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Whether treatment response in patients with Parkinson disease depends on brain atrophy is insufficiently understood. The goal of this study is to identify specific atrophy patterns associated with response to dopaminergic therapy and deep brain stimulation.In this study, we analyzed the association of gray matter brain atrophy patterns, as identified by voxel-based morphometry, with acute response to levodopa (N = 118) and subthalamic nucleus deep brain stimulation (N = 39). Motor status was measured as a change in points on the Unified Parkinson's Disease Rating Scale III score. Baseline values were obtained before surgery, after cessation of dopaminergic medication for at least 12 hours; response to medication was assessed after administration of a standardized dose of levodopa. Response to deep brain stimulation was measured three months after surgery in the clinical condition after withdrawal of dopaminergic medication.Although frontoparietal brain gray matter loss was associated with subpar response to deep brain stimulation, there was no significant link between brain atrophy and response to levodopa.We conclude that response to deep brain stimulation relies on gray matter integrity; hence, gray matter loss may present a risk factor for poor response to deep brain stimulation and may be considered when making decision regarding clinical practice.

OBJECTIVE The treatment of symptomatic, progressive or recurrent acquired intracerebral cysts is challenging, especially when they are localized in eloquent structures. In addition to resection, endoscopic fenestration, or stereotactic puncture, the implantation of a cystoventricular shunt by stereotactic guidance (SCVS) has been reported as a minimally invasive procedure; however, only scarce data are available regarding its feasibility and efficacy. Here, the authors evaluated the feasibility and efficacy of frame-based SCVS in patients with acquired intracranial cysts. METHODS In this single-center retrospective analysis, the authors included all patients with acquired intracerebral cysts treated by SCVS following a standardized prospective protocol between 2012 and 2020. They analyzed clinical symptoms, complications, and radiological outcome with regard to cyst volume reduction by 3D volumetry. RESULTS Thirty-four patients (17 females and 17 males; median age 44 years, range 5–77 years) were identified. The median initial cyst volume was 11.5 cm3 (range 1.6–71.6 cm3), and the mean follow-up was 20 months (range 1–82 months). At the last follow-up, 27 of 34 patients (79%) showed a cyst volume reduction of more than 50%. Initial symptoms improved or resolved in 74% (n = 25) and remained stable in 24% (n = 8). No permanent clinical deterioration after treatment was observed. The total complication rate was 5.9%, comprising transient neurological deterioration (n = 1) and ventriculitis (n = 1). There were no deaths. The overall recurrence rate was 11.8%. CONCLUSIONS In this study, SCVS proved to be a safe, minimally invasive, and effective treatment with reliable long-term volume reduction, resulting in clinical improvement and a minor complication rate.

ObjectiveThis study aims to shed light on structural networks associated with stimulation-induced dysarthria (SID) and to derive a data-driven model to predict SID in patients with Parkinson’s Disease (PD) and deep brain stimulation (DBS) of the subthalamic nucleus (STN).MethodsRandomized, double-blinded monopolar reviews determining SID thresholds were conducted in 25 patients with PD and STN-DBS. A fiber-based mapping approach, based on the calculation of fiber-wise Odds Ratios for SID, was employed to identify the distributional pattern of SID in the STN’s vicinity. The ability of the data-driven model to classify stimulation volumes as “causing SID” or “not causing SID” was validated by calculating receiver operating characteristics (ROC) in an independent out-of-sample cohort comprising 14 patients with PD and STN-DBS.ResultsLocal fiber-based stimulation maps showed an involvement of fibers running lateral and postero-medial to the STN in the pathogenesis of SID, independent of the investigated hemisphere. ROC-analysis in the independent out-of-sample cohort resulted in a good fit of the data-driven model for both hemispheres (AUCleft= 0.88, AUCright= 0.88).InterpretationThis study reveals an involvement of both, cerebello-thalamic fibers, as well as the pyramidal tract, in the pathogenesis of SID in STN-DBS. The results may impact future postoperative programming strategies to avoid SID in patients with PD and STN-DBS.

OBJECTIVE To obtain individual clinical and neuroimaging data of patients undergoing Deep Brain Stimulation for essential tremor from five different European centers to identify predictors of outcome and to identify an optimal stimulation site. METHODS We analysed retrospectively baseline covariates, pre- and postoperative clinical tremor scores (12-month) as well as individual imaging data from 119 patients to obtain individual electrode positions and stimulation volumes. Individual imaging and clinical data was used to calculate a probabilistic stimulation map in normalized space using voxel-wise statistical analysis. Finally, we used this map to train a classifier to predict tremor improvement. RESULTS Probabilistic mapping of stimulation effects yielded a statistically significant cluster that was associated with a tremor improvement greater than 50%. This cluster of optimal stimulation extended from the posterior subthalamic area to the ventralis intermedius nucleus and coincided with a normative structural-connectivity-based cerebello-thalamic tract (CTT). The combined features "distance between the stimulation volume and the significant cluster" and "CTT activation" were used as a predictor of tremor improvement. This correctly classified a greater than 50% tremor improvement with a sensitivity of 89% and a specificity of 57%. INTERPRETATION Our multicentre ET probabilistic stimulation map identified an area of optimal stimulation along the course of the CTT. The results of this study are mainly descriptive until confirmed in independent datasets, ideally through prospective testing. This target will be made openly available and may be used to guide surgical planning and for computer-assisted programming of deep brain stimulation in the future. This article is protected by copyright. All rights reserved.

Background: The satisfaction with life and, in particular, with treatment in Parkinson’s disease (PD) is understudied. Objective: To explore a new 7-item rating tool assessing satisfaction with life and treatment (SLTS-7) in PD. Methods: In this cross-sectional, multi-center study, including patients screened for advanced therapies, psychometric characteristics of the SLTS-7 were analyzed. An exploratory factor analysis identified the underlying factorial structure of the SLTS-7. Results: 117 patients were included, and the data quality of the SLTS-7 was excellent (computable data 100%), and acceptability measures satisfied standard criteria. Besides the global assessment (item 1), the exploratory factor analysis produced item 2 (physical satisfaction) as an independent item and two factors among the remaining items: items 3–5 (psycho-social satisfaction), and items 6 and 7 (treatment satisfaction). Cronbach’s alpha was 0.89, indicative of high internal consistency. The SLTS-7 total score correlated moderately with motor symptoms and weakly with non-motor symptoms total scores. SLTS-7 showed the highest correlations with the European Quality of Life with 5 items (EQ-5D) visual analog scale (0.43–0.58, p

IntroductionDeep brain stimulation (DBS) is an established treatment in patients with pharmaco-resistant neurological disorders of different ages. Surgical targeting and postoperative programming of DBS depend on the spatial location of the stimulating electrodes in relation to the surrounding anatomical structures and on electrode connectivity to a specific distributed pattern of brain networks. Such information is usually collected using group-level analysis which relies on the availability normative imaging-resources (atlases and connectomes). To this end, analyzing DBS data of children with debilitating neurological disorders like dystonia would make benefit from such resources, especially given the developmental differences between adults and children neuroimaging data. We assembled pediatric, normative neuroimaging-resources from open-access neuroimaging datasets and illustrated their utility on a cohort of children with dystonia treated with pallidal DBS. We aimed to derive a local pallidal sweetspot and explore a connectivity fingerprint associated with pallidal stimulation to exemplify the utility of the assembled imaging resources.MethodsA pediatric average brain template was implemented and used to localize DBS electrodes of twenty patients of the GEPESTIM registry cohort. Next, a pediatric subcortical atlas was also employed to highlight anatomical structures of interest. Local pallidal sweetspot was modeled and its degree of overlap with stimulation volumes was calculated as a correlate of individual clinical outcome. Additionally, a pediatric functional connectome of neurotypical subjects was built to allow network-based analyses and decipher a connectivity fingerprint responsible for clinical improvement in our cohort.ResultsWe successfully implemented a pediatric neuroimaging dataset that will be made available to public use as a tool for DBS-analyses. Overlap of stimulation volumes with the identified DBS-sweetspot model correlated significantly with improvement on a local spatial level (R = 0.46,permuted p= 0.019). Functional connectivity fingerprint of DBS-outcome was determined as a network correlate of therapeutic pallidal stimulation in children with dystonia (R = 0.30,permuted p= 0.003).ConclusionsLocal sweetspot and distributed network models provide neuroanatomical substrates for DBS-associated clinical outcome in dystonia using pediatric neuroimaging surrogate data. The current implementation of pediatric neuroimaging dataset might help improving the practice of DBS-neuroimaging analyses in pediatric patients.

