Deep Brain Stimulation Treatment Research Articles

Whole transcriptome RNA sequencing data from blood leukocytes derived from Parkinson's disease patients prior to and following deep brain stimulation treatment.

Recent evidence demonstrates the power of RNA sequencing (RNA-Seq) for identifying valuable and urgently needed blood biomarkers and advancing both early and accurate detection of neurological diseases, and in particular Parkinson's disease (PD). RNA sequencing technology enables non-biased, high throughput, probe-independent inspection of expression data and high coverage and both quantification of global transcript levels as well as the detection of expressed exons and junctions given a sufficient sequencing depth (coverage). However, the analysis of sequencing data frequently presents a bottleneck. Tools for quantification of alternative splicing from sequenced libraries hardly exist at the present time, and methods that support multiple sequencing platforms are especially lacking. Here, we describe in details a whole RNA-Seq transcriptome dataset produced from PD patient's blood leukocytes. The samples were taken prior to, and following deep brain stimulation (DBS) treatment while being on stimulation and following 1 h of complete electrical stimulation cessation and from healthy control volunteers. We describe in detail the methodology applied for analyzing the RNA-Seq data including differential expression of long noncoding RNAs (lncRNAs). We also provide details of the corresponding analysis of in-depth splice isoform data from junction and exon reads, with the use of the software AltAnalyze. Both the RNA-Seq raw (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE42608) and analyzed data (https://www.synapse.org/#!Synapse:syn2805267) may be found valuable towards detection of novel blood biomarkers for PD.

Temporal profile of improvement of tardive dystonia after globus pallidus deep brain stimulation.

Several case reports and small series have indicated that tardive dystonia is responsive to globus pallidus deep brain stimulation. Whether different subtypes or distributions of tardive dystonia are associated with different outcomes remains unknown. We assessed the outcomes and temporal profile of improvement of eight tardive dystonia patients who underwent globus pallidus deep brain stimulation over the past six years through record review. Due to the retrospective nature of this study, it was not blinded or placebo controlled. Consistent with previous studies, deep brain stimulation improved the overall the Burke-Fahn-Marsden motor scores by 85.1 ± 13.5%. The distributions with best responses in descending order were upper face, lower face, larynx/pharynx, limbs, trunk, and neck. Patients with prominent cervical dystonia demonstrated improvement in the Toronto Western Spasmodic Torticollis Rating Scale but improvements took several months. In four patients the effects of deep brain stimulation on improvement in Burke Fahn Marsden score was rapid, while in four cases there was partial rapid response of neck and trunk dystonia followed by was gradual resolution of residual symptoms over 48 months. Our retrospective analysis shows excellent resolution of tardive dystonia after globus pallidus deep brain stimulation. We found instantaneous response, except with neck and trunk dystonia where partial recovery was followed by further resolution at slower rate. Such outcome is encouraging for using deep brain stimulation in treatment of tardive dystonia.

Stimulating the Self: The Influence of Conceptual Frameworks on Reactions to Deep Brain Stimulation

Deep brain stimulation (DBS) is generally considered to have great practical potential. Yet along with its remarkable efficacy, which is currently being tested in application to many pathologies, come a certain number of complications. In particular, there seem to be several adverse psychological implications behind a relevant number of postoperative situations. Whether these effects have to be attributed to a reactive response to a new situation or whether they are caused by the stimulation itself, or both, remains to be elucidated. This article takes up this issue, and evaluates how various views and conceptual schemes concerning the mind–brain relationship might play a role in the ensuing (mal)adaptation to DBS treatment. It is valuable to investigate the relationship between different conceptual assumptions and the onset of psychosocial maladaptations in clinical settings. In particular, we hypothesize that the frequently reported maladaptations might be partially caused by a concep-tual shift away from dualism and toward a “neurocentric” materialism, promoted by the scientific explanation of the pathological situation. This article examines which conceptual framework is likely to play a dominant role in the perception of the general public of how the mind relates to the brain, and how this contrasts with the opinions of experts in cognitive neuroscience. We investigate how these different conceptual frameworks might play a role in the occurrence of psychosocial maladaptations to DBS treatment in clinical settings. Finally, we suggest how a more inclusive, embodied embedded stance toward the mind–brain relationship might help to overcome such maladaptations.

Discovery of high-frequency deep brain stimulation for treatment of Parkinson disease: 2014 Lasker Award.

Discovery of high-frequency deep brain stimulation for treatment of Parkinson disease: 2014 Lasker Award.

