Although Parkinson's disease (PD) is classically defined by its motor features, non-motor symptoms exert a substantial and often under-recognized influence on disease trajectory. Among these, weight loss has long been observed in PD and other neurodegenerative disorders, yet the mechanisms remain incompletely understood. This limited mechanistic insight has left few treatment options for weight loss in PD. Emerging research highlights the role of metabolic regulation, neuroendocrine signaling, pharmacologic treatment, cognitive decline, gastrointestinal dysfunction, and brain stimulation in shaping weight trajectories in PD. In this review, we synthesize current evidence surrounding weight in PD, beginning with an overview of epidemiologic trends and their implications for morbidity and mortality. The sections that follow examine proposed mechanisms, clinical and treatment-related factors associated with weight change, and insights derived from deep brain stimulation studies. Finally, we summarize cross-mechanism interactions, current knowledge gaps and discuss practical recommendations for translating these insights into therapeutic strategies. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Objectives Weight loss is a common manifestation of Parkinson's disease (PD) associated with frailty, morbidity, and mortality. Deep brain stimulation (DBS) often leads to significant postoperative weight gain, which confers a survival benefit. This weight gain has traditionally been attributed to reduced energy expenditure from improved hyperkinetic motor symptoms. We aimed to critically examine the evidence for this hyperkinetic hypothesis and explore alternative mechanisms. Materials and Methods We performed a structured narrative review of the MEDLINE/PubMed and Embase databases (from inception through December 2025), identifying English-language abstracts and clinical studies examining the relationship between motor symptom improvement and postoperative weight changes following DBS in PD. Results Correlations between weight gain and improvements in tremor, rigidity, or dyskinesia are inconsistent and often absent, particularly when confounders are controlled. Converging evidence supports alternative mechanisms involving altered resting and total energy expenditure, neuroendocrine dysregulation, and neuromodulation of hypothalamic and limbic circuits influencing appetite and metabolism. Conclusions The hyperkinetic hypothesis alone does not explain post-DBS weight gain. A broader, systems-level framework integrating motor, metabolic, and neuroendocrine pathways is needed to guide future research and inform therapeutic strategies for addressing weight loss in PD.

BACKGROUND:Motivational disturbances, such as apathy and impulse control disorders (ICDs), frequently co-occur in patients with Parkinson's disease (PD). The assessment of these motivational disturbances has proven to be challenging due the absence of validated objective behavioral measures for evaluating motivation in older adults. This scenario may contribute to underdiagnosis. The present study aimed to investigate the clinical utility of a modified version of an existing effort-based decision-making task which required cognitive (e.g., working memory) instead of physical (e.g., finger tapping) effort. METHODS:Ninety-five non-demented individuals (45-85 years of age) with idiopathic PD completed a cognitive screening measure, self-report questionnaires, and a cognitive adaptation of the Effort Expenditure for Rewards Task (COG-EEfRT), which is a multi-trial game where a participant can choose whether to expend greater effort for larger rewards which vary in magnitude and probability. Patients were classified as having clinically significant symptoms of apathy and/or an ICD based on recommended cut-off scores on the Apathy Scale (AS) and Questionnaire for Impulse Control Disorders in Parkinson's Disease - Rating Scale (QUIP-RS). The methodological cutoffs defined two groups: Apathy (36.8 %), and ICD (48.4 %). RESULTS:The level of effort expended by patients significantly predicted apathy and ICD status with high accuracy (88.2 % and 82.4 %, respectively), above and beyond age, levodopa equivalent dose and self-report measures of motivation. Additionally, we found that greater symptoms of apathy and ICD (i.e., negative urgency) were significantly correlated with patients choosing to expend greater effort. This result varied based on reward probability and outcome. CONCLUSION:We offer preliminary evidence suggesting the clinical utility of the COG-EEfRT for identifying and quantifying motivational disturbances in PD. Additionally, anticipatory anhedonia and impulsive traits may be important predictors of cognitive effort-based decision-making. Compared to tasks requiring physical effort, the COG-EEfRT may be a more suitable tool for PD and perhaps for people with motor impairment.