Introduction: Deep brain stimulation (DBS) is a well-established treatment for patients with Parkinson's disease (PD) improving quality of life, motor, and non-motor symptoms. However, non-motor effects in PD subtypes are understudied. We hypothesized that patients with 'postural instability and gait difficulty' (PIGD) experience more beneficial non-motor effects than 'tremor-dominant' patients undergoing DBS for PD.Methods: In this prospective, observational, international multicentre study with a 6-month follow-up, we assessed the Non-Motor Symptom Scale (NMSS) as primary and the following secondary outcomes: Unified PD Rating Scale-motor examination (UPDRS-III), Scales for Outcomes in PD (SCOPA)-activities of daily living (ADL) and -motor complications, PDQuestionnaire-8 (PDQ-8), and levodopa-equivalent daily dose (LEDD). We analysed within-group longitudinal changes with Wilcoxon signed-rank test and Benjamini-Hochberg correction for multiple comparisons. Additionally, we explored outcome between-group differences of motor subtypes with Mann-Whitney U-tests.Results: In 82 PIGD and 33 tremor-dominant patients included in this study, baseline NMSS total scores were worse in PIGD patients, both groups experienced postoperative improvements of the NMSS sleep/fatigue domain, and between-group differences in postoperative outcomes were favourable in the PIGD group for the NMSS total and miscellaneous domain scores.Conclusions: This study provides evidence of a favourable outcome of total non-motor burden in PIGD compared to tremor-dominant patients undergoing DBS for PD. These differences of clinical efficacy on non-motor aspects should be considered when advising and monitoring patients with PD undergoing DBS.Keywords: Deep brain stimulation; Nonmotor symptoms; Postural instability and gait difficulty; Quality of life; Tremor-dominant.

Obsessive-compulsive disorder is among the most disabling psychiatric disorders. Although deep brain stimulation is considered an effective treatment, its use in clinical practice is not fully established. This is, at least in part, due to ambiguity about the best suited target and insufficient knowledge about underlying mechanisms. Recent advances suggest that changes in broader brain networks are responsible for improvement of obsessions and compulsions, rather than local impact at the stimulation site. These findings were fueled by innovative methodological approaches using brain connectivity analyses in combination with neuromodulatory interventions. Such a connectomic approach for neuromodulation constitutes an integrative account that aims to characterize optimal target networks. In this critical review, we integrate findings from connectomic studies and deep brain stimulation interventions to characterize a neural network presumably effective in reducing obsessions and compulsions. To this end, we scrutinize methodologies and seemingly conflicting findings with the aim to merge observations to identify common and diverse pathways for treating obsessive-compulsive disorder. Ultimately, we propose a unified network that-when modulated by means of cortical or subcortical interventions-alleviates obsessive-compulsive symptoms. https://doi.org/10.1016/j.biopsych.2021.07.010

Intra- and perioperatively recorded local field potential (LFP) activity of the nucleus subthalamicus (STN) has been suggested to guide contact selection in patients undergoing deep brain stimulation (DBS) for Parkinson’s disease (PD). Despite the invention of sensing capacities in chronically implanted devices, a comprehensible algorithm that enables contact selection using such recordings is still lacking. We evaluated a fully automated algorithm that uses the weighted average of bipolar recordings to determine effective monopolar contacts based on elevated activity in the beta band. LFPs from 14 hemispheres in seven PD patients with newly implanted directional DBS leads of the STN were recorded. First, the algorithm determined the stimulation level with the highest beta activity. Based on the prior determined level, the directional contact with the highest beta activity was chosen in the second step. The mean clinical efficacy of the contacts chosen using the algorithm did not statistically differ from the mean clinical efficacy of standard contact selection as performed in clinical routine. All recording sites were projected into MNI standard space to investigate the feasibility of the algorithm with respect to the anatomical boundaries of the STN. We conclude that the proposed algorithm is a first step towards LFP-based contact selection in STN-DBS for PD using chronically implanted devices.

Background There is still a lack of controlled studies to prove efficacy of thalamic deep brain stimulation for Tourette's Syndrome. Objectives In this controlled trial, we investigated the course of tic severity, comorbidities and quality of life during thalamic stimulation and whether changes in tic severity can be assigned to ongoing compared to sham stimulation. Methods We included eight adult patients with medically refractory Tourette's syndrome. Bilateral electrodes were implanted in the centromedian-parafascicular-complex and the nucleus ventro-oralis internus. Tic severity, quality of life and comorbidities were assessed before surgery as well as six and twelve months after. Short randomized, double-blinded sham-controlled crossover sequences with either active or sham stimulation were implemented at both six- and twelve-months’ assessments. The primary outcome measurement was the difference in the Yale Global Tic Severity Scale tic score between active and sham stimulation. Adverse events were systematically surveyed for all patients to evaluate safety. Results Active stimulation resulted in significantly higher tic reductions than sham stimulation (F = 79.5; p = 0.001). Overall quality of life and comorbidities improved significantly in the open-label-phase. Over the course of the trial two severe adverse events occurred that were resolved without sequelae. Conclusion Our results provide evidence that thalamic stimulation is effective in improving tic severity and overall quality of life. Crucially, the reduction of tic severity was primarily driven by active stimulation. Further research may focus on improving stimulation protocols and refining patient selection to improve efficacy and safety of deep brain stimulation for Tourette's Syndrome.

Self-injurious behavior (SIB) is associated with diverse psychiatric conditions. Sometimes (e.g., in patients with autism spectrum disorder or acquired brain injuries), SIB is the most dominant symptom, severely restricting the psychosocial functioning and quality of life of the patients and inhibiting appropriate patient care. In severe cases, it can lead to permanent physical injuries or even death. Primary therapy consists of medical treatment and if implementable, behavioral therapy. For patients with severe SIB refractory to conventional therapy, neuromodulation can be considered as a last recourse. In scientific literature, several successful lesioning and deep brain stimulation targets have been described that can indicate a common underlying neuronal pathway. The objectives of this study were to evaluate the short- and long-term clinical outcome of patients with severe, therapy refractory SIB who underwent DBS with diverse underlying psychiatric disorders and to correlate these outcomes with the activated connectivity networks. We retrospectively analyzed 10 patients with SIB who underwent DBS surgery with diverse psychiatric conditions including autism spectrum disorder, organic personality disorder after hypoxic or traumatic brain injury or Tourette syndrome. DBS targets were chosen according to the underlying disorder, patients were either stimulated in the nucleus accumbens, amygdala, posterior hypothalamus, medial thalamus or ventrolateral thalamus. Clinical outcome was measured 6 months after surgery and at long-term follow-up after 10 or more years using the Early Rehabilitation Barthel index (ERBI) and time of restraint. Connectivity patterns were analyzed using normative connectome. Based on previous literature the orbitofrontal cortex, superior frontal gyrus, the anterior cingulate cortex, the amygdala and the hippocampus were chosen as regions of interest. This analysis showed a significant improvement in the functionality of the patients with DBS in the short- and long-term follow-up. Good clinical outcome correlated with higher connectivity to the amygdala and hippocampus. These findings may suggest a common pathway, which can be relevant when planning a surgical procedure in patients with SIB.

