Deep Brain Stimulation In Patients Research Articles

Structural and microstructural predictors of cognitive decline in deep brain stimulation of subthalamic nucleus in Parkinson’s disease

Background and objectivesThe intricate relationship between deep brain stimulation (DBS) in Parkinson’s disease (PD) and cognitive impairment has lately garnered substantial attention. The presented study evaluated pre-DBS structural and microstructural cerebral patterns as possible predictors of future cognitive decline in PD DBS patients. MethodsPre-DBS MRI data in 72 PD patients were combined with neuropsychological examinations and follow-up for an average of 2.3 years after DBS implantation procedure using a screening cognitive test validated for diagnosis of mild cognitive impairment in PD in a Czech population – Dementia Rating Scale 2. ResultsPD patients who would exhibit post-DBS cognitive decline were found to have, already at the pre-DBS stage, significantly lower cortical thickness and lower microstructural complexity than cognitively stable PD patients. Differences in the regions directly related to cognition as bilateral parietal, insular and cingulate cortices, but also occipital and sensorimotor cortex were detected. Furthermore, hippocampi, putamina, cerebellum and upper brainstem were implicated as well, all despite the absence of pre-DBS differences in cognitive performance and in the position of DBS leads or stimulation parameters between the two groups. ConclusionsOur findings indicate that the cognitive decline in the presented PD cohort was not attributable primarily to DBS of the subthalamic nucleus but was associated with a clinically silent structural and microstructural predisposition to future cognitive deterioration present already before the DBS system implantation.

Factors for Success: Deep Brain Stimulation in Patients with Parkinson’s Disease and Low Socioeconomic Status (P2-3.015)

Factors for Success: Deep Brain Stimulation in Patients with Parkinson’s Disease and Low Socioeconomic Status (P2-3.015)

439 Optimal Targets, Connectivity, and Tissue Integrity for Deep Brain Stimulation in Patients With Disorders of Consciousness

INTRODUCTION: Disorders of consciousness (DOC) are characterized by alterations in arousal and/or awareness resulting from brain injuries. Deep brain stimulation (DBS) is an emerging treatment to restore arousal/awareness in DOC. However, little is known about optimal targets and whether outcomes depend on brain connectivity, tissue integrity, or reorganization potential. METHODS: Retrospective analysis of 38 patients with DOC who underwent unilateral DBS targeting thalamic centromedian nucleus (ages = 12-65 years). DOC resulted from anoxic (n = 26) or traumatic (n = 12) injuries. Patients were classified as ‘responders’ or ‘non-responders’ using Coma/Near Coma and Coma Recovery Scales. Volumes of tissue activated (VTAs) assessed DBS locations associated with favorable response. Correlations were also performed with age, regional brain volumes from pre-operative MRI, and structural connectivity calculated from patients’ VTAs using normative diffusion MRI. RESULTS: 8/38 patients were responders and 24/38 non-responders; outcomes are pending in 6/38 patients due to <3 months follow-up. Favorable response was associated with younger age (median age = 19 years in responders, 42 years in non-responders) and greater volumes of whole-brain grey matter and subcortical regions including putamen, pallidum, caudate, and cerebellum. Responders also tended to have deeper and more medial implantations, with VTAs engaging parafascicular nucleus, reticular nucleus, and peri-midbrain red nucleus. In responders, VTA connectivity was higher with superior frontal gyrus, caudate, pallidum, and cerebellum, and lower with sensorimotor and occipital cortex. CONCLUSIONS: Efficacious DBS for DOC is linked to younger age, greater preservation of whole-brain grey-matter, greater volumes of and connectivity with select subcortical areas (pallidum, caudate, cerebellum), stronger connectivity with superior frontal gyrus, and stimulation of locations inferomedial to the centromedian nucleus. Findings may assist with optimizing patient selection, DBS targeting, and post-implantation programming.