No Impact of Deep Brain Stimulation on Fear-Potentiated Startle in Obsessive–Compulsive Disorder

Deep brain stimulation (DBS) of the ventral internal capsule is effective in treating therapy refractory obsessive–compulsive disorder (OCD). Given the close proximity of the stimulation site to the stria terminalis (BNST), we hypothesized that the striking decrease in anxiety symptoms following DBS could be the result of the modulation of contextual anxiety. However, the effect of DBS in this region on contextual anxiety is as of yet unknown. Thus, the current study investigated the effect of DBS on contextual anxiety in an experimental threat of shock paradigm. Eight patients with DBS treatment for severe OCD were tested in a double-blind crossover design with randomly assigned 2-week periods of active and sham stimulation. DBS resulted in significant decrease of obsessive–compulsive symptoms, anxiety, and depression. However, even though the threat manipulation resulted in a clear context-potentiated startle effect, none of the parameters derived from the startle recordings was modulated by the DBS. This suggests that DBS in the ventral internal capsule is effective in treating anxiety symptoms of OCD without modulating the startle circuitry. We hypothesize that the anxiety symptoms present in OCD are likely distinct from the pathological brain circuits in defensive states of other anxiety disorders.

A novel method for removal of deep brain stimulation artifact from electroencephalography.

Deep brain stimulation (DBS) has treatment efficacy in neurological and psychiatric disorders such as Parkinson's disease and major depression. Electroencephalography (EEG) is a versatile neurophysiological tool that can be used to better understand DBS treatment mechanisms. DBS causes artifacts in EEG recordings that preclude meaningful neurophysiological activity from being quantified during stimulation. In this study, we modeled the DBS stimulation artifact and illustrated a technique for removing the artifact using matched filters. The approach was validated using a synthetically generated DBS artifact superimposed on EEG data. Mean squared error (MSE) between the recovered signal and the artifact-free signal was used to quantify the effectiveness of the approach. The DBS artifact was characterized by a series of narrow band components at the harmonic frequencies of DBS stimulation. The filtering approach successfully removed the DBS artifact with MSE value being less than 2% of base signal power for the typical stimulation and recording setups. General guidelines on how to setup DBS EEG studies and configure the subsequent artifact removal process are described. To avoid stimulus artifacts, a number of EEG studies with DBS subjects have resorted to turning the stimulator off during recording, while other studies have used low pass filters to remove artifacts and look at frequencies well below 50 Hz. This study establishes a method through which DBS artifact in EEG recordings can be reliably eliminated, thereby preserving a meaningful neurophysiological signal through which to better understand DBS treatment mechanisms.

Neurotransmitter levels in basal ganglia during levodopa and deep brain stimulation treatment in Parkinson's disease

Background The mechanism by which deep brain stimulation of the nucleus subthalamicus improves Parkinson's disease symptoms remains unclear. In a previous perioperative study, we showed that there might be alterations of neurotransmitter levels in the globus pallidum interna during deep brain stimulation of the nucleus subthalamicus. Aim In this study, we examined whether deep brain stimulation of the nucleus subthalamicus and levodopa infusion interact and affect the levels of neurotransmitters. Methods Five patients with advanced Parkinson's disease took part in the study. During subthalamic nucleus surgery, microdialysis catheters were inserted bilaterally in the globus pallidum interna and unilaterally in the right putamen. A study protocol was set up and was followed for 3 days. Levodopa infusion with and without concomitant bilateral deep brain stimulation of the nucleus subthalamicus was also carried out. Results The putaminal dopamine levels increased during deep brain stimulation of the nucleus subthalamicus. In addition, an increase of gamma amino buturic acid concentrations in the globus pallidum interna during deep brain stimulation of the nucleus subthalamicus and during levodopa infusion was found. Conclusions These findings provide evidence that the subthalamic nucleus has a direct action on the substantia nigra pars compacta, and that deep brain stimulation of the nucleus subthalamicus might indirectly release putaminal dopamine. There is also evidence that deep brain stimulation of the nucleus subthalamicus interferes with levodopa therapy resulting in higher levels of levodopa in the brain, explaining why it is possible to decrease levodopa medication after deep brain stimulation surgery.

A new feature extraction method and classification of early stage Parkinsonian rats with and without DBS treatment.

