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Deep brain stimulation (DBS) is a neurosurgical procedure that utilizes implanted electrodes and electrical stimulation for the treatment of neurological disorders. In cases where patients present with severe functional impairment while being refractory to less invasive treatment options, DBS is considered \"gold standard.\" Still, DBS-related work is still widely under investigation, with ethical issues arising that may impact a patient\'s physical and psycho-social status. These include patient selection, informed consent, patient autonomy, pre-operation counseling and professional psycho-social preparation and follow-up support. Bioethicists and philosophers have increasingly worked together with in clinicians and researchers to identify, address and present ethical consideration in both clinical practice and research to balance the risk-benefit ratio in DBS treatment for obsessive-compulsive disorder.

Electrical neurostimulation is currently used to manage epilepsy, but the most effective approach for minimizing seizure occurrence is uncertain. While functional MRI (fMRI) can reveal which brain areas are affected by stimulation, simultaneous deep brain stimulation (DBS)-fMRI examinations in patients are rare and the possibility to investigate multiple stimulation protocols is limited. In this study, we utilized the intrahippocampal kainate mouse model of mesial temporal lobe epilepsy (mTLE) to systematically examine the brain-wide responses to electrical stimulation using fMRI. We compared fMRI responses of saline-injected controls and epileptic mice during stimulation in the septal hippocampus (HC) at 10 Hz and demonstrated the effects of different stimulation amplitudes (80-230 μA) and frequencies (1-100 Hz) in epileptic mice. Motivated by recent studies exploring 1 Hz stimulation to prevent epileptic seizures, we furthermore investigated the effect of prolonged 1 Hz stimulation with fMRI. Compared to sham controls, epileptic mice showed less propagation to the contralateral HC, but significantly stronger responses in the ipsilateral HC and a wider spread to the entorhinal cortex and septal region. Varying the stimulation amplitude had little effect on the resulting activation patterns, whereas the stimulation frequency represented the key parameter and determined whether the induced activation remained local or spread from the hippocampal formation into cortical areas. Prolonged stimulation of epileptic mice at 1 Hz caused a slight reduction in local excitability. In this way, our study contributes to a better understanding of these stimulation paradigms.

Objectives: Deep-brain stimulation (DBS) has been used for the treatment of medically refractory dystonia with excellent results. In this study, we compared in detail the therapeutic advantages of two DBS targets for generalized isolated dystonia. Methods: In this retrospective study, we recruited 29 patients with generalized isolated dystonia who had undergone DBS treatment targeting either the globus pallidus interna (GPi) or the subthalamic nucleus (STN) in the Department of Functional Neurosurgery at Tiantan Hospital, Beijing, China, between January 2016 and December 2021. The movement and disability subscales of the Burke-Fahn-Marsden dystonia rating scale (BFMDRS) were used to assess the severity of their dystonic symptoms and their activities of daily living, respectively. SF-36 was used to evaluate the patients\' health-related quality of life. Results: The percentage improvement in the BFMDRS-M score at 6 months relative to the baseline score was clearly higher in the STN group (63.91%) than in the GPi group (38.36%). At the 3-, 6-, and 12-month follow-ups, the percentage improvement in arm symptoms was significantly higher after DBS of the STN (70.64%, 80.66%, and 76.89%, respectively) than after stimulation of the GPi (36.75%, 34.21%, and 38.47%, respectively). At 12 months after surgery, patient quality of life had improved on all SF-36 subscales in both groups. Conclusions: STN-DBS may have more advantages than GPi-DBS in patients with obvious arm dystonia. STN-DBS had a better clinical effect than GPi-DBS within 6 months after surgery.

UNASSIGNED: Whether low-frequency deep brain stimulation (DBS) in the caudal zona incerta (cZi) can improve cerebellar ataxia symptoms remains unexplored.
UNASSIGNED: We report a 66-year-old man initially diagnosed with essential tremor and subsequently developed cerebellar ataxia after bilateral cZi DBS implantation. We tested the effects of low-frequency DBS stimulations (sham, 10 Hz, 15 Hz, 30 Hz) on ataxia severity.
UNASSIGNED: Low-frequency cZi DBS improves ataxic speech at 30 Hz, but not at 10 Hz or 15 Hz in this patient. Low-frequency DBS did not improve gait or stance. Therefore, low-frequency stimulation may play a role in treating ataxic speech.
UNASSIGNED: The finding of this case study suggests that bilateral low-frequency DBS at 30 Hz in the caudal zona incerta has the potential to improve ataxic speech but has limited impact on gait and stance. The involvement of zona incerta in speech warrants further investigation.