121 The Effectiveness of Deep Brain Stimulation in Patients With Disorders of Consciousness During Short- and Long-Term

INTRODUCTION: Disorders of consciousness (DoCs) impose heavy medical and economic burdens on families and society. Deep brain stimulation (DBS) has been preliminarily applied to treat patients with disorders of consciousness (DoCs). METHODS: Data from 365 patients with DoCs who were consecutively admitted from 15 July 2011 to 31 December 2021 were retrospectively analysed. Multivariate regression and subgroup analysis were performed to adjust for potential confounders. The primary outcome was improvement in consciousness at 1 year. The CRS-R was used to assess the level of consciousness of each patient. Scores on this scale may vary from 0 to 23, and six subscores are used to quantify auditory, visual, motor and verbal functions as well as communication and arousal. During the surgery, an electrode was implanted into the CM-Pf complex. RESULTS: An overall improvement in consciousness at 1 year was achieved in 32.4% (12/37) of the DBS group compared with 4.3% (14/328) of the conservative group. After full adjustment, DBS significantly improved consciousness at 1 year (adjusted OR 11.90, 95% CI 3.65–38.46, p < 0.001). There was a significant treatment × follow-up interaction (H = 14.99, p < 0.001). An priliminary improvement after DBS treatment could also be seen at 6 months. DBS had significantly better effects in patients with minimally conscious state (MCS) compared with patients with vegetative state/unresponsive wakefulness syndrome (p for interaction <0.001). A nomogram based on age, state of consciousness, pathogeny and duration of DoCs indicated excellent predictive performance (c-index = 0.882). CONCLUSIONS: DBS was associated with better outcomes in patients with DoC, and the effect was likely to be significantly greater in patients with MCS. DBS should be cautiously evaluated by nomogram preoperatively, and randomised controlled trials are still needed.

Progressive thalamic nuclear atrophy in blepharospasm and blepharospasm-oromandibular dystonia.

The thalamus is considered a key region in the neuromechanisms of blepharospasm. However, previous studies considered it as a single, homogeneous structure, disregarding potentially useful information about distinct thalamic nuclei. Herein, we aimed to examine (i) whether grey matter volume differs across thalamic subregions/nuclei in patients with blepharospasm and blepharospasm-oromandibular dystonia; (ii) causal relationships among abnormal thalamic nuclei; and (iii) whether these abnormal features can be used as neuroimaging biomarkers to distinguish patients with blepharospasm from blepharospasm-oromandibular dystonia and those with dystonia from healthy controls. Structural MRI data were collected from 56 patients with blepharospasm, 20 with blepharospasm-oromandibular dystonia and 58 healthy controls. Differences in thalamic nuclei volumes between groups and their relationships to clinical information were analysed in patients with dystonia. Granger causality analysis was employed to explore the causal effects among abnormal thalamic nuclei. Support vector machines were used to test whether these abnormal features could distinguish patients with different forms of dystonia and those with dystonia from healthy controls. Compared with healthy controls, patients with blepharospasm exhibited reduced grey matter volume in the lateral geniculate and pulvinar inferior nuclei, whereas those with blepharospasm-oromandibular dystonia showed decreased grey matter volume in the ventral anterior and ventral lateral anterior nuclei. Atrophy in the pulvinar inferior nucleus in blepharospasm patients and in the ventral lateral anterior nucleus in blepharospasm-oromandibular dystonia patients was negatively correlated with clinical severity and disease duration, respectively. The proposed machine learning scheme yielded a high accuracy in distinguishing blepharospasm patients from healthy controls (accuracy: 0.89), blepharospasm-oromandibular dystonia patients from healthy controls (accuracy: 0.82) and blepharospasm from blepharospasm-oromandibular dystonia patients (accuracy: 0.94). Most importantly, Granger causality analysis revealed that a progressive driving pathway from pulvinar inferior nuclear atrophy extends to lateral geniculate nuclear atrophy and then to ventral lateral anterior nuclear atrophy with increasing clinical severity in patients with blepharospasm. These findings suggest that the pulvinar inferior nucleus in the thalamus is the focal origin of blepharospasm, extending to pulvinar inferior nuclear atrophy and subsequently extending to the ventral lateral anterior nucleus causing involuntary lower facial and masticatory movements known as blepharospasm-oromandibular dystonia. Moreover, our results also provide potential targets for neuromodulation especially deep brain stimulation in patients with blepharospasm and blepharospasm-oromandibular dystonia.

7-Tesla Magnetic Resonance Imaging Scanning in Deep Brain Stimulation for Parkinson's Disease: Improving Visualization of the Dorsolateral Subthalamic Nucleus.

