Deep brain stimulation normalizes amygdala responsivity in treatment-resistant depression.

Deep brain stimulation (DBS) of the ventral anterior limb of the internal capsule (vALIC) is a promising intervention for treatment-resistant depression (TRD). However, the working mechanisms of vALIC DBS in TRD remain largely unexplored. As major depressive disorder has been associated with aberrant amygdala functioning, we investigated whether vALIC DBS affects amygdala responsivity and functional connectivity. To investigate the long-term effects of DBS, eleven patients with TRD performed an implicit emotional face-viewing paradigm during functional magnetic resonance imaging (fMRI) before DBS surgery and after DBS parameter optimization. Sixteen matched healthy controls performed the fMRI paradigm at two-time points to control for test-retest effects. To investigate the short-term effects of DBS de-activation after parameter optimization, thirteen patients additionally performed the fMRI paradigm after double-blind periods of active and sham stimulation. Results showed that TRD patients had decreased right amygdala responsivity compared to healthy controls at baseline. Long-term vALIC DBS normalized right amygdala responsivity, which was associated with faster reaction times. This effect was not dependent on emotional valence. Furthermore, active compared to sham DBS increased amygdala connectivity with sensorimotor and cingulate cortices, which was not significantly different between responders and non-responders. These results suggest that vALIC DBS restores amygdala responsivity and behavioral vigilance in TRD, which may contribute to the DBS-induced antidepressant effect.

Surgical Complications in Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease: Experience in 800 Patients.

INTRODUCTION: We present our surgical complications resulting in neurological deficit or additional surgery during 25 years of DBS of the subthalamic nucleus (STN) for Parkinson's disease (PD). METHODS: We conducted a retrospective chart review of all PD patients that received STN DBS in our DBS center between 1998 and 2023. Outcomes were complications resulting in neurological deficit or additional surgery. Potential risk factors (number of microelectrode recording tracks, age, anesthesia method, hypertension, and sex) for symptomatic intracerebral hemorrhage (ICH) were analyzed. Furthermore, lead fixation techniques were compared. RESULTS: Eight hundred PD patients (507 men, 293 women) received unilateral (n = 11) or bilateral (n = 789) implantation of STN electrodes. Neurological deficit due to ICH, edema, delirium, or infarction was seen in 8.4% of the patients (7.4% transient, 1.0% permanent). Twenty-two patients (2.8%) had a symptomatic ICH following STN DBS, for which we did not find any risk factors, and five had permanent sequelae due to ICH (0.6%). Of all patients, 18.4% required additional surgery; the proportion was reduced from 27% in the first 300 cases to 13% in the last 500 cases (p < 0.001). The infection rate was 3.5%, which decreased from 5.3% in the first 300 cases to 2.2% in the last 500 cases. The use of a lead anchoring device led to significantly less lead migrations than miniplate fixation. CONCLUSION: STN DBS leads to permanent neurological deficit in a small number of patients (1.0%), but a substantial proportion needs some additional surgical procedure after the first DBS system implantation. The risk of revision surgery was reduced over time but remained significant. These findings need to be discussed with the patient in the preoperative informed consent process in addition to the expected health benefit.

Perspectives of Implementation of Closed-Loop Deep Brain Stimulation: From Neurological to Psychiatric Disorders.

BACKGROUND: Deep brain stimulation (DBS) is a highly efficient, evidence-based therapy to alleviate symptoms and improve quality of life in movement disorders such as Parkinson's disease, essential tremor, and dystonia, which is also being applied in several psychiatric disorders, such as obsessive-compulsive disorder and depression, when they are otherwise resistant to therapy. SUMMARY: At present, DBS is clinically applied in the so-called open-loop approach, with fixed stimulation parameters, irrespective of the patients' clinical state(s). This approach ignores the brain states or feedback from the central nervous system or peripheral recordings, thus potentially limiting its efficacy and inducing side effects by stimulation of the targeted networks below or above the therapeutic level. KEY MESSAGES: The currently emerging closed-loop (CL) approaches are designed to adapt stimulation parameters to the electrophysiological surrogates of disease symptoms and states. CL-DBS paves the way for adaptive personalized DBS protocols. This review elaborates on the perspectives of the CL technology and discusses its opportunities as well as its potential pitfalls for both clinical and research use in neuropsychiatric disorders.

