Anterior capsulotomy combined with subthalamic nucleus deep brain stimulation for tardive dystonia.

BACKGROUND: Deep brain stimulation (DBS) has been reported as a therapy option for the motor dysfunction of severe tardive dystonia (TD). The major psychiatric diseases, however, are contraindications to DBS treatment in TD patients. METHODS: Six severe, medically refractory TD patients undergoing bilateral anterior capsulotomy combined with bilateral subthalamic nucleus (STN)-DBS treatment were studied retrospectively at two time points: pre-operation, and 1-3 years post-operation. Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) was used to assess the dystonia and disability. Depressive, anxiety, psychiatric symptoms, and Quality of Life (QoL) were evaluated using the 17-item Hamilton Depression Scale (HAMD-17), the 14-item Hamilton Anxiety Scale (HAMA-14), the Positive and Negative Syndrome Scale (PANSS), and 36-item Short-Form Health Survey (SF-36), respectively. RESULTS: After receiving the combination treatment for 25 ± 11.6 months (range, 12-41 months), significant clinical symptom improvements were reported in TD patients. BFMDRS motor and disability scores were ameliorated by 78.5 ± 32.0% (p = 0.031) and 76.5 ± 38.6% (p = 0.031), respectively. The HAMD-17 and HAMA-14 scores were reduced by 60.3 ± 27.9% (p = 0.007) and 60.0 ± 24.6% (p = 0.009), respectively. Furthermore, the PANSS scores of the comorbidity schizophrenia TD patients decreased by 58.1 ± 6.0% (p = 0.022), and the QoL improved by 59.7 ± 14.1% (SF-36, p = 0.0001). During the research, there were no notable adverse effects or problems. CONCLUSION: Bilateral anterior capsulotomy combined with bilateral STN-DBS may be an effective and relatively safe treatment option for severe TD comorbid with major psychiatric disorders.

Presurgical structural imaging and clinical outcome in combined bed nucleus of the stria terminalis-nucleus accumbens deep brain stimulation for treatment-resistant depression.

Background: Structural imaging holds great potential for precise targeting and stimulation for deep brain stimulation (DBS). The anatomical information it provides may serve as potential biomarkers for predicting the efficacy of DBS in treatment-resistant depression (TRD). Aims: The primary aim is to identify preoperative imaging biomarkers that correlate with the efficacy of DBS in patients with TRD. Methods: Preoperative imaging parameters were estimated and correlated with the 6-month clinical outcome of patients with TRD receiving combined bed nucleus of the stria terminalis (BNST)-nucleus accumbens (NAc) DBS. White matter (WM) properties were extracted and compared between the response/non-response and remission/non-remission groups. Structural connectome was constructed and analysed using graph theory. Distances of the volume of activated tissue (VAT) to the main modulating tracts were also estimated to evaluate the correlations. Results: Differences in fibre bundle properties of tracts, including superior thalamic radiation and reticulospinal tract, were observed between the remission and non-remission groups. Distance of the centre of the VAT to tracts connecting the ventral tegmental area and the anterior limb of internal capsule on the left side varied between the remission and non-remission groups (p=0.010, t=3.07). The normalised clustering coefficient (γ) and the small-world property (σ) in graph analysis correlated with the symptom improvement after the correction of age. Conclusions: Presurgical structural alterations in WM tracts connecting the frontal area with subcortical regions, as well as the distance of the VAT to the modulating tracts, may influence the clinical outcome of BNST-NAc DBS. These findings provide potential imaging biomarkers for the DBS treatment for patients with TRD.

Prediction of subthalamic stimulation efficacy on isolated dystonia via support vector regression.

