain stimulation (DBS) in the thalamus, globus pallidus interna, and anterior limb of the internal capsule/nucleus accumbens region.Objective: To investigate panic and fear resulting from DBS.Methods: Intraoperative DBS in the region of the right and then left anterior limb of the internal capsule and nucleus accumbens region was undertaken to treat a 52 year old man with treatment refractory obsessive-compulsive disorder (OCD). Mood, anxiety, OCD, alertness, heart rate, and subjective feelings were recorded during intraoperative test stimulation and at follow up programming sessions.Results: DBS at the distal (0) contact (cathode 0-, anode 2+, pulse width 210 ms, rate 135 Hz, at 6 volts) elicited a panic attack (only seen at the (0) contact). The patient felt flushed, hot, fearful, and described himself as having a "panic attack." His heart rate increased from 53 to 111. The effect (present with either device) was witnessed immediately after turning the device on, and abruptly ceased in the off conditionConclusions: DBS of the anterior limb of the internal capsule and nucleus accumbens region caused severe "panic." This response may result from activation of limbic and autonomic networks. [ABSTRACT FROM AUTHOR]

Objective: To assess the effect on growth and iron status in preterm infants of a specially devised weaning strategy compared with current best practices in infant feeding. The preterm weaning strategy recommended the early onset of weaning and the use of foods with a higher energy and protein content than standard milk formula, and foods that are rich sources of iron and zinc.Subjects and Design: In a blinded, controlled study, 68 preterm infants (mean (SD) birth weight 1470 (430) g and mean (SD) gestational age 31.3 (2.9) weeks) were randomised to either the preterm weaning strategy group (n = 37) or a current best practice control group (n = 31), from hospital discharge until 1 year gestation corrected age (GCA).Main Outcome Measures: Weight, supine length, occipitofrontal head circumference, and intakes of energy, protein, and minerals were determined at 0, 6, and 12 months GCA. Levels of haemoglobin, serum iron, and serum ferritin were assayed at 0 and 6 months GCA.Results: Significant positive effects of treatment included: greater increase in standard deviation length scores and length growth velocity; increased intake of energy, protein, and carbohydrate at 6 months GCA and iron at 12 months GCA; increased haemoglobin and serum iron levels at 6 months GCA.Conclusions: The preterm weaning strategy significantly influenced dietary intakes with consequent beneficial effects on growth in length and iron status. This strategy should be adopted as the basis of feeding guidelines for preterm infants after hospital discharge. [ABSTRACT FROM AUTHOR]

Purpose: Researchers have consistently observed in right-handed individuals across normal and disease states that the 'dominant' left hemisphere has greater ipsilateral control of the left side than the right hemisphere has over the right. We sought to determine whether this ipsilateral influence of the dominant hemisphere reported in Parkinson's disease extends to treatments such as deep brain stimulation (DBS) and whether it affects outcome. We hypothesised that among Parkinson right-handers, unilateral left DBS would provide greater ipsilateral motor improvement compared with the ipsilateral motor improvement experienced on the right side.Scope: A total of 73 Parkinson patients who underwent unilateral DBS of the subthalamic nucleus (STN) or globus palidus internus (GPi) participated. Left and right 'composite scores', were computed by separately adding all items on the left and right side from the motor section of the Unified Parkinson Disease Rating Scale. The change in the pre- and 4-month post-implantation score was the primary outcome measure. The mean motor scores improved by 4.96 ± 11.79 points (p < 0.001) post-surgery on the ipsilateral side of the DBS implantation. Regression analyses revealed that the side (left vs. right) and target (STN vs. GPi) did not significantly contribute in the effect of ipsilateral motor improvement (p = 0.3557).Conclusion: While DBS on the 'dominant' left side failed to exert a greater ipsilateral influence compared with DBS on the non-dominant right side, significant ipsilateral motor improvements were observed after unilateral stimulation regardless of site of implantation and laterality. [ABSTRACT FROM AUTHOR]

Background: Deep Brain Stimulation (DBS) surgery can effectively treat many debilitating motor symptoms of Parkinson's disease (PD), but axial symptom improvement is variable. Predictors for post-DBS axial symptom performance have yet to be identified. Pre-surgery ventricle volume may be one predictor, for increasing ventricular size has been associated with worsening gait disturbance. In PD, ventricle size may also increase with the advancement of motor symptoms.Objective: To examine the hypotheses that 1) lateral ventricular volumes would predict motor and axial motor symptom change from pre to four months post unilateral DBS, and 2) PD patients have larger ventricle volumes contralateral to side of symptom onset.Methods: Idiopathic PD patients (n = 37) completed pre-surgery volumetric brain scans and UPDRS motor testing (off-medication), unilateral DBS (Globus Pallidus interna, n = 11; subthalamic nucleus, n = 26), and 4-month follow-up motor assessments (on-stimulation). Ventricle volumes were normalized using total intracranial volume.Results: Total ventricular volume as well as measurements of contralateral/ipsilateral volumes to side of symptom onset or DBS lead placement did not predict outcome motor measures or correlate to axial motor change. Patients improving at least 2 standard errors of measurement (n = 6) did not have smaller ventricles relative to those without significant change. Post-operative hemorrhage (n = 1) had ventricle volumes similar to the group average. There was no asymmetry in ventricular volume by side of onset or side of lead placement.Conclusion: Ventricular volume was a poor predictor of acute motor change following DBS. Asymmetrical ventricles may not be a consistent imaging marker for PD motor dysfunction. [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) has been associated with increased apathy in patients with PD, yet studies lack longitudinal data and have not assessed differences between sites of implantation (i.e. STN versus GPi). We assessed apathy prior to surgery and 6 months post-surgery using a longitudinal design-latent growth curve modeling. We hypothesized that apathy would increase post-surgery, and be related to subthalamic nucleus (versus globus pallidus interna) implantation. Forty-eight PD patients underwent unilateral surgery to either GPi or STN and completed the Apathy Scale prior to surgery and 2, 4, and 6 months post-surgery. Forty-eight matched PD controls completed the Apathy Scale at a 6-month interval. Results indicated apathy increased linearly from pre- to 6-months post-DBS by .66 points bi-monthly, while apathy in the control group did not change. There was no relationship between apathy and DBS site. Higher baseline depression was associated with higher baseline apathy, but not with change in apathy. Middle-aged adults (<65) had a steeper trajectory of apathy than older adults (≥ 65). Apathy trajectory was not related to motor severity, laterality of DBS, levodopa medication reduction, or motor changes after surgery. [ABSTRACT FROM AUTHOR]

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.

Alpha-synuclein (αSyn) forms pathologic aggregates in Parkinson's disease (PD) and is implicated in mechanisms underlying neurodegeneration. While pathologic αSyn has been extensively studied, there is currently no method to evaluate αSyn within the brains of living patients. Patients with PD are often treated with deep brain stimulation (DBS) surgery in which surgical instruments are in direct contact with neuronal tissue; herein, we describe a method by which tissue is collected from DBS surgical instruments in PD and essential tremor (ET) patients and demonstrate that αSyn is detected. 24 patients undergoing DBS surgery for PD (17 patients) or ET (7 patients) were enrolled; from patient samples, 81.2 ± 44.8 µg of protein (n = 15), on average, was collected from surgical instruments. Light microscopy revealed axons, capillaries, and blood cells as the primary components of purified tissue (n = 3). ELISA assay further confirmed the presence of neuronal and glial tissue in DBS samples (n = 4). Further analysis was conducted using western blot, demonstrating that multiple αSyn antibodies are reactive in PD (n = 5) and ET (n = 3) samples; truncated αSyn (1-125 αSyn) was significantly increased in PD (n = 5) compared to ET (n = 3), in which αSyn misfolding is not expected (0.64 ± 0.25 vs. 0.25 ± 0.12, P = 0.046), thus showing that multiple forms of αSyn can be detected from living PD patients with this method., (© 2024. The Author(s).)

