Parkinson’s disease (PD) disrupts cortico-basal ganglia communication, producing exaggerated beta-band (13–30 Hz) synchronization expressed as prolonged beta bursts that correlate with bradykinesia and rigidity. In healthy systems, brief beta bursts support flexible motor control, including reactive and proactive motor inhibition. However, in PD it remains unclear whether pathological beta bursts facilitate motor inhibition or if their prolonged nature and temporal inflexibility hinder both movement initiation and the timely engagement of inhibition. We addressed this by examining cortical beta bursts from high-density EEG acquired during a stop-signal task in 14 PD patients in practically defined medication OFF state with beep brain stimulation (DBS) ON and OFF, and 15 age-matched controls. At rest, PD patients exhibited prolonged cortical beta bursts that were normalized by DBS. During stopping, beta burst frequency increased in all groups, but bursts occurred earlier and more broadly across frontal regions in PD patients. DBS shifted burst properties toward the healthy range, improving reactive stopping while also reducing proactive inhibition. These findings suggest that DBS over subthalamic nucleus restores temporal flexibility in cortical beta bursting but may attenuate proactive control, underscoring the need for adaptive DBS approaches that normalize pathologically prolonged bursts without excessively reducing burst features that support proactive adjustments.

BACKGROUND:Psychiatric disorders are increasingly contributing to global disability. Despite advances in conservative management, the prevalence of treatment-resistant cases remains high. Meanwhile, neurosurgery for psychiatric disorders (NPD) remains underused, largely due to strict regulations and historical concerns, particularly those related to neuropsychological side effects (NPSE). OBJECTIVE:To address this issue, we conducted a systematic review with meta-analysis to compare NPSE associated with radiofrequency ablative NPD to those observed in neuro-oncological, neurovascular and epilepsy surgeries. METHODS:PubMed, Embase and LILACS databases were searched in April 2024 for articles published in English/Spanish from 1990 to 2022, following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. RESULTS:A total of 48 articles with 2678 participants were included. The frequency of transient and permanent NPSE in the NPD group ranged from 0.94% to 11.50% and 0.94% to 2.03%, respectively, comparable to the other surgical groups (epilepsy: 0.31-11.70%; vascular: 0.52-22.90%; oncology: 0.94-17.60% for transient NPSE; epilepsy: 0.31-12%; vascular: 0.40-1.96% and oncology: 0.84-1.48% for permanent NPSE). Regarding permanent NPSE, arguably the most critical consideration, the NPD group showed better outcomes in memory, language and social cognition than the epilepsy group, but worse outcomes in executive and perceptual-motor functions. Compared with the vascular group, the NPD group had better executive function but worse complex attention. Finally, the NPD group had fewer permanent deficits than the oncology group in executive function, complex attention and perceptual-motor domains, although language performance was lower. CONCLUSIONS:Contemporary NPD apparently carries a similar risk of NPSE as other conventional neurosurgical procedures, challenging misconceptions and this unjustified barrier to its broader use.

Objectives: We aimed to investigate the impact of acute cortical stroke (ACS) on neural activity in subthalamic nucleus (STN). We then examined the correlation between changes in STN activity and motor disability. Methods: Forty-four Sprague-Dawley rats were used. While rats were anesthetized, we inserted electrodes in STN and induced an ACS by creating photothrombotic lesion in ipsilateral motor cortex. Local field potentials were recorded before and after ACS. The motor behavior was assessed before and after ACS using single pellet reaching task. Results: Rats experienced significant motor disability after ACS. STN firing rate significantly decreased after ACS. Additionally, delta (0.5-4 Hz) and gamma (50-140 Hz) power significantly decreased after ACS. Furthermore, the decrease in delta mean power correlated with decreases in success rate (r =0.77, p =0.009) and first try success rate (r =0.69, p =0.028). The decreases in gamma mean power (r =0.68, p =0.029) and gamma peak power (r =0.74, p =0.015) correlated with the decrease in success rate. The decrease in gamma power significantly correlated with the decreased STN firing rate. However, decreased delta power exhibited no correlation with decreased gamma power. Interpretation: ACS causes abnormal STN activity, which correlated with motor disability. Post-stroke STN inhibition may partially compensate for ACS. However, it could also lead to pathological consequences. This STN abnormal activity may serve as a biomarker for motor disability severity after ACS. Furthermore, our findings may provide a possibility for developing neuromodulation strategies, allowing to mitigate post-stroke motor disability through modulating abnormal STN activity. ### Competing Interest Statement The authors have declared no competing interest.