Introduction: Deep brain stimulation (DBS) of subthalamic nucleus (STN) has been well-established and increasingly applied in patients with isolated dystonia. Nevertheless, the surgical efficacy varies among patients. This study aims to explore the factors affecting clinical outcomes of STN-DBS on isolated dystonia and establish a well-performed prediction model. Methods: In this prospective study, thirty-two dystonia patients were recruited and received bilateral STN-DBS at our center. Their baseline characteristics and up to one-year follow-up outcomes were assessed. Implanted electrodes of each subject were reconstructed with their contact coordinates and activated volumes calculated. We explored correlations between distinct clinical characteristics and surgical efficacy. Those features were then trained for the model in outcome prediction via support vector regression (SVR) algorithm and testified through cross-validation. Results: Patients demonstrated an average clinical improvement of 56 ± 25 % after STN-DBS, significantly affected by distinct symptom forms and activated volumes. The optimal targets and activated volumes were concentratedly located at the dorsal posterior region to STN. Most patients had a rapid response to STN-DBS, and their motor score improvement within one week was highly associated with long-term outcomes. The trained SVR model, contributed by distinct weights of features, could reach a maximum prediction accuracy with mean errors of 11 ± 7 %. Conclusion: STN-DBS demonstrated significant and rapid therapeutic effects in patients with isolated dystonia, by possibly affecting the pallidofugal fibers. Early improvement highly indicates the ultimate outcomes. SVR proves valid in outcome prediction. Patients with predominant phasic and generalized symptoms, shorter disease duration, and younger onset age may be more favorable to STN-DBS in the long run.

Superior cerebellar peduncle deep brain stimulation for cerebral palsy.

OBJECTIVE: Patients with coexisting spastic cerebral palsy (CP) and dystonia have limited treatment options. In this study, the authors aimed to evaluate the efficacy of deep brain stimulation (DBS) targeting the superior cerebellar peduncles (SCPs) in adults with CP. METHODS: Five patients with CP and medically refractory dystonia and spasticity underwent SCP DBS. Assessments included the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), modified Ashworth scale (mAS), and tests of cognition, mental status, and quality of life preoperatively and at 3, 6, and 12 months postoperatively (in both DBS ON and OFF states, double blinded). Active contacts and fiber bundles were examined. RESULTS: Four patients completed follow-up. The BFMDRS motor score decreased from 74 to 52 at 12 months postoperatively (30%, p = 0.008). The mean mAS score indicated significant spasticity reduction (from 2.9 ± 0.9 to 1.9 ± 0.6 after 12 months, p = 0.0454). Quality of life improved (p < 0.01), while cognition remained unaffected. Active contacts were found within the dentato-rubro-thalamic tract, with variable efficiency in decussating and nondecussating portions. CONCLUSIONS: In this pilot trial, SCP DBS showed promise as a well-tolerated treatment for CP, improving dystonic symptoms, spasticity, quality of life, and functional capacities. However, caution is needed when interpreting the results given the small sample size and heterogeneous motor outcomes.

Effects of deep brain stimulation on dopamine D2 receptor binding in patients with treatment-refractory depression.

BACKGROUND: Depression is a chronic psychiatric disorder related to diminished dopaminergic neurotransmission. Deep brain stimulation (DBS) has shown effectiveness in treating patients with treatment-refractory depression (TRD). This study aimed to evaluate the effect of DBS on dopamine D2 receptor binding in patients with TRD. METHODS: Six patients with TRD were treated with bed nucleus of the stria terminalis (BNST)-nucleus accumbens (NAc) DBS were recruited. Ultra-high sensitivity [11C]raclopride dynamic total-body positron emission tomography (PET) imaging was used to assess the brain D2 receptor binding. Each patient underwent a [11C]raclopride PET scan for 60-min under DBS OFF and DBS ON, respectively. A simplified reference tissue model was used to generate parametric images of binding potential (BPND) with the cerebellum as reference tissue. RESULTS: Depression and anxiety symptoms improved after 3-6 months of DBS treatment. Compared with two-day-nonstimulated conditions, one-day BNST-NAc DBS decreased [11C]raclopride BPND in the amygdala (15.9 %, p < 0.01), caudate nucleus (15.4 %, p < 0.0001) and substantia nigra (10.8 %, p < 0.01). LIMITATIONS: This study was limited to the small sample size and lack of a healthy control group. CONCLUSIONS: Chronic BNST-NAc DBS improved depression and anxiety symptoms, and short-term stimulation decreased D2 receptor binding in the amygdala, caudate nucleus, and substantia nigra. The findings suggest that DBS relieves depression and anxiety symptoms possibly by regulating the dopaminergic system.

