INTRODUCTION:Deep brain stimulation (DBS) targeting the posterior subthalamic area (PSA) is a more recent target to manage medication-refractory essential tremor (ET), with some studies suggesting enhanced tremor control and more favorable side-effects profile compared to traditional ventral intermediate nucleus (Vim). This study aims to assess the long-term efficacy and side effect profile of PSA-DBS in ET patients. METHODS:Fourteen ET patients who underwent bilateral PSA-DBS were evaluated using the Fahn-Tolosa-Marin Tremor Rating Scale preoperatively, at 12 months, and at the last follow-up (range 10-63 months). Within the first 6 months postoperatively, systematic monopolar contact testing was performed to determine individual thresholds for tremor suppression and adverse effects. Standardized neurological examinations and blinded video assessments were used to document stimulation-induced side effects. RESULTS:Tremor was significantly reduced postoperatively, allowing a 59% reduction at 12 months and 39% at last follow-up. Common side effects at last follow-up included dysarthria (93%), ataxia (57%), and gait disturbances (79%), mainly mild to moderate in severity. Additionally, stimulation-induced dyskinesia occurred in 21% of patients. Patient satisfaction remained high, with 85.7% reporting significant improvements. CONCLUSIONS:Bilateral PSA-DBS demonstrates sustained tremor reduction but can frequently present stimulation-induced side-effects, highlighting the importance of careful long-term monitoring and programming adjustments.

Arterial spin labeling (ASL) at ultra‑high field MRI at 7 T provides enhanced signal‑to‑noise ratio and spatial resolution, enabling more sensitive functional imaging. The objective of this study was to investigate regional perfusion changes and their relationship to perceived pain during sustained capsaicin‑induced nociception. Twenty‑seven healthy right‑handed volunteers (mean age 31.9 ± 4.1 years; 12 female) underwent two MRI sessions: at baseline and during capsaicin-induced tonic pain. Participants rated pain and were classified as responders or weak responders. MRI included T1‑weighted structural imaging, resting BOLD‑fMRI and 3D turbo‑FLASH pCASL. Images were segmented, normalized to MNI space, and CBF maps calculated. Mean CBF was extracted from gray matter and 10 predefined pain‑matrix regions. Voxel‑wise linear regression analyzed correlations between CBF and pain ratings, with false discovery rate correction. Group differences between responders and weak responders were assessed voxel‑wise. Global gray matter CBF was unchanged between baseline and capsaicin conditions and did not differ by responder status. However, CBF increased significantly with pain in a network including the contralateral insular cortex, primary and secondary somatosensory cortices, supplementary motor area, bilateral anterior cingulate cortex, right dorsolateral prefrontal cortex and contralateral thalamus. Average perfusion in these regions rose by 8-15% and correlated strongly with pain scores (r ≈ 0.66; p < 0.001). Weak responders showed higher CBF in right fusiform and bilateral primary visual cortices and lower CBF in bilateral superior frontal gyrus compared with responders. In conclusion, pCASL at 7 T enables quantitative mapping of brain perfusion during sustained pain. Sustained capsaicin stimulation increases regional CBF in a distributed cortico‑subcortical network, with perfusion changes closely tracking perceived pain intensity. These findings demonstrate that tonic nociception engages broader associative networks and highlight the utility of ultra‑high field ASL for studying chronic pain mechanisms.