The occurrence of tics in Tourette syndrome (TS) has often been linked to impaired cognitive control, but empirical findings are still inconclusive. A recent view proposes that tics may be the result of an abnormally strong interrelation between perceptual processes and motor actions, commonly referred to as perception-action binding. The general aim of the present study was to examine proactive control and binding effects in the context of task switching in adult human patients with TS and matched healthy controls. A cued task switching paradigm was employed in 24 patients (18 male, 6 female) and 25 controls while recording electroencephalography (EEG). Residue iteration decomposition (RIDE) was applied to analyze cue-locked proactive cognitive control and target-locked binding processes. Behavioral task switching performance was unaltered in patients with TS. A cue-locked parietal switch positivity, reflecting proactive control processes involved in the reconfiguration of the new task did not differ between groups. Importantly, target-locked fronto-central (N2) and parietal (P3) modulations, reflecting binding processes between perception and action, differed between groups. Underlying neurophysiological processes were best depicted after temporal decomposition of the EEG signal. The present results argue for unaltered proactive control but altered perception-action binding processes in the context of task switching, supporting the view that the integration of perception and action is processed differently in patients TS. Future studies should further investigate the specific conditions under which binding may be altered in TS and the influence of top-down processes, such as proactive control, on bindings.

Background: Subthalamic nucleus deep brain stimulation (STN-DBS) is a well-established treatment for patients with Parkinson’s disease. Previous acute challenge studies suggested that short pulse widths might increase the therapeutic window while maintaining motor symptom control with a decrease in energy consumption. However, only little is known about the effect of short pulse width stimulation beyond the setting of an acute challenge. Objective: To compare 4 weeks of STN-DBS with conventional pulse width stimulation (60 μs) to 4 weeks of STN-DBS with short pulse width stimulation (30 μs) regarding motor symptom control. Methods: This study was a monocentric, double-blinded, randomized crossover non-inferiority trial investigating whether short pulse width stimulation with 30 μs maintains equal motor control as conventional 60 μs stimulation over a period of 4 weeks (German Clinical Trials Register No. DRKS00017528). Primary outcome was the difference in motor symptom control as assessed by a motor diary. Secondary outcomes included energy consumption measures, non-motor effects, side-effects, and quality of life. Results: Due to a high dropout rate, the calculated sample size of 27 patients was not met and 24 patients with Parkinson’s disease and STN-DBS were included in the final analysis. However, there were no differences in any investigated outcome parameter between the two treatment conditions. Conclusion: This study demonstrates that short pulse width settings (30 μs) provide non-inferior motor symptom control as conventional (60 μs) stimulation without significant differences in energy consumption. Future studies are warranted to evaluate a potential benefit of short pulse width settings in patients with pronounced dyskinesia.

Due to the increasing number of cases of Alzheimer's disease and the relatively moderate success with the available symptomatic and causal pharmacological therapies, there is a considerable need to explore non-pharmacological treatment options. In the field of non-invasive brain stimulation (NIBS), various methods have been investigated, particularly transcranial magnetic stimulation and transcranial electrical stimulation. In addition, deep brain stimulation (DBS) is currently being researched as an innovative method for targeted neuromodulation. Both non-invasive and invasive approaches aim to modulate neuronal activity and improve cognitive-mnestic functions. Secondary mechanisms such as long-term potentiation in NIBS or neurogenesis in DBS could also achieve long-term positive effects. Preclinical and clinical studies have already shown promising results in patients in early stages of Alzheimer's disease. However, inconsistent study and stimulation protocols and small sample sizes make it difficult to assess efficacy. Further research is warranted to enable the use of non-invasive or invasive neuromodulatory approaches in clinical practice in the near future.Aufgrund steigender Fallzahlen der Alzheimer-Erkrankung und bislang eher mäßigem Erfolg der verfügbaren symptomatischen und kausalen pharmakologischen Therapien besteht ein erheblicher Bedarf, nicht-pharmakologische Behandlungsmöglichkeiten zu erforschen. Im Bereich der nicht-invasiven Hirnstimulation (non-invasive brain stimulation; NIBS) wurden verschiedene Verfahren untersucht, insbesondere die transkranielle Magnetstimulation und die transkranielle elektrische Stimulation. Zusätzlich wird derzeit die Tiefe Hirnstimulation (deep brain stimulation; DBS) als innovatives Verfahren zur gezielten Neuromodulation erforscht. Nicht-invasiven und invasiven Ansätzen gemein ist der Versuch, neuronale Aktivität zu modulieren und kognitiv-mnestische Funktionen zu verbessern. Durch sekundäre Mechanismen wie die Langzeit-Potenzierung bei NIBS oder Neurogenese bei DBS könnten auch längerfristige positive Effekte erzielt werden. Präklinische und klinische Studien ergaben bereits vielversprechende Ergebnisse bei Patientinnen und Patienten in frühen Stadien der Alzheimer-Erkrankung. Inkonsistente Studien- und Stimulationsprotokolle sowie kleine Stichproben erschweren jedoch die Bewertung der Wirksamkeit. Weitere Forschungsbemühungen sind angebracht, um einen zeitnahen Einzug nicht-invasiver oder invasiver neuromodulatorischer Ansätze in die klinische Praxis zu ermöglichen.

OBJECTIVE This study was undertaken to gain insights into structural networks associated with stimulation-induced dysarthria (SID) and to predict stimulation-induced worsening of intelligibility in essential tremor patients with bilateral thalamic deep brain stimulation (DBS). METHODS Monopolar reviews were conducted in 14 essential tremor patients. Testing included determination of SID thresholds, intelligibility ratings, and a fast syllable repetition task. Volumes of tissue activated (VTAs) were calculated to identify discriminative fibers for stimulation-induced worsening of intelligibility in a structural connectome. The resulting fiber-based atlas structure was then validated in a leave-one-out design. RESULTS Fibers determined as discriminative for stimulation-induced worsening of intelligibility were mainly connected to the ipsilateral precentral gyrus as well as to both cerebellar hemispheres and the ipsilateral brain stem. In the thalamic area, they ran laterally to the thalamus and posteromedially to the subthalamic nucleus, in close proximity, mainly anterolaterally, to fibers beneficial for tremor control as published by Al-Fatly et al in 2019. The overlap of the respective clinical stimulation setting's VTAs with these fibers explained 62.4% (p

Background: Directional leads are increasingly used in deep brain stimulation. They allow shaping the electrical field in the axial plane. These new possibilities increase the complexity of programming. Thus, optimized programming approaches are needed to assist clinical testing and to obtain full clinical benefit. Objectives: This simulation study investigates to what extent the electrical field can be shaped by directional steering to compensate for lead malposition. Method: Binary volumes of tissue activated (VTA) were simulated, by using a finite element method approach, for different amplitude distributions on the three directional electrodes. VTAs were shifted from 0 to 2 mm at different shift angles with respect to the lead orientation, to determine the best compensation of a target volume. Results: Malpositions of 1 mm can be compensated with the highest gain of overlap with directional leads. For larger shifts, an improvement of overlap of 10–30% is possible, depending on the stimulation amplitude and shift angle of the lead. Lead orientation and shift determine the amplitude distribution of the electrodes. Conclusion: To get full benefit from directional leads, both the shift angle as well as the shift to target volume are required to choose the correct amplitude distribution on the electrodes. Current directional leads have limitations when compensating malpositions >1 mm; however, they still outperform conventional leads in reducing overstimulation. Further, their main advantage probably lies in the reduction of side effects. Databases like the one from this simulation could serve for optimized lead programming algorithms in the future.