Proceedings of the 11th Annual Deep Brain Stimulation Think Tank: pushing the forefront of neuromodulation with functional network mapping, biomarkers for adaptive DBS, bioethical dilemmas, AI-guided neuromodulation, and translational advancements.

The Deep Brain Stimulation (DBS) Think Tank XI was held on August 9-11, 2023 in Gainesville, Florida with the theme of "Pushing the Forefront of Neuromodulation". The keynote speaker was Dr. Nico Dosenbach from Washington University in St. Louis, Missouri. He presented his research recently published in Nature inn a collaboration with Dr. Evan Gordon to identify and characterize the somato-cognitive action network (SCAN), which has redefined the motor homunculus and has led to new hypotheses about the integrative networks underpinning therapeutic DBS. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers, and researchers (from industry and academia) can freely discuss current and emerging DBS technologies, as well as logistical and ethical issues facing the field. The group estimated that globally more than 263,000 DBS devices have been implanted for neurological and neuropsychiatric disorders. This year's meeting was focused on advances in the following areas: cutting-edge translational neuromodulation, cutting-edge physiology, advances in neuromodulation from Europe and Asia, neuroethical dilemmas, artificial intelligence and computational modeling, time scales in DBS for mood disorders, and advances in future neuromodulation devices.

Mapping dysfunctional circuits in the frontal cortex using deep brain stimulation.

Frontal circuits play a critical role in motor, cognitive and affective processing, and their dysfunction may result in a variety of brain disorders. However, exactly which frontal domains mediate which (dys)functions remains largely elusive. We studied 534 deep brain stimulation electrodes implanted to treat four different brain disorders. By analyzing which connections were modulated for optimal therapeutic response across these disorders, we segregated the frontal cortex into circuits that had become dysfunctional in each of them. Dysfunctional circuits were topographically arranged from occipital to frontal, ranging from interconnections with sensorimotor cortices in dystonia, the primary motor cortex in Tourette's syndrome, the supplementary motor area in Parkinson's disease, to ventromedial prefrontal and anterior cingulate cortices in obsessive-compulsive disorder. Our findings highlight the integration of deep brain stimulation with brain connectomics as a powerful tool to explore couplings between brain structure and functional impairments in the human brain.

Preoperative Attention/Memory Problem Affects the Quality of Life of Parkinson's Disease Patients after Deep Brain Stimulation: A Cohort Study.

Objectives: The aim of this study was to investigate the impact of nonmotor symptoms (NMS) on the quality of life (QoL) outcome after subthalamic nucleus deep brain stimulation (STN-DBS) at the 1-year follow-up. Methods: Ninety-three patients diagnosed with Parkinson's disease (PD), who underwent subthalamic nucleus deep brain stimulation (STN-DBS) between April 2020 and August 2021, were included in this study. Demographic information was gathered through a self-designed questionnaire. The severity of both motor and non-motor symptoms, along with the quality of life (QoL), was assessed using the Unified Parkinson's Disease Rating Scale-III (UPDRS-III), Nonmotor Symptoms Scale (NMSS), and 8-item Parkinson's Disease Questionnaire (PDQ-8), respectively. Results: Significant differences were observed in the UPDRS-III score, NMSS summary index (SI), and subscores of six domains (sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, urinary, and sexual function) between the baseline and the 6- and 12-month follow-ups. The correlation analysis revealed positive correlations between the preoperative NMSS SI and subscores of seven domains (cardiovascular, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastrointestinal, and urinary) and ΔPDQ-8. Moreover, the preoperative PDQ-8 SI (ß = 0.869, P < 0.001) and the preoperative attention/memory subscore (ß = -0.154, P = 0.026) were predictive of the postsurgery improvement in quality of life (QoL). Conclusion: Deep brain stimulation (DBS) led to an improvement in the patients' nonmotor symptoms (NMS) at the 1-year follow-up, along with a correlation observed between NMS and the patients' quality of life (QoL). Notably, the severity of preoperative attention/memory problems emerged as the most significant predictor of NMS influencing the QoL outcome after STN-DBS at the 1-year follow-up.

