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Deep brain stimulation (DBS) is a surgical neuromodulation procedure with a historically wide range of possible therapeutic indications, including movement disorders, neuropsychiatric conditions, and cognitive disorders. Ongoing research in this field is critical to gain further insights into the mechanisms of DBS, to discover novel brain targets for new and existing indications, and to refine targeting and post-operative programming techniques for the optimization of therapeutic outcomes. To update on the state of DBS-related clinical human research by cataloging and summarizing clinical trials that have been completed or are currently ongoing in this field worldwide. A search was conducted for clinical trials pertaining to DBS, currently listed on the ClinicalTrials.gov database. Trials were analyzed to generate a detailed overview of ongoing DBS-related research. Specifically, trials were categorized by trial start date, study completion status, clinical phase, projected subject enrollment, disorder, brain target, country of origin, device manufacturer, funding source, and study topic. In total, 384 relevant clinical trials were identified. The trials spanned 28 different disorders across 26 distinct brain targets, with almost 40% of trials being for conditions other than movement disorders. The majority of DBS trials have been US-based (41.9% of studies) but many countries are becoming increasingly active. The ratio of investigator-sponsored to industry-sponsored trials was 3:1. Emphasizing the need to better understand the mechanism of action of DBS, one-third of the studies predominantly focus on imaging or electrophysiological changes associated with DBS. This overview of current DBS-related clinical trials provides insight into the status of DBS research and what we can anticipate in the future concerning new brain targets, indications, techniques, and developing a better understanding of the mechanisms of action of DBS. • 384 clinical trials on deep brain stimulation span 28 disorders across 26 brain targets. • Most trials are US-based, pertain to movement disorders, and are non-industry-sponsored. • 1/3 of studies focus on imaging or electrophysiological changes associated with DBS. [ABSTRACT FROM AUTHOR]

Panic attacks affect a sizeable proportion of the population. The neurocircuitry of panic remains incompletely understood. To investigate the neuroanatomical underpinnings of panic attacks induced by deep brain stimulation (DBS) through (1) connectomic analysis of an obsessive-compulsive disorder patient who experienced panic attacks during inferior thalamic peduncle DBS; (2) appraisal of existing clinical reports on DBS-induced panic attacks. Panicogenic, ventral contact stimulation was compared with benign stimulation at other contacts using volume of tissue activated (VTA) modelling. Networks associated with the panicogenic zone were investigated using state-of-the-art normative connectivity mapping. In addition, a literature search for prior reports of DBS-induced panic attacks was conducted. Panicogenic VTAs impinged primarily on the tuberal hypothalamus. Compared to non-panicogenic VTAs, panicogenic loci were significantly functionally coupled to limbic and brainstem structures, including periaqueductal grey and amygdala. Previous studies found stimulation of these areas can also provoke panic attacks. DBS in the region of the tuberal hypothalamus elicited panic attacks in a single obsessive-compulsive disorder patient and recruited a network of structures previously implicated in panic pathophysiology, reinforcing the importance of the hypothalamus as a hub of panicogenic circuitry. [ABSTRACT FROM AUTHOR]

Copyright of Revista Chilena de Derecho is the property of Revista Chilena de Derecho and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract Background Several different surgical procedures targeting the limbic circuit have been utilized for severe, treatment resistant obsessive-compulsive disorder; however, there has only been limited exploration of the inferior thalamic peduncle (ITP). The aim of this study was to determine the safety and initial efficacy of ITP deep brain stimulation (DBS) in patients with severe obsessive-compulsive disorder. Methods Patients with severe, treatment-refractory obsessive-compulsive disorder were enrolled into this open-label phase 1 DBS pilot study. Bilateral ITP DBS devices were implanted between November 2010 and December 2015. The primary outcome was safety. The initial efficacy was determined by Yale-Brown Obsessive-Compulsive scale (YBOCs) scores. Component Y-BOCs scores, Hamilton Depression Severity Scale, Quality of Life Assessment (SF-36), Oxford Happiness Questionnaire, Warwick-Edinburgh Mental Well-Being Scale, and Sheehan Disability Scale were also analyzed for a minimum of 2 years after surgery. Additionally, preoperative and three-month postoperative FDG-PET studies were performed on two patients. Results Five patients (2 males, 3 females; age range 25–48 years) received ITP DBS. All five patients were considered responders at one year (52% improvement in YBOCs scores compared to baseline (range 39–73%, p < 0.01) and last follow-up (54% improvement; range 38–85%; p < 0.01). At two years follow-up, there were three adverse events that occurred in two patients. One patient had his DBS system removed after one year due to the device becoming the object of his obsession. The other two adverse events were not related to the device. Post-operative FDG-PET imaging in two patients demonstrated decreased glucose uptake within the right caudate, right putamen, right supplementary motor area, and right cingulum and increased glucose uptake in bilateral motor areas, left temporal pole, and left orbitfrontal cortex. Conclusions ITP DBS has a favorable safety profile and is potentially an efficacious treatment for severe obsessive-compulsive disorder. Larger clinical trials are necessary to determine efficacy. Highlights • Inferior thalamic peduncle deep brain stimulation for treatment refractory obsessive-compulsive disorder has a favorable safety profile. • ITP DBS is a potentially efficacious treatment, as all five patients in this study were considered treatment responders. • After three months of chronic ITP DBS, PET imaging was consistent with network engagement. [ABSTRACT FROM AUTHOR]