Background: Directional deep brain stimulation (DBS) enlarges the therapeutic window by increasing side-effect thresholds and improving clinical benefits. To determine the optimal stimulation settings and interpret clinical observations, knowledge of the lead orientation in relation to the patient’s anatomy is required. Objective: To determine if directional leads remain in a fixed orientation after implantation or whether orientation changes over time. Method: Clinical records of 187 patients with directional DBS electrodes were screened for CT scans in addition to the routine postoperative CT. The orientation angle of each electrode at a specific point in time was reconstructed from CT artifacts using the DiODe algorithm implemented in Lead-DBS. The orientation angles over time were compared with the originally measured orientations from the routine postoperative CT. Results: Multiple CT scans were identified in 18 patients and the constancy of the orientation angle was determined for 29 leads at 48 points in time. The median time difference between the observations and the routine postoperative CT scan was 82 (range 1–811) days. The mean difference of the orientation angles compared to the initial measurement was –1.1 ± 3.9° (range –7.6 to 8.7°). Linear regression showed no relevant drift of the absolute value of the orientation angle over time (0.8°/year, adjusted R2: 0.040, p = 0.093). Conclusion: The orientation of directional leads was stable and showed no clinically relevant changes either in the first weeks after implantation or over longer periods of time.

Recent translational data suggest that deep brain stimulation (DBS) of the cortico-striato-thalamo-cortical (CSTC) loops improves sensorimotor gating in psychiatric disorders that show deficient prepulse inhibition (PPI), a robust operational measure of sensorimotor gating. To our knowledge we are the first to investigate this effect in patients with Tourette syndrome (TS). We measured PPI of the acoustic startle reflex in patients with TS (N = 10) or Obsessive-Compulsive Disorder (OCD) (N = 8) treated with DBS of the centromedian and ventro-oral internal thalamic nucleus and the anterior limb of internal capsule-nucleus accumbens area respectively, and aged- and gender-matched healthy controls (HC). PPI of the DBS groups was measured in randomized order in the ON and OFF stimulation condition. Statistical analysis revealed no significant difference in PPI (%) of patients with TS between ON (M = 20.5, SD = 14.9) and OFF (M = 25.2, SD = 29.7) condition. There were significantly reduced PPI levels in patients with TS in the ON condition compared to HC (M = 49.2, SD = 10.7), but no significant difference in PPI between TS in the OFF condition and HC. Furthermore, we found no significant stimulation or group effect for OCD and HC (OCD ON: M = 57.0, SD = 8.3; OCD OFF: 67.8, SD = 19.6; HC: M = 63.0, SD = 24.3). Our study has a number of limitations. Sample sizes are small due to the restricted patient collective. The study was not controlled for use of psychoactive medication or nicotine. Furthermore, we were not able to assess presurgical PPI measurements. In conclusion, we were able to show that PPI is impaired in patients with TS. This finding is in line with recent translational work. With respect to the OCD cohort we were not able to replicate our previously published data. A disability in sensorimotor gating plays a pivotal role in many psychiatric disorders therefore more research should be conducted to disentangle the potential and limitations of modulating sensorimotor gating via brain stimulation techniques.

Deep brain stimulation may be an effective therapy for select cases of severe, treatment-refractory Tourette syndrome; however, patient responses are variable, and there are no reliable methods to predict clinical outcomes. The objectives of this retrospective study were to identify the stimulation-dependent structural networks associated with improvements in tics and comorbid obsessive-compulsive behaviour, compare the networks across surgical targets, and determine if connectivity could be used to predict clinical outcomes. Volumes of tissue activated for a large multisite cohort of patients (n = 66) implanted bilaterally in globus pallidus internus (n = 34) or centromedial thalamus (n = 32) were used to generate probabilistic tractography to form a normative structural connectome. The tractography maps were used to identify networks that were correlated with improvement in tics or comorbid obsessive-compulsive behaviour and to predict clinical outcomes across the cohort. The correlated networks were then used to generate ‘reverse’ tractography to parcellate the total volume of stimulation across all patients to identify local regions to target or avoid. The results showed that for globus pallidus internus, connectivity to limbic networks, associative networks, caudate, thalamus, and cerebellum was positively correlated with improvement in tics; the model predicted clinical improvement scores (P = 0.003) and was robust to cross-validation. Regions near the anteromedial pallidum exhibited higher connectivity to the positively correlated networks than posteroventral pallidum, and volume of tissue activated overlap with this map was significantly correlated with tic improvement (P 0.23). For obsessive-compulsive behaviour, both targets showed that connectivity to the prefrontal cortex, orbitofrontal cortex, and cingulate cortex was positively correlated with improvement; however, only the centromedial thalamus maps predicted clinical outcomes across the cohort (P = 0.034), but the model was not robust to cross-validation. Collectively, the results demonstrate that the structural connectivity of the site of stimulation are likely important for mediating symptom improvement, and the networks involved in tic improvement may differ across surgical targets. These networks provide important insight on potential mechanisms and could be used to guide lead placement and stimulation parameter selection, as well as refine targets for neuromodulation therapies for Tourette syndrome.

Objective To compare directional monopolar, bipolar, and directional bipolar thalamic deep brain stimulation (DBS) in tremor patients. Methods Fourteen tremor patients (7 Essential Tremor and 7 Parkinson's Disease) implanted with directional DBS electrodes in the ventral intermediate nucleus (VIM) were enrolled. Side-effect thresholds of monopolar directional stimulation (DIRECT) were compared to circular DBS as well as, in a randomized design, to those of two different bipolar stimulation settings (BIPOLAR = circular anode; BI-DIRECT = directional anode). Tremor suppression (Tremor Rating Scale, TRS) right below the side-effect threshold was also assessed. Results Directional DBS in the individually best direction showed higher side-effect thresholds than circular DBS (p = 0.0063). The thresholds were raised further using either one of the bipolar stimulation paradigms (BIPOLAR p = 0.0029, BI-DIRECT p = 0.0022). The side-effect thresholds did not differ between both bipolar settings, but side-effects were less frequent with BI-DIRECT. No difference in TRS scores with stimulation just below the side-effect threshold was found between all stimulation conditions. Conclusions Side-effect thresholds of monopolar directional and bipolar stimulation with both circular and directional anodes were higher compared to traditional monopolar circular stimulation in the VIM. Bipolar DBS with directional anodes evoked side-effect less frequently than bipolar and monopolar directional stimulation. All stimulation settings had comparable effects on tremor suppression just below their side-effect thresholds. Thus, directional and different bipolar settings should be explored in patients with bothersome side-effects of thalamic stimulation when monopolar stimulation settings are not satisfying. Further studies are needed to explore the efficiency of the different bipolar stimulation paradigms.