Parkinson Disease (PD) is one of the most common neural disorders worldwide. Different treatments such as medication and deep brain stimulation (DBS) have been proposed to minimize and control Parkinson's symptoms. DBS has been recognized as an effective approach to decrease most movement disorders of PD. In this study, a new method is proposed for feature extraction and separation of treated and untreated Parkinsonan rats. For this purpose, unilateral intrastriatal 6-hydroxydopamine (6-OHDA, 12.5μg/5μl of saline-ascorbate)-lesioned rats were treated with DBS. We performed a behavioral experiment and video tracked traveled trajectories of rats. Then, we investigated the effect of deep brain stimulation of subthalamus nucleus on their behavioral movements. Time, frequency and chaotic features of traveled trajectories were extracted. These features provide the ability to quantify the behavioral movements of Parkinsonian rats. The results showed that the traveled trajectories of untreated were more convoluted with the different time/frequency response. Compared to the traditional features used before to quantify the animals' behavior, the new features improved classification accuracy up to 80% for untreated and treated rats.

Cost-Effectiveness of Subthalmic Nucleus Deep Brain Stimulation for the Treatment of Advanced Parkinson Disease in Hong Kong: A Prospective Study

Deep brain stimulation (DBS) is an effective but costly treatment for patients with advanced Parkinson disease (PD). This study examined the cost-effectiveness of DBS in relation to its improved effectiveness to help funding decision makers decide whether the treatment should be adopted. The incremental cost-effective ratio (ICER) per quality-adjusted life year has been benchmarked as being between US$50,000 and US$100,000 by US agencies, whereas it is less than €30,000 per quality-adjusted life year in Europe. To provide cost-effectiveness information of subthalamic nucleus DBS for patients with advanced PD. Direct medical expenses during the year before the DBS treatment were used to measure the baseline cost. Cost-effectiveness was measured by the ICER for the Unified Parkinson's Disease Rating Scale Part III and the ICER for the EuroQol Group's Health-Related Quality of Life measurement. Thirteen patients with advanced PD were recruited between January 2009 and January 2011. A 1-point improvement in the Unified Parkinson's Disease Rating Scale Part III score was associated with an ICER of US$926 in the first year and US$421 in the second year. A 1-point improvement on the EuroQol Group's Health-Related Quality of Life measurement was associated with an ICER of US$123,110 in the first year and US$62,846 in the second year. Cost-effectiveness of subthalamic nucleus DBS for treatment of advanced PD is greater during a 2-year period than 1 year only. These results can be used as a reference for the use of DBS for PD in a region with public health financing.

Deep brain stimulation for treatment-refractory obsessive compulsive disorder: a systematic review.

BackgroundObsessive-compulsive disorder is one of the most disabling of all psychiatric illnesses. Despite available pharmacological and psychotherapeutic treatments about 10% of patients remain severely affected and are considered treatment-refractory. For some of these patients deep brain stimulation offers an appropriate treatment method. The scope of this article is to review the published data and to compare different target structures and their effectiveness.MethodsPubMed search, last update June 2013, was conducted using the terms “deep brain stimulation” and “obsessive compulsive disorder”.ResultsIn total 25 studies were found that reported five deep brain stimulation target structures to treat obsessive-compulsive disorder: the anterior limb of the internal capsule (five studies including 14 patients), nucleus accumbens (eight studies including 37 patients), ventral capsule/ventral striatum (four studies including 29 patients), subthalamic nucleus (five studies including 23 patients) and inferior thalamic peduncle (two studies including 6 patients). Despite the anatomical diversity, deep brain stimulation treatment results in similar response rates for the first four target structures. Inferior thalamic peduncle deep brain stimulation results in higher response rates but these results have to be interpreted with caution due to a very small number of cases. Procedure and device related adverse events are relatively low, as well as stimulation or therapy related side effects. Most stimulation related side effects are transient and decline after stimulation parameters have been changed.ConclusionDeep brain stimulation in treatment-refractory obsessive-compulsive disorder seems to be a relatively safe and promising treatment option. However, based on these studies no superior target structure could be identified. More research is needed to better understand mechanisms of action and response predictors that may help to develop a more personalized approach for these severely affected obsessive compulsive patients.

Dynamic tension EMG to characterize the effects of DBS treatment of advanced Parkinson's disease.