Per- and polyfluoroalkyl substances (PFAS) are anthropogenic fluorine-containing compounds largely used in industrial and consumer applications. They tend to bioaccumulate in the human body after intake from various sources in daily life. Following repeated exposure to PFAS, a broad range of adverse health outcomes has been reported. Consequently, monitoring PFAS levels in human blood is of paramount importance for public health policies. In contrast with traditional venipuncture, dried blood spots (DBS) constitute a reliable, cheap, and less invasive technique to allow microsampling by capillary blood collected on a specific device. This work aimed to develop and validate an innovative analytical method, combining quantitative DBS with UHPLC-MS/MS instrumentation to identify and quantify 25 PFAS. The extraction procedure was developed and optimized within the range 2-100 ng/mL. Specifically, fortified blood was applied on Capitainer®B devices providing 10 μL of blood volume through a microfluidic channel. After 3 h of drying, the extraction was performed by methanol under sonication, followed by centrifugation. Then, the extraction solvent was evaporated; the residue was reconstituted with the mobile phase solution. The validated method evidenced good sensitivity, with limits of detection ranging from 0.4 ng/mL (PFODA, PFOS) to 1.0 ng/mL (PFOA, 3,6-OPFHpA). The ± 20% acceptability criteria established for intra- and inter-day precision and accuracy were fulfilled for all analytes. High recovery-above 80%-was recorded, whereas significant matrix effect resulted in ion enhancement (> 50%) for 13 analytes. In conclusion, the proposed workflow proved to be reliable, fit for purpose, and easily adaptable in the laboratory routine.

BACKGROUND: The number of opioid-related deaths in the United States has more than tripled over the past 7 years, with a steep increase beginning at the same time as the COVID-19 pandemic. There is an urgent need for novel treatment options that can help alleviate the individual and social effects of refractory opioid use disorder (OUD). Deep brain stimulation (DBS), an intervention that involves implanting electrodes in the brain to deliver electrical impulses, is one potential treatment. Currently in clinical trials for many psychiatric conditions, including OUD, DBS\'s use for psychiatric indications is not without controversy. Several studies have examined ethical issues raised by using DBS to counter treatment-resistant depression, obsessive-compulsive disorder, and eating disorders. In contrast, there has been limited literature regarding the use of DBS for OUD.
OBJECTIVE: This study aims to gain empirical neuroethical insights into public perceptions regarding the use of DBS for OUD, specifically via the analysis of web-based comments on news media stories about the topic.
METHODS: Qualitative thematic content analysis was performed on 2 Washington Post newspaper stories that described a case of DBS being used to treat OUD. A total of 292 comments were included in the analysis, 146 comments from each story, to identify predominant themes raised by commenters.
RESULTS: Predominant themes raised by commenters across the 2 samples included the hopes and expectations with treatment outcomes, whether addiction is a mental health disorder, and issues related to resource allocation. Controversial comments regarding DBS as a treatment method for OUD seemingly decreased when comparing the first printed newspaper story to the second. In comparison, the number of comments relating to therapeutic need increased over time.
CONCLUSIONS: The general public\'s perspectives on DBS as a treatment method for OUD elucidated themes via this qualitative thematic content analysis that include overarching sociopolitical issues, positions on the use of technology, and technological and scientific issues. A better understanding of the public perceptions around the use of DBS for OUD can help address misinformation and misperceptions about the use of DBS for OUD, and identify similarities and differences regarding ethical concerns when DBS is used specifically for OUD compared to other psychiatric disorders.