Introduction Deep learning-based algorithms have demonstrated enormous performance in segmentation of medical images. We collected a dataset of multiparametric MRI and contour data acquired for use in radiosurgery, to evaluate the performance of deep convolutional neural networks (DCNN) in automatic segmentation of brain metastases (BM). Methods A conventional U-Net (cU-Net), a modified U-Net (moU-Net) and a U-Net trained only on BM smaller than 0.4 ml (sU-Net) were implemented. Performance was assessed on a separate test set employing sensitivity, specificity, average false positive rate (AFPR), the dice similarity coefficient (DSC), Bland-Altman analysis and the concordance correlation coefficient (CCC). Results A dataset of 509 patients (1223 BM) was split into a training set (469 pts) and a test set (40 pts). A combination of all trained networks was the most sensitive (0.82) while maintaining a specificity 0.83. The same model achieved a sensitivity of 0.97 and a specificity of 0.94 when considering only lesions larger than 0.06 ml (75% of all lesions). Type of primary cancer had no significant influence on the mean DSC per lesion (p = 0.60). Agreement between manually and automatically assessed tumor volumes as quantified by a CCC of 0.87 (95% CI, 0.77–0.93), was excellent. Conclusion Using a dataset which properly captured the variation in imaging appearance observed in clinical practice, we were able to conclude that DCNNs reach clinically relevant performance for most lesions. Clinical applicability is currently limited by the size of the target lesion. Further studies should address if small targets are accurately represented in the test data.

The pterygopalatine fossa (PPF) is a complex and paired anatomical structure located at the skull base. A clinically and surgically relevant structure located in the pterygopalatine fossa is the sphenopalatine ganglion. Electrical stimulation of the sphenopalatine ganglion is one possible method of treating cluster headache. The pterygomaxillary fissure (PMF) defines the pterygopalatine fossa laterally and determines the surgical approach. As part of preoperative surgical planning, each patient undergoes a preoperative head computed tomography or a cone beam computed tomography. In our study cone beam computed tomography images of 90 male and 110 female PMF were analyzed. Generally, males have a wider fissure than females. Moreover, a significant inter-subject difference could be shown between males and females. The analysis of the right and left PMF according to gender and age does not show any significant intra-subject differences. Following an established protocol for high-resolution CT images the measurements were classified into four fissure types and also analyzed according to gender and age. Fissure type I is significantly more often present in males, whereas the smaller fissure types (II, III, and IV) are significantly more often found in females. Older patients presented statistically significant more often with type I, whereas the younger patients showed more often the narrower types II and IV. Due to the fact that narrow fissures smaller than 2 mm could limit the insertion of neurostimulator implants in the PPF, special attention should be paid to females and younger patients during preoperative planning.

Brain lesions are a rare cause of tic disorders. However, they can provide uniquely causal insights into tic pathophysiology and can also inform on possible neuromodulatory therapeutic targets. Based on a systematic literature review, we identified 22 cases of tics causally attributed to brain lesions and employed ‘lesion network mapping’ to interrogate whether tic-inducing lesions would be associated with a common network in the average human brain. We probed this using a normative functional connectome acquired in 1000 healthy participants. We then examined the specificity of the identified network by contrasting tic-lesion connectivity maps to those seeding from 717 lesions associated with a wide array of neurological and/or psychiatric symptoms within the Harvard Lesion Repository. Finally, we determined the predictive utility of the tic-inducing lesion network as a therapeutic target for neuromodulation. Specifically, we collected retrospective data of 30 individuals with Tourette disorder, who underwent either thalamic (n = 15; centromedian/ventrooralis internus) or pallidal (n = 15; anterior segment of globus pallidus internus) deep brain stimulation and calculated whether connectivity between deep brain stimulation sites and the lesion network map could predict clinical improvements. Despite spatial heterogeneity, tic-inducing lesions mapped to a common network map, which comprised the insular cortices, cingulate gyrus, striatum, globus pallidus internus, thalami and cerebellum. Connectivity to a region within the anterior striatum (putamen) was specific to tic-inducing lesions when compared with control lesions. Connectivity between deep brain stimulation electrodes and the lesion network map was predictive of tic improvement, regardless of the deep brain stimulation target. Taken together, our results reveal a common brain network involved in tic generation, which shows potential as a therapeutic target for neuromodulation.

Background: Freezing of gait (FOG) is among the most common and disabling symptoms of Parkinson’s disease (PD). Studies show that deep brain stimulation (DBS) of the subthalamic nucleus (STN) can reduce FOG severity. However, there is uncertainty about pathways that need to be modulated to improve FOG. Objective: To investigate whether STN-DBS effectively reduces FOG postoperatively and whether structural connectivity of the stimulated tissue explains variance of outcomes. Methods: We investigated 47 patients with PD and preoperative FOG. Freezing prevalence and severity was primarily assessed using the Freezing of Gait Questionnaire (FOG-Q). In a subset of 18 patients, provoked FOG during a standardized walking course was assessed. Using a publicly available model of basal-ganglia pathways we determined stimulation-dependent connectivity associated with postoperative changes in FOG. A region-of-interest analysis to a priori defined mesencephalic regions was performed using a disease-specific normative connectome. Results: Freezing of gait significantly improved six months postoperatively, marked by reduced frequency and duration of freezing episodes. Optimal stimulation volumes for improving FOG structurally connected to motor areas, the prefrontal cortex and to the globus pallidus. Stimulation of the lenticular fasciculus was associated with worsening of FOG. This connectivity profile was robust in a leave-one-out cross-validation. Subcortically, stimulation of fibers crossing the pedunculopontine nucleus and the substantia nigra correlated with postoperative improvement. Conclusion: STN-DBS can alleviate FOG severity by modulating specific pathways structurally connected to prefrontal and motor cortices. More differentiated FOG assessments may allow to differentiate pathways for specific FOG subtypes in the future.

Contains fulltext : 241592.pdf (Publisher’s version ) (Open Access) Objectives: Obsessive-compulsive disorder (OCD) is a psychiatric disorder with alterations of cortico-striato-thalamo-cortical loops and impaired performance monitoring. Electrophysiological markers such as conflict-related medial frontal theta (MFT) and error-related negativity (ERN) may be altered by clinically effective deep brain stimulation (DBS) of the anterior limb of the internal capsule and nucleus accumbens (ALIC/NAc). We hypothesized that ALIC/NAc DBS modulates electrophysiological performance monitoring markers. Materials and Methods: Fifteen patients (six male) with otherwise treatment-refractory OCD receiving ALIC/NAc DBS performed a flanker task with EEG recordings at three sessions: presurgery, and at follow-up with DBS on and off. We examined MFT, ERN, and task performance. Furthermore, we investigated interrelations with clinical efficacy and the explored the influence of the location of individual stimulation volumes on EEG modulations. Results: MFT and ERN were significantly attenuated by DBS with differences most pronounced between presurgery and DBS-on states. Also, we observed reaction time slowing for erroneous responses during DBS-off. Larger presurgery ERN amplitudes were associated with decreased clinical efficacy. Exploratory anatomical analyses suggested that stimulation volumes encompassing the NAc were associated with MFT modulation, whereas ALIC stimulation was associated with modulation of the ERN and clinical efficacy. Conclusion: ALIC/NAc DBS diminished MFT and ERN, demonstrating modulation of the medial frontal performance monitoring system in OCD. Furthermore, our findings encourage further studies to explore the ERN as a potential predictor for clinical efficacy. 8 p.