Identifying the dorsolateral subthalamic nucleus (STN) for deep brain stimulation (DBS) in Parkinson's disease (PD) can be challenging due to the size and double-oblique orientation. Since 2015 we implemented 7-Tesla T2 weighted magnetic resonance imaging (7 T T2) for improving visualization and targeting of the dorsolateral STN. We describe the changes in surgical planning and outcome since implementation of 7 T T2 for DBS in PD. By comparing two cohorts of STN DBS patients in different time periods we evaluated the influence of 7 T T2 on STN target planning, the number of microelectrode recording (MER) trajectories, length of STN activity and the postoperative motor (UPDRS) improvement. From February 2007 to January 2014, 1.5 and 3-Tesla T2 guided STN DBS with 3 MER channels was performed in 76 PD patients. Average length of recorded STN activity in the definite electrode trajectory was 3.9 ± 1.5 mm. From January 2015 to January 2022 7 T T2 and MER-guided STN DBS was performed in 182 PD patients. Average length of recorded STN activity in the definite electrode trajectory was 5.1 ± 1.3 mm and used MER channels decreased from 3 to 1. Average UPDRS improvement was comparable. Implementation of 7 T T2 for STN DBS enabled a refinement in targeting. Combining classical DBS targeting with dorsolateral STN alignment may be used to determine the optimal trajectory. The improvement in dorsolateral STN visualization can be used for further target refinements, for example adding probabilistic subthalamic connectivity, to enhance clinical outcome of STN DBS.

Neurocognitive changes at different follow-up times after bilateral subthalamic nucleus deep brain stimulation in patients with Parkinson's disease

BackgroundBilateral deep thalamic nucleus brain stimulation (STN-DBS) surgery is often used to treat the motor symptoms of patients with Parkinson's disease. The change of neurocognitive symptoms in patients is, however, still unclear. ObjectiveWe aimed at analyzing the deterioration of neurocognitive symptoms in patients with Parkinson's disease after deep brain stimulation surgery under different follow-up times. MethodsA comprehensive literature review was conducted using Pubmed, Cochrane Library, and Web of Science to screen eligible study records, the meta-analysis was performed using an inverse variance method and a random-effects model. Additionally, the areas of analysis include five: cognition, executive function, memory capacity, and verbal fluency (phonetic fluency and semantic fluency). They were analyzed for changes at six and twelve months postoperatively compared to baseline. The Meta-analysis has been registered with PROSPERO under the registration number: CRD42022308786. ResultsIn terms of overall cognitive performance, executive function, and memory capacity, the original studies show a trend of improvement in these areas at 12 months postoperatively compared with 6 months, at variance, patients did not improve or deteriorated in phonetic fluency(d = −0.42 at both 6-month and 12-month follow-up) and semantic fluency from 6 to 12 months postoperatively. ConclusionIn terms of most neurocognitive symptoms, including cognitive ability, executive function, and learning memory capacity, bilateral STN-DBS surgery appears to be safe at relatively long follow-up times. However, postoperative phonetic and semantic fluency changes should still not be underestimated, and clinicians should pay more attention to patients' changes in both.

An individualized tractography pipeline for the nucleus basalis of Meynert lateral tract