Parameter-based analysis of clinical efficacy of combined bed nucleus of the stria terminalis-nucleus accumbens deep brain stimulation for treatment-resistant depression.

OBJECTIVE: Treatment-resistant depression (TRD) is a severely disabling psychiatric condition that responds poorly to conventional treatments. Deep brain stimulation (DBS) has been proposed for the treatment of patients with TRD in numerous studies. Several deep brain nuclei are considered as potential targets for TRD-DBS, but their clinical efficacy needs further validation. This study carried out dual-target combined stimulation of the bed nucleus of the stria terminalis (BNST) and nucleus accumbens (NAc) to investigate the effectiveness of the treatment for TRD patients. METHODS: An 8-contact DBS electrode was used in the study with a surgical path that crossed the BNST and NAc targets. Stimulation parameters and the corresponding severity of symptoms evaluated by the 17-item Hamilton Depression Rating Scale (HAMD-17) and other scales were obtained at each follow-up. The accuracy of electrode positions, the effect of combined stimulation, and the corresponding stimulation parameters were evaluated. Sweet spot prediction models were used to assess the effective stimulation sites in the treatment. RESULTS: The study included 23 TRD patients undergoing DBS at a single center from March 2021 to May 2023. At the last follow-up (range 4-24 months), 14 patients had responded to the treatment (HAMD-17 score improved ≥ 50%), 7 of whom had achieved clinical remission (HAMD-17 score ≤ 7). Electrode position analysis suggested that the BNST may be more important for the improvement of depressive symptoms than the NAc. Overlapped volumes of volume of tissue activated (VTA) and BNST were significantly correlated with absolute (ρleft = -0.377, p < 0.001; ρright = -0.251, p < 0.001) and percent (ρleft = -0.249, p < 0.001; ρright = -0.098, p = 0.102) changes in HAMD-17 score. The sweet spot model of HAMD-17 improvement also suggested that the VTA overlap with the dorsal side of BNST was associated with the impact on depressive symptoms (t = -4.10, p < 0.05). CONCLUSIONS: Combined BNST-NAc stimulation of TRD can effectively improve depressive symptoms, in which the BNST seems to have a dominant therapeutic effect. The results of this study not only help to optimize the DBS programming parameters, but also offer an opportunity to further understand the differences between the two targets. In the future, larger prospective cohorts are needed to verify the results of combined BNST-NAc DBS.

Enhanced Beta2-band Oscillations Denote Auditory Hallucination in Schizophrenia Patients and a Monkey Model of Psychosis.

An electroencephalographic (EEG) signature of auditory hallucinations (AHs) is important for facilitating the diagnosis and treatment of AHs in schizophrenia. We recorded EEG from 25 schizophrenia patients with recurrent AHs. During the period of AHs, EEG recordings exhibited significantly elevated beta2-band power in the temporal region, as compared to those recorded in the absence of AHs or during stimulation with verbal sounds. We further generated methamphetamine-treated rhesus monkeys exhibiting psychosis-like behaviors, including repetitive sudden searching actions in the absence of external intrusion, suggesting the occurrence of AHs. Epidural EEG beta2-band power in the temporal region of these monkeys was enhanced immediately after methamphetamine treatment and positively correlated with the frequency of sudden searching actions. Thus, the enhancement of temporal beta2-band oscillations represents a signature for AHs in both patients and a monkey model of psychosis, and this monkey model can be used for developing closed-loop neuromodulation approaches for the treatment of refractory AHs in schizophrenia.

Theta Oscillations Support Prefrontal-hippocampal Interactions in Sequential Working Memory.

The prefrontal cortex and hippocampus may support sequential working memory beyond episodic memory and spatial navigation. This stereoelectroencephalography (SEEG) study investigated how the dorsolateral prefrontal cortex (DLPFC) interacts with the hippocampus in the online processing of sequential information. Twenty patients with epilepsy (eight women, age 27.6 ± 8.2 years) completed a line ordering task with SEEG recordings over the DLPFC and the hippocampus. Participants showed longer thinking times and more recall errors when asked to arrange random lines clockwise (random trials) than to maintain ordered lines (ordered trials) before recalling the orientation of a particular line. First, the ordering-related increase in thinking time and recall error was associated with a transient theta power increase in the hippocampus and a sustained theta power increase in the DLPFC (3-10 Hz). In particular, the hippocampal theta power increase correlated with the memory precision of line orientation. Second, theta phase coherences between the DLPFC and hippocampus were enhanced for ordering, especially for more precisely memorized lines. Third, the theta band DLPFC → hippocampus influence was selectively enhanced for ordering, especially for more precisely memorized lines. This study suggests that theta oscillations may support DLPFC-hippocampal interactions in the online processing of sequential information.