Functional ultrasound (fUS) imaging is a well-established neuroimaging technology that offers high spatiotemporal resolution and a large field of view. Typical strategies for analyzing fUS data comprise either region-based averaging, typically based on reference atlases, or correlation with experimental events. Nevertheless, these methodologies possess several inherent limitations, including a restricted utilization of the spatial dimension and a pronounced bias influenced by preconceived notions about the recorded activity. In this study, we put forth single-voxel clustering as a third method to address these issues. A comparison was conducted between the three strategies on a typical dataset comprising visually evoked activity in the superior colliculus in awake mice. The application of single-voxel clustering yielded the generation of detailed activity maps, which revealed a consistent layout of activity and a clear separation between hemodynamic responses. This method is best considered as a complement to region-based averaging and correlation. It has direct applicability to challenging contexts, such as paradigm-free analysis on behaving subjects and brain decoding.

Accurate electrode implantation in the subthalamic nucleus (STN) of rats is essential for high-quality electrophysiological and neuromodulation studies but remains technically challenging due to the small size and deep location of the STN. Traditional stereotactic methods, relying on bregma or averaged bregma-interaural-based coordinates, often result in misplacement of electrode. Here, we introduce a combined anatomical and functional approach—bregma-interaural and electrophysiology-guided technique (BITE)—designed to enhance targeting accuracy for STN electrode implantation in male Sprague Dawley rats. In this method, anterior-posterior (AP), medial-lateral (ML), and dorsal-ventral (DV) coordinates are initially determined using the average of bregma and interaural references. Electrode depth (DV axis) is fine-tuned based on real-time detection of characteristic STN neuronal firing patterns. If STN featured activity is not observed on the first implantation, additional adjustments in the AP and ML axes are made, followed by electrophysiology-guided DV tuning. Using BITE, we achieved an 83% overall success rate for STN electrode implantation, with 50% of electrodes precisely located in the dorsal STN (dSTN). This represents a significant improvement compared with the bregma-based method (17%, p = 0.0005) and the averaged bregma-interaural-based method (40%, p = 0.0188). BITE offers two main advantages: (1) increased accuracy in targeting the STN and (2) improved access to the dSTN, a region of growing interest in basal ganglia research. These findings demonstrate that BITE is a reliable and effective method for precise electrode placement in the STN and may serve as a valuable tool in rat models of deep brain stimulation and basal ganglia function.

Over the past decade, interest in lesion-based neuromodulation has experienced a resurgence fueled in large part by the noninvasive nature of new technologies, especially high-intensity focused ultrasound (HIFU). The noninvasiveness and relatively low cost of these outpatient methods are key attributes contributing to growing acceptance. A recent resurgent embrace of stereotactic radiosurgery (SRS) for brain lesioning, especially in the treatment of tremor via thalamotomy, builds on this new trend. While we believe this development for treating well-established movement (tremor) and behavioral (obsessive-compulsive) disorders is warranted and perhaps even applauded, we are worried that enthusiasm for lesioning using SRS may now be getting ahead of itself. This concern stems from the exuberance for using SRS to treat additional behavioral diseases, as showcased during the recent American Society for Radiation Oncology (ASTRO) 2025 meeting. The near giddiness observed in San Francisco regarding the use of SRS to treat patients with psychiatric disorders prompts us to write the present cautionary editorial. The aim of this editorial is to caution against premature clinical enthusiasm for using ablative SRS to target the nucleus accumbens (NAc) for psychiatric disorders. Our objectives are to (1) contextualize this proposal within the troubling history of psychosurgical overreach, (2) summarize the substantial neuroscientific and clinical risks inherent to NAc ablation, and (3) advocate for a strict, evidence-based, and ethically grounded approach that prioritizes reversible neuromodulation over irreversible lesioning.