Abstract Background: At the center of the cortical cholinergic network, the nucleus basalis of Meynert (NBM) is crucial for the cognitive domains most vulnerable in Parkinson’s disease (PD). Preclinical evidence has demonstrated the positive impact of NBM deep brain stimulation (DBS) on cognition but early human trials have had mixed results. It is possible that DBS of the lateral NBM efferent white matter fiber bundle may be more effective at improving cognitive-motor function. However, precise tractography modelling is required to identify the optimal target for neurosurgical planning. Individualized tractography approaches have been shown to be highly effective for accurately identifying DBS targets but have yet to be developed for the NBM. Methods: Using structural and diffusion-weighted imaging, we developed a tractography pipeline using manually segmented regions of interest for precise individualized identification of the lateral NBM target tract. Using dice similarity coefficients, the reliability of the tractography outputs was assessed across three cohorts to investigate: 1) whether this manual segmentation pipeline is more reliable than an existing automatic segmentation pipeline currently used in the literature; 2) the inter- and intra-rater reliability of our pipeline in research scans of patients with PD; and 3) the reliability and practicality of this pipeline in clinical scans of DBS patients. Results: The individualized manual pipeline was found to be significantly more reliable than the existing automated pipeline for both the segmentation of the NBM region itself (p < 0.001) and the reconstruction of the target lateral tract (p = 0.002). There was also no significant difference between the reliability of two different raters in the PD cohort (p = 0.25), which showed high inter- (mean Dice coefficient >0.6) and intra-rater (mean Dice coefficient >0.7) reliability across runs. Finally, the pipeline was shown to be highly reliable within the clinical scans (mean Dice coefficient = 0.77). However, accurate reconstruction was only evident in 7/10 tracts. Conclusion: We have developed a reliable tractography pipeline for the identification and analysis of the NBM lateral tract in research and clinical-grade imaging of healthy young adult and PD patient scans.

Improving naturalistic neuroscience with patient engagement strategies.

The clinical implementation of chronic electrophysiology-driven adaptive deep brain stimulation (DBS) algorithms in movement disorders requires reliable representation of motor and non-motor symptoms in electrophysiological biomarkers, throughout normal life (naturalistic). To achieve this, there is the need for high-resolution and -quality chronic objective and subjective symptom monitoring in parallel to biomarker recordings. To realize these recordings, an active participation and engagement of the investigated patients is necessary. To date, there has been little research into patient engagement strategies for DBS patients or chronic electrophysiological recordings. We here present our concept and the first results of a patient engagement strategy for a chronic DBS study. After discussing the current state of literature, we present objectives, methodology and consequences of the patient engagement regarding study design, data acquisition, and study infrastructure. Nine patients with Parkinson's disease and their caregivers participated in the meeting, and their input led to changes to our study design. Especially, the patient input helped us designing study-set-up meetings and support structures. We believe that patient engagement increases compliance and study motivation through scientific empowerment of patients. While considering patient opinion on sensors or questionnaire questions may lead to more precise and reliable data acquisition, there was also a high demand for study support and engagement structures. Hence, we recommend the implementation of patient engagement in planning of chronic studies with complex designs, long recording durations or high demand for individual active study participation.

Double dissociation of dopamine and subthalamic nucleus stimulation on effortful cost/benefit decision making

Deep brain stimulation (DBS) and dopaminergic therapy (DA) are common interventions for Parkinson's disease (PD). Both treatments typically improve patient outcomes, and both can have adverse side effects on decision making (e.g., impulsivity).1,2 Nevertheless, they are thought to act via different mechanisms within basal ganglia circuits.3 Here, we developed and formally evaluated their dissociable predictions within a single cost/benefit effort-based decision-making task. In the same patients, we manipulated DA medication status and subthalamic nucleus (STN) DBS status within and across sessions. Using a series of descriptive and computational modeling analyses of participant choices and their dynamics, we confirm a double dissociation: DA medication asymmetrically altered participants' sensitivities to benefits vs. effort costs of alternative choices (boosting the sensitivity to benefits while simultaneously lowering sensitivity to costs); whereas STN DBS lowered the decision threshold of such choices. To our knowledge, this is the first study to show, using a common modeling framework, a dissociation of DA and DBS within the same participants. As such, this work offers a comprehensive account for how different mechanisms impact decision making, and how impulsive behavior (present in DA-treated patients with PD and DBS patients) may emerge from separate physiological mechanisms.

Day one postoperative MRI findings following electrode placement for deep brain stimulation: analysis of a large case series.