Deep brain stimulation (DBS) is an effective treatment method for motor symptoms of advanced Parkinson's disease. DBS-electrode is implanted to subthalamic nucleus to give precisely allocated electrical stimuli to brain. The optimal stimulus type has to be adjusted individually. Disease severity, main symptoms and biological factors play a role in correctly setting up the device. Currently there are no objective methods to assess the efficacy of DBS, hence the adjustment is based solely on clinical assessment. In optimal case an objectively measurable feature would point the right settings of DBS. Surface electromyographic and kinematic measurements have been used in Parkinson's disease research. As Parkinson's disease symptoms are known to change the EMG signal properties, these methods could be helpful aid in the clinical adjustment of DBS. In this study, 13 patients with advanced Parkinson's disease who received DBS treatment were measured. The patients were measured with seven different settings of the DBS in clinical range including changes in stimulation amplitude, frequency and pulse width. The EMG analysis was based on parameters that characterize EMG signal morphology. Correlation dimension and recurrence rate made the most significant difference in relation to optimal settings. In conclusion, EMG analysis is able to detect differences between the DBS setups, and can help in finding the correct parameters.

Deep Brain Stimulation in Major Depression: Plastic Changes of 5-Hydroxytryptamine Neurons

Major depressive disorder (MDD) is a severe psychiatric syndrome with a very high socioeconomic impact. The high cost of MDD is attributable to its large incidence in the general population (lifetime prevalence is close to 20%); the long duration of depressive episodes; and emergence of depressive episodes during active periods of adult life, which results in very large labor costs. The large and increasing impact of MDD is not paralleled by marked improvements in its treatment. The antidepressant market is dominated by drugs targeting the monoamine systems, such as selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors, which are pharmacologic refinements of tricyclic antidepressant drugs, which were discovered serendipitously in the 1950s. Selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors have increased treatment compliance because of the absence of severe side effects. However, their speed and efficacy are suboptimal, leaving a large percentage of patients with partial or incomplete responses after several months of treatment. Many patients are refractory to numerous pharmacologic treatments and require nonstandard interventions to improve their quality of life and reduce suicide risk. Antidepressant-like Effects of Cortical Deep Brain Stimulation Coincide With Pro-neuroplastic Adaptations of Serotonin SystemsBiological PsychiatryVol. 76Issue 3PreviewCortical deep brain stimulation (DBS) is a promising therapeutic option for treatment-refractory depression, but its mode of action remains enigmatic. Serotonin (5-HT) systems are engaged indirectly by ventromedial prefrontal cortex (vmPFC) DBS. Resulting neuroplastic changes in 5-HT systems could thus coincide with the long-term therapeutic activity of vmPFC DBS. Full-Text PDF ErratumBiological PsychiatryVol. 76Issue 5PreviewErratum to: “Deep Brain Stimulation in Major Depression: Plastic Changes of 5-Hydroxytryptamine Neurons” by Artigas which appeared in Biological Psychiatry (2014;76:174-175). On page 175, column 1, 8th line from the bottom, the findings were inadvertently misstated as a decrease rather than an increase. The full corrected sentence is: “Using this procedure, the authors found that CSDS induced a robust and significant increase of the density of 5-HT nerve endings in various forebrain areas, including the vmPFC, the basolateral amygdala, and the dentate gyrus of the hippocampal formation, which was normalized after long-term DBS treatment.” Full-Text PDF

Rebound of affective symptoms following acute cessation of deep brain stimulation in obsessive-compulsive disorder.

Deep brain stimulation (DBS) is regarded as an effective way to treat refractory obsessive-compulsive disorder (OCD). Little is known about the effects of DBS cessation following a longer period of stimulation. To determine the relapse and rebound effects of psychiatric symptoms, and their impact on Quality of Life (QoL) following acute cessation of DBS in OCD patients. We included 16 out of 32 patients who were treated with DBS between April 2005 and January 2011 at the Academic Medical Center, Amsterdam. After treatment for at least one year, patients entered a 1-week phase in which DBS was switched off. We evaluated psychiatric symptoms and QoL at three time points: before DBS surgery (pre-DBS), following at least one year of DBS treatment (DBS-on) and following 1 week of DBS off (DBS-off). Psychiatric symptoms were assessed with the Yale-Brown obsessive-compulsive disorder scale (Y-BOCS), the Hamilton anxiety rating scale (HAM-A) and the Hamilton depression rating scale (HAM-D). QoL was assessed using the World Health Organization QOL scale (WHOQOL-Bref). Switching from DBS-on to DBS-off, Y-BOCS scores increased with 50%, HAM-A scores with 80% and HAM-D scores with 83%. In the DBS-off period, HAM-A and HAM-D scores exceeded pre-surgery levels with approximately 40%, suggesting a rebound phenomenon. Furthermore, a deterioration of physical and psychological QoL to levels comparable with pre-surgery was found during DBS-off. Acute DBS cessation causes a relapse of obsessions and compulsions and a rebound of anxiety and depression. Additionally, improvements on QoL disappear.