Background: Responsive deep brain stimulation (rDBS) uses physiological signals to deliver stimulation when needed. rDBS is hypothesized to reduce stimulation-induced speech effects associated with continuous DBS (cDBS) in patients with essential tremor (ET)., Objective: To determine if rDBS reduces cDBS speech-related side effects while maintaining tremor suppression., Methods: Eight ET participants with thalamic DBS underwent unilateral rDBS. Both speech evaluations and tremor severity were assessed across three conditions (DBS OFF, cDBS ON, and rDBS ON). Speech was analyzed using intelligibility ratings. Tremor severity was scored using the Fahn-Tolosa-Marin Tremor Rating Scale (TRS)., Results: During unilateral cDBS, participants experienced reduced speech intelligibility (P = 0.025) compared to DBS OFF. rDBS was not associated with a deterioration of intelligibility. Both rDBS (P = 0.026) and cDBS (P = 0.038) improved the contralateral TRS score compared to DBS OFF., Conclusions: rDBS maintained speech intelligibility without loss of tremor suppression. A larger prospective chronic study of rDBS in ET is justified. © 2024 International Parkinson and Movement Disorder Society., (© 2024 International Parkinson and Movement Disorder Society.)

Clinical Vignette: We present the case of a patient who developed intra-operative pneumocephalus during left globus pallidus internus deep brain stimulation (DBS) placement for Parkinson's disease (PD). Microelectrode recording (MER) revealed that we were anterior and lateral to the intended target., Clinical Dilemma: Clinically, we suspected brain shift from pneumocephalus. Removal of the guide-tube for readjustment of the brain target would have resulted in the introduction of movement resulting from brain shift and from displacement from the planned trajectory., Clinical Solution: We elected to leave the guide-tube cannula in place and to pass the final DBS lead into a channel that was located posterior-medially from the center microelectrode pass., Gap in Knowledge: Surgical techniques which can be employed to minimize brain shift in the operating room setting are critical for reduction in variation of the final DBS lead placement. Pneumocephalus after dural opening is one potential cause of brain shift. The recognition that the removal of a guide-tube cannula could worsen brain shift creates an opportunity for an intraoperative team to maintain the advantage of the 'fork' in the brain provided by the initial procedure's requirement of guide-tube placement., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Prader-Willi syndrome (PWS) is a complex, genetic disorder characterized by multisystem involvement, including hyperphagia, maladaptive behaviors and endocrinological derangements. Recent developments in advanced neuroimaging have led to a growing understanding of PWS as a neural circuit disorder, as well as subsequent interests in the application of neuromodulatory therapies. Various non-invasive and invasive device-based neuromodulation methods, including vagus nerve stimulation (VNS), transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), and deep brain stimulation (DBS) have all been reported to be potentially promising treatments for addressing the major symptoms of PWS. In this systematic literature review, we summarize the recent literature that investigated these therapies, discuss the underlying circuits which may underpin symptom manifestations, and cover future directions of the field. Through our comprehensive search, there were a total of 47 patients who had undergone device-based neuromodulation therapy for PWS. Two articles described VNS, 4 tDCS, 1 rTMS and 2 DBS, targeting different symptoms of PWS, including aberrant behavior, hyperphagia and weight. Multi-center and multi-country efforts will be required to advance the field given the low prevalence of PWS. Finally, given the potentially vulnerable population, neuroethical considerations and dialogue should guide the field., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Aysegul Gunduz reports a relationship with Medtronic Inc that includes: funding grants. Casey H. Halpern reports a relationship with Boston Scientific Corp that includes: consulting or advisory and speaking and lecture fees. Casey H. Halpern reports a relationship with Insightec that includes: consulting or advisory and speaking and lecture fees. Casey H. Halpern reports a relationship with SynchNeuro Inc that includes: board membership and equity or stocks. Michael S. Okun reports a relationship with Parkinson's Foundation that includes: consulting or advisory and funding grants. Michael S. Okun reports a relationship with National Institutes of Health that includes: funding grants. Michael S. Okun reports a relationship with Michael J. Fox Foundation, Parkinson Alliance, Smallwood Foundation, Bachmann-Strauss Foundation, Tourette Syndrome Association, UF Foundation that includes: funding grants. Casey H. Halpern has patent #USPTO serial number: 63/170,404 and 63/220,432 issued to Stanford University. Casey H. Halpern has patent #USPTO serial number: 63/210,472 pending to SynchNeuro. Michael S. Okun has received royalties for publications with 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. He 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. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

To report the results of 'responsive' deep brain stimulation (DBS) for Tourette syndrome (TS) in a National Institutes of Health funded experimental cohort. The use of 'brain derived physiology' as a method to trigger DBS devices to deliver trains of electrical stimulation is a proposed approach to address the paroxysmal motor and vocal tic symptoms which appear as part of TS. Ten subjects underwent bilateral staged DBS surgery and each was implanted with bilateral centromedian thalamic (CM) region DBS leads and bilateral M1 region cortical strips. A series of identical experiments and data collections were conducted on three groups of consecutively recruited subjects. Group 1 (n = 2) underwent acute responsive DBS using deep and superficial leads. Group 2 (n = 4) underwent chronic responsive DBS using deep and superficial leads. Group 3 (n = 4) underwent responsive DBS using only the deep leads. The primary outcome measure for each of the 8 subjects with chronic responsive DBS was calculated as the pre-operative baseline Yale Global Tic Severity Scale (YGTSS) motor subscore compared to the 6 month embedded responsive DBS setting. A responder for the study was defined as any subject manifesting a ≥ 30 points improvement on the YGTSS motor subscale. The videotaped Modified Rush Tic Rating Scale (MRVTRS) was a secondary outcome. Outcomes were collected at 6 months across three different device states: no stimulation, conventional open-loop stimulation, and embedded responsive stimulation. The experience programming each of the groups and the methods applied for programming were captured. There were 10 medication refractory TS subjects enrolled in the study (5 male and 5 female) and 4/8 (50%) in the chronic responsive eligible cohort met the primary outcome manifesting a reduction of the YGTSS motor scale of ≥ 30% when on responsive DBS settings. Proof of concept for the use of responsive stimulation was observed in all three groups (acute responsive, cortically triggered and deep DBS leads only). The responsive approach was safe and well tolerated. TS power spectral changes associated with tics occurred consistently in the low frequency 2-10 Hz delta-theta-low alpha oscillation range. The study highlighted the variety of programming strategies which were employed to achieve responsive DBS and those used to overcome stimulation induced artifacts. Proof of concept was also established for a single DBS lead triggering bi-hemispheric delivery of therapeutic stimulation. Responsive DBS was applied to treat TS related motor and vocal tics through the application of three different experimental paradigms. The approach was safe and effective in a subset of individuals. The use of different devices in this study was not aimed at making between device comparisons, but rather, the study was adapted to the current state of the art in technology. Overall, four of the chronic responsive eligible subjects met the primary outcome variable for clinical effectiveness. Cortical physiology was used to trigger responsive DBS when therapy was limited by stimulation induced artifacts., (© 2024. The Author(s).)