Probabilistic Mapping Reveals Optimal Stimulation Site in Essential Tremor.

OBJECTIVE: The objective of this study was to obtain individual clinical and neuroimaging data of patients undergoing deep brain stimulation (DBS) for essential tremor (ET) from 5 different European centers to identify predictors of outcome and to identify an optimal stimulation site. METHODS: We analyzed retrospectively baseline covariates, pre- and postoperative clinical tremor scores (for 12 months) as well as individual imaging data from 119 patients to obtain individual electrode positions and stimulation volumes. Individual imaging and clinical data were 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 >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 cerebellothalamic 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 >50% tremor improvement with a sensitivity of 89% and a specificity of 57%. INTERPRETATION: Our multicenter 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 DBS in the future. ANN NEUROL 2022;91:602-612.

Deep brain stimulation for refractory obsessive-compulsive disorder (OCD): emerging or established therapy?

A consensus has yet to emerge whether deep brain stimulation (DBS) for treatment-refractory obsessive-compulsive disorder (OCD) can be considered an established therapy. In 2014, the World Society for Stereotactic and Functional Neurosurgery (WSSFN) published consensus guidelines stating that a therapy becomes established when "at least two blinded randomized controlled clinical trials from two different groups of researchers are published, both reporting an acceptable risk-benefit ratio, at least comparable with other existing therapies. The clinical trials should be on the same brain area for the same psychiatric indication." The authors have now compiled the available evidence to make a clear statement on whether DBS for OCD is established therapy. Two blinded randomized controlled trials have been published, one with level I evidence (Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score improved 37% during stimulation on), the other with level II evidence (25% improvement). A clinical cohort study (N = 70) showed 40% Y-BOCS score improvement during DBS, and a prospective international multi-center study 42% improvement (N = 30). The WSSFN states that electrical stimulation for otherwise treatment refractory OCD using a multipolar electrode implanted in the ventral anterior capsule region (including bed nucleus of stria terminalis and nucleus accumbens) remains investigational. It represents an emerging, but not yet established therapy. A multidisciplinary team involving psychiatrists and neurosurgeons is a prerequisite for such therapy, and the future of surgical treatment of psychiatric patients remains in the realm of the psychiatrist.

Multicenter Validation of Individual Preoperative Motor Outcome Prediction for Deep Brain Stimulation in Parkinson's Disease.

BACKGROUND: Subthalamic nucleus deep brain stimulation (STN DBS) is an established therapy for Parkinson's disease (PD) patients suffering from motor response fluctuations despite optimal medical treatment, or severe dopaminergic side effects. Despite careful clinical selection and surgical procedures, some patients do not benefit from STN DBS. Preoperative prediction models are suggested to better predict individual motor response after STN DBS. We validate a preregistered model, DBS-PREDICT, in an external multicenter validation cohort. METHODS: DBS-PREDICT considered eleven, solely preoperative, clinical characteristics and applied a logistic regression to differentiate between weak and strong motor responders. Weak motor response was defined as no clinically relevant improvement on the Unified Parkinson's Disease Rating Scale (UPDRS) II, III, or IV, 1 year after surgery, defined as, respectively, 3, 5, and 3 points or more. Lower UPDRS III and IV scores and higher age at disease onset contributed most to weak response predictions. Individual predictions were compared with actual clinical outcomes. RESULTS: 322 PD patients treated with STN DBS from 6 different centers were included. DBS-PREDICT differentiated between weak and strong motor responders with an area under the receiver operator curve of 0.76 and an accuracy up to 77%. CONCLUSION: Proving generalizability and feasibility of preoperative STN DBS outcome prediction in an external multicenter cohort is an important step in creating clinical impact in DBS with data-driven tools. Future prospective studies are required to overcome several inherent practical and statistical limitations of including clinical decision support systems in DBS care.