A deep unrolled neural network for real-time MRI-guided brain intervention.

Accurate navigation and targeting are critical for neurological interventions including biopsy and deep brain stimulation. Real-time image guidance further improves surgical planning and MRI is ideally suited for both pre- and intra-operative imaging. However, balancing spatial and temporal resolution is a major challenge for real-time interventional MRI (i-MRI). Here, we proposed a deep unrolled neural network, dubbed as LSFP-Net, for real-time i-MRI reconstruction. By integrating LSFP-Net and a custom-designed, MR-compatible interventional device into a 3 T MRI scanner, a real-time MRI-guided brain intervention system is proposed. The performance of the system was evaluated using phantom and cadaver studies. 2D/3D real-time i-MRI was achieved with temporal resolutions of 80/732.8 ms, latencies of 0.4/3.66 s including data communication, processing and reconstruction time, and in-plane spatial resolution of 1 × 1 mm2. The results demonstrated that the proposed method enables real-time monitoring of the remote-controlled brain intervention, and showed the potential to be readily integrated into diagnostic scanners for image-guided neurosurgery.

Neuronal and synaptic adaptations underlying the benefits of deep brain stimulation for Parkinson's disease.

Deep brain stimulation (DBS) is a well-established and effective treatment for patients with advanced Parkinson's disease (PD), yet its underlying mechanisms remain enigmatic. Optogenetics, primarily conducted in animal models, provides a unique approach that allows cell type- and projection-specific modulation that mirrors the frequency-dependent stimulus effects of DBS. Opto-DBS research in animal models plays a pivotal role in unraveling the neuronal and synaptic adaptations that contribute to the efficacy of DBS in PD treatment. DBS-induced neuronal responses rely on a complex interplay between the distributions of presynaptic inputs, frequency-dependent synaptic depression, and the intrinsic excitability of postsynaptic neurons. This orchestration leads to conversion of firing patterns, enabling both antidromic and orthodromic modulation of neural circuits. Understanding these mechanisms is vital for decoding position- and programming-dependent effects of DBS. Furthermore, patterned stimulation is emerging as a promising strategy yielding long-lasting therapeutic benefits. Research on the neuronal and synaptic adaptations to DBS may pave the way for the development of more enduring and precise modulation patterns. Advanced technologies, such as adaptive DBS or directional electrodes, can also be integrated for circuit-specific neuromodulation. These insights hold the potential to greatly improve the effectiveness of DBS and advance PD treatment to new levels.

Anterior Capsulotomy for Refractory Obsessive-Compulsive Disorder: A Tractography and Lesion Geometry study.

INTRODUCTION: A bilateral anterior capsulotomy effectively treats refractory obsessive-compulsive disorder (OCD). We investigated the geometry of lesions and disruption of white matter pathways within the anterior limb of the internal capsule (ALIC) in patients with different outcomes. METHODS: In this retrospective study, we analyzed data from 18 patients with refractory OCD who underwent capsulotomies. Patients were grouped into "responders" and "nonresponders" based on the percentage of decrease in the Yale-Brown Obsessive-Compulsive Scale (YBOCS) after surgery. We investigated neurobehavioral adverse effects and analyzed the overlap between lesions and the ventromedial prefrontal (vmPFC) and dorsolateral prefrontal (dlPFC) pathways. Probabilistic maps were constructed to investigate the relationship between lesion location and clinical outcomes. RESULTS: Of the 18 patients who underwent capsulotomies, 12 were responders (>35% improvement in YBOCS), and six were nonresponders. The vmPFC pathway was more involved than the dlPFC pathway in responders (p = 0.01), but no significant difference was observed in nonresponders (p = 0.10). The probabilistic voxel-wise efficacy map showed a relationship between ventral voxels within the ALIC with symptom improvement. Weight gains occurred in 11/18 (61%) patients and could be associated with medial voxels within the ALIC. CONCLUSION: The optimal outcome after capsulotomy in refractory OCD is linked to vmPFC disruption in the ALIC. Medial voxels within the ALIC could be associated with weight gains following capsulotomy.