The Deep Brain Stimulation (DBS) Think Tank XI was held on August 9-11, 2023 in Gainesville, Florida with the theme of "Pushing the Forefront of Neuromodulation". The keynote speaker was Dr. Nico Dosenbach from Washington University in St. Louis, Missouri. He presented his research recently published in Nature inn a collaboration with Dr. Evan Gordon to identify and characterize the somato-cognitive action network (SCAN), which has redefined the motor homunculus and has led to new hypotheses about the integrative networks underpinning therapeutic DBS. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers, and researchers (from industry and academia) can freely discuss current and emerging DBS technologies, as well as logistical and ethical issues facing the field. The group estimated that globally more than 263,000 DBS devices have been implanted for neurological and neuropsychiatric disorders. This year's meeting was focused on advances in the following areas: cutting-edge translational neuromodulation, cutting-edge physiology, advances in neuromodulation from Europe and Asia, neuroethical dilemmas, artificial intelligence and computational modeling, time scales in DBS for mood disorders, and advances in future neuromodulation devices., Competing Interests: ND has a financial interest in Turing Medical Inc. and may financially benefit if the company is successful in marketing FIRMM motion monitoring software products, may receive royalty income based on FIRMM technology developed at Washington University School of Medicine and Oregon Health and Sciences University and licensed to Turing Medical Inc, and is a co-founder of Turing Medical Inc. These potential conflicts of interest have been reviewed and are managed by Washington University School of Medicine. AH reports lecture fees for Boston Scientific and is a consultant for FxNeuromodulation and Abbott. RG is an employee of Rune Labs. JO'K is CEO and Founder of Machine Medicine Technologies. W-JN received honoraria for consulting from InBrain – Neuroelectronics that is a neurotechnology company and honoraria for talks from Medtronic that is a manufacturer of deep brain stimulation devices unrelated to this manuscript. SL has received speaking honoraria from Medtronic and is a consultant for Iota Biosciences. SS is a consultant for Zimmer Biomet, Neuropace, Koh Young, Boston Scientfic, Sensoria Therapeutics, Varian Medical; co-founder for Motif Neurotech. LM is an employee of Boston Scientific. AF has stock ownership in Inbrain Pharma and has received payments as consultant and/or speaker from Abbvie, Abbott, Boston Scientific, Ceregate, Dompé Farmaceutici, Inbrain Neuroelectronics, Ipsen, Medtronic, Iota, Syneos Health, Merz, Sunovion, Paladin Labs, UCB, Sunovion, and he has received research support from Abbvie, Boston Scientific, Medtronic, Praxis, ES and receives royalties from Springer. AH-B and RR are employees of Medtronic Inc. LM is an employee of Boston Scientific. YP is an employee of Abbott. DG is an employee of NeuroPace, owns NeuroPace stock, and has NeuroPace stock options. SM is a founder and shareholder of Newronika SpA. LK is the CEO of Newronika. MP-N has received speaker honoraria/travel costs from Medtronic, Boston Scientific, Abbott, Bial, and Abbvie and study reimbursements from Zambon, Licher, Boston Scientific, and Abbott. LC has received research support from National Institutes of Health and the National Network of Depression Centers and serves on the Board of Directors for the International Neuroethics Society (unpaid) as well as on the Advisory Council for the Institute of Neuroethics think and do thank (unpaid). CM is a paid consultant for Boston Scientific Neuromodulation, receives royalties from Hologram Consultants, Neuros Medical, Qr8 Health, and is a shareholder in the following companies: Hologram Consultants, Surgical Information Sciences, BrainDynamics, CereGate, Cardionomic, Enspire DBS. NH is a co-founder of Surgical Information Sciences (SIS), Inc. HM received consulting and IP licensing fees from Abbott Laboratories. AK has stock options in Neurawell and Big Health and is a consultant for Axsome Therapeutics, Big Health, Eisai, Evecxia, Harmony Biosciences, Idorsia, Janssen Pharmaceuticals, Jazz Pharmaceuticals, Millenium Pharmaceuticals, Merck, Neurocrine Biosciences, Neurawell, Pernix, Otsuka Pharmaceuticals, Sage, and Takeda. NP is a consultant for Abbott and Sensoria Therapeutics. PS receives free research devices from Medtronic and fellowship support funding from Medtronic and BSCI and no personal income from anyone. KF reports receiving research support and fellowship support from Medtronic and Boston Scientific and research support from Functional Neuromodulation. MO serves as Medical Advisor 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. MO has received royalties for publications with Demos, Manson, Amazon, Smashwords, Books4Patients, Perseus, Robert Rose, Oxford and Cambridge (movement disorders books). MO is an associate editor for New England Journal of Medicine Journal, Watch Neurology, and JAMA Neurology. MO 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 MO receives grants from industry. MO 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. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Johnson, Dosenbach, Gordon, Welle, Wilkins, Bronte-Stewart, Voon, Morishita, Sakai, Merner, Lázaro-Muñoz, Williamson, Horn, Gilron, O'Keeffe, Gittis, Neumann, Little, Provenza, Sheth, Fasano, Holt-Becker, Raike, Moore, Pathak, Greene, Marceglia, Krinke, Tan, Bergman, Pötter-Nerger, Sun, Cabrera, McIntyre, Harel, Mayberg, Krystal, Pouratian, Starr, Foote, Okun and Wong.)

Spatial normalization-the process of mapping subject brain images to an average template brain-has evolved over the last 20+ years into a reliable method that facilitates the comparison of brain imaging results across patients, centers & modalities. While overall successful, sometimes, this automatic process yields suboptimal results, especially when dealing with brains with extensive neurodegeneration and atrophy patterns, or when high accuracy in specific regions is needed. Here we introduce WarpDrive, a novel tool for manual refinements of image alignment after automated registration. We show that the tool applied in a cohort of patients with Alzheimer's disease who underwent deep brain stimulation surgery helps create more accurate representations of the data as well as meaningful models to explain patient outcomes. The tool is built to handle any type of 3D imaging data, also allowing refinements in high-resolution imaging, including histology and multiple modalities to precisely aggregate multiple data sources together., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: A.H. reports a relationship with Boston Scientific Corporation that includes: speaking and lecture fees. L.A. reports a relationship with Boston Scientific Corporation that includes: consulting or advisory. L.A. reports a relationship with Medtronic that includes: consulting or advisory. K.F. reports a relationship with Medtronic that includes: consulting or advisory. K.F. reports a relationship with Boston Scientific Corporation that includes: consulting or advisory. K.F. reports a relationship with Abbott that includes: funding grants. K.F. reports a relationship with Functional Neuromodulation that includes: funding grants. D.W. reports a relationship with Functional Neuromodulation that includes: funding grants. D.W. reports a relationship with Avid Lily that includes: funding grants. D.W. reports a relationship with Merck that includes: funding grants. D.W. reports a relationship with Jannsen that includes: consulting or advisory. D.W. reports a relationship with GE Healthcare that includes: consulting or advisory. D.W. reports a relationship with Biogen that includes: consulting or advisory. D.W. reports a relationship with Neuronix that includes: consulting or advisory. S.S. reports a relationship with Elsai that includes: consulting or advisory. S.S. reports a relationship with Lilly that includes: consulting or advisory. S.S. reports a relationship with Roche that includes: consulting or advisory. S.S. reports a relationship with Novartis that includes: consulting or advisory. S.S. reports a relationship with Biogen that includes: consulting or advisory. G.S. reports a relationship with NIH that includes: funding grants. M.S. reports a relationship with Allergan that includes: consulting or advisory. M.S. reports a relationship with Biogen that includes: consulting or advisory. M.S. reports a relationship with Roche that includes: consulting or advisory. M.S. reports a relationship with Cortexyme that includes: consulting or advisory. M.S. reports a relationship with Bracket that includes: consulting or advisory. M.S. reports a relationship with Brain Health Inc that includes: consulting or advisory. M.S. reports a relationship with uMethod Health that includes: consulting or advisory. C.L. reports a relationship with Functional Neuromodulation that includes: funding grants. C.L. reports a relationship with Avanir that includes: funding grants. C.L. reports a relationship with Eli Lily that includes: funding grants. C.L. reports a relationship with NFL Benefits Office that includes: funding grants. M.O. reports a relationship with NIH that includes: funding grants. M.O. reports a relationship with Tourette Association of America Grant that includes: funding grants. M.O. reports a relationship with Parkinson's Alliance that includes: funding grants. M.O. reports a relationship with Smallwood Foundation that includes: funding grants. M.O. reports a relationship with Parkinson's Foundation Medical Director that includes: consulting or advisory. M.O. reports a relationship with Books4Patients that includes: consulting or advisory. M.O. reports a relationship with American Academy of Neurology that includes: consulting or advisory. M.O. reports a relationship with Peerview that includes: consulting or advisory. M.O. reports a relationship with WebMD Medscape that includes: consulting or advisory. M.O. reports a relationship with Mededicus that includes: consulting or advisory. M.O. reports a relationship with Movement Disorders Society that includes: consulting or advisory. M.O. reports a relationship with Taylor and Francis that includes: consulting or advisory. M.O. reports a relationship with Demos that includes: consulting or advisory. M.O. reports a relationship with Robert Rose that includes: consulting or advisory. M.O. reports a relationship with Medtronic that includes: non-financial support. A.L. reports a relationship with Medtronic that includes: funding grants. A.L. reports a relationship with Functional Neuromodulation that includes: funding grants. A.L. reports a relationship with Medtronic that includes: consulting or advisory. A.L. reports a relationship with St. Jude that includes: consulting or advisory. A.L. reports a relationship with Boston Scientific that includes: consulting or advisory. A.L. has patent #US Patent 8346,365 licensed to Functional Neuromodulation., (Copyright © 2023. Published by Elsevier B.V.)