BACKGROUND:Sleep architecture and circadian rhythms are frequently disrupted in Parkinson's disease (PD). BrainSense-enabled neurostimulators combined with wearable technology enable chronic assessment of nocturnal brain activity, with potential for future diagnostics and personalized treatments. OBJECTIVES:To neurophysiologically characterize and decode sleep architecture and circadian rhythmicity from ambulatory subthalamic nucleus (STN) recordings in PD and to evaluate the influence of clinical factors. METHODS:Eighteen PD patients implanted with the Medtronic Percept system underwent 4-8 weeks of ambulatory STN local field potential recordings, alongside wearable-based sleep monitoring. Spectral dynamics of three biomarkers (low-frequency-, beta-, and finely-tuned-gamma [FTG]-activity) were characterized across circadian cycles and sleep stages (Awake, Core, Deep, REM [rapid eye movement]). Machine-learning classifiers were developed for state decoding. RESULTS:A total of 3140 hr of representative sleep data were analyzed. All biomarkers exhibited circadian modulation, most evident in beta and FTG activity. REM sleep and nocturnal wakefulness were associated with increased beta/FTG, whereas Deep sleep showed increased low-frequency and reduced beta/FTG. Classifiers showed that beta and FTG decoded circadian states, while low-frequency identified Deep sleep. Bilateral biomarker combination improved prediction. Clinically, greater motor impairment correlated with reduced REM beta power. Levodopa dosage and electrocardiogram artefacts influenced beta-based predictions, whereas age and sleep quality affected FTG-related predictions. CONCLUSIONS:This proof-of-concept study demonstrates that ambulatory basal ganglia recordings from implantable neurostimulators can capture key aspects of sleep stage architecture in PD. Distinct spectral biomarkers show differential sleep insights and practical utility, supporting the development of diagnostic tools and sleep-informed adaptive deep brain stimulation. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Introduction: Deep brain stimulation (DBS) has become an efficacious therapy for multiple indications. With the advent of directional leads, increasing stimulation options complexify manual programming. Therefore, automated programming algorithms based on probablisitic mapping are being tested for parameter prediction. Such approaches require computational lead reconstruction routines that are already broadly used. However, the robustness of lead reconstruction across distinct image sets of a same patient remains unclear. Methods: To assess lead reconstruction systematically, we identified retrospectively 34 DBS patients with Parkinson's disease (PD) or essential tremor, who received two distinct postoperative CT-scans. Each CT-scan was processed independently using the Lead-DBS toolbox. Between both image sets, we compared lead tip coordinates and volumes of tissue activation (VTA) for each hemisphere. Group-level probabilistic maps of clinical improvement were compared between sets for PD patients. Results: Mean lead tip translation between CTs was 0.79 mm (range: 0.21-2.35 mm). Pneumocephalus did not significantly affect reconstruction robustness. Lead translation was comparable in the patient native space and after normalization to the template brain. Individual-level VTA comparison revealed a mean Dice coefficient of 0.73 (range: 0.33-0.94), which decreased with lower amplitudes of stimulation. Group-level N-images and clinical improvement maps were robust (Dice coefficient, respectively, 0.88 and 0.90). Conclusion: Computational normalization and pneumocephalus correction were satisfying in our cohort. However, individual-level VTA variability was observed, potentially caused by slightly inaccurate CT-to-MRI co-registration or by brain shift sources other than pneumocephalus. These variabilities vanish at the group level, suggesting that current lead reconstruction routines are sufficient for probabilistic sweet spot identification.

OBJECTIVE:Dysarthria is one of the most common and disabling side effects of subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD). Stimulation often exacerbates speech dysfunction beyond the effects of PD progression, likely because of current spread to structures surrounding the STN. This study aimed to develop speech biomarkers sensitive to DBS-induced dysarthria by isolating stimulation side effects and mapping their emergence across incrementally increased amplitudes. METHODS:Twenty-four PD patients with bilateral STN-DBS completed a standardized speech assessment in each hemisphere separately, including sustained phonations, rapid syllable repetitions, and reading passages across 7 increasing stimulation amplitudes defined relative to a clinically determined stimulation-induced dysarthria threshold. A composite dysarthria index based on 7 key acoustic features, patient perceptual self-ratings, and intelligibility scores were extracted. RESULTS:More than 2,500 speech task recordings were analyzed. Both the composite dysarthria index and subjective self-ratings worsened rapidly with increasing stimulation amplitude above a threshold (p < 0.001), whereas intelligibility scores varied markedly and did not reach significance. Among individual acoustic features, phonation duration, voice quality, and monopitch exhibited significant sensitivity to increasing stimulation amplitudes. Left-sided stimulation induced greater speech deterioration than right-sided stimulation. INTERPRETATION:We systematically identified speech biomarkers that capture DBS-induced dysarthria, characterized the progressive deterioration of speech with increasing amplitude, and highlighted the pivotal role of left basal ganglia circuitry in speech production. Our objective metric holds promise as safety outcome measure for surgical therapies, guidepost for initial and troubleshooting DBS programming, and input for adaptive, closed-loop stimulation control. ANN NEUROL 2026;100:628-640.