Characterizing motor and cognitive effects associated with deep brain stimulation in the GPi of hemi-Parkinsonian rats.

The globus pallidus internus (GPi) is the main output nucleus of the basal ganglia, which is associated with a variety of functions including motor performance and cognition. The GPi is one of the primary targets of deep brain stimulation (DBS) in patients with movement disorders. However, the therapeutic mechanism of GPi-DBS is poorly understood and rodent models have not been characterized. Cognitive side effects, such as impulsivity and depression, of DBS treatment for Parkinson's disease are known, but their relationship to the efficacy of the treatment is not well explained. The goal of this study is to illuminate the effects of GPi-DBS on both motor and cognitive function in a hemi-Parkinsonian rat model. In this work, we study the motor performance of the rodents in multiple behaviors, as well as of impulsivity and depression, and consider the relationship between these behavioral variables and the stimulation frequency of the DBS signal. For the first time, the connection is directly established between stimulating the GPi, motor performance and cognition is directly established in the hemi-Parkinsonian rodent model.

Neuroradiology, Anesthesia, Bioengineering, and Hardware Programming in the Clinical Applications of Deep Brain Stimulation

Deep brain stimulation (DBS) is an interventional surgical procedure used to treat an array of sensorimotor, cognitive, and psychiatric diseases originating in distinct brain regions. Although the Food and Drug Adminstration has approved DBS for the treatment of essential tremor and Parkinson disease, this technique is currently being used to treat major depression, dystonia, and obsessive compulsive disorder. Pathophysiological brain areas responsible for abnormal functions are targeted with implanted electrodes that are subsequently attached to battery packs to provide targeted electrical stimulation within the necessary parameters of stimulation required to decrease the phenotypic expressions of these debilitating diseases. DBS regularly targets the stimulation of the ventral thalamic nuclei, subthalamic nucleus, globus pallidus and the basal ganglion in an attempt to diminish symptoms of tremor, Parkinson disease, Tourette syndrome, and pain. Herein, we aim to address the bioengineering that dictates the limitations of current DBS treatments, as well as the history, current use, and potential of DBS as it relates to a variety of motor and neuropsychiatric diseases. This will serve as an insightful analysis about the current landscape of DBS and its potential for more widespread applications in the clinical arena.

STN vs. GPi Deep Brain Stimulation: Translating the Rematch into Clinical Practice.

When formulating a deep brain stimulation (DBS) treatment plan for a patient with Parkinson's disease (PD), two critical questions should be addressed: 1- Which brain target should be chosen to optimize this patient's outcome? and 2- Should this patient's DBS operation be unilateral or bilateral? Over the past two decades, two targets have emerged as leading contenders for PD DBS; the subthalamic nucleus (STN) and the globus pallidus internus (GPi). While the GPi target does have a following, most centers have uniformly employed bilateral STN DBS for all Parkinson's disease cases (Figure 1). This bilateral STN "one-size-fits-all" approach was challenged by an editorial entitled "STN vs. GPi: The Rematch," which appeared in the Archives of Neurology in 2005. Since 2005, a series of well designed clinical trials and follow-up studies have addressed the question as to whether a more tailored approach to DBS therapy might improve overall outcomes. Such a tailored approach would include the options of targeting the GPi, or choosing a unilateral operation. The results of the STN vs. GPi 'rematch' studies support the conclusion that bilateral STN DBS may not be the best option for every Parkinson's disease surgical patient. Off period motor symptoms and tremor improve in both targets, and with either unilateral or bilateral stimulation. Advantages of the STN target include more medication reduction, less frequent battery changes, and a more favorable economic profile. Advantages of GPi include more robust dyskinesia suppression, easier programming, and greater flexibility in adjusting medications. In cases where unilateral stimulation is anticipated, the data favor GPi DBS. This review summarizes the accumulated evidence regarding the use of bilateral vs. unilateral DBS and the selection of STN vs. GPi DBS, including definite and possible advantages of different targets and approaches. Based on this evidence, a more patient-tailored, symptom specific approach will be proposed to optimize outcomes of PD DBS therapy. Finally, the importance of an interdisciplinary care team for screening and effective management of DBS patients will be reaffirmed. Interdisciplinary teams can facilitate the proposed patient-specific DBS treatment planning and provide a more thorough analysis of the risk-benefit ratio for each patient.