In 2011 the European Society for the Study of Tourette Syndrome (ESSTS) published its first European clinical guidelines for the treatment of Tourette Syndrome (TS) with part IV on deep brain stimulation (DBS). Here, we present a revised version of these guidelines with updated recommendations based on the current literature covering the last decade as well as a survey among ESSTS experts. Currently, data from the International Tourette DBS Registry and Database, two meta-analyses, and eight randomized controlled trials (RCTs) are available. Interpretation of outcomes is limited by small sample sizes and short follow-up periods. Compared to open uncontrolled case studies, RCTs report less favorable outcomes with conflicting results. This could be related to several different aspects including methodological issues, but also substantial placebo effects. These guidelines, therefore, not only present currently available data from open and controlled studies, but also include expert knowledge. Although the overall database has increased in size since 2011, definite conclusions regarding the efficacy and tolerability of DBS in TS are still open to debate. Therefore, we continue to consider DBS for TS as an experimental treatment that should be used only in carefully selected, severely affected and otherwise treatment-resistant patients.

Background: Hyperkinetic movement disorders secondary to brain tissue damage due to hyperglycemia are a rare complication of diabetes mellitus. Nonketotic hyperglycemic hemichorea (NH-HC) is characterized by a rapid onset of involuntary movements after increased serum glucose levels. Case Description: We report on a case of a 62-year-old male patient with a 28-year history of Type II diabetes mellitus with NH-HC following an infect-associated exacerbation of blood glucose levels. Choreiform movements of the right upper extremity, face, and trunk persisted 6 months after onset. Due to failure of conservative treatments, we opted for unilateral deep brain stimulation of the globus pallidus internus, which led to complete cessation of symptoms within a week after initial programming. Symptom control was still satisfactory 12 months after surgery. No side-effects or surgery-associated complications were observed. Conclusion: Globus pallidus internus DBS is an effective and safe treatment option for hyperkinetic movement disorders secondary to brain tissue damage caused by hyperglycemia. Postoperatively, stimulation effects can be observed quickly and effects persist even after 12 months.

Postoperative choice of the most effective deep brain stimulation (DBS) contact in patients with essential tremor (ET) so far relies on lengthy clinical testing. Previous studies showed that the postoperative effectiveness of DBS contacts depends on the distance to the dentatorubrothalamic tract (DRTT). Here, we investigated whether the most effective DBS contact could be determined from calculating stimulation overlap with the individual DRTT. Seven ET patients with bilateral thalamic deep brain stimulation were included retrospectively. Tremor control was assessed for each contact during test stimulation with 2mA. Individual DRTTs were identified from diffusion tensor imaging and contacts were ranked by their stimulation overlap with the respective DRTT in relation to their clinical effectiveness. A linear mixed-effects model was calculated to determine the influence of the DRTT overlap on tremor control. In 92.9% of investigated DBS leads, the contact with the best clinical effect was the contact with the highest or second-highest DRTT-overlap. At the group level, the DRTT-overlap explained 26.7% of the variance in the clinical outcomes (

Directional deep brain stimulation (DBS) leads are now widely used, but the orientation of directional leads needs to be taken into account when relating DBS to neuroanatomy. Methods that can reliably and unambiguously determine the orientation of directional DBS leads are needed. In this study, we provide an enhanced algorithm that determines the orientation of directional DBS leads from postoperative CT scans. To resolve the ambiguity of symmetric CT artifacts, which in the past, limited the orientation detection to two possible solutions, we retrospectively evaluated four different methods in 150 Cartesia™ directional leads, for which the true solution was known from additional X-ray images. The method based on shifts of the center of mass (COM) of the directional marker compared to its expected geometric center correctly resolved the ambiguity in 100% of cases. In conclusion, the DiODe v2 algorithm provides an open-source, fully automated solution for determining the orientation of directional DBS leads.

Background: Extended research has pointed to the efficacy of deep brain stimulation (DBS) in treatment of patients with treatment-refractory Tourette syndrome (TS). The four most commonly used DBS targets for TS include the centromedian nucleus–nucleus ventrooralis internus (CM-Voi) and the centromedian nucleus–parafascicular (CM-Pf) complexes of the thalamus, and the posteroventrolateral (pvIGPi) and the anteromedial portion of the globus pallidus internus (amGPi). Differences and commonalities between those targets need to be compared systematically.Objective: Therefore, we evaluated whether DBS is effective in reducing TS symptoms and target-specific differences.Methods: A PubMed literature search was conducted according to the PRISMA guidelines. Eligible literature was used to conduct a systematic review and meta-analysis.Results: In total, 65 studies with 376 patients were included. Overall, Yale Global Tic Severity Scale (YGTSS) scores were reduced by more than 50 in 69% of the patients. DBS also resulted in significant reductions of secondary outcome measures, including the total YGTSS, modified Rush Video-Based Tic Rating Scale (mRVRS), Yale-Brown Obsessive Compulsive Scale (YBOCS), and Becks Depression Inventory (BDI). All targets resulted in significant reductions of YGTSS scores and, with the exception of the CM-Pf, also in reduced YBOCS scores. Interestingly, DBS of pallidal targets showed increased YGTSS and YBOCS reductions compared to thalamic targets. Also, the meta-analysis including six randomized controlled and double-blinded trials demonstrated clinical efficacy of DBS for TS, that remained significant for GPi but not thalamic stimulation in two separate meta-analyses.Conclusion: We conclude that DBS is a clinically effective treatment option for patients with treatment-refractory TS, with all targets showing comparable improvement rates. Future research might focus on personalized and symptom-specific target selection.

BackgroundDeep brain stimulation (DBS) of the medial thalamus is an evolving therapy for severe, treatment-refractory Tourette syndrome (TS). It remains unanswered which functionally connected networks need to be modulated to obtain optimal treatment results.MethodsWe assessed treatment response of 15 patients with TS untergoing thalamic DBS six and twelve months postoperatively using the Yale Global Tic Severity Scale (YGTSS) tic score. For each time point, functional connectivity maps seeding from stimulation sites were calculated based on a normative functional connectome derived from 1000 healthy subjects. Resulting maps were analyzed in a voxel-wise mixed model for repeated measurements to identify patterns of connectivity associated with tic reduction.ResultsConnectivity of stimulation to the medial frontal cortex, bilateral insulae and sensorimotor cortex was associated with tic reduction. Connectivity with the temporal lobe, cerebellum, ventral striatum and orbitofrontal cortex was negatively associated. The overall connectivity pattern was robust to leave-one-out cross-validation, explaining 25 % of outcome variance (R = 0.500; p = 0.005).ConclusionsWe delineated a functional connectivity profile seeding from stimulation sites associated with TS-DBS outcome. This pattern comprised areas linked to the processing of premonitory urges and tic execution, thereby extending our current understanding of effective neuromodulation for TS.

The development of robotic systems has provided an alternative to frame-based stereotactic procedures. The aim of this experimental phantom study was to compare the mechanical accuracy of the Robotic Surgery Assistant (ROSA) and the Leksell stereotactic frame by reducing clinical and procedural factors to a minimum.To precisely compare mechanical accuracy, a stereotactic system was chosen as reference for both methods. A thin layer CT scan with an acrylic phantom fixed to the frame and a localizer enabling the software to recognize the coordinate system was performed. For each of the five phantom targets, two different trajectories were planned, resulting in 10 trajectories. A series of five repetitions was performed, each time based on a new CT scan. Hence, 50 trajectories were analyzed for each method. X-rays of the final cannula position were fused with the planning data. The coordinates of the target point and the endpoint of the robot- or frame-guided probe were visually determined using the robotic software. The target point error (TPE) was calculated applying the Euclidian distance. The depth deviation along the trajectory and the lateral deviation were separately calculated.Robotics was significantly more accurate, with an arithmetic TPE mean of 0.53 mm (95% CI 0.41-0.55 mm) compared to 0.72 mm (95% CI 0.63-0.8 mm) in stereotaxy (Both the robotic and frame-based approach proved accurate. The robotic procedure showed significantly higher accuracy. For both methods, procedural factors occurring during surgery might have a more relevant impact on overall accuracy.

