Deep Brain Stimulation In Patients Research Articles

Design of multi-row parallel-transmit coil arrays for enhanced SAR efficiency with deep brain electrodes at 3T: an electromagnetic simulation study.

Tissue heating near the implanted deep brain stimulation (DBS) during magnetic resonance imaging (MRI) poses a significant safety constraint. This study aimed to evaluate the performance of parallel transmit (pTx) head transmit radiofrequency (RF) coils in DBS patients, with a focus on excitation fidelity under specific absorption rate (SAR) control for brain imaging at 3T MRI. We employed electromagnetic simulations to assess different coil configurations, including multi-row pTx coils of 16-24 channels arranged in 1, 2, and 3 rows, and compared these to a circularly polarised and pTx birdcage coil using a realistic human model without and with DBS leads and electrodes. Two- and three-row pTx coils with overlapping loop elements exhibited similar performance, which was superior in excitation homogeneity and local SAR compared to the single-row coil and the birdcage coil both without and with DBS. These findings suggest that multi-row coils can enhance the safety and efficacy of MRI in patients with DBS devices, so potentially improving imaging performance in this expanding patient population. There was a minimal difference in performance between the 2 and 3-row coils, favouring the simpler, lower channel count design for practical implementation.

Simplifying Complex Figure scoring: Data from the Emory Healthy Brain Study and initial clinical validation.

To introduce the Emory 10-element Complex Figure (CF) scoring system and recognition task. We evaluated the relationship between Emory CF scoring and traditional Osterrieth CF scoring approach in cognitively healthy volunteers. Additionally, a cohort of patients undergoing deep brain stimulation (DBS) evaluation was assessed to compare the scoring methods in a clinical population. The study included 315 volunteers from the Emory Healthy Brain Study (EHBS) with Montreal Cognitive Assessment (MoCA) scores of 24/30 or higher. The clinical group consisted of 84 DBS candidates. Scoring time differences were analyzed in a subset of 48 DBS candidates. High correlations between scoring methods were present for non-recognition components in both cohorts (EHBS: Copy r = 0.76, Immediate r = 0.86, Delayed r = 0.85, Recognition r = 47; DBS: Copy r = 0.80, Immediate r = 0.84, Delayed Recall r = 0.85, Recognition r = 0.37). Emory CF scoring times were significantly shorter than Osterrieth times across non-recognition conditions (all p < 0.00001, individual Cohen's d: 1.4-2.4), resulting in an average time savings of 57%. DBS patients scored lower than EHBS participants across CF memory measures, with larger effect sizes for Emory CF scoring (Cohen's d range = 1.0-1.2). Emory CF scoring demonstrated better group classification in logistic regression models, improving DBS candidate classification from 16.7% to 32.1% compared to Osterrieth scoring. Emory CF scoring yields results that are highly correlated with traditional Osterrieth scoring, significantly reduces scoring time burden, and demonstrates greater sensitivity to memory decline in DBS candidates. Its efficiency and sensitivity make Emory CF scoring well-suited for broader implementation in clinical research.

The Scalp Nerve Block Combined with Intercostal Nerve Block Improves Recovery After Deep Brain Stimulation in Patients with Parkinson's Disease: A Prospective, Randomized Controlled Trial.

To explore the effect of scalp nerve block (SNB) combined with intercostal nerve block (ICNB) on quality of recovery (QoR) after deep brain stimulation (DBS) in patients with Parkinson's disease (PD). We conducted a prospective randomized controlled trial in which 88 patients with PD were randomly assigned to undergo SNB combined with ICNB (SNB group) or not (control group) before surgery. The primary outcome was the 15-item QoR (QoR-15) score 24h after surgery. The secondary outcomes included QoR-15 scores at 72h and 1 month after surgery, pain-related events, recovery events in post-anesthesia care unit (PACU), duration of anesthesia and surgery, and nerve block-related adverse events. The QoR-15 score at 24h after surgery was significantly higher in SNB group than Control group: 122.0 ± 7.6 vs 113.5 ± 11.3 (P = 0.006). SNB combined with ICNB improved QoR-15 scores at 72h (P = 0.004) but not at 1 month after surgery (P = 0.230). The SNB group was positively related to QoR-15 scores 24h after surgery (β = 8.92; 95% CI = 4.52~13.32) after adjusting for confounding variables. The numeric rating scale pain scores at PACU discharge and at 24h, intraoperative opioid consumption, rescue analgesic use, and the incidence of postoperative nausea and vomiting (PONV) in SNB group were significantly lower than Control group (P < 0.05). Preoperative SNB combined with ICNB improved QoR and analgesia after surgery, and reduced intraoperative opioid consumption and the incidence of PONV in patients with PD who underwent DBS.

Significance of neurodegeneration and neuroplasticity serum biomarkers in Parkinson’s disease patients treated with subthalamic stimulation

The ability of serum biomarkers to predict the prognosis and response to deep-brain stimulation (DBS) therapy in Parkinson’s disease (PD) patients is promising. Here, we showed that NfL differed between healthy individuals and PD patients and that changes in NfL, GFAP, and BDNF occurred only transiently after DBS surgery. Therefore, subthalamic stimulation does not promote neurodegeneration, and these biomarkers do not serve as clinical improvement endpoints in PD DBS patients.