Optimizing Deep Brain Stimulation Parameters in Obsessive-Compulsive Disorder.

OBJECTIVES: Deep brain stimulation (DBS) is an innovative and effective treatment for patients with therapy-refractory obsessive-compulsive disorder (OCD). DBS offers unique opportunities for personalized care, but no guidelines on how to choose effective and safe stimulation parameters in patients with OCD are available. Our group gained relevant practical knowledge on DBS optimization by treating more than 80 OCD patients since 2005, the world's largest cohort. The article's objective is to share this experience. MATERIALS AND METHODS: We provide guiding principles for optimizing DBS stimulation parameters in OCD and discuss the neurobiological and clinical basis. RESULTS: Adjustments in stimulation parameters are performed in a fixed order. First, electrode contact activation is determined by the position of the electrodes on postoperative imaging. Second, voltage and pulse width are increased stepwise, enlarging both the chance of symptom reduction and of inducing side effects. Clinical evaluation of adjustments in stimulation parameters needs to take into account: 1) the particular temporal sequence in which the various OCD symptoms and DBS side-effects change; 2) the lack of robust response predictors; 3) the limited sensitivity of the Yale-Brown Obsessive-Compulsive Scale to assess DBS-induced changes in OCD symptoms; and 4) a patient's fitness for additional cognitive-behavioral therapy (CBT). CONCLUSIONS: Decision-making in stimulation parameter optimization needs to be sensitive to the particular time-courses on which various symptoms and side effects change.

Impulsivity and decision-making in obsessive-compulsive disorder after effective deep brain stimulation or treatment as usual.

OBJECTIVE: Impulsivity and impaired decision-making have been proposed as obsessive-compulsive disorder (OCD) endophenotypes, running in OCD and their healthy relatives independently of symptom severity and medication status. Deep brain stimulation (DBS) targeting the ventral limb of the internal capsule (vALIC) and the nucleus accumbens (Nacc) is an effective treatment strategy for treatment-refractory OCD. The effectiveness of vALIC-DBS for OCD has been linked to its effects on a frontostriatal network that is also implicated in reward, impulse control, and decision-making. While vALIC-DBS has been shown to restore reward dysfunction in OCD patients, little is known about the effects of vALIC-DBS on impulsivity and decision-making. The aim of the study was to compare cognitive impulsivity and decision-making between OCD patients undergoing effective vALIC-DBS or treatment as usual (TAU), and healthy controls. METHODS: We used decision-making performances under ambiguity on the Iowa Gambling Task and reflection impulsivity on the Beads Task to compare 20 OCD patients effectively treated with vALIC-DBS, 40 matched OCD patients undergoing effective TAU (medication and/or cognitive behavioural therapy), and 40 healthy subjects. Effective treatment was defined as at least 35% improvement of OCD symptoms. RESULTS: OCD patients, irrespective of treatment modality (DBS or TAU), showed increased reflection impulsivity and impaired decision-making compared to healthy controls. No differences were observed between OCD patients treated with DBS or TAU. CONCLUSION: OCD patients effectively treated with vALIC-DBS or TAU display increased reflection impulsivity and impaired decision-making independent of the type of treatment.

Cognitive effects of deep brain stimulation in patients with obsessive-compulsive disorder.