Contains fulltext : 214745.pdf (Publisher’s version ) (Closed access) 3 p.

OBJECTIVE To investigate whether functional sweet spots of deep brain stimulation (DBS) in the subthalamic nucleus (STN) can predict motor improvement in Parkinson disease (PD) patients. METHODS Stimulation effects of 449 DBS settings in 21 PD patients were clinically and quantitatively assessed through standardized monopolar reviews and mapped into standard space. A sweet spot for best motor outcome was determined using voxelwise and nonparametric permutation statistics. Two independent cohorts were used to investigate whether stimulation overlap with the sweet spot could predict acute motor outcome (10 patients, 163 settings) and long-term overall Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) improvement (63 patients). RESULTS Significant clusters for suppression of rigidity and akinesia, as well as for overall motor improvement, resided around the dorsolateral border of the STN. Overlap of the volume of tissue activated with the sweet spot for overall motor improvement explained R2 = 37% of the variance in acute motor improvement, more than triple what was explained by overlap with the STN (R2 = 9%) and its sensorimotor subpart (R2 = 10%). In the second independent cohort, sweet spot overlap explained R2 = 20% of the variance in long-term UPDRS-III improvement, which was equivalent to the variance explained by overlap with the STN (R2 = 21%) and sensorimotor STN (R2 = 19%). INTERPRETATION This study is the first to predict clinical improvement of parkinsonian motor symptoms across cohorts based on local DBS effects only. The new approach revealed a distinct sweet spot for STN DBS in PD. Stimulation overlap with the sweet spot can predict short- and long-term motor outcome and may be used to guide DBS programming. ANN NEUROL 2019;86:527-538.

To predict radiation-induced lung injury and outcome in non-small cell lung cancer (NSCLC) patients treated with robotic stereotactic body radiation therapy (SBRT) from radiomic features of the primary tumor. In all, 110 patients with primary stage I/IIa NSCLC were analyzed for local control (LC), disease-free survival (DFS), overall survival (OS) and development of local lung injury up to fibrosis (LF). First-order (histogram), second-order (GLCM, Gray Level Co-occurrence Matrix) and shape-related radiomic features were determined from the unprocessed or filtered planning CT images of the gross tumor volume (GTV), subjected to LASSO (Least Absolute Shrinkage and Selection Operator) regularization and used to construct continuous and dichotomous risk scores for each endpoint. Continuous scores comprising 1–5 histogram or GLCM features had a significant (p = 0.0001–0.032) impact on all endpoints that was preserved in a multifactorial Cox regression analysis comprising additional clinical and dosimetric factors. At 36 months, LC did not differ between the dichotomous risk groups (93% vs. 85%, HR 0.892, 95%CI 0.222–3.590), while DFS (45% vs. 17%, p

BackgroundFor more than 15 years, deep brain stimulation (DBS) has served as a last-resort treatment for severe treatment-resistant obsessive-compulsive disorder (OCD).MethodsFrom 2010 to 2016, 20 patients with OCD (10 men/10 women) were included in a single-centre trial with a naturalistic open-label design over 1 year to evaluate the effects of DBS in the anterior limb of the internal capsule and nucleus accumbens region (ALIC-NAcc) on OCD symptoms, executive functions, and personality traits.ResultsALIC-NAcc-DBS significantly decreased OCD symptoms (mean Yale-Brown Obsessive Compulsive Scale reduction 33%, 40% full responders) and improves global functioning without loss of efficacy over 1 year. No significant changes were found in depressive or anxiety symptoms. Our study did not show any effect of ALIC-NAcc-DBS on personality traits or executive functions, and no potential outcome predictors were identified in a post hoc analysis. Other than several individual minor adverse events, ALIC-NAcc-DBS has been shown to be safe, but 35% of patients reported a sudden increase in anxiety and anhedonia after acute cessation of stimulation.ConclusionsWe conclude that ALIC-NAcc-DBS is a well-tolerated and promising last-resort treatment option for OCD. The cause of variability in the outcome remains unclear, and the aspect of reversibility must be examined critically. The present data from one of the largest samples of patients with OCD treated with DBS thus far support the results of previous studies with smaller samples.

The nucleus basalis of Meynert (nbM) was first described at the end of the 19th century and named after its discoverer, Theodor Meynert. The nbM contains a large population of cholinergic neurons that project their axons to the entire cortical mantle, the olfactory tubercle, and the amygdala. It has been functionally associated with the control of attention and maintenance of arousal, both key functions for appropriate learning and memory formation. This structure is well-conserved across vertebrates, although its degree of organization varies between species. Since early in the investigation of its functional and pathological significance, its degeneration has been linked to various major neuropsychiatric disorders. For instance, Lewy bodies, a hallmark in the diagnosis of Parkinson's disease, were originally described in the nbM. Since then, its involvement in other Lewy body and dementia-related disorders has been recognized. In the context of recent positive outcomes following nbM deep brain stimulation in subjects with dementia-associated disorders, we review the literature from an historical perspective focusing on how the nbM came into focus as a promising therapeutic option for patients with Alzheimer's disease. Moreover, we will discuss what is needed to further develop and widely implement this approach as well as examine novel medical indications for which nbM deep brain stimulation may prove beneficial.

Background Multiple deep brain stimulation (DBS) targets have been proposed for treating intractable obsessive-compulsive disorder (OCD). Here, we investigated whether stimulation effects of different target sites would be mediated by one common or several segregated functional brain networks. Methods First, seeding from active electrodes of 4 OCD patient cohorts (N = 50) receiving DBS to anterior limb of the internal capsule or subthalamic nucleus zones, optimal functional connectivity profiles for maximal Yale-Brown Obsessive Compulsive Scale improvements were calculated and cross-validated in leave-one-cohort-out and leave-one-patient-out designs. Second, we derived optimal target-specific connectivity patterns to determine brain regions mutually predictive of clinical outcome for both targets and others predictive for either target alone. Functional connectivity was defined using resting-state functional magnetic resonance imaging data acquired in 1000 healthy participants. Results While optimal functional connectivity profiles showed both commonalities and differences between target sites, robust cross-predictions of clinical improvements across OCD cohorts and targets suggested a shared network. Connectivity to the anterior cingulate cortex, insula, and precuneus, among other regions, was predictive regardless of stimulation target. Regions with maximal connectivity to these commonly predictive areas included the insula, superior frontal gyrus, anterior cingulate cortex, and anterior thalamus, as well as the original stereotactic targets. Conclusions Pinpointing the network modulated by DBS for OCD from different target sites identified a set of brain regions to which DBS electrodes associated with optimal outcomes were functionally connected—regardless of target choice. On these grounds, we establish potential brain areas that could prospectively inform additional or alternative neuromodulation targets for obsessive-compulsive disorder.