Movement-related gamma activity (> 60 Hz) in cortico-basal ganglia networks reflects pro-kinetic synchronization dynamics. While in the cortex these temporal dynamics are known to unfold spatially across topographically distributed networks, it remains unclear whether a similar spatial propagation occurs within the basal ganglia, and how such spatial encoding may contribute to both physiological and disease-related mechanisms. The subthalamic nucleus (STN) is a key integrative hub for motor processing within the basal ganglia-cortical circuitry. At rest, STN activity is topographically distributed according to its spectral frequency components. To assess whether this spectral topography is dynamic and underlies movement encoding, we dissected the spatiotemporal properties of STN local field potentials recorded intraoperatively at rest and during movement across 63 hemispheres from patients with Parkinson's disease. Using multi-contact deep brain stimulation leads, we captured high-resolution anatomical signal dynamics and contrasted a broad frequency spectrum (60-400 Hz), including high-gamma, fast-gamma, slow high-frequency oscillations and fast high-frequency oscillations. Moreover, we compared these signals to upper limb muscle activity and movement-related beta desynchronization, and examined their association with clinical impairment and levodopa responsiveness. All sub-bands exhibited significant movement-related synchronization in both the contralateral and ipsilateral STN, however, with distinct magnitude and temporal dynamics. The presence and degree of temporal locking to muscle activity and inverse relationship to movement-related beta desynchronization also varied by sub-band. Importantly, each sub-band exhibited spatially segregated hotspots located within the STN that propagate primarily along the inferior-superior axis, yet in band-specific directions. This spatial propagation evolved throughout the movement period but temporally decoupled from synchronization magnitude, indicating that spatial dynamics reflect a distinct property relevant for motor encoding. Notably, propagation of frequencies above 110 Hz inversely correlated with dopamine-related motor improvement, suggesting that exaggerated spatial dynamics may reflect compensatory mechanisms secondary to neurodegeneration. These findings demonstrated that synchronization within the basal ganglia is not a spatially static phenomenon but rather unfolds in space which expands on the current understanding of the basal ganglia mechanism. Propagation of movement-related activity may serve as a potential marker for motor impairment in Parkinson's disease, opening new avenues for spectro-behavioural research and spatially informed neuromodulation strategies.

How can one trace the brain’s orderly directed signals amid a tangle of nerve fibers? Because direct access to actual brain signaling is rare in humans, the precise wiring diagrams for cortico-limbic communication during sleep and wake remain essentially unmapped, hampering progress in neuroscience. Now, a unique neurosurgical window on the human brain allows for electrically mapping cortical connections at the hospital, but studies so far have relied on average signals, masking the dynamic nature of signal flow across brain regions and vigilance states. To causally estimate signal flow, we repeatedly probed cortico-limbic networks with short-lived electrical pulses over days and assessed the variable fate of each transmitted signal on a single-trial basis. In the resulting openly available dataset, we characterized signaling probabilities and directionality across thousands of local and long-range cortico-limbic connections over days. Challenging established views, we found that limbic structures send twice as many signals as they receive, in both wakefulness and sleep. Our findings provide a fundamental framework for causally interpreting signal flow in the brain and formulating therapeutic strategies for brain network disorders. Here, the authors mapped signal flow over days from intracranial brain recordings in humans. Across vigilance stages, limbic structures sent twice as many signals as they received from the neocortex, challenging the long-standing hypothesis of flow reversal in sleep.