Abstract Background Deep brain stimulation (DBS) is currently used to treat addiction, with the nucleus accumbens (NAc) as one promising target. The anterior limb of the internal capsule (ALIC) is also a potential target, as it carries fiber tracts connecting the mesocorticolimbic circuits that are crucially involved in several psychiatric disorders, including addiction. Stimulating the NAc and ALIC simultaneously may have a synergistic effect against addiction. Methods Eight patients with a long history of heroin use and multiple relapses, despite optimal conventional treatments, were enrolled. Customized electrodes were implanted through the ALIC into the NAc, and deep brain stimulation (DBS) treatment began two weeks after surgery. The patients were followed for at least 24 months. The duration of drug-free time, severity of drug cravings, psychometric evaluations, and PET studies of glucose metabolism before and after DBS were conducted. All adverse events were recorded. Results With DBS, five patients were abstinent for more than three years, two relapsed after abstaining for six months, and one was lost of follow-up at three months. The degree of cravings for drug use after DBS was reduced if the patients remained abstinent (p < 0.001). Simultaneous DBS of the NAc and ALIC also improved the quality of life, alleviated psychiatric symptoms, and increased glucose metabolism in addiction-related brain regions. Moreover, stimulation-related adverse events were few and reversible. Conclusions Simultaneous DBS of the NAc and ALIC appears to be safe, with few side effects, and may prevent long-term heroin relapse after detoxification in certain patients. (This trial was registered at ClinicalTrials.gov , NCT01274988). Highlights • Bilateral NAc and ALIC were simultaneously stimulated in heroin addicts for preventing relapse after detoxification. • Five of eight patients have kept abstinent for more than 3 years, with few side effects. • Decreased cravings for drug use, improved quality of life and alleviated mental disorders were observed. • Simultaneous DBS of NAc and ALIC appears to be safe, and produces long-term effects for preventing heroin relapse. [ABSTRACT FROM AUTHOR]

Abstract Background There is an emerging need for noninvasive neuromodulation techniques to improve patient outcomes while minimizing adverse events and morbidity. Low-intensity focused ultrasound (LIFUS) is gaining traction as a non-surgical experimental approach of modulating brain activity. Several LIFUS sonication parameters have been found to potentiate neural firing, suppress cortical and epileptic discharges, and alter behavior when delivered to cortical and subcortical mammalian brain regions. Objective This review introduces the elements of an effective sonication protocol and summarizes key preclinical studies on LIFUS as a neuromodulation modality. The state of the art in human ultrasound neuromodulation is then comprehensively summarized, and current hypotheses regarding the underlying mechanism of action on neural activity are presented. Methods Peer-reviewed literature on human ultrasound neuromodulation was obtained by searching several electronic databases. The abstracts of all reports were read and publications which examined low-intensity transcranial ultrasound applied to human subjects were selected for review. Results LIFUS can noninvasively influence human brain activity by suppressing cortical evoked potentials, influencing cortical oscillatory dynamics, and altering outcomes of sensory/motor tasks compared to sham sonication. Proposed mechanisms include cavitation, direct effects on neural ion channels, and plasma membrane deformation. Conclusions Though optimal sonication paradigms and transcranial delivery methods are still being established, future applications may include non-invasive human brain mapping experiments, and nonsurgical treatments for functional neurological disorders. Highlights • Low-intensity ultrasound can noninvasively modulate mammalian brain activity. • Pulsing parameters and intensity determine excitatory or inhibitory neural effects. • Human US neuromodulation has been achieved in cortical and deep structures. • Ultrasound holds promise as a precise, nonsurgical and safe brain stimulation tool. [ABSTRACT FROM AUTHOR]