Corrigendum: Fixed-life or rechargeable battery for deep brain stimulation: preference and satisfaction in Chinese patients with Parkinson's disease.

[This corrects the article DOI: 10.3389/fneur.2021.668322.].

Tourette-like syndrome secondary to Kleefstra syndrome 1 with a de novo microdeletion in the EHMT1 gene.

BACKGROUND: Gills de la Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder manifested by motor and vocal tics. Kleefstra syndrome 1 (KS1), a rare genetic disorder, is caused by haploinsufficiency of the EHMT1 gene and is characterized by intellectual disability (ID), childhood hypotonia, and distinctive facial features. Tourette-like syndrome in KS1 has rarely been reported. CASE PRESENTATION: Here we describe a 7-year-old girl presenting involuntary motor and vocal tics, intellectual disability, childhood hypotonia, and dysmorphic craniofacial appearances, as well as comorbidities including attention deficit-hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), and self-injurious behavior (SIB). The patient's CNV-seq testing revealed a de novo 320-kb deletion in the 9q34.3 region encompassing the EHMT1 gene. CONCLUSIONS: This is the first case reporting Tourette-like syndrome secondary to KS1 with a de novo microdeletion in the EHMT1 gene. Our case suggests TS with ID and facial anomalies indicate a genetic cause and broadens the phenotypic and genotypic spectrum of both TS and KS1.

Time-locked acute alpha-frequency stimulation of subthalamic nuclei during the evaluation of emotional stimuli and its effect on power modulation.

Introduction: Deep brain stimulation (DBS) studies in Parkinson's Disease (PD) targeting the subthalamic nucleus (STN) have characterized its spectral properties across cognitive processes. In emotional evaluation tasks, specific alpha frequency (8-12 Hz) event-related de-synchronization (ERD) (reduced power) has been demonstrated. The time-locked stimulation of STN relative to stimuli onset has shown subjective positive valence shifts with 10 Hz but not with 130 Hz. However, neurophysiological effects of stimulation on power modulation have not been investigated. We aim to investigate effects of acute stimulation of the right STN on concurrent power modulation in the contralateral STN and frontal scalp EEG. From our previous study, we had a strong a priori hypothesis that negative imagery without stimulation would be associated with alpha ERD; negative imagery with 130 Hz stimulation would be also associated with alpha ERD given the lack of its effect on subjective valence ratings; negative imagery with 10 Hz stimulation was to be associated with enhanced alpha power given the shift in behavioral valence ratings. Methods: Twenty-four subjects with STN DBS underwent emotional picture-viewing tasks comprising neutral and negative pictures. In a subset of these subjects, the negative images were associated with time-locked acute stimulation at either 10 or 130 Hz. Power of signals was estimated relative to the baseline and subjected to non-parametric statistical testing. Results: As hypothesized, in 130 Hz stimulation condition, we show a decrease in alpha power to negative vs. neutral images irrespective of stimulation. In contrast, this alpha power decrease was no longer evident in the negative 10 Hz stimulation condition consistent with a predicted increase in alpha power. Greater beta power in the 10 Hz stimulation condition along with correlations between beta power across the 10 Hz stimulation and unstimulated conditions suggest physiological and cognitive generalization effects. Conclusion: Acute alpha-specific frequency stimulation presumably was associated with a loss of this expected decrease or desynchronization in alpha power to negative images suggesting the capacity to facilitate the synchronization of alpha and enhance power. Acute time-locked stimulation has the potential to provide causal insights into the spectral frequencies and temporal dynamics of emotional processing.

Utility of hybrid PET/MRI in stereoelectroencephalography guided radiofrequency thermocoagulation in MRI negative epilepsy patients.