This study sought to characterize postoperative day one MRI findings in deep brain stimulation (DBS) patients. DBS patients were identified by CPT and had their reviewed by a trained neuroradiologist and neurosurgeon blinded to MR sequence and patient information. The radiographic abnormalities of interest were track microhemorrhage, pneumocephalus, hematomas, and edema, and the occurrence of these findings in compare the detection of these complications between T1/T2 gradient-echo (GRE) and T1/T2 fluid-attenuated inversion recovery (FLAIR) magnetic resonance (MR) sequences was compared. The presence, size, and association of susceptibility artifact with other radiographic abnormalities was also described. Lastly, the association of multiple microelectrode cannula passes with each radiographic finding was evaluated. Ad-hoc investigation evaluated hemisphere-specific associations. Multiple logistic regression with Bonferroni correction (corrected p = 0.006) was used for all analysis. Out of 198 DBS patients reviewed, 115 (58%) patients showed entry microhemorrhage; 77 (39%) track microhemorrhage; 44 (22%) edema; 69 (35%) pneumocephalus; and 12 (6%) intracranial hematoma. T2 GRE was better for detecting microhemorrhage (OR = 14.82, p < 0.0001 for entry site and OR = 4.03, p < 0.0001 for track) and pneumocephalus (OR = 11.86, p < 0.0001), while T2 FLAIR was better at detecting edema (OR = 123.6, p < 0.0001). The relatively common findings of microhemorrhage and edema were best visualized by T2 GRE and T2 FLAIR sequences, respectively. More passes intraoperatively was associated with detection of ipsilateral track microhemorrhage (OR = 7.151, p < 0.0001 left; OR = 8.953, p < 0.0001 right). Susceptibility artifact surrounding electrodes possibly interfered with further detection of ipsilateral edema (OR = 4.323, p = 0.0025 left hemisphere only). Day one postoperative magnetic resonance imaging (MRI) for DBS patients can be used to detect numerous radiographic abnormalities not identifiable on a computed tomographic (CT) scan. For this cohort, multiple stimulating cannula passes intraoperatively was associated with increased microhemorrhage along the electrode track. Further studies should be performed to evaluate the clinical relevance of these observations.

Long-term follow-up of subthalamic nucleus deep brain stimulation in patients with Parkinson's disease: An analysis of survival and disability milestones

BackgroundData on the long-term survival and incidence of disability milestones after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) is limited. ObjectivesTo estimate mortality and assess the frequency/time-to-development of disability milestones (falls, freezing, hallucinations, dementia, and institutionalization) among PD patients post STN-DBS. MethodsA longitudinal retrospective study of patients undergoing STN-DBS. For mortality, Cox proportional hazards regression analysis was performed. For disease milestones, competing risk analyses were performed and cumulative incidence functions reported. The strength of association between baselines features and event occurrence was calculated based on adjusted hazard ratios. ResultsThe overall mortality for the 109 patients was 16 % (62.1 ± 21.3 months after surgery). Falls (73 %) and freezing (47 %) were both the earliest (40.4 ± 25.4 and 39.6 ± 28.4 months, respectively) and most frequent milestones. Dementia (34 %) and hallucinations (32 %) soon followed (56.2 ± 21.2 and mean 60.0 ± 20.7 months after surgery, respectively). Higher ADL scores in the OFF state and higher age at surgery were associated with falls, freezing, dementia and institutionalization. ConclusionsLong-term mortality rate is low after STN-DBS. Disease milestones occur later during the disease course, with motor milestones appearing first and at a higher frequency than cognitive ones.