Over the last decade, functional ultrasound (fUS) has risen as a critical tool in functional neuroimaging, leveraging hemodynamic changes to infer neural activity indirectly. Recent studies have established a strong correlation between neural spike rates (SR) and functional ultrasound signals. However, understanding their spatial distribution and variability across different brain areas is required to thoroughly interpret fUS signals. In this regard, we conducted simultaneous fUS imaging and Neuropixels recordings during stimulus-evoked activity in awake mice within three regions of the visual pathway. Our findings indicate that the temporal dynamics of fUS and SR signals are linearly correlated, providing an approximate calibration between the two signals. Conversely, the spatial correlation between the two signals remains consistent across all regions with a spread of approximately 300 micrometers. Finally, we introduce a model that integrates the spatial and temporal components of the fUS signal, allowing for a more accurate interpretation of fUS images.

BACKGROUND:The subthalamic nucleus (STN) plays a role in motor control, yet it is unclear whether acute cortical stroke (ACS) causes abnormal STN activity and neural oscillations. Moreover, the correlation between these subthalamic neurophysiological changes and motor disability remains unknown. To address this, we studied the impact of ACS on neural activity in the STN. We then examined the correlation between changes in STN activity and motor disability. METHODS:Fifty-six Sprague-Dawley rats were used. Although rats were anesthetized, we inserted electrodes in the STN and induced an ACS by creating a photothrombotic lesion in the ipsilateral motor cortex. Local field potentials were recorded before and after ACS. The motor behavior was assessed before and after ACS using a single-pellet reaching task. RESULTS:Rats experienced significant motor disability after ACS. STN firing rate significantly decreased after ACS. Additionally, delta (0.5-4 Hz) and gamma (80-130 Hz) power significantly decreased after ACS. Furthermore, the decrease in delta mean power correlated with decreases in success rate (r=0.77; P=0.009) and first try success rate (r=0.69; P=0.028). The decreases in gamma mean power (r=0.68; P=0.029) and gamma peak power (r=0.74; P=0.015) correlated with the decrease in success rate. The decrease in gamma power significantly correlated with the decreased STN firing rate. However, decreased delta power exhibited no correlation with decreased gamma power. CONCLUSIONS:Our study provides the first evidence that ACS causes significant subthalamic inhibition and abnormal oscillatory activity in rats, with these effects significantly correlated with motor disability. Notably, these abnormal STN oscillations serve as a predictive biomarker for motor disability during the acute phase of cortical stroke. Furthermore, our findings highlight the potential of neuromodulation strategies to mitigate poststroke motor disability by targeting and reducing abnormal STN activity.