OBJECTIVE The effectiveness and optimal stimulation site of deep brain stimulation (DBS) for central poststroke pain (CPSP) remain elusive. The objective of this retrospective international multicenter study was to assess clinical as well as neuroimaging-based predictors of long-term outcomes after DBS for CPSP. METHODS The authors analyzed patient-based clinical and neuroimaging data of previously published and unpublished cohorts from 6 international DBS centers. DBS leads were reconstructed and normalized. A stimulation map was constructed on the basis of individual stimulation settings and associated outcomes. Furthermore, the authors projected the individual segmented stroke lesions and volumes of tissue activated (VTAs) of the stimulating electrode onto a normalized human connectome to obtain the connectivity profiles of the individual lesions and VTAs. RESULTS The authors analyzed the data of 54 patients, of whom 15 were excluded from the final analysis due to a lack of imaging data. Among the remaining 39 patients from 6 different cohorts, the authors found 14 (35.9%) responders who were defined by pain relief of at least 50% at 12-month follow-up. Stimulation mapping identified areas in the posterior limb of the internal capsule, the sensorimotor thalamus, and the medial and intralaminar thalamus as effective for pain reduction. Baseline characteristics did not differ between responders and nonresponders. The stimulation sites of the responders showed significantly reduced structural connectivity to the sensory areas of the cerebral cortex compared to nonresponders. CONCLUSIONS This comprehensive, multicenter analysis corroborates the efficacy of DBS in treating CPSP for a relevant number of patients. The posterior limb of the internal capsule and the sensorimotor thalamus emerged as potential stimulation sweet spots. The difference in structural connectivity between responders and nonresponders may constitute a biomarker of effective stimulation that can help guide surgical planning in future well-designed prospective trials.

Background; Impulse control disorders (ICD) are common side effects of dopaminergic treatment in Parkinson's disease (PD). Whereas some studies show a reduction in ICD after subthalamic nucleus deep brain stimulation (STN-DBS), others report worsening of ICD or impulsivity. Objective: The aim was to study ICD in the context of STN-DBS using an objective measure of decision-making. Methods: Ten PD patients performed an effort-based decision-making task alongside neuropsychiatric and cognitive evaluation before and 4 months after STN-DBS. Further, 33 PD patients underwent the same experimental procedures just once after an average 40 months of chronic STN-DBS. Participants were examined preoperatively in the medication on state and postoperatively in the medication on/stimulation ON state. Mixed linear models were used to assess the impact of ICD and STN-DBS on acceptance rate and decision time in the task while controlling for motor symptom burden, cognitive measures, and dopaminergic medication. Results: Results revealed an increased willingness to exert high levels of effort in return for reward in patients with ICD, but acceptance rate was not modulated by chronic STN-DBS. Further, ICD, cognitive processing speed, and STN-DBS were all identified as positive predictors for faster decision speed. ICD scores showed a tendency to improve 4 months after STN-DBS, without an increase in apathy scores. Conclusions: Chronic STN-DBS and ICD facilitate effort-based decision-making by speeding up judgment. Furthermore, ICD enhances the willingness to exert high levels of effort for reward. Both STN-DBS and dopaminergic medication impact motivated behavior and should be titrated carefully to balance neuropsychiatric symptoms.