BACKGROUND: Deep brain stimulation (DBS) is a promising treatment for treatment-refractory obsessive-compulsive disorder (OCD). However, the effects of DBS on cognitive functioning remain unclear. Therefore, we aimed to assess cognitive safety of DBS for treatment-refractory OCD and the association between clinical changes and cognitive functioning. METHODS: Patients with treatment-refractory OCD treated with DBS targeted at the nucleus accumbens (NAcc) were compared with a control group of 14 patients with treatment-refractory OCD treated with care as usual. We assessed cognitive functioning at baseline, 3 weeks postoperatively and following 8 months of DBS. We compared change in clinical symptoms with cognitive changes. RESULTS: There were 16 patients in the DBS group and 14 patients in the control group. Three weeks postoperatively, the DBS group showed a significantly reduced performance on measures of visual organization and verbal fluency and a trend toward reduced performance on measures of visual memory and abstract reasoning. Cognitive functioning was found to be stable on all other measures. After 8 months of DBS, reduced performances persisted, except for a significant improvement in verbal fluency. Cognitive functioning in all other domains remained unaffected. We found no correlation between improvement of clinical symptoms and cognitive changes. LIMITATIONS: A limitation of this study was its relatively small sample size. CONCLUSION: Deep brain stimulation targeted at the NAcc may be considered a safe method in terms of cognition because cognitive functioning was unaffected on most neuropsychological measures. Nevertheless, we observed some minor reduced performance on specific measures of executive functioning that were possibly associated with surgical intervention. Our results suggest that severity of OCD symptoms is independent of cognitive functioning.

Consensus on guidelines for stereotactic neurosurgery for psychiatric disorders.

BACKGROUND: For patients with psychiatric illnesses remaining refractory to 'standard' therapies, neurosurgical procedures may be considered. Guidelines for safe and ethical conduct of such procedures have previously and independently been proposed by various local and regional expert groups. METHODS: To expand on these earlier documents, representative members of continental and international psychiatric and neurosurgical societies, joined efforts to further elaborate and adopt a pragmatic worldwide set of guidelines. These are intended to address a broad range of neuropsychiatric disorders, brain targets and neurosurgical techniques, taking into account cultural and social heterogeneities of healthcare environments. FINDINGS: The proposed consensus document highlights that, while stereotactic ablative procedures such as cingulotomy and capsulotomy for depression and obsessive-compulsive disorder are considered 'established' in some countries, they still lack level I evidence. Further, it is noted that deep brain stimulation in any brain target hitherto tried, and for any psychiatric or behavioural disorder, still remains at an investigational stage. Researchers are encouraged to design randomised controlled trials, based on scientific and data-driven rationales for disease and brain target selection. Experienced multidisciplinary teams are a mandatory requirement for the safe and ethical conduct of any psychiatric neurosurgery, ensuring documented refractoriness of patients, proper consent procedures that respect patient's capacity and autonomy, multifaceted preoperative as well as postoperative long-term follow-up evaluation, and reporting of effects and side effects for all patients. INTERPRETATION: This consensus document on ethical and scientific conduct of psychiatric surgery worldwide is designed to enhance patient safety.

Deep brain stimulation of the central thalamus restores arousal and motivation in a zolpidem-responsive patient with akinetic mutism after severe brain injury.

After severe brain injury, zolpidem is known to cause spectacular, often short-lived, restorations of brain functions in a small subgroup of patients. Previously, we showed that these zolpidem-induced neurological recoveries can be paralleled by significant changes in functional connectivity throughout the brain. Deep brain stimulation (DBS) is a neurosurgical intervention known to modulate functional connectivity in a wide variety of neurological disorders. In this study, we used DBS to restore arousal and motivation in a zolpidem-responsive patient with severe brain injury and a concomitant disorder of diminished motivation, more than 10 years after surviving hypoxic ischemia. We found that DBS of the central thalamus, targeted at the centromedian-parafascicular complex, immediately restored arousal and was able to transition the patient from a state of deep sleep to full wakefulness. Moreover, DBS was associated with temporary restoration of communication and ability to walk and eat in an otherwise wheelchair-bound and mute patient. With the use of magnetoencephalography (MEG), we revealed that DBS was generally associated with a marked decrease in aberrantly high levels of functional connectivity throughout the brain, mimicking the effects of zolpidem. These results imply that 'pathological hyperconnectivity' after severe brain injury can be associated with reduced arousal and behavioral performance and that DBS is able to modulate connectivity towards a 'healthier baseline' with lower synchronization, and, can restore functional brain networks long after severe brain injury. The presence of hyperconnectivity after brain injury may be a possible future marker for a patient's responsiveness for restorative interventions, such as DBS, and suggests that lower degrees of overall brain synchronization may be conducive to cognition and behavioral responsiveness.