Background: Weight loss in Parkinson's disease (PD) is common and associated with increased mortality. The clinical significance of weight changes following deep brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus internus (GPi) is unclear., Objectives: To address (1) whether PD patients exhibit progressive weight loss, (2) whether staged DBS surgery is associated with weight changes, and (3) whether survival after DBS correlates with post-DBS weight., Methods: This is a single-center, longitudinal, retrospective cohort study of 1625 PD patients. We examined trends in weight over time and the relationship between weight and years survival after DBS using regression and mixed model analyses., Results: There was a decline in body weight predating motor symptom onset (n = 756, 0.70 ± 0.03% decrease per year, p < 0.001). Weight decline accelerated in the decade preceding death (n = 456, 2.18 ± 0.31% decrease per year, p < 0.001). DBS patients showed a weight increase of 2.0 ± 0.33% at 1 year following the first DBS lead implant (n = 455) and 2.68 ± 1.1% at 3 years if a contralateral DBS lead was placed (n = 249). The bilateral STN DBS group gained the most weight after surgery during 6 years of follow up (vs bilateral GPi, 3.03 ± 0.45% vs 1.89 ± 0.31%, p < 0.01). An analysis of the DBS cohort with date of death available (n = 72) revealed that post-DBS weight (0-12 months after the first or 0-36 months after the second surgery) was positively associated with survival (R 2  = 0.14, p < 0.001)., Discussion: Though PD is associated with significant weight loss, DBS patients gained weight following surgery. Higher post-operative weight was associated with increased survival. These results should be replicated in other cohorts., Competing Interests: Declaration of competing interest No conflict of interest, (Copyright © 2023. Published by Elsevier Ltd.)