26 Correlates of Neuropsychological Decline Following Deep Brain Stimulation in Patients with Parkinson's Disease

Objective:Deep Brain Stimulation (DBS) is an FDA-approved treatment for Parkinson's Disease (PD), for which the medical workup includes routine pre- and post- operative neuropsychological assessment to determine potential surgical cognitive risk. Existing research suggests that cognitively normal individuals experience good cognitive outcome, whereas those with pre-existing cognitive deficits are prone to accelerated cognitive decline post-DBS. The goal of this study is to identify characteristics that determine which individuals with PD are at risk for accelerated post-DBS cognitive loss, and to characterize the nature of the decline in this population.Participants and Methods:We conducted a retrospective chart review of PD- DBS patients who completed their DBS workup and surgery at Mount Sinai Hospital NYC between 2015 and 2022. Non-English speakers were excluded from this study due to small sample size and use of a neurocognitive battery different from that of English speakers. Using repeated measures t-tests, chi square, and regression analyses, we explored variables related to disease (e.g., duration, L-Dopa burden, DBS target), socio-demographic background (e.g., age onset, current age, education), assessment modality (telehealth vs in-office), neurocognitive performances (e.g., WMS-IV Logical Memory (LM), HVLT-R, WASI-II Matrix &amp; Similarities, WAIS-IV Digit Span), and cognitive diagnosis (amnestic vs non-amnestic MCI) for all individuals in the sample. At the individual level, we utilized Reliable Change Indices (RCI) to identify clinically significant cognitive differences from pre- to post-DBS exam. We considered LM- Delayed Recall (LMDR) as a proxy for memory loss, as this cognitive function is expected to remain generally unchanged post PD-DBS. Therefore, decline on this measure in the first year after DBS could indicate a change in global memory function and possible evidence of accelerated postoperative decline.Results:Of 65 charts reviewed, 44 patients were native English-speaking and included in our analyses. At the group level, there were no significant differences in disease characteristics, socio-demographic variables, or cognitive classification between those who declined versus those who did not decline on LMDR. Regression statistics for predictors of cognitive decline also were non-significant. Of the eight individuals who declined on LMDR, one patient declined on a total of one neuropsychological measure, four declined on a total of two measures, two declined on a total of three measures, and one declined on a total of four measures. Two of these eight individuals had a diagnosis that changed to amnestic MCI based on concomitant interval history of ADL compromise. Of these two individuals, one declined in two tests and the other declined in four tests. Six of the eight individuals who declined also showed abnormalities in their imaging with either edema or hemorrhage.Conclusions:Our analysis is unique in that we explored cognitive decline at both the group and individual levels. Despite this, we did not find predictors of post-DBS cognitive decline. Further detailed analysis of additional post-operative factors that might play a greater role in our understanding of this phenomenon is warranted. This said, our data do support that the majority of individuals with non-amnestic MCI did not decline cognitively.

Directional versus ring-mode deep brain stimulation for Parkinson’s disease: protocol of a multi-centre double-blind randomised crossover trial

BackgroundThe effectiveness of Deep Brain Stimulation (DBS) therapy for Parkinson’s disease can be limited by side-effects caused by electrical current spillover into structures adjacent to the target area. The objective of the STEEred versus RING-mode DBS for Parkinson’s disease (STEERING) study is to investigate if directional DBS for Parkinson’s disease results in a better clinical outcome when compared to ring-mode DBS.MethodsThe STEERING study is a prospective multi-centre double-blind randomised crossover trial. Inclusion criteria are Parkinson’s disease, subthalamic nucleus DBS in a ‘classic’ ring-mode setting for a minimum of six months, and optimal ring-mode settings have been established. Participants are categorised into one of two subgroups according to their clinical response to the ring-mode settings as ‘responders’ (i.e., patient with a satisfactory effect of ring-mode DBS) or ‘non-responder’ (i.e., patient with a non-satisfactory effect of ring-mode DBS). A total of 64 responders and 38 non-responders will be included (total 102 patients). After an optimisation period in which an optimal directional setting is found, participants are randomised to first receive ring-mode DBS for 56 days (range 28–66) followed by directional DBS for 56 days (28–66) or vice-versa. The primary outcome is the difference between ring-mode DBS and directional DBS settings on the Movement Disorders Society Unified Parkinson’s Disease Rating Scale – Motor Evaluation (MDS-UPDRS-ME) in the off-medication state. Secondary outcome measures consist of MDS-UPDRS-ME in the on-medication state, MDS-UPDRS Activities of Daily Living, MDS-UPDRS Motor Complications–Dyskinesia, disease related quality of life measured with the Parkinson’s Disease Questionnaire 39, stimulation-induced side-effects, antiparkinsonian medication use, and DBS-parameters. Participants’ therapy preference is measured at the end of the study. Outcomes will be analysed for both responder and non-responder groups, as well as for both groups pooled together.DiscussionThe STEERING trial will provide insights into whether or not directional DBS should be standardly used in all Parkinson’s disease DBS patients or if directional DBS should only be used in a case-based approach.Trial registrationThis trial was registered on the Netherlands Trial Register, as trial NL6508 (NTR6696) on June 23, 2017.

Weight and survival after deep brain stimulation for Parkinson's disease

BackgroundWeight 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. ObjectivesTo 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. MethodsThis 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. ResultsThere 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 (R2 = 0.14, p < 0.001). DiscussionThough 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.