INTRODUCTION:The present study aimed to define a structural network of stroke-induced and spasticity-related lesions and to relate this network to target sites and reported effects of deep brain stimulation (DBS) to treat poststroke spasticity. METHODS:The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed (online suppl. Table 2). We performed two separate systematic literature reviews, collecting data from previously published voxel-based lesion-symptom mapping (VLSM) studies for poststroke spasticity patients searching the Medline database on Pubmed using the keywords "stroke," "spasticity," and "lesion mapping" as well as data from previously published cohorts undergoing DBS for poststroke spasticity using the keywords "brain stimulation" and "spasticity." Data collected from each study included patient demographic characteristics, stroke diagnosis, movement disorder, DBS target, stimulation parameters, complications, and outcomes. Data from VLSM studies were used to calculate coordinate-based activation likelihood clusters, which were then used as seeds for enhanced fiber tracking to analyze affected networks. RESULTS:Data from five studies on voxel-based lesion-symptom mapping for stroke-induced spasticity were included in the analysis. Meta-analytical mapping of stroke-related lesions identified significant clusters located in the basal ganglia-thalamo-cortical network which were predominantly connected to the sensorimotor cortex. We identified eight studies (four retrospective case series, two prospective open-label non-randomized trials, and two prospective double-blind trials) fulfilling our inclusion and exclusion criteria on DBS for spasticity reporting on 107 patients in total. Most studies reported outcomes in patients with cerebral palsy, a condition associated with both stroke-related spasticity and hypertonia-related dystonia, which are difficult to differentiate clinically. Target sites included different parts of the cerebellum and the motor thalamus with overall mixed results. CONCLUSION:Because all reported effective DBS target sites are situated along the cerebello-thalamo-cortical network, we hypothesize that the therapeutic effect of DBS on spasticity might be induced by resetting a functional imbalance between the basal ganglia-thalamo-cortical and the cerebello-thalamo-cortical networks in patients with a supraspinal etiology of spasticity. However, the results need to be interpreted cautiously due to the inevitable inclusion of stroke-related dystonia.

Ictal SPECT is an informative seizure imaging technique to tailor epilepsy surgery. However, capturing the onset of unpredictable seizures is a medical and logistic challenge. Here, we sought to image planned seizures triggered by direct stimulation of epileptic networks via stereotactic electroencephalography (sEEG) electrodes. Methods: In this case series of 3 adult participants with left temporal epilepsy, we identified and stimulated sEEG contacts able to trigger patient-typical seizures. We administered 99mTc-HMPAO within 12 s of ictal onset and acquired SPECT images within 40 min without any adverse events. Results: Ictal hyperperfusion maps partially overlapped concomitant sEEG seizure activity. In both participants known for periictal aphasia, SPECT imaging revealed hyperperfusion in the speech cortex lacking sEEG coverage. Conclusion: Triggering of seizures for ictal SPECT complements discrete sEEG sampling with spatially complete images of early seizure propagation. This readily implementable method revives interest in seizure imaging to guide resective epilepsy surgery.

Implantable brain recording and stimulation devices apply to a broad spectrum of conditions, such as epilepsy, movement disorders and depression. For long-term monitoring and neuromodulation in epilepsy patients, future extracranial subscalp implants may offer a promising, less-invasive alternative to intracranial neurotechnologies. To inform the design and assess the safety profile of such next-generation devices, we estimated extracranial complication rates of deep brain stimulation (DBS), cranial peripheral nerve stimulation (PNS), responsive neurostimulation (RNS) and existing subscalp EEG devices (sqEEG), as proxy for future implants. Pubmed was searched systematically for DBS, PNS, RNS and sqEEG studies from 2000 to February 2024 (48 publications, 7329 patients). We identified seven categories of extracranial adverse events: infection, non-infectious cutaneous complications, lead migration, lead fracture, hardware malfunction, pain and hemato-seroma. We used cohort sizes, demographics and industry funding as metrics to assess risks of bias. An inverse variance heterogeneity model was used for pooled and subgroup meta-analysis. The pooled incidence of extracranial complications reached 14.0%, with infections (4.6%, CI 95% [3.2 - 6.2]), surgical site pain (3.2%, [0.6 - 6.4]) and lead migration (2.6%, [1.0 - 4.4]) as leading causes. Subgroup analysis showed a particularly high incidence of persisting pain following PNS (12.0%, [6.8 - 17.9]) and sqEEG (23.9%, [12.7 - 37.2]) implantation. High rates of lead migration (12.4%, [6.4 - 19.3]) were also identified in the PNS subgroup. Complication analysis of DBS, PNS, RNS and sqEEG studies provides a significant opportunity to optimize the safety profile of future implantable subscalp devices for chronic EEG monitoring. Developing such promising technologies must address the risks of infection, surgical site pain, lead migration and skin erosion. A thin and robust design, coupled to a lead-anchoring system, shall enhance the durability and utility of next-generation subscalp implants for long-term EEG monitoring and neuromodulation.