Introduction: Hybrid positron emission tomography/magnetic resonance imaging (PET/MRI) is a novel advanced non-invasive presurgical examination tool for patients with drug-resistant epilepsy (DRE). This study aims to evaluate the utility of PET/MRI in patients with DRE who undergo stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-guided RFTC). Methods: This retrospective study included 27 patients with DRE who underwent hybrid PET/MRI and SEEG-guided RFTC. Surgery outcome was assessed using a modified Engel classification, 2 years after RFTC. Potential areas of the seizure onset zone (SOZ) were identified on PET/MRI and confirmed by SEEG. Results: Fifteen patients (55%) became seizure-free after SEEG-guided RFTC. Engel class II, III, and IV were achieved in six, two, and four patients, respectively at the 2 years follow-up. MRI was negative in 23 patients and structural abnormalities were found in four patients. Hybrid PET/MRI contributed to the identification of new structural or metabolic lesions in 22 patients. Concordant results between PET/MRI and SEEG were found in 19 patients in the identification of SOZ. Among the patients with multifocal onset, seizure-free status was achieved in 50% (6/12). Conclusion: SEEG-guided RFTC is an effective and safe treatment for drug-resistant epilepsy. Hybrid PET/MRI serves as a useful tool for detecting the potential SOZs in MRI-negative patients and guide the implantation of SEEG electrodes. Patients with multifocal epilepsy may also benefit from this palliative treatment.

Evidence Accumulation and Neural Correlates of Uncertainty in Obsessive-Compulsive Disorder.

BACKGROUND: Decision making is frequently associated with risk taking under uncertainty. Elevated intolerance of uncertainty is suggested to be a critical feature of obsessive-compulsive disorder (OCD). However, impairments of latent constructs of uncertainty processing and its neural correlates remain unclear in OCD. METHODS: In 83 participants (24 OCD patients treated with capsulotomy, 28 OCD control participants, and 31 healthy control participants), we performed magnetic resonance imaging using a card gambling task in which participants made decisions whether to bet or not that the next card would be larger than the current one. A hierarchical drift diffusion model was used to dissociate speed and amount of evidence accumulated before a decisional threshold (i.e., betting or no betting) was reached. RESULTS: High uncertainty was characterized by a smaller amount of evidence accumulation (lower thresholds), thus dissociating uncertainty from conflict tasks and highlighting the specificity of this task to test value-based uncertainty. OCD patients exhibited greater caution with poor performance and greater evidence accumulation overall along with slower speed of accumulation, particularly under low uncertainty. Bilateral dorsal anterior cingulate and anterior insula distinguished high- and low-uncertainty decision processes in healthy control participants but not in the OCD groups, indicating impairments in anticipation of differences in outcome variance and salience network activity. There were no behavioral or imaging differences relating to capsulotomy despite improvements in OCD symptoms. CONCLUSIONS: Our findings highlight greater impairments particularly in more certain trials in the OCD groups along with impaired neural differentiation of high and low uncertainty and suggest uncertainty processing as a trait cognitive endophenotype rather than a state-specific factor.

Platelet-Membrane-Coated Polydopamine Nanoparticles for Neuroprotection by Reducing Oxidative Stress and Repairing Damaged Vessels in Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) has a high morbidity and mortality rate. Excessive reactive oxygen species (ROS) caused by primary and second brain injury can induce neuron death and inhibit neurological functional recovery after ICH. Therefore, exploring an effective way to noninvasively target hemorrhage sites to scavenge ROS is urgently needed. Inspired by the biological function of platelets to target injury vessel and repair injury blood vessels, platelet-membrane-modified polydopamine (Menp@PLT) nanoparticles are developed with targeting to hemorrhage sites of ICH. Results demonstrate that Menp@PLT nanoparticles can effectively achieve targeting to the location of intracranial hematoma. Furthermore, Menp@PLT with excellent anti-ROS properties can scavenge ROS and improve neuroinflammation microenvironment of ICH. In addition, Menp@PLT may play a role in decreasing hemorrhage volume by repairing injury blood vessels. Combining platelet membrane and anti-ROS nanoparticles for targeting brain hemorrhage sites provide a promising strategy for efficiently treating ICH.