OBJECTIVE:To determine if the co-occurrence of apathy and impulse control disorders (ICDs) in Parkinson disease is dependent on instrument selection and assess the concurrent validity of three motivation measures by examining interrelationships between them. METHOD:Ninety-seven cognitively normal individuals with idiopathic Parkinson disease (PD) completed the Questionnaire for Impulsive-Compulsive Disorders in Parkinson Disease-Rating Scale (QUIP-RS) and three apathy measures: the Apathy Scale, Lille Apathy Rating Scale, and Item 4 of the Movement Disorder Society-Unified Parkinson Disease Rating Scale. RESULTS:Fifty (51.5%) participants were classified as apathetic on at least one measure, and only four individuals (4.3%) obtained clinically elevated scores on all three measures. The co-occurrence of apathy and ICD varied across measures. CONCLUSIONS:We observed a co-occurrence of apathy and ICDs in PD patients with each apathy instrument; however, limited concurrent validity exists across measures. This is important for future investigations into shared pathophysiology and the design of future clinical trials aimed at improving the early detection and treatment of these debilitating syndromes.

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.

BackgroundThe effect of surgery on impulse control disorders (ICDs) remains unclear in Parkinson's disease (PD) patients undergoing deep brain stimulation (DBS). ObjectiveTo examine changes in ICD symptoms in PD patients undergoing DBS compared to a medication-only control group. MethodsThe study was a 2-center, 12-month, prospective, observational investigation of PD patients undergoing DBS and a control group matched on age, sex, dopamine agonist use, and baseline presence of ICDs. Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) and total levodopa equivalent daily dose (LEDD) were collected at baseline, 3, 6, and 12 months. Linear mixed-effects models assessed changes in mean QUIP-RS score (sum of buying, eating, gambling, and hypersexuality items). ResultsThe cohort included 54 participants (DBS = 26, controls = 28), mean (SD) age 64.3 (8.1) and PD duration 8.0 (5.2) years. Mean baseline QUIP-RS was higher in the DBS group at baseline (8.6 (10.7) vs. 5.3 (6.9), P = 0.18). However, scores at 12 months follow-up were nearly identical (6.6 (7.3) vs. 6.0 (6.9) P = 0.79). Predictors of change in QUIP-RS score were baseline QUIP-RS score (beta = 0.483, P < 0.001) and time-varying LEDD (beta = 0.003, P = 0.02). Eight patients (four in each group) developed de novo ICD symptoms during follow-up, although none met diagnostic criteria for an impulse control disorder. ConclusionsICD symptoms (including de novo symptoms) at 12 months follow-up were similar between PD patients undergoing DBS and patients treated with pharmacological therapy only. Monitoring for emergence of ICD symptoms is important in both surgically- and medication-only-treated PD patients.

Background: Spontaneous aneurysmal subarachnoid hemorrhage (aSAH) recovery may be hampered by delayed cerebral ischemia (DCI). Herein, we sought to identify whether frequently administered medications in the intensive care unit (ICU) are associated with DCI. Methods: In this retrospective study, patients admitted to a tertiary care center neuro-ICU between 2012 and 2019 with aSAH who could verbalize pain intensity scores were included. Medication dosages and clinical characteristics were abstracted from the medical record. Both paired and unpaired analyses were utilized to measure individual DCI risk for a given patient in relation to drug dosages. Results: 119 patients were included; average age was 61.7 +/- 15.2 (SD) years, 89 (74.7%) were female, and 32 (26.9%) experienced DCI during admission. Patients with DCI had longer length of stay (19.3 +/- 7.4 vs 12.7 +/- 5.3 days, p < 0.0001). The combination medication of acetaminophen 325 mg/butalbital 50 mg/caffeine 40 mg (A/B/C) was associated with decreased DCI on paired (2.3 +/- 2.0 vs 3.1 +/- 1.9 tabs, p = 0.034) and unpaired analysis (1.84 +/- 2.4 vs 2.6 +/- 2.4 tabs, p < 0.001). No associations were found between DCI and opioids, dexamethasone, levetiracetam, or acetaminophen. Max and mean daily headache pain was not associated with DCI occurrence. Conclusion: We identified an association between a commonly administered analgesic and DCI. A/B/C is associated with decreased DCI in this study, while other medications are not associated with DCI risk.