Background: There has been substantial controversy in the neuroethics literature regarding the extent to which deep brain stimulation (DBS) impacts dimensions of personality, mood, and behavior., Objective/hypothesis: Despite extensive debate in the theoretical literature, there remains a paucity of empirical data available to support or refute claims related to the psychosocial changes following DBS., Methods: A mixed-methods approach was used to examine the perspectives of patients who underwent DBS regarding changes to their personality, authenticity, autonomy, risk-taking, and overall quality of life., Results: Patients (n = 21) who were enrolled in adaptive DBS trials for Parkinson's disease, essential tremor, obsessive-compulsive disorder, Tourette's syndrome, or dystonia participated. Qualitative data revealed that participants, in general, reported positive experiences with alterations in what was described as 'personality, mood, and behavior changes.' The majority of participants reported increases in quality of life. No participants reported 'regretting the decision to undergo DBS.', Conclusion(s): The findings from this patient sample do not support the narrative that DBS results in substantial adverse changes to dimensions of personality, mood, and behavior. Changes reported as "negative" or "undesired" were few in number, and transient in nature., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Despite advances in the treatment of psychiatric diseases, currently available therapies do not provide sufficient and durable relief for as many as 30-40% of patients. Neuromodulation, including deep brain stimulation (DBS), has emerged as a potential therapy for persistent disabling disease, however it has not yet gained widespread adoption. In 2016, the American Society for Stereotactic and Functional Neurosurgery (ASSFN) convened a meeting with leaders in the field to discuss a roadmap for the path forward. A follow-up meeting in 2022 aimed to review the current state of the field and to identify critical barriers and milestones for progress., Design: The ASSFN convened a meeting on June 3, 2022 in Atlanta, Georgia and included leaders from the fields of neurology, neurosurgery, and psychiatry along with colleagues from industry, government, ethics, and law. The goal was to review the current state of the field, assess for advances or setbacks in the interim six years, and suggest a future path forward. The participants focused on five areas of interest: interdisciplinary engagement, regulatory pathways and trial design, disease biomarkers, ethics of psychiatric surgery, and resource allocation/prioritization. The proceedings are summarized here., Conclusion: The field of surgical psychiatry has made significant progress since our last expert meeting. Although weakness and threats to the development of novel surgical therapies exist, the identified strengths and opportunities promise to move the field through methodically rigorous and biologically-based approaches. The experts agree that ethics, law, patient engagement, and multidisciplinary teams will be critical to any potential growth in this area., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Sarah Bick receives funding from the Neurosurgery Research and Career Development Program (K12 NS080223) and consulting honoraria from Varian Medical Systems. Rafael Carbunaru owns stock options and is an employee of Boston Scientific, a manufacturer of DBS devices. Jennifer Chandler receives funding from CIHR (Canadian Institutes of Health Research) through the ERANET-Neuron program. Binith Cheeran owns stock options and is an employee of Abbott, a manufacturer of DBS devices. Rachel Davis receives consulting honoraria from Medtronic and speaker fees from Baylor for an OCD conference. Darin Dougherty's research has been funded by the International OCD Foundation, Brain and Behavior Research Foundation, National Institute of Mental Health, Tiny Blue Dot Foundation and Medtronic; he has received honoraria and consultation fees from Medtronic, Sage, and Celanese and has equity in Neurable, Innercosmos, and Intrinsic Powers. Ashley Feinsinger receives funding from the NIH (RF1MH121373 and UH3NS103442), received honoraria for her work on the NIH Neuroethics Workgroup, she is on an advisory board of Vivani Medical Products (Orion Early Feasibility Study), and she is on the data safety monitoring board of R01 MH122431. Kelly Foote reported grants from the National Institutes of Health during the conduct of the study; nonfinancial support from Medtronic (donation of closed-loop DBS devices) outside the submitted work; and grants from Medtronic, Boston Scientific, and Functional Neuromodulation outside the submitted work. Wayne Goodman receives funding from NIH (UH3NS100459), the McNair Foundation, and Biohaven. WG receives royalties from Nview, LLC and OCDscales, LLC as well as consulting honoraria from Biohaven. Aysegul Gunduz receives investigational device donations from Medtronic under the NIH BRAIN Public-Private Partnership agreements, and her research is funded by NIH grants UH3NS095553, R01NS096008, UH3NS119844. Casey Halpern has patents related to sensing and brain stimulation for the treatment of neuropsychiatric disorders, and he works as a consultant for Boston Scientific Neuromodulation and Insightec. Brian Kopell has received consulting honoraria from Abbott and Medtronic. Cynthia Kubu receives grant funding from the NIH (5RO1MH114853, 5RC1NS068086, 3RF1MH123407-01S1) and participates on the data safety monitoring boards for studies investigating the use of DBS for pain (UHS3 BRIAN/UH3 HEAL, 3UH3NS113661). She is the president of the Society for Clinical Neuropsychology. Sarah Lisanby receives funding from the NIMH (1ZIAMH002955) and has a role on the Scientific Advisory Boards of the Aalto University School of Science and the German Center for Brain Stimulation. Cameron McIntyre is a paid consultant for Boston Scientific Neuromodulation, receives royalties from Hologram Consultants, Neuros Medical, Qr8 Health, and is a shareholder in the following companies: Hologram Consultants, Surgical Information Sciences, BrainDynamics, CereGate, Autonomic Technologies, Cardionomic, Enspire DBS. Michael Okun serves as Medical Advisor for 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. Michael Okun's research is supported by: NIHR01 NR014852, R01NS096008, UH3NS119844, U01NS119562. Michael Okun is PI of the NIH R25NS108939 Training Grant. Michael Okun has received royalties for publications with Demos, Manson, Amazon, Smashwords, Books4Patients, Perseus, Robert Rose, Oxford and Cambridge (movement disorders books). Nader Pouratian receives research funding from NIH (R24 MH114796, UH3 NS103442, UH3 NS103549, R01 NS097782, UH3 NS113661, R01 GM135420, RF1 MH121373), consulting/presentation honoraria from Abbott, Sensoria Therapeutics, Boston Scientific, and BrainLab. Nader Pouratian is on an advisory board at Abbott Laboratories and has leadership positions in the Congress of Neurological Surgeons and American Society of Stereotactic and Functional Neurosurgery. Robert Raike owns stock options and is an employee of Medtronic, a manufacturer of DBS devices. Patricio Riva-Posse has received honoraria for consulting for Janssen Pharmaceuticals, Abbott Neuromodulation, and LivaNova. Sameer Sheth received funding from the McNair Foundation for this work. SS receives consulting honoraria from Boston Scientific, Neuropace, Zimmer Biomet, and Koh Young. Nora Vanegas-Arroyave receives research funding from NIH and the Michael J. Fox foundation. Alik Widge has received honoraria for consulting for Abbott, he has received device donations from Medtronic, and he has unlicensed patents in the area of deep brain stimulation., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Deep brain stimulation (DBS) devices with neural recording capabilities are commercially available and may potentially improve clinical care and advance research. However, tools, to visualize neural recording data have been limited. These tools in general, require custom-made software for processing and analysis. The development of new tools will be critical for clinicians and researchers to fully leverage the latest device capabilities., Objective: There is an urgent need for a user-friendly tool for in-depth visualization and analysis of brain signals and of DBS data., Methods and Results: The Brain Recording Analysis and Visualization Online (BRAVO) platform was developed to easily import, visualize, and analyze brain signals. This Python-based web interface has been designed and implemented on a Linux server. The tool processes the session files from DBS programming generated by a clinical 'programming' tablet. The platform is capable of parsing and organizing neural recordings for longitudinal analysis. We present the platform and cases exemplifying its application and use., Conclusion: The BRAVO platform is an accessible easy-to-use, open-source web interface for clinicians and researchers to apply for analysis of longitudinal neural recording data. The tool can be used for both clinical and research applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD), but its efficacy is tied to DBS programming, which is often time consuming and burdensome for patients, caregivers, and clinicians. Our aim is to test whether the Mobile Application for PD DBS (MAP DBS), a clinical decision support system, can improve programming., Methods: We conducted an open-label, 1:1 randomized, controlled, multicenter clinical trial comparing six months of SOC standard of care (SOC) to six months of MAP DBS-aided programming. We enrolled patients between 30 and 80 years old who received DBS to treat idiopathic PD at six expert centers across the United States. The primary outcome was time spent DBS programming and secondary outcomes measured changes in motor symptoms, caregiver strain and medication requirements., Results: We found a significant reduction in initial visit time (SOC: 43.8 ± 28.9 min n = 37, MAP DBS: 27.4 ± 13.0 min n = 35, p = 0.001). We did not find a significant difference in total programming time between the groups over the 6-month study duration. MAP DBS-aided patients experienced a significantly larger reduction in UPDRS III on-medication scores (-7.0 ± 7.9) compared to SOC (-2.7 ± 6.9, p = 0.01) at six months., Conclusion: MAP DBS was well tolerated and improves key aspects of DBS programming time and clinical efficacy., Competing Interests: Conflicts of interest There are potential conflicts of interested related to Medtronic, Boston Scientific, and Abbott, who are the device manufacturers who produced the DBS systems implanted in the study subjects. The University of Florida has received grants from Medtronic, Boston Scientific, and Abbott, but the authors have financial interest in these grants. ARZ serves as a consultant for Medtronic and Boston Scientific. IUH has performed research for Boston Scientific, and has consulted for Boston Scientific and Medtronic. JLO has received grant support from Boston Scientific and Medtronic, has consulted for Medtronic and Abbott, and received non-financial research support from Boston Scientific. MSS has received grant support from Boston Scientific, and honoraria/nonfinancial support as a scientific advisor from Boston Scientific. As the director of the Movement Disorders Fellowship at the University of Florida, CWH has received industry grants for educational support for the fellowship program that are paid directly to the University of Florida and used solely for fellow salary support from Medtronic, Boston Scientific, and Abbott. MHP has received consultation fees from Medtronic, Boston Scientific, and Abbot. MSL has received consulting fees from Boston Scientific. CRB has received consulting feeds from Boston Scientific and Abbott, and he holds intellectual property related to DBS. KDF has received occasional consulting fees from Medtronic and Boston Scientific for DBS related work. University of Florida has received implantable devices for KDF's DBS-related research, but not for this trial, from Medtronic. The University of Florida receives partial funding for KDF's functional neurosurgery fellowship from Medtronic. KDF holds three DBS related patents for which he has received no royalties. KDF has participated as a site implanting surgeon in multicenter DBS-related research studies sponsored by Abbott and Boston Scientific. MV has received consultation fees from Medtronic. PZ has received honorariums as a consultant and part of an advisory panel with Medtronic. JJS has received research support from Medtronic and Abbott, and has received consulting fees from Medtronic, Abbott, and, Boston Scientific. MSO, EM, BJL, CCA, SC, AT, GD, JLW, CG, AB, NN, DS, JC, MH, MA, and AS have nothing to disclose., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Globus pallidus internus deep brain stimulation is an established therapy for patients with medication-refractory Parkinson's disease. Clinical outcomes are highly dependent on applying stimulation to precise locations in the brain. However, robust neurophysiological markers are needed to determine the optimal electrode location and to guide postoperative stimulation parameter selection. In this study, we evaluated evoked resonant neural activity in the pallidum as a potential intraoperative marker to optimize targeting and stimulation parameter selection to improve outcomes of deep brain stimulation for Parkinson's disease. Intraoperative local field potential recordings were acquired in 22 patients with Parkinson's disease undergoing globus pallidus internus deep brain stimulation implantation ( N = 27 hemispheres). A control group of patients undergoing implantation in the subthalamic nucleus ( N = 4 hemispheres) for Parkinson's disease or the thalamus for essential tremor ( N = 9 patients) were included for comparison. High-frequency (135 Hz) stimulation was delivered from each electrode contact sequentially while recording the evoked response from the other contacts. Low-frequency stimulation (10 Hz) was also applied as a comparison. Evoked resonant neural activity features, including amplitude, frequency and localization were measured and analysed for correlation with empirically derived postoperative therapeutic stimulation parameters. Pallidal evoked resonant neural activity elicited by stimulation in the globus pallidus internus or externus was detected in 26 of 27 hemispheres and varied across hemispheres and across stimulating contacts within individual hemispheres. Bursts of high-frequency stimulation elicited evoked resonant neural activity with similar amplitudes ( P = 0.9) but a higher frequency ( P = 0.009) and a higher number of peaks ( P = 0.004) than low-frequency stimulation. We identified a 'hotspot' in the postero-dorsal pallidum where stimulation elicited higher evoked resonant neural activity amplitudes ( P < 0.001). In 69.6% of hemispheres, the contact that elicited the maximum amplitude intraoperatively matched the contact empirically selected for chronic therapeutic stimulation by an expert clinician after 4 months of programming sessions. Pallidal and subthalamic nucleus evoked resonant neural activity were similar except for lower pallidal amplitudes. No evoked resonant neural activity was detected in the essential tremor control group. Given its spatial topography and correlation with postoperative stimulation parameters empirically selected by expert clinicians, pallidal evoked resonant neural activity shows promise as a potential marker to guide intraoperative targeting and to assist the clinician with postoperative stimulation programming. Importantly, evoked resonant neural activity may also have the potential to guide directional and closed-loop deep brain stimulation programming for Parkinson's disease., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Tourette syndrome is a chronic neurodevelopmental disorder characterised by motor and phonic tics that can substantially diminish the quality of life of affected individuals. Evaluating and treating Tourette syndrome is complex, in part due to the heterogeneity of symptoms and comorbidities between individuals. The underlying pathophysiology of Tourette syndrome is not fully understood, but recent research in the past 5 years has brought new insights into the genetic variations and the alterations in neurophysiology and brain networks contributing to its pathogenesis. Treatment options for Tourette syndrome are expanding with novel pharmacological therapies and increased use of deep brain stimulation for patients with symptoms that are refractory to pharmacological or behavioural treatments. Potential predictors of patient responses to therapies for Tourette syndrome, such as specific networks modulated during deep brain stimulation, can guide clinical decisions. Multicentre data sharing initiatives have enabled several advances in our understanding of the genetics and pathophysiology of Tourette syndrome and will be crucial for future large-scale research and in refining effective treatments., Competing Interests: Declaration of interests KAJ reports receiving fellowship funding from the National Science Foundation and travel grant awards from the International Congress of Parkinson's Disease and Movement Disorders. AG has received grant funding from the National Institutes of Health (NIH; R01NS096008) and the National Science Foundation (NSF PECASE 1553482); support from the Tourette Association of America; device donations from Medtronic under an NIH contract; and serves as a board member of the Brain Computer Interfaces Society. KDF 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. MSO serves as a medical advisor for the Parkinson's Foundation; 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; has received support for research by NIH (R01 NR014852, R01NS096008, UH3NS119844, and U01NS119562); and is principal investigator of the NIH R25NS108939 Training Grant. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Deep brain stimulation (DBS) to the fornix is an investigational treatment for patients with mild Alzheimer's Disease. Outcomes from randomized clinical trials have shown that cognitive function improved in some patients but deteriorated in others. This could be explained by variance in electrode placement leading to differential engagement of neural circuits. To investigate this, we performed a post-hoc analysis on a multi-center cohort of 46 patients with DBS to the fornix (NCT00658125, NCT01608061). Using normative structural and functional connectivity data, we found that stimulation of the circuit of Papez and stria terminalis robustly associated with cognitive improvement (R = 0.53, p < 0.001). On a local level, the optimal stimulation site resided at the direct interface between these structures (R = 0.48, p < 0.001). Finally, modulating specific distributed brain networks related to memory accounted for optimal outcomes (R = 0.48, p < 0.001). Findings were robust to multiple cross-validation designs and may define an optimal network target that could refine DBS surgery and programming., (© 2022. The Author(s).)