Structural brain differences in essential tremor and Parkinson’s disease deep brain stimulation patients

BackgroundEssential tremor (ET) and Parkinson’s disease (PD) are the most common tremor disorders and are common indications for deep brain stimulation (DBS). In some patients, PD and ET symptoms overlap and diagnosis can be challenging based on clinical criteria alone. The objective of this study was to identify structural brain differences between PD and ET DBS patients to help differentiate these disorders and improve our understanding of the different brain regions involved in these pathologic processes. MethodsWe included ET and PD patients scheduled to undergo DBS surgery in this observational study. Patients underwent 3T brain MRI while under general anesthesia as part of their procedure. Cortical thicknesses and subcortical volumes were quantified from T1-weighted images using automated multi-atlas segmentation. We used logistic regression analysis to identify brain regions associated with diagnosis of ET or PD. Results149 ET and 265 PD patients were included. Smaller volumes in the pallidum and thalamus and reduced thickness in the anterior orbital gyrus, lateral orbital gyrus, and medial precentral gyrus were associated with greater odds of ET diagnosis. Conversely, reduced volumes in the caudate, amygdala, putamen, and basal forebrain, and reduced thickness in the orbital part of the inferior frontal gyrus, supramarginal gyrus, and posterior cingulate were associated with greater odds of PD diagnosis. ConclusionsThese findings identify structural brain differences between PD and ET patients. These results expand our understanding of the different brain regions involved in these disorders and suggest that structural MRI may help to differentiate patients with these two disorders.

Long Term Antidepressant Effects of Deep Brain Stimulation for Treatment Resistant Depression – A Research Protocol

Introduction: Individuals with treatment resistant depression (TRD) are those with severe major depressive disorder who fail to respond to conventional pharmacological treatment. As a result, novel technologies in the field of neuromodulation have been investigated to alleviate depressive symptoms in this population. One such neuromodulation therapy is deep brain stimulation (DBS), in which electrodes are neurosurgically implanted into target regions of the brain associated with depression, such as the subgenual anterior cingulate cortex (sgACC). While previous studies have explored the use of DBS as a therapy for TRD, few studies with adequate statistical power have explored the sustained antidepressant effects of DBS when targeting the sgACC of the brain. Methods: This study aims to explore the long-term effects in DBS patients for TRD by measuring changes in cerebral blood flow and cerebral metabolic rate in the sgACC, and its correlation to changes in self-reported depressive symptoms. Forty-five participants will be enlisted into this study. Psychometric evaluation and positron-emission topography imaging will be conducted prior to neurosurgery. Electrodes will be implanted into the sgACC, with extension wires attaching the electrodes to the internal pulse generator. In the six-week blinded phase, progressive increases in stimulation will be administered within the blinded group and sham stimulation in controls. The three-month open label phase will administer the same degree of high-frequency biphasic stimulation to the control and blinded groups and assess depression scores, neuroimaging, and adverse events. After cessation of active stimulation, a one-year, three-year, seven-year, and ten-year follow-up will monitor changes in antidepressant effects of DBS using simple linear contrasts and paired-sample t-tests. Expected Results: This study expects to find a sustained antidepressant response marked by decreases in sgACC metabolism and cerebral blood flow, and a reduction in self-report depression scores. Discussion: The use of DBS shows promise as a successful treatment intervention with sustained long-term effects for individuals with TRD. Additional secondary outcomes to be expected are improved quality of life and health behaviours. Conclusion: Though minor fluctuations are expected due to the presence of comorbidities, this study expects to showcase the long-term efficacy of deep brain stimulation for treatment resistant depression.

Racial disparities in access to DBS: results of a real-world U.S. claims data analysis.