BACKGROUND AND OBJECTIVES:Current practice in clinical neurophysiology is limited to short recordings with conventional EEG (days) that fail to capture a range of brain (dys)functions at longer timescales (months). The future ability to optimally manage chronic brain disorders, such as epilepsy, hinges upon finding methods to monitor electrical brain activity in daily life. We developed a device for full-head subscalp EEG (Epios) and tested here the feasibility to safely insert the electrode leads beneath the scalp by a minimally invasive technique (primary outcome). As secondary outcome, we verified the noninferiority of subscalp EEG in measuring physiologic brain oscillations and pathologic discharges compared with scalp EEG, the established standard of care. METHODS:Eight participants with pharmacoresistant epilepsy undergoing intracranial EEG received in the same surgery subscalp electrodes tunneled between the scalp and the skull with custom-made tools. Postoperative safety was monitored on an inpatient ward for up to 9 days. Sleep-wake, ictal, and interictal EEG signals from subscalp, scalp, and intracranial electrodes were compared quantitatively using windowed multitaper transforms and spectral coherence. Noninferiority was tested for pairs of neighboring subscalp and scalp electrodes with a Bland-Altman analysis for measurement bias and calculation of the interclass correlation coefficient (ICC). RESULTS:As primary outcome, up to 28 subscalp electrodes could be safely placed over the entire head through 1-cm scalp incisions in a ∼1-hour procedure. Five of 10 observed perioperative adverse events were linked to the investigational procedure, but none were serious, and all resolved. As a secondary outcome, subscalp electrodes advantageously recorded EEG percutaneously without requiring any maintenance and were noninferior to scalp electrodes for measuring (1) variably strong, stage-specific brain oscillations (alpha in wake, delta, sigma, and beta in sleep) and (2) interictal spikes peak-potentials and ictal signals coherent with seizure propagation in different brain regions (ICC >0.8 and absence of bias). DISCUSSION:Recording full-head subscalp EEG for localization and monitoring purposes is feasible up to 9 days in humans using minimally invasive techniques and noninferior to the current standard of care. A longer prospective ambulatory study of the full system will be necessary to establish the safety and utility of this innovative approach. TRIAL REGISTRATION INFORMATION:clinicaltrials.gov/study/NCT04796597.

Epilepsy is defined by the abrupt emergence of harmful seizures, but the nature of these regime shifts remains enigmatic. From the perspective of dynamical systems theory, such critical transitions occur upon inconspicuous perturbations in highly interconnected systems and can be modeled as mathematical bifurcations between alternative regimes. The predictability of critical transitions represents a major challenge, but the theory predicts the appearance of subtle dynamical signatures on the verge of instability. Whether such dynamical signatures can be measured before impending seizures remains uncertain. Here, we verified that predictions on bifurcations applied to the onset of hippocampal seizures, providing concordant results from in silico modeling, optogenetics experiments in male mice and intracranial EEG recordings in human patients with epilepsy. Leveraging pharmacological control over neural excitability, we showed that the boundary between physiological excitability and seizures can be inferred from dynamical signatures passively recorded or actively probed in hippocampal circuits. Of importance for the design of future neurotechnologies, active probing surpassed passive recording to decode underlying levels of neural excitability, notably when assessed from a network of propagating neural responses. Our findings provide a promising approach for predicting and preventing seizures, based on a sound understanding of their dynamics. Understanding the sudden regime shifts leading to epileptic seizures is crucial for developing preventive measures. This research reveals that subtle dynamical changes can indicate impending seizures, and highlights the effectiveness of active probing over passive recording in assessing neural excitability in hippocampal circuits.