Introduction: Mood symptoms are common features of Parkinson's disease (PD) and essential tremor (ET) and have been linked to worse cognition. The goals of the present study were to compare the severity of anxiety, apathy, and depressive symptoms in PD, ET, and healthy controls (HC) and to examine differential relationships between mood and cognition., Method: Older adults with idiopathic PD ( N = 448), ET ( N = 128), or HC ( N = 136) completed a multi-domain neuropsychological assessment consisting of memory, executive function, and attention/working memory domains. Participants also completed self-reported mood measures. Between-group differences in mood and cognition were assessed, and hierarchical regression models were conducted to examine relationships between mood and cognition in each group., Results: Relative to the HC group, the PD and ET groups reported more mood symptoms and scored lower across all cognitive measures. There were no differences between the two movement disorder groups. Mood variables explained 3.9-13.7% of the total variance in cognitive domains, varying by disease group. For PD, apathy was the only unique predictor of executive function ( β  = -.114, p = .05), and trait anxiety was the only unique predictor of attention/working memory ( β  = -.188, p < .05). For ET, there were no unique predictors, though the overall models significantly predicted performance in the executive function and attention/working memory domains., Conclusions: In a large cohort of ET and PD, we observed that the two groups had similar self-reported mood symptoms. Mood symptoms were differentially associated with cognition in PD versus ET. In PD, increased apathy was associated with worse executive function and higher trait anxiety predicted worse attention/working memory. For ET, there were no unique predictors, though the overall mood symptom severity was related to cognition. Our study highlights the importance of considering the relationship between mood and neuropsychological performance in individuals with movement disorders.

Importance: Because Tourette syndrome (TS) is a paroxysmal disorder, symptomatic relief in individuals with TS may be possible through the application of stimulation only during the manifestation of human tic neural signatures. This technique could be capable of suppressing both motor and vocal tics and would have similar effectiveness to conventional continuous deep brain stimulation (DBS)., Objective: To evaluate the feasibility, safety, and clinical effectiveness of bilateral centromedian-parafascicular complex thalamic closed-loop DBS as a treatment for medication-refractory TS., Design, Setting, and Participants: This single-center double-blinded safety and feasibility trial was conducted between February 2014 and June 2020. Six individuals with TS were screened and recruited from the Norman Fixel Institute at the University of Florida. The primary outcome was measured at 6 months, and participants were followed up for the duration of the neurostimulator battery life. Independent ratings that compared closed-loop and conventional DBS were videotaped. The first 2 of 6 individuals with TS were excluded from the study because the technology for embedded closed-loop capability was not yet available. The date of analysis was August 2020., Interventions: DBS therapy controlled by an embedded closed-loop stimulation system., Main Outcomes and Measures: The primary clinical outcome measure was a minimum of a 40% reduction in the YGTSS score at 6 months following DBS. There was also a comparison of conventional DBS with closed-loop DBS using the Modified Rush Videotape Rating Scale for Tic., Results: The mean (SD) age at TS diagnosis for the cohort was 8.5 (2.9), and the mean (SD) disease duration was 23.7 (5.8) years. Four individuals with TS were analyzed (2 male, 2 female; mean [SD] age, 23.7 [5.8] years). The study showed the closed-loop approach was both feasible and safe. One of the novelties of this study was that a patient-specific closed-loop paradigm was created for each participant. The features and stimulation transition speed were customized based on the signal quality and the tolerance to adverse reactions. The mean (SD) therapeutic outcome with conventional DBS was 33.3% (35.7%) improvement on the YGTSS and 52.8% (21.9%) improvement on the Modified Rush Videotape Rating Scale. Two of 4 participants had a primary outcome variable improvement of 40% meeting the primary efficacy target. When comparing closed-loop DBS with conventional DBS using a Wilcoxon sign-rank test, there was no statistical difference between tic severity score and both approaches revealed a lower tic severity score compared with baseline. The study was feasible in all 4 participants, and there were 25 total reported adverse events with 3 study-related events (12%). The most common adverse events were headache and anxiety., Conclusions and Relevance: Embedded closed-loop deep DBS was feasible, safe, and had a comparable outcome to conventional TS DBS for the treatment of tics., Trial Registration: ClinicalTrials.gov Identifier: NCT02056873.

Objective: Essential tremor (ET) is a common neurological disorder that has been associated with 60% increased risk of developing dementia. The goals of the present study were to: (a) learn whether individuals with advanced ET symptoms seeking deep brain stimulation (DBS) surgery would fall into distinct cognitive subgroups, and (b) learn how empirically derived subgroups map onto criteria for mild cognitive impairment (MCI). Method: Patients with ET ( N  = 201; mean age = 68.9 ± 8.9 years) undergoing pre-surgical evaluation for DBS completed a multi-domain neurocognitive assessment consisting of memory, executive function, visuospatial skill, language, and processing speed. Two cluster analytic approaches ( K -means, hierarchical) were independently conducted to classify cognitive patterns using domain composites. Demographics, clinical characteristics, and proportion of cases meeting neuropsychologically defined criteria for MCI were examined among clusters. Results: A three-cluster solution reflected a Low Executive group ( N  = 64), Low Memory Multi-Domain group ( N  = 41), and Cognitively Normal group ( N  = 96). The Cognitively Normal group was older and more educated, with a higher Dementia Rating Scale-2 score. In total, 27.4% of participants met criteria for MCI. Of the MCI cases, most were in the Low Executive (41.8%) or Low Memory Multi-Domain groups (49.1%). In the latter, 65.9% of its members were classified as MCI versus 35.9% in the Low Executive group. Conclusions: Our study identified three cognitive subtypes of ET patients presenting for DBS. Future work should examine the subgroups for progression to dementia, particularly the Low Memory Multi-Domain subgroup which may be at highest risk.