Background Deep brain stimulation (DBS) is an important form of neuromodulation that is being applied to patients with motor, mood, or cognitive circuit disorders. Despite the efficacy and widespread use of DBS, the precise mechanisms by which it works remain unknown. Over the last decade, magnetoencephalography (MEG) has become an important functional neuroimaging technique used to study DBS. Objective This review summarizes the literature related to the use of MEG to characterize the effects of DBS. Methods Peer reviewed literature on DBS-MEG was obtained by searching the publicly accessible literature databases available on PubMed. The abstracts of all reports were scanned and publications which combined DBS-MEG in human subjects were selected for review. Results A total of 32 publications met the selection criteria, and included studies which applied DBS for Parkinson's disease, dystonia, chronic pain, phantom limb pain, cluster headache, and epilepsy. DBS-MEG studies provided valuable insights into network connectivity, pathological coupling, and the modulatory effects of DBS. Conclusions As DBS-MEG research continues to develop, we can expect to gain a better understanding of diverse pathophysiological networks and their response to DBS. This knowledge will improve treatment efficacy, reduce side-effects, reveal optimal surgical targets, and advance the development of closed-loop neuromodulation. [ABSTRACT FROM AUTHOR]

Background Deep brain stimulation of the ventro-intermedius nucleus of the thalamus is an established treatment for tremor of differing etiologies but factors that may predict the short- and especially long-term outcome of surgery are still largely unknown. Methods We retrospectively investigated the clinical, pharmacological, electrophysiological and anatomical features that might predict the initial response and preservation of benefit in all patients who underwent deep brain stimulation for tremor. Data were collected at the following time points: baseline (preoperative), one-year post-surgery, and most recent visit. Tremor severity was recorded using the Fahn-Tolosa-Marin Tremor Rating Scale and/or the Unified Parkinson's Disease Rating Scale. Results A total of 52 patients were included in the final analysis: 31 with essential tremor, 15 with cerebellar tremor of different etiologies, and 6 with Parkinson's disease. Long-term success (mean follow-up duration 34.7 months, range 1.7–121.1 months) was reported in 63.5%. Predictors of long-term benefit were: underlying tremor etiology (best outcome in Parkinson's disease, worst outcome in cerebellar tremor); age at surgery (the older the better); baseline tremor severity (the greater the better); lack of response to benzodiazepines; a more anterior electrode placement and single-unit beta power (the greater the better). Conclusions Specific patients' features (including single unit beta activity) and electrode locations may predict the short- and long-term benefit of thalamic stimulation for tremor. Future prospective studies enrolling a much larger sample of patients are needed to substantiate the associations detected by this retrospective study. [ABSTRACT FROM AUTHOR]

Background Alzheimer's disease (AD) is a progressive degenerative disorder that currently remains extremely disabling. Recent work has shown that deep brain stimulation (DBS) has promising effects in AD patients. In parallel to the clinical trials, we investigated the impact of chronic DBS in 3xTg mice, a well-established animal model of AD. Methods AD mice were assigned to control (Cont), non-stimulation (NS) and stimulation (DBS) groups, along with age matched wild type controls (WT-Cont). Bilateral electrodes were implanted in the entorhinal cortex to deliver chronic high frequency stimulation for 25 days. Animals were tested in memory behavioral tasks, with post-mortem measurements of pathological markers. Results We found that chronic DBS in AD mice normalized their impaired performance in the Morris water maze task to that of the WT group in the probe test. In the novel object and novel place preference tasks, AD-DBS mice spent more time at the novel object and novice location compared to AD-NS mice. These cognitive improvements in AD-DBS mice were associated with DBS induced increased neurogenesis in the dentate gyrus, a significant reduction in β−amyloid plaques, a reduction in CA-1 cellular β−amyloid-42 levels, decreased cortical total-tau and phosphorylated-tau, along with decreased hippocampal total-tau. Conclusion Overall, we show that chronic DBS of the entorhinal cortex in AD mice improves both memory and AD specific pathological markers. These results support further testing of DBS as a potential treatment in AD patients. [ABSTRACT FROM AUTHOR]

The PtPd nanoparticles are synthesized following different methods and intensively investigated for their catalytic properties oxygen reduction reaction (ORR), with a potential application in fuel cells. The galvanic replacement is an attractive method to prepare bimetallic particles with high catalytic activity and a high control of the morphology and chemical composition, varying with the experimental conditions during the synthesis. The influence of the time with the transformation from pure Pd nanocubes to concave core-shell PtPd nanoparticles synthesized by galvanic replacement is examined: after different times of preparation, the morphology of the particles was monitored by transmission electron microscopy (TEM) coupled with energy Dispersive X-ray spectroscopy (EDS). Via X-Ray diffraction spectroscopy (XRD), the crystallographic structure and the variation of size, lattice parameters, d-spacing, and composition were determined. The extended X-ray fine structure (EXAFS) measurements show the formation of a PtPd alloy at the surface of the particles for all samples. Finally, the electrochemical determination of the catalytic activity and stability tests revealed two different particle types as candidates to replace pure Pt as catalyst in the proton exchange membrane fuel cells (PEMFC) due to their enhanced stability, higher catalytic activity, and lower Pt content. [ABSTRACT FROM AUTHOR]