Modeling electrical impedance in brain tissue with diffusion tensor imaging for functional neurosurgery applications

Objective.Decades ago, neurosurgeons used electrical impedance measurements in the brain for coarse intraoperative tissue differentiation. Over time, these techniques were largely replaced by more refined imaging and electrophysiological localization. Today, advanced methods of diffusion tensor imaging (DTI) and finite element method (FEM) modeling may permit non-invasive, high-resolution intracerebral impedance prediction. However, expectations for tissue-impedance relationships and experimentally verified parameters for impedance modeling in human brains are lacking. This study seeks to address this need.Approach.We used FEM to simulate high-resolution single- and dual-electrode impedance measurements along linear electrode trajectories through (1) canonical gray and white matter tissue models, and (2) selected anatomic structures within whole-brain patient DTI-based models. We then compared intraoperative impedance measurements taken at known locations along deep brain stimulation (DBS) surgical trajectories with model predictions to evaluate model accuracy and refine model parameters.Main results.In DTI-FEM models, single- and dual-electrode configurations performed similarly. While only dual-electrode configurations were sensitive to white matter fiber orientation, other influences on impedance, such as white matter density, enabled single-electrode impedance measurements to display significant spatial variation even within purely white matter structures. We compared 308 intraoperative single-electrode impedance measurements in five DBS patients to DTI-FEM predictions at one-to-one corresponding locations. After calibration of model coefficients to these data, predicted impedances reliably estimated intraoperative measurements in all patients (R=0.784±0.116,n=5). Through this study, we derived an updated value for the slope coefficient of the DTI conductance model published by Tuchet al,k=0.0649 S⋅smm-3 (originalk=0.844), for use specifically in humans at physiological frequencies.Significance.This is the first study to compare impedance estimates from imaging-based models of human brain tissue to experimental measurements at the same locationsin vivo. Accurate, non-invasive, imaging-based impedance prediction has numerous applications in functional neurosurgery, including tissue mapping, intraoperative electrode localization, and DBS.

Deep Brain Stimulation for Childhood Treatment-Resistant Obsessive-Compulsive Disorder: Mental Health Clinician Views on Candidacy Factors

Introduction Deep brain stimulation (DBS) is approved under a humanitarian device exemption to manage treatment-resistant obsessive-compulsive disorder (TR-OCD) in adults. It is possible that DBS may be trialed or used clinically off-label in children and adolescents with TR-OCD in the future. DBS is already used to manage treatment-resistant childhood dystonia. Evidence suggests it is a safe and effective intervention for certain types of dystonia. Important questions remain unanswered about the use of DBS in children and adolescents with TR-OCD, including whether mental health clinicians would refer pediatric patients for DBS, and who would be a good candidate for DBS. Objectives To explore mental health clinicians’ views on what clinical and psychosocial factors they would consider when determining which children with OCD would be good DBS candidates. Materials and Methods In depth, semi-structured interviews were conducted with n = 25 mental health clinicians who treat pediatric patients with OCD. The interviews were transcribed, coded, and analyzed using thematic content analysis. Three questions focused on key, clinical, and psychosocial factors for assessing candidacy were analyzed to explore respondent views on candidacy factors. Our analysis details nine overarching themes expressed by clinicians, namely the patient’s previous OCD treatment, OCD severity, motivation to commit to treatment, presence of comorbid conditions, family environment, education on DBS, quality of life, accessibility to treatment, and patient age and maturity. Conclusions Clinicians generally saw considering DBS treatment in youth as a last resort and only for very specific cases. DBS referral was predominantly viewed as acceptable for children with severe TR-OCD who have undertaken intensive, appropriate treatment without success, whose OCD has significantly reduced their quality of life, and who exhibit strong motivation to continue treatment given the right environment. Appropriate safeguards, eligibility criteria, and procedures should be discussed and identified before DBS for childhood TR-OCD becomes practice.

Surgical Concepts and Long-term Outcomes of Thalamic Deep Brain Stimulation in Patients with Severe Tourette Syndrome: A Single-center Experience.

Tourette syndrome (TS) is a developmental neuropsychiatric disorder that is characterized by tic movements. Deep brain stimulation (DBS) may be a treatment option for severe cases refractory to medical and behavioral therapies. In this study, we reviewed the surgical techniques used for DBS in patients with severe TS and its clinical outcomes and sought to determine the optimal surgical procedure and current issues based on our experience and the literature. A total of 14 patients, consisting of 13 men and 1 woman, who underwent centromedian thalamic DBS and were followed up for a mean duration of 2.3 ± 1.0 years, participated in this study. The mean Yale Global Tic Severity Scale severity score significantly improved from 41.4 ± 7.0 at baseline to 19.8 ± 11.4 at 6 months (P = 0.01) and 12.7 ± 6.2 at the last follow-up (P < 0.01). Moreover, the mean Yale Global Tic Severity Scale impairment score significantly improved from 47.1 ± 4.7 at baseline to 23.1 ± 11.1 at 6 months (P < 0.01) and 7.6 ± 2.9 at the last follow-up (P < 0.01). However, there were problems with continuous postoperative monitoring (three cases were lost to follow-up) and surgery-related adverse events, including one case each of lead misplacement and a delayed intracerebral hemorrhage due to severe self-injurious tics. This study aimed to highlight not only the clinical efficacy of DBS for TS but also its challenges. Clinicians should understand the three-dimensional brain anatomy so that they can perform precise surgical procedures, avoid adverse events, and achieve favorable outcomes of DBS for TS.