Background: Data are scarce on the efficacy of a second radiosurgery (SRS) treatment of vestibular schwannoma that has progressed following initial treatment with SRS. We sought to report the outcome of our repeat SRS series with long-term imaging follow-up., Materials and Methods: We retrospectively analyzed 6 patients who met the following criteria: Repeat SRS at our institution between 1995 and 2018; solitary unilateral tumor; no evidence of neurofibromatosis; and magnetic resonance (MR) planning for both SRS treatments. All treatments were delivered with a linear accelerator-based system using head frame immobilization. The prescribed dose to the periphery of the tumor was 12.5 Gy in all initial and repeat SRS treatments, except for one repeat treatment to 10 Gy., Results: Follow-up with MR scan following the second SRS treatment was a median 8.4 years. The tumor control rate (lack of progression) following the second SRS treatment was 83% (5/6). Actuarial 10-year outcomes following repeat SRS were: tumor control, 80%; absolute survival, 80%; and cause-specific survival, 100%. Of the patients with at least minimal hearing retention before initial SRS, none had ipsilateral hearing preservation after initial radiation treatment. Improvement in any pretreatment cranial nerve deficits was not seen. The only permanent grade ≥ 3 toxicity from repeat SRS was a case of infraorbital nerve deficit. No patient developed a stroke, malignant transformation, induced second tumor, or facial nerve deficit., Conclusion: There was excellent overall survival, tumor control, and low morbidity in our series for recurrent vestibular schwannoma submitted to repeat single-fraction SRS, supporting additional studies of this treatment strategy., Competing Interests: Conflict of interest The authors have no conflicts of interest to declare., (© 2022 Greater Poland Cancer Centre.)

Background: Clinical trial participants who benefit from experimental neural devices for the treatment of debilitating and otherwise treatment-resistant conditions are generally not ensured continued access to effective therapy or maintenance of devices at the conclusion of trials., Objective/hypothesis: Post-trial obligations have been extensively examined in the context of drug trials, but there has been little empirical examination of stakeholder perspectives regarding these obligations in the rapidly growing field of neural device research., Methods: This study examined the perspectives of 44 stakeholders (i.e., 23 researchers and 21 patient-participants) involved in implantable neural device trials., Results: Researchers were concerned about current post-trial management, identified barriers like cost, and suggested ways to improve the system. Many patient-participants were unaware of whether they would have post-trial access, but most thought they should keep devices if beneficial, and agreed with researchers that more should be done to help them keep and maintain these neural devices., Conclusion: To our knowledge, this is the first in-depth examination of researcher perspectives regarding continued access to experimental neural devices and only the second such examination of patient-participant perspectives. These data can help inform future ethical and policy decisions about post-trial access to implantable neurotechnology., Competing Interests: Declaration of competing interest None., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Deep brain stimulation (DBS) of the ventralis intermedius (VIM) nucleus of the thalamus has been successful in mitigating upper limb tremor, but the effect on gait and balance performance is unclear. Here, we aim to examine the effectiveness of VIM DBS on stride length variability, sway path length, and task-relevant tremor of various body segments in essential tremor (ET)., Methods: Seventeen ET individuals treated with DBS (ET DBS) and 17 age-and sex-matched healthy controls (HC) performed a postural balance and overground walking task. In separate and consecutive visits, ET DBS performed gait and balance tasks with DBS ON or OFF. The main outcome measures were sway path length, stride length variability, and tremor quantified from upper limb, lower limb, upper and lower trunk (axial) during the gait and balance tasks., Results: With DBS OFF, ET DBS exhibited significantly greater stride length variability, sway path length, and tremor during gait and balance task relative to HC. Relative to DBS OFF, DBS ON reduced stride length variability and sway path length in ET DBS. The DBS-induced reduction in stride length variability was associated with the reduction in both upper trunk tremor and upper limb tremor. The DBS-induced reduction in sway path length was associated with the reduction in upper trunk tremor., Discussion: The findings of this study revealed that VIM DBS was effective in improving gait and balance in ET DBS and that improvements in gait and postural balance were associated with a reduction of axial tremor during the tasks., Highlights: ET patients exhibit tremor in various body locations during gait and balance.DBS reduced stride length variability and sway path length.DBS-induced improvements in gait and balance were associated with reduction in axial tremor., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2022 The Author(s).)

This review article provides a brief historical perspective on the use of DBS for tremor, reviews the various etiologies for tremor that can be effectively managed with DBS therapy, discusses the DBS targets that have been used for suppression of tremor, and reviews in detail important aspects of DBS surgical technique, including significant technological advances over the past several years that, when applied, can substantially improve the outcomes of DBS for tremor. This article is part of the Special Issue "Tremor" edited by Daniel D. Truong, Mark Hallett, and Aasef Shaikh., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Tremor is a common symptom in multiple sclerosis and can present as a severe postural and action tremor, leading to significant disability. Owing to the diffuse and progressive nature of the disease, it has been challenging to characterize the pathophysiology underlying multiple sclerosis tremor. Deep brain stimulation of the ventralis intermedius and the ventralis oralis posterior thalamic nuclei has been used to treat medically refractory multiple sclerosis tremors with variable results. The aim of this study was to characterize multiple sclerosis tremor at the network level by applying modern connectomic techniques to data from a previously completed single-centre, randomized, single-blind prospective trial of 12 subjects who were treated with unilateral dual-lead (ventralis intermedius + ventralis oralis posterior) thalamic deep brain stimulation. Preoperative T 1 -weighted MRI and postoperative head CTs were used, along with applied programming settings, to estimate the volume of tissue activated for each patient. The volumes of tissue activated were then used to make voxel-wise and structural connectivity correlations with clinically observed tremor suppression. The volume of the tissue-activated analyses identified the optimal region of stimulation at the ventralis oralis posterior ventralis intermedius border intersecting with the dentato-rubro-thalamic tract. A regression model showed strong connectivity to the supplemental motor area was positively associated with tremor suppression ( r  = 0.66) in this cohort, whereas connectivity to the primary motor cortex was negatively associated with tremor suppression ( r  = -0.69), a finding opposite to that seen in ventralis intermedius deep brain stimulation for essential tremor. Comparing the structural connectivity to that of an essential tremor cohort revealed a distinct network that lies anterior to the essential tremor network. Overall, the volumes of tissue activated and connectivity observations converge to suggest that optimal suppression of multiple sclerosis tremor will likely be achieved by directing stimulation more anteriorly toward the ventralis oralis posterior and that a wide field of stimulation synergistically modulating the ventralis oralis posterior and ventralis intermedius nuclei may be more effective than traditional ventralis intermedius deep brain stimulation at suppressing the severe tremors commonly seen in complex tremor syndromes such as multiple sclerosis tremor., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

DBS Think Tank IX was held on August 25-27, 2021 in Orlando FL with US based participants largely in person and overseas participants joining by video conferencing technology. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers and researchers (from industry and academia) can freely discuss current and emerging deep brain stimulation (DBS) technologies as well as the logistical and ethical issues facing the field. The consensus among the DBS Think Tank IX speakers was that DBS expanded in its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. After collectively sharing our experiences, it was estimated that globally more than 230,000 DBS devices have been implanted for neurological and neuropsychiatric disorders. As such, this year's meeting was focused on advances in the following areas: neuromodulation in Europe, Asia and Australia; cutting-edge technologies, neuroethics, interventional psychiatry, adaptive DBS, neuromodulation for pain, network neuromodulation for epilepsy and neuromodulation for traumatic brain injury., Competing Interests: RR was employed by Medtronic, Inc. HBo was employed by Boston Scientific Neuromodulation Corporation. DG was employed by the NeuroPace, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wong, Deuschl, Wolke, Bergman, Muthuraman, Groppa, Sheth, Bronte-Stewart, Wilkins, Petrucci, Lambert, Kehnemouyi, Starr, Little, Anso, Gilron, Poree, Kalamangalam, Worrell, Miller, Schiff, Butson, Henderson, Judy, Ramirez-Zamora, Foote, Silburn, Li, Oyama, Kamo, Sekimoto, Hattori, Giordano, DiEuliis, Shook, Doughtery, Widge, Mayberg, Cha, Choi, Heisig, Obatusin, Opri, Kaufman, Shirvalkar, Rozell, Alagapan, Raike, Bokil, Green and Okun.)