Deep brain stimulation (DBS) is an effective and standard-of-care therapy for Parkinson's Disease and other movement disorders when symptoms are inadequately controlled with conventional medications. It requires expert care for patient selection, surgical targeting, and therapy titration. Despite the known benefits, racial/ethnic disparities in access have been reported. Technological advancements with smartphone-enabled devices may influence racial disparities. Real-world evidence investigations can shed further light on barriers to access and demographic disparities for DBS patients. A retrospective cross-sectional study was performed using Medicare claims linked with manufacturer patient data tracking to analyze 3,869 patients who received DBS. Patients were divided into two categories: traditional omnidirectional DBS systems with dedicated proprietary controllers ("traditional"; n = 3,256) and directional DBS systems with smart controllers ("smartphone-enabled"; n = 613). Demographics including age, sex, and self-identified race/ethnicity were compared. Categorical demographics, including race/ethnicity and distance from implanting facility, were analyzed for the entire population. A significant disparity in DBS utilization was evident. White individuals comprised 91.4 and 89.9% of traditional and smartphone-enabled DBS groups, respectively. Non-White patients were significantly more likely to live closer to implanting facilities compared with White patients. There is great racial disparity in utilization of DBS therapy. Smartphone-enabled systems did not significantly impact racial disparities in receiving DBS. Minoritized patients were more likely to live closer to their implanting facility than White patients. Further research is warranted to identify barriers to access for minoritized patients to receive DBS. Technological advancements should consider the racial discrepancy of DBS utilization in future developments.

Technical note: System uncertainty on four- and eight-channel parallel RF transmission for safe MRI of deep brain stimulation devices.

Parallel radiofrequency transmission (pTx) remains a promising technology for addressing high-field magnetic resonance imaging (MRI) challenges, particularly regarding the safety of patients with implanted deep brain stimulation (DBS) devices. Radiofrequency (RF) shim optimization methods utilizing pTx technology have shown the potential to minimize induced RF heating effects at the electrode tips of DBS devices at 3 T. Research pTx system implementations often involve the combination of custom and commercial hardware that are integrated onto an existing MRI system. As a result, system characterization is important to ensure implant-friendly safe imaging conditions are satisfied for the operating range of the hardware. Utilizing electromagnetic and thermal simulations, the impact of system uncertainty is studied for the proposed 4- and 8-channel pTx system setupand its associated "safe mode" for DBS applications. Electromagnetic simulations indicated that instrumentation errors can affect the overall electric field strength experienced at the DBS lead tip, and a worst-case system uncertainty analysis predicted temperature elevations of +1.5°C in the 4-channel setup and +0.9°C in the 8-channel setup. In conclusion, system uncertainty can impact the precision of pTx RF inputs which in the worst-case, may lead to an unsafe imaging scenario and the proposed 8-channel setup may provide more robustness and thus, safer conditions for MRI of DBS patients.

Voice Improvement After Essential Tremor Treatment via Focused Ultrasound and Deep Brain Stimulation.

The primary objective of this study was to determine whether two neurosurgical procedures, deep brain stimulation (DBS) and focused ultrasound (FUS), to treat essential tremor (ET) of the upper limb also reduce vocal tremor (VT) in patients with comorbid dysphonia. Twelve patients with ET and concomitant VT scheduled for neurosurgical intervention (FUS or DBS) or returning for follow-up after DBS implantation were assessed. FUS patients were assessed pre- and post-intervention and DBS patients were assessed with the electrodes turned on and off post-implantation. Three voice recordings of a sustained /a/ were obtained for each participant condition. Percent fundamental frequency variability (FFV) was calculated for each recorded sustained vowel. Additionally, blinded expert perceptual VT rating (VTR) was performed to assess subjective changes in tremors. Of the 12 patients, seven underwent unilateral FUS, and five underwent bilateral DBS. Mean FFV without neurosurgical intervention was 18.3%, SD = 7.8 and with neurosurgical intervention was 6.3%, SD = 3.0 (t (70) =8.7, p < 0.001). Mean FFV decreased in the FUS cohort from 22.0%, SD = 7.1 pre-ablation to 6.7%, SD = 2.4 post-ablation (t (40) = 7.7, p < 0.001). Mean FFV also decreased in the DBS cohort from 15.7%, SD = 7.0 to 6.0%, SD = 3.3 when stimulation was turned on (t (28)=5.7 p < 0.001). In the FUS group, mean VTR decreased from 4.0 to 1.4 post-ablation (Z = 7.8, p < 0.001). In the DBS group, mean VTR decreased from 3.3 to 2.1 with stimulation (Z = 4.1, p < 0.001). Neurosurgical interventions for ET (bilateral DBS and unilateral FUS) demonstrate acoustic and perceptual benefits for VT. 4 Laryngoscope, 134:367-373, 2024.