Objective: Cerebrospinal fluid (CSF) leak occurs most commonly following skull fracture, with a CSF leakage complicating up to 2% of all head traumas. This study aims to identify demographic and injury characteristics correlated with the highest risk of CSF leak in patients with known facial fractures.& nbsp;Methods: Retrospective data was collected from a previously described trauma registry from 2010 to 2019. Patients over 18 years old with any type of facial fracture, known CSF leak status, available neuroimaging, and hospital admission were included. Chi-Square analysis for demographic and injury characteristic data were utilized.& nbsp;Results: A total of 79 patients with CSF leak and 4907 patients without CSF leak were included in the database. Patients with CSF leak tended to be younger than those without CSF leak (38.45 +/-0.28 vs 44.08 +/-0.28, M +/-SE, p = 0.0197). CSF leak depended on the mechanism of injury (MOI; X2 =27.02, df=2, p = 0.0000013), with CSF leak rates highest in penetrating injuries (4.87%) and motor vehicle accidents (1.78%) compared to blunt injuries (0.95%); age did not significantly differ between the MOI groups (p = 0.11). CSF leak was also more common in patients with a lower Glasgow coma scale (GCS; 7.95 +/-0.58 vs 12.21 +/-0.10, p = 10(-15)), LeFort type 2 & 3 and pan-facial fractures compared to all other facial fracture types (8.9% vs 1.2%, p = 10-15), and radiographic midline shift (29.4% vs 9.1%, p = 10-15). There was a trend towards a higher proportion of males in those with CSF leak compared to those without (83.3% vs 73.7% males, p = 0.073), and in patients with prolonged loss of consciousness (LOC; 9.43% with LOC > 1 h vs 2.69% LOC < 1 h, p = 0.056).& nbsp;Conclusion: Facial fractures often present with CSF leak, and certain demographic and injury risk factors including younger age, worse GCS score, evidence of midline shift, and certain mechanisms of injury (penetrating and motor vehicle) are correlated with increased risk and warrant close screening and follow-up for CSF leak detection. LeFort type 2 & 3 and pan-facial fractures are at high risk of CSF leak.

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.

Background and Objective Social desirability bias, the tendency to underreport undesirable behaviors, may be one reason patients with Parkinson disease (PD) underreport symptoms of impulse control disorders (ICDs). Methods We compared rates of ICD endorsement on questionnaires administered face-to-face and online in 60 patients with mild-to-moderate idiopathic PD. Participants also completed a self-report measure of social desirability. Results We found a significantly higher prevalence of any ICD based on online (56.7%) vs in-person (33.3%) administration. Significantly higher endorsement of items related to hypersexuality in men and compulsive eating and buying in women were found with online administration. Social desirability bias was positively correlated with ICD symptom endorsement across all items and subscales. Discussion The results highlight the importance of social context/setting and the need for sensitivity and discretion when screening for ICD symptoms. Although a higher level of symptom endorsement does not necessarily imply a greater level of accuracy, more work is needed to determine which method of administration is most accurate for clinical and research practice.

IntroductionApathy and impulse control disorders (ICD) are common comorbid motivational syndromes in Parkinson disease (PD). This study aimed to determine if patients with these motivational disturbances exhibit different patterns of anhedonia and trait impulsivity.MethodsSixty-four non-demented patients with PD completed questionnaires assessing apathy and ICD symptoms, which were used to classify participants into one of the following groups: apathy only, ICD only, both, and neither. Participants also completed multidimensional measures of anhedonia and trait impulsivity, which were compared across groups defined by motivational status.ResultsIndividuals with both apathy and ICD had significantly greater symptoms of positive and negative urgency than all other groups and had significantly greater consummatory anhedonia and lack of premeditation and perseverance than those with ICD only and neither. Patients with apathy only also reported significantly greater anticipatory anhedonia than those with ICD only and the neither group. There were no significant between-group differences in sensation seeking.ConclusionDistinct patterns of impulsivity and anhedonia characterize unique behavioral phenotypes of motivational disturbances in PD and may reflect important differences in the underlying neurobiological mechanisms. Clinicians should be aware that motivational disturbances may be more severe in cases where apathy co-occurs with one or more ICD.HIGHLIGHTSHighlights are mandatory for all submissions except letters. They consist of a short collection of bullet points that convey the core findings of the article and should be submitted in a separate file in the online submission system. Please use "Highlights" in the file name and include 3-5 bullet points (maximum 85 characters, including spaces, per bullet point). See https://www.elsevier.com/highlights for examples.

ABSTRACT Background A clinical hallmark of aneurysmal SAH (aSAH) is headache. Little is known about post-aSAH headache factors which may point to underlying mechanisms. In this study, we aimed to characterize the severity and trajectory of headaches in relation to clinical features of patients with aSAH. Methods This is a retrospective longitudinal study of adult patients admitted to an academic tertiary care center between 2012 and 2019 with aSAH who could verbalize pain scores. Factors recorded included demographics, aneurysm characteristics, analgesia, daily morning serum sodium concentration, and occurrence of vasospasm. Group-based trajectory modeling was used to identify headache pain trajectories, and clinical factors were compared between trajectories. Results Of 91 patients included in the analysis, mean age was 57 years and 20 (22%) were male. Headache score trajectories clustered into two groups: patients with mild-moderate and moderate-severe pain. Patients in the moderate-severe pain group were younger (P<0.05), received more opioid analgesia (P<0.001), and had lower sodium concentrations (P<0.001) than patients in the mild-moderate pain group. Conclusion We identified two distinct post-aSAH headache pain trajectory cohorts and identified an association with age, analgesia, and sodium levels. Future prospective studies considering sodium homeostasis and volume status under standardized analgesic regimens are warranted.