Background Survivors of stroke often experience significant disability and impaired quality of life related to ongoing maladaptive responses and persistent neurologic deficits. Novel therapeutic options are urgently needed to augment current approaches. One way to promote recovery and ameliorate symptoms may be to electrically stimulate the surviving brain. Various forms of brain stimulation have been investigated for use in stroke, including deep brain stimulation (DBS). Objective/Methods We conducted a comprehensive literature review in order to 1) review the use of DBS to treat post-stroke maladaptive responses including pain, dystonia, dyskinesias, and tremor and 2) assess the use and potential utility of DBS for enhancing plasticity and recovery from post-stroke neurologic deficits. Results/Conclusions A large variety of brain structures have been targeted in post-stroke patients, including motor thalamus, sensory thalamus, basal ganglia nuclei, internal capsule, and periventricular/periaqueductal grey. Overall, the reviewed clinical literature suggests a role for DBS in the management of several post-stroke maladaptive responses. More limited evidence was identified regarding DBS for post-stroke motor deficits, although existing work tentatively suggests DBS—particularly DBS targeting the posterior limb of the internal capsule—may improve paresis in certain circumstances. Substantial future work is required both to establish optimal targets and parameters for treatment of maladapative responses and to further investigate the effectiveness of DBS for post-stroke paresis. [ABSTRACT FROM AUTHOR]

Introduction Deep Brain Stimulation (DBS) is an effective treatment extended broadly to many neurological and psychiatric disorders. Nevertheless, complications may arise during DBS procedures or following implantation due to implanted hardware. This may result in both minor and major adverse events that may necessitate hardware removal and/or compromise maximal therapeutic benefit for the patient. Objectives and methods To identify relevant literature on hardware-related complications from DBS procedures by performing a systematic review, and propose how to identify at-risk group and possible preventive approaches. Results Of 4592 abstract screened, 96 articles fulfilled the selection criteria and were reviewed. Overall, the most common hardware-related complications were infections (5.12% of patients), followed by lead migration (1.60%), fracture or failure of the lead or other parts of the implant (1.46% and 0.73%, respectively), IPG malfunctions (1.06% of patients), and skin erosions without infections (0.48% of patients). New indications for DBS, including Tourette's syndrome, cluster headache, and refractory partial epilepsy, were found to bear a higher incidence of hardware-related infections than established indications such as Parkinson's disease. The highest rate of lead fracture or failure was found in dystonia patients (4.22%). Ultimately, the highest rate of pain at the implantation sites was found in refractory partial epilepsy patients (16.55%). Conclusion Our analysis identified a variety of potential hardware-related complications among patients who underwent DBS procedures. Patients who were at risk of complications, such as patients with dystonia and off-label indications (e.g. Tourette's syndrome) should be informed prior to surgery and closely followed thereafter. [ABSTRACT FROM AUTHOR]

Copyright of Revista de Salud Pública is the property of Universidad Nacional de Colombia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background Parkinson's disease patients undergoing subthalamic nucleus deep brain stimulation (STN DBS) at standard frequency (>100 Hz) often develop gait impairment, postural instability and speech difficulties. Low frequency stimulation (<100 Hz, LFS) can improve such axial symptoms, but there are concerns that improvement may be transient. Objective To identify long-term outcome and predictors of low-frequency subthalamic stimulation in Parkinson's disease. Methods Through a chart review we identified 85 out of 324 STN DBS patients who received a trial of LFS and describe their characteristics and outcome predictors. Results Patients were switched to LFS (<100 Hz) 3.8 ± 3.3 years after surgery. Most patients (64%) attained a subjective improvement of gait, speech or balance for 2.0 ± 1.9 years. Motor scores improved within the first year after the stimulation change and showed a slower progression over time when compared to patients switched back to high frequency stimulation. UPDRS III axial score on medication before surgery and the y-axis coordinate of the active contact were independent predictors of LFS retention. Conclusions This report provides evidence that the use of LFS yields an enduring benefit in a considerable percentage of patients who develop axial motor symptoms during conventional stimulation. [ABSTRACT FROM AUTHOR]