BackgroundThe effects of subthalamic stimulation (subthalamic nucleus-deep brain stimulation, STN-DBS) on impulsive and compulsive behaviours (ICB) in Parkinson’s disease (PD) are understudied.ObjectiveTo investigate clinical predictors of STN-DBS effects on ICB.MethodsIn this prospective, open-label, multicentre study in patients with PD undergoing bilateral STN-DBS, we assessed patients preoperatively and at 6-month follow-up postoperatively. Clinical scales included the Questionnaire for Impulsive-Compulsive Disorders in PD-Rating Scale (QUIP-RS), PD Questionnaire-8, Non-Motor Symptom Scale (NMSS), Unified PD Rating Scale in addition to levodopa-equivalent daily dose total (LEDD-total) and dopamine agonists (LEDD-DA). Changes at follow-up were analysed with Wilcoxon signed-rank test and corrected for multiple comparisons (Bonferroni method). We explored predictors of QUIP-RS changes using correlations and linear regressions. Finally, we dichotomised patients into ‘QUIP-RS improvement or worsening’ and analysed between-group differences.ResultsWe included 55 patients aged 61.7 years±8.4 with 9.8 years±4.6 PD duration. QUIP-RS cut-offs and psychiatric assessments identified patients with preoperative ICB. In patients with ICB, QUIP-RS improved significantly. However, we observed considerable interindividual variability of clinically relevant QUIP-RS outcomes as 27.3% experienced worsening and 29.1% an improvement. In post hoc analyses, higher baseline QUIP-RS and lower baseline LEDD-DA were associated with greater QUIP-RS improvements. Additionally, the ‘QUIP-RS worsening’ group had more severe baseline impairment in the NMSS attention/memory domain.ConclusionsOur results show favourable ICB outcomes in patients with higher preoperative ICB severity and lower preoperative DA doses, and worse outcomes in patients with more severe baseline attention/memory deficits. These findings emphasise the need for comprehensive non-motor and motor symptoms assessments in patients undergoing STN-DBS.Trial registration numberDRKS00006735.

Die funktionelle Neurochirurgie umfasst die Operationen am zentralen und peripheren Nervensystem, um eine elektrische Dysfunktion, die zu bestimmten neurologischen Symptomen fuhrt, zu modifizieren und dadurch diese Symptome zu lindern. Zu den operativen Eingriffen der funktionellen Neurochirurgie gehoren zum einen die tiefe Hirnstimulation (THS), wobei hier der Morbus Parkinson eine der bekanntesten und haufigsten Indikationen darstellt, zum anderen die operative Behandlung chronischer Schmerzen und neuerdings auch der Demenzerkrankung. In diesem Kapitel werden sowohl die Moglichkeiten und Besonderheiten der operativen Therapie der chronischen Schmerzen als auch die Behandlungsoptionen im Rahmen der tiefen Hirnstimulation bei Patienten in hoherem Lebensalter dargelegt.

Background: Assessment of affective-behavioral states in patients with Parkinson’s disease (PD) undergoing deep brain stimulation (DBS) is essential. Objective: To analyze well-established questionnaires as a pilot-study with the long term aim to develop a screening tool evaluating affective-behavioral dysfunction, including depression, anxiety, apathy, mania, and impulse control disorders, in PD patients screened for DBS. Methods: Two hundred ninety-seven inpatients with PD underwent standardized neuropsychiatric testing including German versions of Beck Depression Inventory-II, Hospital Anxiety and Depression Scale, Apathy Evaluation Scale, Self-Report Manic Inventory, and Questionnaire for Impulsive-Compulsive Disorders in PD-Rating Scale, to assess appropriateness for DBS. Statistical item reduction was based on exploratory factor analysis, Cronbach’s alpha, item-total correlations, item difficulty, and inter-item correlations. Confirmatory factor analysis was conducted to assess factorial validity. An expert rating was performed to identify clinically relevant items in the context of PD and DBS, to maintain content validity. We compared the shortened subscales with the original questionnaires using correlations. To determine cutoff points, receiver operating characteristics analysis was performed. Results: The items of the initial questionnaires were reduced from 129 to 38 items. Results of confirmatory factor analyses supported the validity of the shortened pool. It demonstrated high internal consistency (Cronbach’s alpha = 0.72–0.83 across subscales), and the individual subscales were correlated with the corresponding original scales (rs = 0.84–0.95). Sensitivities and specificities exceeded 0.7. Conclusion: The shortened item pool, including 38 items, provides a good basis for the development of a screening tool, capturing affective-behavioral symptoms in PD patients before DBS implantation. Confirmation of the validity of such a screening tool in an independent sample of PD patients is warranted.

Background: Sleep disturbances and neuropsychiatric symptoms are some of the most common nonmotor symptoms in Parkinson’s disease (PD). The effect of subthalamic stimulation (STN-DBS) on these symptoms beyond a short-term follow-up is unclear. Objective: To examine 36-month effects of bilateral STN-DBS on quality of sleep, depression, anxiety, and quality of life (QoL) compared to standard-of-care medical therapy (MED) in PD. Methods: In this prospective, controlled, observational, propensity score matched, international multicenter study, we assessed sleep disturbances using the PDSleep Scale-1 (PDSS), QoL employing the PDQuestionnaire-8 (PDQ-8), motor disorder with the Scales for Outcomes in PD (SCOPA), anxiety and depression with the Hospital Anxiety and Depression Scale (HADS), and dopaminergic medication requirements (LEDD). Within-group longitudinal outcome changes were tested using Wilcoxon signed-rank and between-group longitudinal differences of change scores with Mann-Whitney U tests. Spearman correlations analyzed the relationships of outcome parameter changes at follow-up. Results: Propensity score matching applied on 159 patients (STN-DBS n = 75, MED n = 84) resulted in 40 patients in each treatment group. At 36-month follow-up, STN-DBS led to significantly better PDSS and PDQ-8 change scores, which were significantly correlated. We observed no significant effects for HADS and no significant correlations between change scores in PDSS, HADS, and LEDD. Conclusions: We report Class IIb evidence of beneficial effects of STN-DBS on quality of sleep at 36-month follow-up, which were associated with QoL improvement independent of depression and dopaminergic medication. Our study highlights the importance of sleep for assessments of DBS outcomes.

Background Drugs, psychotherapy, and other treatment modalities are effective for many patients with mental illness. Nonetheless, many patients do not achieve a total remission with the currently available interventions, and the recurrence rates are high. As part of the ongoing search for further treatment options for refractory disorders, there is renewed interest in focal neuromodulatory techniques, including invasive ones, and deep brain stimulation (DBS) in particular. Methods In this review article, a group consisting of neurosurgeons, psychiatrists, and one practicing ethicist/neurologist summarizes the main aspects of the use of DBS to treat mental illness and offers recommendations on its indications and practical implementation. Results The efficacy of DBS against mental illness has not been confirmed in the randomized, controlled trials (RCTs) that have been published to date. This may be because the follow-up times were too short. In contrast to the negative RCTs, case series have indeed shown a positive effect of DBS on severe depression, but this effect can only be seen several months after the operation. Conclusion DBS may be a therapeutic option for selected patients with otherwise intractable mental illness. Patients should only be treated in the setting of clinical trials. RCTs with longer follow-up times must be conducted in order to substantiate, if possible, the promising evidence that has been found in case series.

We investigated whether Deep Brain Stimulation (DBS) of the subthalamic nucleus (STN) influences social validation as measured by a Judge-Advisor task. In contrast to healthy controls and patients with their DBS OFF, patients with their stimulation switched on do not experience a gain of confidence after receiving competent advice.