BACKGROUND: Midline Tremor is defined as an isolated or combined tremor that affects the neck, trunk, jaw, tongue, and/or voice and could be part of Essential Tremor (ET), or dystonic tremor. The clinical efficacy of deep brain stimulation for Midline Tremor has been rarely reported. The Ventral Intermediate Nucleus and Globus Pallidus Internus are the preferred targets, but with variable outcomes. Thalamic Ventral-Oralis (VO) complex and Zona Incerta (ZI) are emerging targets for tremor control in various etiologies.
OBJECTIVE: To report on neuroradiological, neurophysiological targeting and long-term efficacy of thalamic Ventral-Oralis complex and Zona Incerta deep brain stimulation in Midline Tremor.
METHODS: Three patients (two males and one female) with Midline Tremor in dystonic syndromes were recruited for this open-label study. Clinical, surgical, neurophysiological intraoperative testing and long-term follow-up data are reported.
RESULTS: Intraoperative testing and reconstruction of volume of tissue activated confirmed the position of the electrodes in the area stimulated between the thalamic Ventral-Oralis complex and Zona Incerta in all patients. All three patients showed optimal control of both tremor and dystonic features at short-term (6 months) and long-term follow-up (up to 6 years). No adverse events occurred.
CONCLUSIONS: In the syndromes of Midline Tremor of various origins, the best target for DBS might be difficult to identify. Our results showed that thalamic Ventral-Oralis complex/Zona Incerta may be a viable and safe option even in specific forms of tremor with axial distribution.

BACKGROUND: Increased 4-12 Hz oscillatory activity in the cortico-basal ganglia-thalamo-cortical (CBGTC) loop is reported in dystonia. Coherence analysis is a measure of linear coupling between two signals, revealing oscillatory activity drives that are common across motor units. By performing coherence analysis, activity of the CBGTC-loop can be measured with modalities like local field potentials (LFPs), electromyography (EMG), and electro-encephalography (EEG). The aim of this study is to perform a systematic review on the use of coherence analysis for clinical assessment and treatment of dystonia.
METHODS: A systematic review was performed on a search in Embase and PubMed on June 28th, 2023. All studies incorporating coherence analysis and an adult dystonia cohort were included. Three authors evaluated the eligibility of the articles. Quality was assessed using the QUADAS-2 checklist.
RESULTS: A total of 41 articles were included, with data of 395 adult dystonia patients. In the selected records, six different types of coherence were investigated: corticocortical, corticopallidal, corticomuscular, pallidopallidal, pallidomuscular, and intermuscular coherence. Various types of 4-12 coherence were found to be increased in all dystonia subtypes.
CONCLUSIONS: There is increased 4-12 Hz coherence found between the cortex, basal ganglia, and affected muscles in all dystonia subtypes. However, the relationship between 4-12 Hz coherence and the dystonic clinical state has not been established. DBS treatment leads to a reduction of 4-12 Hz coherence. In combination with the results of this review, the 4-12 Hz frequency band can be used as a promising phenomenon for the development of a biomarker.

The metabolism of 3-chloromethcathinone (3-CMC) was studied after controlled administration in a murine model using the dried blood spot (DBS) technique for the sampling, storage and purification of blood samples. Liquid chromatography-high-resolution mass spectrometry (LC-HRMS) was used for the identification of metabolites and investigation of their fragmentation pattern. Subsequently, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for their identification and 3-CMC quantification in routine workload. The main metabolites identified were two stereoisomers of dihydro-CMC, N-demethyl-CMC, and dihydro-N-demethyl-CMC. The stability of 3-CMC and of its metabolites deposited on DBS was evaluated by replicate analyses after 30, 50, and 90 days, demonstrating a decrease in concentration. It was more pronounced for 3-CMC, with -67% and -82% percentage deviation from the initial concentrations, and for N-demethyl 3-CMC (decrease comprised between -48% and -88%) than for the di-hydro metabolites, ranging from -5% to -37%. Regardless, all of them were detectable till 90 days after deposition as DBS. The possibility of identifying 3-CMC and its metabolites with high sensitivity is an invaluable tool for the diagnosis of exposure to the substance, also in low doses or after some hours, and for various applications in clinical and forensic toxicology, such as driving under the influence, drug-facilitated crimes, and addiction to intoxications. DBS demonstrated to be a reliable technique for the sampling, storage, and purification of the blood specimen for 3-CMC and metabolite detection.