Background: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus internus (GPi) is an accepted therapy for Parkinson's disease (PD) with disabling motor complications. For elderly patients with poorer cognition and postural instability, GPi has been proposed as the preferable DBS target based on expert opinion, arguing GPi-DBS may be less complicated by depression, apathy, worsened verbal fluency, and executive dysfunction, resulting in greater improvement in quality of life (QoL). However, data supporting such patient-tailored approach are lacking. Objectives: The aims were to analyze whether the DBS target influences QoL in a PD cohort and a matched subgroup of frail patients with poor cognitive status and reduced postural stability, and whether other factors affect the QoL outcomes. Methods: In this retrospective study, we analyzed a single-center cohort of 138 PD patients who received bilateral STN-DBS (117) or GPi-DBS (21) using the mentioned approach for target selection. All patients underwent standardized clinical evaluations of motor- and nonmotor signs as well as QoL before and 1 year after surgery. Results: DBS of both targets improved motor signs, dyskinesias, and pain. QoL improved without significant difference between the targets, but with a trend for greater improvement across all QoL domains in favor of the STN, even in an STN subgroup matched to the GPi group. Conclusion: Our results contradict the prevailing belief that GPi-DBS is superior in frail PD patients with cognitive decline and postural instability, questioning the proposed patient-tailored approach of DBS target selection. Further studies are needed for a data-driven approach.

Background Subthalamic nucleus deep brain stimulation (STN-DBS) is a well-established treatment for motor complications in Parkinson’s disease (PD). However, its effects on neuropsychiatric symptoms remain disputed. The aim of this study was to evaluate the effects of STN-DBS on neuropsychiatric symptoms in PD.Methods We retrospectively assessed 26 patients with PD who underwent a preoperative levodopa challenge and postoperative levodopa and stimulation challenges 1 year after STN-DBS. Based on the Neuropsychiatric Fluctuations Scale, Neuropsychiatric State Scores and Neuropsychiatric Fluctuation Indices (NFIs) were calculated. Mixed-effects models with random effects for intercept were used to examine the association of Neuropsychiatric State Score and NFI with the different assessment conditions.Results In acute challenge conditions, there was an estimated increase of 15.9 points in the Neuropsychiatric State Score in stimulation ON conditions (95% CI 11.4 to 20.6, p<0.001) and 7.6 points in medication ON conditions (95% CI 3.3 to 11.9, p<0.001). Neuropsychiatric fluctuations induced by levodopa, quantified with NFI, decreased by 35.54% (95% CI 49.3 to 21.8, p<0.001) 1 year after STN-DBS.Conclusions Bilateral STN-DBS at therapeutic parameters has acute psychotropic effects similar to levodopa and can modulate and decrease levodopa-induced neuropsychiatric fluctuations.

BACKGROUND:Deep brain stimulation (DBS) programming of multicontact DBS leads relies on a very time-consuming manual screening procedure, and strategies to speed up this process are needed. Beta activity in subthalamic nucleus (STN) local field potentials (LFP) has been suggested as a promising marker to index optimal stimulation contacts in patients with Parkinson disease.OBJECTIVE:In this study, we investigate the advantage of algorithmic selection and combination of multiple resting and movement state features from STN LFPs and imaging markers to predict three relevant clinical DBS parameters (clinical efficacy, therapeutic window, side-effect threshold).MATERIALS AND METHODS:STN LFPs were recorded at rest and during voluntary movements from multicontact DBS leads in 27 hemispheres. Resting- and movement-state features from multiple frequency bands (alpha, low beta, high beta, gamma, fast gamma, high frequency oscillations [HFO]) were used to predict the clinical outcome parameters. Subanalyses included an anatomical stimulation sweet spot as an additional feature.RESULTS:Both resting- and movement-state features contributed to the prediction, with resting (fast) gamma activity, resting/movement-modulated beta activity, and movement-modulated HFO being most predictive. With the proposed algorithm, the best stimulation contact for the three clinical outcome parameters can be identified with a probability of almost 90% after considering half of the DBS lead contacts, and it outperforms the use of beta activity as single marker. The combination of electrophysiological and imaging markers can further improve the prediction.CONCLUSION:LFP-guided DBS programming based on algorithmic selection and combination of multiple electrophysiological and imaging markers can be an efficient approach to improve the clinical routine and outcome of DBS patients.