Introduction Deep brain stimulation (DBS) has become an established therapy for otherwise treatment-refractory obsessive-compulsive disorder (OCD). Although several studies and meta-analyses have demonstrated its efficacy, the results thus far have not been analyzed with the novel tool of an umbrella review. Here, we aim to provide an umbrella review and an updated meta-analysis of all previously published data concerning the outcomes of DBS for OCD. Methods In adherence to PRISMA guidelines, an umbrella review and meta-analysis was conducted, systematically searching PubMed, Medline, Embase, and Web of Science for meta-analyses on the treatment of OCD with DBS. Individual studies within the included meta-analyses, along with new studies, were meticulously reviewed, and duplications were removed. The results were collected and pooled to generate forest plots. The primary outcome was the relative change in Y-BOCS, HAM-A, HAM-D and Global Assessment of Functioning (GAF) scores at the last available follow-up after DBS. Results This umbrella review encompassed seven meta-analyses evaluating the outcomes of DBS in patients with OCD published between 2014 and 2022. The current updated meta-analysis, including 29 studies, revealed significant overall improvement in OCD symptoms following DBS, as measured by Y-BOCS (mean difference (MD = 14.12 95 %CI = 12.43, 15.82, p < 0.00001, I² = 73 %), HAM-A (MD = 10.71, 95 %CI = 8.55, 12.88, p < 0.00001, I² = 63 %), HAM-D (MD = 11.14, 95 %CI = 9.39, 12.89, p < 0.00001, I² = 0 %), and GAF scales (MD = 5.20, 95 %CI = 4.51, 5.89, p < 0.00001, I² = 99 %). Conclusion Our advanced analysis confirms that DBS is an effective therapy for OCD and its associated co-morbidities. Further research is essential to better understand and assess treatment efficacy and its underlying mechanisms.

OBJECTIVES:Deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) is a well-established treatment for Parkinson's disease (PD), yet programming remains empirical and time-consuming. Evoked resonant neural activity (ERNA), a stimulation-evoked oscillatory response recorded from the STN, has shown promise as a biomarker for optimizing DBS therapy. This study aimed to evaluate the utility of ERNA as a physiologically grounded biomarker for optimizing STN DBS by 1) characterizing its sensitivity to stimulation parameters and directional contact location, 2) identifying its spatial distribution using directional leads, and 3) assessing correspondence between the ERNA-defined sweet spot and established clinical targets. MATERIALS AND METHODS:We recorded ERNA intraoperatively from 14 patients with PD who underwent awake STN-DBS implantation with directional leads. ERNA features were analyzed across stimulation amplitudes and contacts. A sweet spot was derived based on the anatomical location of stimulation settings associated with high ERNA magnitudes. Spatial correspondence with previously published clinical sweet spots was evaluated. RESULTS:ERNA magnitude scaled with stimulation intensity and varied across directional contacts, showing consistent directional tuning across depths. Sweet spot analysis localized high-amplitude ERNA responses to a focal dorsal STN cluster at the motor-associative border. This ERNA-defined sweet spot closely aligned (centroid distance: 1.41-2.08 mm) with four independent clinical targets. CONCLUSIONS:ERNA is a spatially specific and physiologically meaningful signal that aligns with clinically effective stimulation sites. Its sensitivity to directional stimulation highlights its high spatial resolution, supporting its use as an objective biomarker to guide DBS programming. Future studies should explore its utility in long-term therapeutic settings. CLINICAL TRIAL REGISTRATION:The Clinicaltrials.gov registration number for the study is NCT04658641.

•DBS impacts the life of OCD patients beyond changes in their core symptoms.•Qualitative methods allow gathering in-depth knowledge of DBS-related experiences.•Positive and negative psychological and physical experiences are reported.•Attention should be given to each individual treatment trajectory.•Proper assessment tools should be developed for continuous monitoring and support.

Objective: Parkinson's disease (PD) patients exhibit changes in mechanisms underlying movement preparation, particularly the suppression of corticospinal excitability - termed "preparatory suppression" - which is thought to facilitate movement execution in healthy individuals. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) being an attractive treatment for advanced PD, we aimed to study the potential contribution of this nucleus to PD-related changes in such corticospinal dynamics. Methods: On two consecutive days, we applied single-pulse transcranial magnetic stimulation to the primary motor cortex of 20 advanced PD patients treated with bilateral STN-DBS (ON vs. OFF), as well as 20 healthy control subjects. Motor-evoked potentials (MEPs) were elicited at rest or during movement preparation in an instructed-delay choice reaction time task including left- or right-hand responses. Preparatory suppression was assessed by expressing MEPs during movement preparation relative to rest. Results: PD patients exhibited a deficit in preparatory suppression when it was probed on the responding hand side, particularly when this corresponded to their most-affected hand, regardless of their STN-DBS status. Conclusions: Advanced PD patients displayed a reduction in preparatory suppression which was not restored by STN-DBS. Significance: The current findings confirm that PD patients lack preparatory suppression, as previously reported. Yet, the fact that this deficit was not responsive to STN-DBS calls for future studies on the neural source of this regulatory mechanism during movement preparation. (c) 2024 Published by Elsevier B.V. on behalf of International Federation of Clinical Neurophysiology.