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.

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.

Background : Treating medication-refractory freezing of gait (FoG) in Parkinson’s disease (PD) remains challenging despite several trials reporting improvements in motor symptoms using subthalamic nucleus or globus pallidus internus (GPi) deep brain stimulation (DBS). Pedunculopontine nucleus (PPN) region DBS has been used for medication-refractory FoG, with mixed findings. FoG, as a paroxysmal phenomenon, provides an ideal framework for the possibility of closed-loop DBS (CL-DBS). Methods : In this clinical trial (NCT02318927), five subjects with medication-refractory FoG underwent bilateral GPi DBS implantation to address levodopa-responsive PD symptoms with open-loop stimulation. Additionally, PPN DBS leads were implanted for CL-DBS to treat FoG. The primary outcome of the study was a 40% improvement in medication-refractory FoG in 60% of subjects at 6 months when “on” PPN CL-DBS. Secondary outcomes included device feasibility to gauge the recruitment potential of this four-lead DBS approach for a potentially larger clinical trial. Safety was judged based on adverse events and explantation rate. Findings : The feasibility of this approach was demonstrated as we recruited five subjects with both “on” and “off” medication freezing. The safety for this population of patients receiving four DBS leads was suboptimal and associated with a high explantation rate of 40%. The primary clinical outcome in three of the five subjects was achieved at 6 months. However, the group analysis of the primary clinical outcome did not reveal any benefit. Interpretation : This study of a human PPN CL-DBS trial in medication-refractory FoG showed feasibility in recruitment, suboptimal safety, and a heterogeneous clinical effect in FoG outcomes.

The pathophysiology of dystonic tremor and essential tremor remains partially understood. In patients with medication-refractory dystonic tremor or essential tremor, deep brain stimulation (DBS) targeting the thalamus or posterior subthalamic area has evolved into a promising treatment option. However, the optimal DBS targets for these disorders remains unknown. This retrospective study explored the optimal targets for DBS in essential tremor and dystonic tremor using a combination of volumes of tissue activated estimation and functional and structural connectivity analyses. We included 20 patients with dystonic tremor who underwent unilateral thalamic DBS, along with a matched cohort of 20 patients with essential tremor DBS. Tremor severity was assessed preoperatively and approximately 6 months after DBS implantation using the Fahn-Tolosa-Marin Tremor Rating Scale. The tremor-suppressing effects of DBS were estimated using the percentage improvement in the unilateral tremor-rating scale score contralateral to the side of implantation. The optimal stimulation region, based on the cluster centre of gravity for peak contralateral motor score improvement, for essential tremor was located in the ventral intermediate nucleus region and for dystonic tremor in the ventralis oralis posterior nucleus region along the ventral intermediate nucleus/ventralis oralis posterior nucleus border (4 mm anterior and 3 mm superior to that for essential tremor). Both disorders showed similar functional connectivity patterns: a positive correlation between tremor improvement and involvement of the primary sensorimotor, secondary motor and associative prefrontal regions. Tremor improvement, however, was tightly correlated with the primary sensorimotor regions in essential tremor, whereas in dystonic tremor, the correlation was tighter with the premotor and prefrontal regions. The dentato-rubro-thalamic tract, comprising the decussating and non-decussating fibres, significantly correlated with tremor improvement in both dystonic and essential tremor. In contrast, the pallidothalamic tracts, which primarily project to the ventralis oralis posterior nucleus region, significantly correlated with tremor improvement only in dystonic tremor. Our findings support the hypothesis that the pathophysiology underpinning dystonic tremor involves both the cerebello-thalamo-cortical network and the basal ganglia-thalamo-cortical network. Further our data suggest that the pathophysiology of essential tremor is primarily attributable to the abnormalities within the cerebello-thalamo-cortical network. We conclude that the ventral intermediate nucleus/ventralis oralis posterior nucleus border and ventral intermediate nucleus region may be a reasonable DBS target for patients with medication-refractory dystonic tremor and essential tremor, respectively. Uncovering the pathophysiology of these disorders may in the future aid in further improving DBS outcomes.