Objective: We aimed to demonstrate the feasibility of using motor evoked responses to intraoperative double-train stimulation to guide lead placement and matching of intraoperative contacts with postoperative electrode programming in spinal cord stimulation for pain performed under general anesthesia.Materials and Methods: The study included a series of 20 consecutive patients with refractory pain operated on under general anesthesia. Either percutaneous or paddle leads were implanted and positioned according to the intraoperative mapping results. Neurophysiologic mapping was performed with a double-train stimulation paradigm (intertrain interval of 60 milliseconds, three to five cathodal pulses with 0.5-millisecond pulse duration, and within-train interstimulus intervals of 2-4 milliseconds). The sites where dorsal column responses of the targeted dermatomes were detected were considered optimal for lead placement (intraoperative best contacts). Following spinal cord stimulator (SCS) lead placement, blinded postoperative programming of electrode contacts was matched with the intraoperative best contacts and the pain-paresthesia overlap for the trial phase. A binominal test was used as a statistical method; pre-and postoperative numeric rating scale (NRS) after three months was obtained.Results: A total of 15 patients underwent spinal cord stimulation trial for intractable pain. Of these, ten patients (66%) had a successful trial and received permanent implants; one patient had a successful trial but was never intended to be implanted because of her poor health condition; four patients (26%) had an unsuccessful trial, leading to trial electrode explantation; and five patients had already had an implant with percutaneous leads and therefore underwent electrode revision, of whom four patients received paddle leads. In 18 of the 20 operated patients (90%), we found a match between the best intraoperative contacts and the postoperatively programmed contacts (significantly better than chance, p = 8.2 x 10(-15)). In 90% of the patients, a pain-paresthesia overlap of 100% was found. In the remaining two patients (10%), the postoperatively best programmed contacts were one contact away from the intraoperative neurophysiologic best contact. A mean preoperative NRS score of 8.2 (variance) and a mean follow-up NRS score after three months of 3.6 (variance) were obtained for all patients with implants.Conclusion: In this proof-of-concept study, we were able to demonstrate that SCS lead placement using a double-train stim-ulation paradigm performed under general anesthesia is a safe and feasible technique, offering reliable prediction of contacts for postoperative programming and excellent pain-paresthesia coverage.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for advanced Parkinson's disease. Stimulation of the hyperdirect pathway (HDP) may mediate the beneficial effects, whereas stimulation of the corticospinal tract (CST) mediates capsular side effects. The study's objective was to suggest stimulation parameters based on the activation of the HDP and CST. This retrospective study included 20 Parkinson's disease patients with bilateral STN DBS. Patient-specific whole-brain probabilistic tractography was performed to extract the HDP and CST. Stimulation parameters from monopolar reviews were used to estimate volumes of tissue activated and to determine the streamlines of the pathways inside these volumes. The activated streamlines were related to the clinical observations. Two models were computed, one for the HDP to estimate effect thresholds and one for the CST to estimate capsular side effect thresholds. In a leave-one-subject-out cross-validation, the models were used to suggest stimulation parameters. The models indicated an activation of 50% of the HDP at effect threshold, and 4% of the CST at capsular side effect threshold. The suggestions for best and worst levels were significantly better than random suggestions. Finally, we compared the suggested stimulation thresholds with those from the monopolar reviews. The median suggestion errors for the effect threshold and side effect threshold were 1 and 1.5 mA, respectively. Our stimulation models of the HDP and CST suggested STN DBS settings. Prospective clinical studies are warranted to optimize tract-guided DBS programming. Together with other modalities, these may allow for assisted STN DBS programming.