IntroductionSymmetric biphasic pulses have been shown to increase the therapeutic window compared to standard cathodic pulses in ET Vim-DBS patients. Furthermore, three hours of stimulation with biphasic pulses caused less stimulation-induced ataxia compared to cathodic pulses. Therefore, an investigation of the longer-term safety of biphasic pulses is warranted.MethodsSeven ET patients were included in a randomized double-blind, cross-over design of one week home-use of symmetric biphasic stimulation (anodic phase first) versus cathodic stimulation. Amplitude was set in a double-blinded way, at the tremor arrest threshold. The primary outcome was safety assessed by documenting the adverse events. Secondary outcome parameters were stimulation amplitude, tremor (Fahn-Tolosa-Marin Tremor Rating Scale) and ataxia (International Cooperative Ataxia Rating Scale) severity, quality of life (Quality of Life in Essential Tremor Questionnaire) and cognition (Montreal Cognitive Assessment). Three patients continued in the open-label extension phase for 3 months, during which biphasic stimulation-only was further assessed by the same outcome parameters.ResultsDuring the 1 week testing, no adverse effects were reported. To obtain equivalent tremor control, the amplitude of the biphasic pulse was significantly higher compared to that of the cathodic pulse (p = 0.003). The other outcome parameters were not significantly different. During the open-label study, one patient used the remote control to increase the amplitude, leading to two falls caused by stimulation-induced ataxia. No other adverse effects occurred.Discussion and conclusionIn a small cohort, when tested for one week, symmetric biphasic pulses suggest to be safe, but require higher stimulation amplitudes. Further follow-up studies are needed to investigate long-term effects and safety.

BACKGROUND:Subthalamic deep brain stimulation (STN-DBS) is a well-established therapy to treat Parkinson's disease (PD). However, the STN-DBS sub-target remains debated. Recently, a white matter tract termed the hyperdirect pathway (HDP), directly connecting the motor cortex to STN, has gained interest as HDP stimulation is hypothesized to drive DBS therapeutic effects. Previously, we have investigated EEG-based evoked potentials (EPs) to better understand the neuroanatomical origins of the DBS clinical effect. We found a 3-ms peak (P3) relating to clinical benefit, and a 10-ms peak (P10) suggesting nigral side effects. Here, we aimed to investigate the neuroanatomical origins of DBS EPs using probabilistic mapping. METHODS:EPs were recorded using EEG whilst low-frequency stimulation was delivered at all DBS-contacts individually. Next, EPs were mapped onto the patients' individual space and then transformed to MNI standard space. Using voxel-wise and fiber-wise probabilistic mapping, we determined hotspots/hottracts and coldspots/coldtracts for P3 and P10. Topography analysis was also performed to determine the spatial distribution of the DBS EPs. RESULTS:In all 13 patients (18 hemispheres), voxel- and fiber-wise probabilistic mapping resulted in a P3-hotspot/hottract centered on the posterodorsomedial STN border indicative of HDP stimulation, while the P10-hotspot/hottract covered large parts of the substantia nigra. CONCLUSION:This study investigated EP-based probabilistic mapping in PD patients during STN-DBS, revealing a P3-hotspot/hottract in line with HDP stimulation and P10-hotspot/hottract related to nigral stimulation. Results from this study provide key evidence for an electrophysiological measure of HDP and nigral stimulation.