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

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

Deep Brain Stimulation for Orthostatic Tremor: An Observational Study.

BACKGROUND: Primary orthostatic tremor (OT) can affect patients' life. Treatment of OT with deep brain stimulation (DBS) of the thalamic ventral intermediate nucleus (Vim) is described in a limited number of patients. The Vim and posterior subthalamic area (PSA) can be targeted in a single trajectory, allowing both stimulation of the Vim and/or dentatorubrothalamic tract (DRT). In essential tremor this is currently often used with positive effects. OBJECTIVE: To evaluate the efficacy of Vim/DRT-DBS in OT-patients, based on standing time and Quality of Life (QoL), also on the long-term. Furthermore, to relate stimulation of the Vim and DRT, medial lemniscus (ML) and pyramidal tract (PT) to beneficial clinical and side-effects. METHODS: Nine severely affected OT-patients received bilateral Vim/DRT-DBS. Primary outcome measure was standing time; secondary measures included self-reported measures, neurophysiological measures, structural analyses, surgical complications, stimulation-induced side-effects, and QoL up to 56 months. Stimulation of volume of tissue activated (VTA) were related to outcome measures. RESULTS: Average maximum standing time increased from 41.0 s ± 51.0 s to 109.3 s ± 65.0 s after 18 months, with improvements measured in seven of nine patients. VTA (n = 7) overlapped with the DRT in six patients and with the ML and/or PT in six patients. All patients experienced side-effects and QoL worsened during the first year after surgery, which improved again during long-term follow-up, although remaining below age-related normal values. Most patients reported a positive effect of DBS. CONCLUSION: Vim/DRT-DBS improved standing time in patients with severe OT. Observed side-effects are possibly related to stimulation of the ML and PT.

The intralaminar thalamus: a review of its role as a target in functional neurosurgery.

The intralaminar thalamus, in particular the centromedian-parafascicular complex, forms a strategic node between ascending information from the spinal cord and brainstem and forebrain circuitry that involves the cerebral cortex and basal ganglia. A large body of evidence shows that this functionally heterogeneous region regulates information transmission in different cortical circuits, and is involved in a variety of functions, including cognition, arousal, consciousness and processing of pain signals. Not surprisingly, the intralaminar thalamus has been a target area for (radio)surgical ablation and deep brain stimulation (DBS) in different neurological and psychiatric disorders. Historically, ablation and stimulation of the intralaminar thalamus have been explored in patients with pain, epilepsy and Tourette syndrome. Moreover, DBS has been used as an experimental treatment for disorders of consciousness and a variety of movement disorders. In this review, we provide a comprehensive analysis of the underlying mechanisms of stimulation and ablation of the intralaminar nuclei, historical clinical evidence, and more recent (experimental) studies in animals and humans to define the present and future role of the intralaminar thalamus as a target in the treatment of neurological and psychiatric disorders.

Deep Brain Stimulation of the Anterior Nucleus of the Thalamus in Drug-Resistant Epilepsy in the MORE Multicenter Patient Registry.