Background: Impulsivity and impulse control disorders are common in Parkinson's disease and lead to increased morbidity and reduced quality of life. Impulsivity is thought to arise from aberrant reward processing and inhibitory control, but it is unclear why deep brain stimulation of either the subthalamic nucleus (STN) or globus pallidus internus (GPi) affects levels of impulsivity. Our aim was to assess the role of the STN and GPi in impulsivity using invasive local field potential (LFP) recordings from deep brain stimulation electrodes., Methods: We measured LFPs during a simple rewarding Go/NoGo paradigm in 39 female and male human patients with Parkinson's disease manifesting variable amounts of impulsivity who were undergoing unilateral deep brain stimulation of either the STN (18 nuclei) or GPi (28 nuclei). We identified reward-specific LFP event-related potentials and correlated them to impulsivity severity., Results: LFPs in both structures modulated during reward-specific Go and NoGo stimulus evaluation, reward feedback, and loss feedback. Motor and limbic functions were anatomically separable in the GPi but not in the STN. Across participants, LFP reward processing responses in the STN and GPi uniquely depended on the severity of impulsivity., Conclusions: This study establishes LFP correlates of impulsivity within the STN and GPi regions. We propose a model for basal ganglia reward processing that includes the bottom-up role of the GPi in reward salience and the top-down role of the STN in cognitive control., (Copyright © 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Deep brain stimulation (DBS) is an effective surgical therapy for individuals with essential tremor (ET). However, DBS operates continuously, resulting in adverse effects such as postural instability or dysarthria. Continuous DBS (cDBS) also presents important practical issues including limited battery life of the implantable neurostimulator (INS). Collectively, these shortcomings impact optimal therapeutic benefit in ET., Objective: The goal of the study was to establish a physiology-driven responsive DBS (rDBS) system to provide targeted and personalized therapy based on electromyography (EMG) signals., Methods: Ten participants with ET underwent rDBS using Nexus-D, a Medtronic telemetry wand that acts as a direct conduit to the INS by modulating stimulation voltage. Two different rDBS paradigms were tested: one driven by one EMG (single-sensor) and another driven by two or more EMGs (multi-sensor). The feature(s) used in the rDBS algorithms was the pow2er in the participant's tremor frequency band derived from the sensors controlling stimulation. Both algorithms were trained on kinetic and postural data collected during DBS off and cDBS states., Results: Using established clinical scales and objective measurements of tremor severity, we confirm that both rDBS paradigms deliver equivalent clinical benefit as cDBS. Moreover, both EMG-driven rDBS paradigms delivered less total electrical energy translating to an increase in the battery life of the INS., Conclusions: The results of this study verify that EMG-driven rDBS provides clinically equivalent tremor suppression compared to cDBS, while delivering less total electrical energy. Controlling stimulation using a dynamic rDBS paradigm can mitigate limitations of traditional cDBS systems., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Because of its involvement in a wide variety of cardiovascular, metabolic and behavioural functions, the hypothalamus constitutes a potential target for neuromodulation in a number of treatment-refractory conditions. The precise neural substrates and circuitry subserving these responses, however, are poorly characterized to date. We sought to retrospectively explore the acute sequelae of hypothalamic region deep brain stimulation and characterize their neuroanatomical correlates. To this end we studied-at multiple international centres-58 patients (mean age: 68.5 ± 7.9 years, 26 females) suffering from mild Alzheimer's disease who underwent stimulation of the fornix region between 2007 and 2019. We catalogued the diverse spectrum of acutely induced clinical responses during electrical stimulation and interrogated their neural substrates using volume of tissue activated modelling, voxel-wise mapping, and supervised machine learning techniques. In total 627 acute clinical responses to stimulation-including tachycardia, hypertension, flushing, sweating, warmth, coldness, nausea, phosphenes, and fear-were recorded and catalogued across patients using standard descriptive methods. The most common manifestations during hypothalamic region stimulation were tachycardia (30.9%) and warmth (24.6%) followed by flushing (9.1%) and hypertension (6.9%). Voxel-wise mapping identified distinct, locally separable clusters for all sequelae that could be mapped to specific hypothalamic and extrahypothalamic grey and white matter structures. K-nearest neighbour classification further validated the clinico-anatomical correlates emphasizing the functional importance of identified neural substrates with area under the receiving operating characteristic curves between 0.67 and 0.91. Overall, we were able to localize acute effects of hypothalamic region stimulation to distinct tracts and nuclei within the hypothalamus and the wider diencephalon providing clinico-anatomical insights that may help to guide future neuromodulation work., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

This research study provides patient and caregiver perspectives as to whether or not to undergo adaptive deep brain stimulation (aDBS) research. A total of 51 interviews were conducted in a multi-site study including patients undergoing aDBS and their respective caregivers along with persons declining aDBS. Reasons highlighted for undergoing aDBS included hopes for symptom alleviation, declining quality of life, desirability of being in research, and altruism. The primary reasons for not undergoing aDBS issues were practical rather than specific to aDBS technology, although some persons highlighted a desire to not be the first to trial the new technology. These themes are discussed in the context of "push" factors wherein any form of surgical intervention is preferable to none and "pull" factors wherein opportunities to contribute to science combine with hopes and/or expectations for the alleviation of symptoms. We highlight the significance of study design in decision making. aDBS is an innovative technology and not a completely new technology. Many participants expressed value in being part of research as an important consideration. We suggest that there are important implications when comparing patient perspectives vs. theoretical perspectives on the choice for or against aDBS. Additionally, it will be important how we communicate with patients especially in reference to the complexity of study design. Ultimately, this study reveals that there are benefits and potential risks when choosing a research study that involves implantation of a medical device., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a shared affiliation with three of the authors, SO, BK, and PS, at the time of review., (Copyright © 2021 Outram, Muñoz, Kostick-Quenet, Sanchez, Kalwani, Lavingia, Torgerson, Sierra-Mercado, Robinson, Pereira, Koenig, Starr, Gunduz, Foote, Okun, Goodman, McGuire, Zuk and Lázaro-Muñoz.)

Background: Deep brain stimulation (DBS) targeting the globus pallidus internus (GPi) can improve tics and comorbid obsessive-compulsive behavior (OCB) in patients with treatment-refractory Tourette syndrome (TS). However, some patients' symptoms remain unresponsive, the stimulation applied across patients is variable, and the mechanisms underlying improvement are unclear. Identifying the fiber pathways surrounding the GPi that are associated with improvement could provide mechanistic insight and refine targeting strategies to improve outcomes., Methods: Retrospective data were collected for 35 patients who underwent bilateral GPi DBS for TS. Computational models of fiber tract activation were constructed using patient-specific lead locations and stimulation settings to evaluate the effects of DBS on basal ganglia pathways and the internal capsule. We first evaluated the relationship between activation of individual pathways and symptom improvement. Next, linear mixed-effects models with combinations of pathways and clinical variables were compared in order to identify the best-fit predictive models of tic and OCB improvement., Results: The best-fit model of tic improvement included baseline severity and the associative pallido-subthalamic pathway. The best-fit model of OCB improvement included baseline severity and the sensorimotor pallido-subthalamic pathway, with substantial evidence also supporting the involvement of the prefrontal, motor, and premotor internal capsule pathways. The best-fit models of tic and OCB improvement predicted outcomes across the cohort and in cross-validation., Conclusions: Differences in fiber pathway activation likely contribute to variable outcomes of DBS for TS. Computational models of pathway activation could be used to develop novel approaches for preoperative targeting and selecting stimulation parameters to improve patient outcomes., (Copyright © 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)