Background and purpose: Deep brain stimulation (DBS) is the most common surgical treatment for essential tremor (ET), yet there is variation in outcome and stimulation targets. This study seeks to consolidate proposed stimulation "sweet spots," as well as assess the value of structural connectivity in predicting treatment outcomes. Materials and methods: Ninety-seven ET individuals with unilateral thalamic DBS were retrospectively included. Using normative brain connectomes, structural connectivity measures were correlated with the percentage improvement in contralateral tremor, based on the Fahn-Tolosa-Marin tremor rating scale (TRS), after parameter optimization (range 3.1-12.9 months) using a leave-one-out cross-validation in 83 individuals. The predictive feature map was used for cross-validation in a separate cohort of 14 ET individuals treated at another center. Lastly, estimated volumes of tissue activated (VTA) were used to assess a treatment "sweet spot," which was compared to seven previously reported stimulation sweet spots and their relationship to the tract identified by the predictive feature map. Results: In the training cohort, structural connectivity between the VTA and dentato-rubro-thalamic tract (DRTT) correlated with contralateral tremor improvement (R = 0.41; p < 0.0001). The same connectivity profile predicted outcomes in a separate validation cohort (R = 0.59; p = 0.028). The predictive feature map represented the anatomical course of the DRTT, and all seven analyzed sweet spots overlapped the predictive tract (DRTT). Conclusions: Our results strongly support the possibility that structural connectivity is a predictor of contralateral tremor improvement in ET DBS. The results suggest the future potential for a patient-specific functionally based surgical target. Finally, the results showed convergence in "sweet spots" suggesting the importance of the DRTT to the outcome.

Objective: The aim of this study is to evaluate the evolution of GPi DBS targeting. Methods: This retrospective, single-center study included patients implanted with GPi DBS leads for dystonia or PD during the years 2004 to 2018 at the University of Florida Fixel Institute for Neurological Diseases. Each patient underwent a high-resolution targeting study on the day prior to the surgery, which was fused with a high resolution CT scan that was acquired on the day of the procedure. Intraoperative target location was selected using a digitized 3D Schaltenbrand-Bailey atlas. All patients underwent a high-resolution head CT scan without contrast approximately one month after lead implantation and accurate measurement of neuroanatomical lead position was acquired after fusion of pre-operative and post-operative image studies. Results: We analyzed 253 PD patients with 352 leads and 80 dystonia patients with 141 leads. During 15 years of follow-up, lead locations in the PD group migrated more laterally (β = 0.09, p < 0.0001), posteriorly [slope (β) = 0.04, p < 0.05], and dorsally (β = 0.07, p < 0.001), whereas leads in the dystonia group did not significantly change position aside from a trend in the dorsal direction (β = 0.06, p = 0.053). Conclusion: The evolving target likely results from multiple factors including improvements in targeting techniques and clinical feedback intraoperatively and post-operatively. Our demonstrates the potential importance of a systematic post-operative DBS lead measurement protocol to ensure quality control and to inform and optimize DBS programming.

Background: The centromedian-parafascicular (Cm-Pf) complex of the thalamus is a common deep brain stimulation (DBS) target for treatment of Tourette syndrome (TS). Currently, there are no standardized functional intraoperative neurosurgical targeting approaches. Collectively, these issues have led to variability in DBS lead placement. Therefore, more defined methods are needed to improve targeting accuracy. Objective: The objective of this observational study was to develop and to verify a functional mapping task capable of differentiating the Cm-Pf region from the nearby ventral intermediate (Vim) nucleus region of the thalamus. The overarching goal was to improve the reproducibility of DBS targeting in the Cm-Pf region. Methods: Seven TS patients completed a modified Go/NoGo task (five in the post-operative setting and two in the intra-operative setting). Post-operative neural signals from Cm-Pf region were collected using sensing-enabled implanted neural stimulators, and intraoperative neural signals from the Cm-Pf region were collected using an external amplifier. Event-related potential (ERP) features were identified by using the grand-average of stimulus onset signals derived from the postoperative participants. These features were correlated with anatomical locations for the specific electrode recordings. The same features were extracted from the intraoperative patients in order to verify electrode positions in the operating room environment. Results: Two features-a positive and a negative deflection-were identified in the average ERP from the postoperative participants. The peak amplitudes of both features were significantly correlated with the electrode depth position (p = 0.025 for positive deflection and p = 0.039 for negative deflection). The same result was reproduced intra-operatively in the two most recent patients, where more ventral electrode contacts revealed stronger peak amplitudes in comparison to the dorsal electrode contacts. Conclusion: This process was used to physiologically confirm accurate lead placement in the operating room setting. The modified Go/NoGo task elicited robust neural responses in the Cm-Pf region however the signal was not present in the Vim nucleus region of thalamus along the DBS electrode trajectory. We conclude that the differences in ERP responses may be a potentially novel LFP based functional approach for future targeting of the Cm-Pf complex for TS DBS.