BACKGROUND AND OBJECTIVES: The efficacy of deep brain stimulation of the anterior nucleus of the thalamus (ANT DBS) in patients with drug-resistant epilepsy (DRE) was demonstrated in the double-blind Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy randomized controlled trial. The Medtronic Registry for Epilepsy (MORE) aims to understand the safety and longer-term effectiveness of ANT DBS therapy in routine clinical practice. METHODS: MORE is an observational registry collecting prospective and retrospective clinical data. Participants were at least 18 years old, with focal DRE recruited across 25 centers from 13 countries. They were followed for at least 2 years in terms of seizure frequency (SF), responder rate (RR), health-related quality of life (Quality of Life in Epilepsy Inventory 31), depression, and safety outcomes. RESULTS: Of the 191 patients recruited, 170 (mean [SD] age of 35.6 [10.7] years, 43% female) were implanted with DBS therapy and met all eligibility criteria. At baseline, 38% of patients reported cognitive impairment. The median monthly SF decreased by 33.1% from 15.8 at baseline to 8.8 at 2 years (p < 0.0001) with 32.3% RR. In the subgroup of 47 patients who completed 5 years of follow-up, the median monthly SF decreased by 55.1% from 16 at baseline to 7.9 at 5 years (p < 0.0001) with 53.2% RR. High-volume centers (>10 implantations) had 42.8% reduction in median monthly SF by 2 years in comparison with 25.8% in low-volume center. In patients with cognitive impairment, the reduction in median monthly SF was 26.0% by 2 years compared with 36.1% in patients without cognitive impairment. The most frequently reported adverse events were changes (e.g., increased frequency/severity) in seizure (16%), memory impairment (patient-reported complaint, 15%), depressive mood (patient-reported complaint, 13%), and epilepsy (12%). One definite sudden unexpected death in epilepsy case was reported. DISCUSSION: The MORE registry supports the effectiveness and safety of ANT DBS therapy in a real-world setting in the 2 years following implantation. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that ANT DBS reduces the frequency of seizures in patients with drug-resistant focal epilepsy. TRIAL REGISTRATION INFORMATION: MORE ClinicalTrials.gov Identifier: NCT01521754, first posted on January 31, 2012.

Effectiveness and safety of deep brain stimulation for patients with refractory obsessive compulsive disorder and comorbid autism spectrum disorder; A case series.

BACKGROUND: Deep brain stimulation (DBS) is effective for patients with treatment refractory obsessive-compulsive disorder (OCD). Autism spectrum disorder (ASD) is present in up to a third of all patients with OCD, but it is unknown whether effectiveness of DBS for OCD also applies for patients with comorbid ASD. The present case series is the first to examine effectiveness on OCD symptoms and safety of DBS in patients with OCD and ASD specifically. METHODS: Six consecutive patients with treatment-refractory OCD and comorbid ASD received DBS of the ventral anterior limb of the internal capsule (vALIC) or medial forebrain bundle (MFB). We examined effectiveness of DBS on symptoms of OCD and depression with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and Hamilton Depression Rating Scale (HAM-D), respectively. We included qualitative data to describe the course of treatment in individual patients with OCD and ASD. RESULTS: We found that DBS significantly decreased symptoms of OCD (p < .001) and depression (p = .007). Four out of six patients with OCD and comorbid ASD were responders (decrease ≥ 35% in Y-BOCS), one patient was partial-responder (decrease 25-35% in Y-BOCS) and one patient did not respond (decrease ≤ 25% in Y-BOCS). Serious adverse events were an infection of the DBS system, and a suicide attempt. CONCLUSIONS: Though present results are preliminary, DBS reduced symptoms of OCD and depression in patients with OCD and comorbid ASD. Comorbid ASD should therefore not be seen as a contra-indication for DBS in OCD.

Clinical and neurophysiological effects of central thalamic deep brain stimulation in the minimally conscious state after severe brain injury.