Dopamine and deep brain stimulation accelerate the neural dynamics of volitional action in Parkinson's disease.

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

Rates and Predictors of Pain Reduction With Intracranial Stimulation for Intractable Pain Disorders.

Intracranial modulation paradigms, namely deep brain stimulation (DBS) and motor cortex stimulation (MCS), have been used to treat intractable pain disorders. However, treatment efficacy remains heterogeneous, and factors associated with pain reduction are not completely understood. We performed an individual patient review of pain outcomes (visual analog scale, quality-of-life measures, complications, pulse generator implant rate, cessation of stimulation) after implantation of DBS or MCS devices. We evaluated 663 patients from 36 study groups and stratified outcomes by pain etiology and implantation targets. Included studies comprised primarily retrospective cohort studies. MCS patients had a similar externalized trial success rate compared with DBS patients (86% vs 81%; P = .16), whereas patients with peripheral pain had a higher trial success rate compared with patients with central pain (88% vs 79%; P = .004). Complication rates were similar for MCS and DBS patients (12% vs 15%; P = .79). Patients with peripheral pain had lower likelihood of device cessation compared with those with central pain (5.7% vs 10%; P = .03). Of all implanted patients, mean pain reduction at last follow-up was 45.8% (95% CI: 40.3-51.2) with a 31.2% (95% CI: 12.4-50.1) improvement in quality of life. No difference was seen between MCS patients (43.8%; 95% CI: 36.7-58.2) and DBS patients (48.6%; 95% CI: 39.2-58) or central (41.5%; 95% CI: 34.8-48.2) and peripheral (46.7%; 95% CI: 38.9-54.5) etiologies. Multivariate analysis identified the anterior cingulate cortex target to be associated with worse pain reduction, while postherpetic neuralgia was a positive prognostic factor. Both DBS and MCS have similar efficacy and complication rates in the treatment of intractable pain. Patients with central pain disorders tended to have lower trial success and higher rates of device cessation. Additional prognostic factors include anterior cingulate cortex targeting and postherpetic neuralgia diagnosis. These findings underscore intracranial neurostimulation as an important modality for treatment of intractable pain disorders.

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 &lt;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 &lt; 0.001). There was a significant treatment × follow-up interaction (H = 14.99, p &lt; 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 &lt;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 &amp;lt; 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 &amp;gt;0.6) and intra-rater (mean Dice coefficient &amp;gt;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.

Prediction of pyramidal tract side effect threshold by intra-operative electromyography in subthalamic nucleus deep brain stimulation for patients with Parkinson's disease under general anaesthesia.

In DBS for patients with PD, STN is the most common DBS target with the sweet point located dorsal ipsilaterally adjacent to the pyramidal tract. During awake DBS lead implantation, macrostimulation is performed to test the clinical effects and side effects especially the pyramidal tract side effect (PTSE) threshold. A too low PTSE threshold will compromise the therapeutic stimulation window. When DBS lead implantation is performed under general anaesthesia (GA), there is a lack of real time feedback regarding the PTSE. In this study, we evaluated the macrostimulation-induced PTSE by electromyography (EMG) during DBS surgery under GA. Our aim is to investigate the prediction of post-operative programming PTSE threshold using EMG-based PTSE threshold, and its potential application to guide intra-operative lead implantation. 44 patients with advanced PD received STN DBS under GA were studied. Intra-operative macrostimulation via EMG was assessed from the contralateral upper limb. EMG signal activation was defined as the amplitude doubling or greater than the base line. In the first programming session at one month post-operation, the PTSE threshold was documented. All patients were followed up for one year to assess clinical outcome. All 44 cases (88 sides) demonstrated activations of limb EMG via increasing amplitude of macrostimulation the contralateral STN under GA. Revision tracts were explored in 7 patients due to a low EMG activation threshold (<= 2.5 mA). The mean intraoperative EMG-based PTSE threshold was 4.3 mA (SD 1.2 mA, Range 2.0-8.0 mA), programming PTSE threshold was 3.7 mA (SD 0.8 mA, Range 2.0-6.5 mA). Linear regression showed that EMG-based PTSE threshold was a statistically significant predictor variable for the programming PTSE threshold (p value <0.001). At one year, the mean improvement of UPDRS Part III score at medication-off/DBS-on was 54.0% (SD 12.7%) and the levodopa equivalent dose (LED) reduction was 59.5% (SD 23.5%). During STN DBS lead implantation under GA, PTSE threshold can be tested by EMG through macrostimulation. It can provide real-time information on the laterality of the trajectory and serves as reference to guide intra-operative DBS lead placement.

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.