Deep brain stimulation (DBS) of the central thalamus is an experimental treatment for restoration of impaired consciousness in patients with severe acquired brain injury. Previous results of experimental DBS are heterogeneous, but significant improvements in consciousness have been reported. However, the mechanism of action of DBS remains unknown. We used magnetoencephalography to study the direct effects of DBS of the central thalamus on oscillatory activity and functional connectivity throughout the brain in a patient with a prolonged minimally conscious state. Different DBS settings were used to improve consciousness, including two different stimulation frequencies (50 Hz and 130 Hz) with different effective volumes of tissue activation within the central thalamus. While both types of DBS resulted in a direct increase in arousal, we found that DBS with a lower frequency (50 Hz) and larger volume of tissue activation was associated with a stronger increase in functional connectivity and neural variability throughout the brain. Moreover, this form of DBS was associated with improvements in visual pursuit, a reduction in spasticity, and improvement of swallowing, eight years after loss of consciousness. However, after DBS, all neurophysiological markers remained significantly lower than in healthy controls and objective increases in consciousness remained limited. Our findings provide new insights on the mechanistic understanding of neuromodulatory effects of DBS of the central thalamus in humans and suggest that DBS can re-activate dormant functional brain networks, but that the severely injured stimulated brain still lacks the ability to serve cognitive demands.

Long-term Outcome of Deep Brain Stimulation of the Ventral Part of the Anterior Limb of the Internal Capsule in a Cohort of 50 Patients With Treatment-Refractory Obsessive-Compulsive Disorder.

BACKGROUND: Deep brain stimulation (DBS) is an effective intervention for patients with severe treatment-refractory obsessive-compulsive disorder (OCD). Our aim was to examine long-term effectiveness and tolerability of DBS and its impact on functioning and well-being. METHODS: Fifty patients with severe treatment-refractory OCD received DBS of the ventral part of the anterior limb of the internal capsule and were followed for at least 3 years following implantation (mean 6.8 ± 3 years). Primary effectiveness was assessed by change in Yale-Brown Obsessive Compulsive Scale scores. Secondary effectiveness measures included Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, World Health Organization Quality of Life Scale-Brief Version, Global Assessment of Functioning, and a scale assessing functioning in work, family, and social life. Adverse effects of DBS were examined with a structured interview (n = 38). RESULTS: At long-term follow-up, OCD symptoms decreased by 39% (p < .001), and half of the patients were responders (≥35% decrease of Yale-Brown Obsessive Compulsive Scale score). Anxiety and depressive symptoms decreased significantly, with reductions of 48% and 50%, respectively. The World Health Organization Quality of Life Scale-Brief Version general score improved significantly, as did 3 of 4 subdomains. Both clinician- and patient-rated functioning improved substantially (p < .001). The unemployment rate decreased from 78% at baseline to 58% at last follow-up (z = -1.90, p = .058), and 21 patients stopped or decreased psychotropic medication (z = -2.887, p = .004). Long-term adverse effects included cognitive complaints and fatigue. Serious adverse events included 1 suicide attempt, related to comorbid depression. CONCLUSIONS: Our results provide evidence that DBS of the ventral part of the anterior limb of the internal capsule is effective and tolerable for treatment-refractory OCD in the long term and improves functioning and overall well-being.

Directional sensory thalamus deep brain stimulation in poststroke refractory pain.

Thalamic deep brain stimulation (DBS) for chronic pain is performed in selected patients with a variable success rate. We report the use of recently developed directional DBS in a patient with hemibody central poststroke pain (CPSP) and its added value in the induction of pleasant, pain-distracting paresthesia's throughout the contralateral body side. A 68-year-old man suffered from multiple strokes in the left hemisphere 11 years before presentation, resulting in medically refractory right-sided hemibody CPSP. He was implanted with a directional DBS electrode in the left ventrocaudal nucleus of the thalamus. A directional single-segment contact configuration produced a better improvement throughout the contralateral body side than ring-mode and other directional configurations. Treatment led to a reduction of almost 50% in pain. This case demonstrates the value of directional DBS in the treatment of chronic pain, as steering increases selectivity and reduces side effects in a small target area surrounded by structures with high functional diversity.