Long Non-Coding RNA and Alternative Splicing Modulations in Parkinson's Leukocytes Identified by RNA Sequencing

The continuously prolonged human lifespan is accompanied by increase in neurodegenerative diseases incidence, calling for the development of inexpensive blood-based diagnostics. Analyzing blood cell transcripts by RNA-Seq is a robust means to identify novel biomarkers that rapidly becomes a commonplace. However, there is lack of tools to discover novel exons, junctions and splicing events and to precisely and sensitively assess differential splicing through RNA-Seq data analysis and across RNA-Seq platforms. Here, we present a new and comprehensive computational workflow for whole-transcriptome RNA-Seq analysis, using an updated version of the software AltAnalyze, to identify both known and novel high-confidence alternative splicing events, and to integrate them with both protein-domains and microRNA binding annotations. We applied the novel workflow on RNA-Seq data from Parkinson's disease (PD) patients' leukocytes pre- and post- Deep Brain Stimulation (DBS) treatment and compared to healthy controls. Disease-mediated changes included decreased usage of alternative promoters and N-termini, 5′-end variations and mutually-exclusive exons. The PD regulated FUS and HNRNP A/B included prion-like domains regulated regions. We also present here a workflow to identify and analyze long non-coding RNAs (lncRNAs) via RNA-Seq data. We identified reduced lncRNA expression and selective PD-induced changes in 13 of over 6,000 detected leukocyte lncRNAs, four of which were inversely altered post-DBS. These included the U1 spliceosomal lncRNA and RP11-462G22.1, each entailing sequence complementarity to numerous microRNAs. Analysis of RNA-Seq from PD and unaffected controls brains revealed over 7,000 brain-expressed lncRNAs, of which 3,495 were co-expressed in the leukocytes including U1, which showed both leukocyte and brain increases. Furthermore, qRT-PCR validations confirmed these co-increases in PD leukocytes and two brain regions, the amygdala and substantia-nigra, compared to controls. This novel workflow allows deep multi-level inspection of RNA-Seq datasets and provides a comprehensive new resource for understanding disease transcriptome modifications in PD and other neurodegenerative diseases.

Efficacy of deep brain stimulation in an adolescent patient with DYT11 myoclonus-dystonia

Myoclonus-dystonia is a movement disorder characterized by myoclonic jerks and dystonia. We herein report the case of an 18-year-old Japanese male patient with DYT11 myoclonus-dystonia who developed myoclonic jerks at 2 years-of-age. He harbored a novel heterozygous mutation in the major responsible gene, ε-sarcoglycan. As medication was ineffective and the myoclonus had become disabling, deep brain stimulation of the bilateral globus pallidus internus was carried out. After surgery, his symptoms showed overt improvement. Although reports of deep brain stimulation treatment in children or adolescents with myoclonus-dystonia are scarce, the treatment should be considered when symptoms, particularly myoclonus, become refractory, sustained and disabling.

Deep-brain magnetic stimulation promotes adult hippocampal neurogenesis and alleviates stress-related behaviors in mouse models for neuropsychiatric disorders

BackgroundRepetitive Transcranial Magnetic Stimulation (rTMS)/ Deep-brain Magnetic Stimulation (DMS) is an effective therapy for various neuropsychiatric disorders including major depression disorder. The molecular and cellular mechanisms underlying the impacts of rTMS/DMS on the brain are not yet fully understood.ResultsHere we studied the effects of deep-brain magnetic stimulation to brain on the molecular and cellular level. We examined the adult hippocampal neurogenesis and hippocampal synaptic plasticity of rodent under stress conditions with deep-brain magnetic stimulation treatment. We found that DMS promotes adult hippocampal neurogenesis significantly and facilitates the development of adult new-born neurons. Remarkably, DMS exerts anti-depression effects in the learned helplessness mouse model and rescues hippocampal long-term plasticity impaired by restraint stress in rats. Moreover, DMS alleviates the stress response in a mouse model for Rett syndrome and prolongs the life span of these animals dramatically.ConclusionsDeep-brain magnetic stimulation greatly facilitates adult hippocampal neurogenesis and maturation, also alleviates depression and stress-related responses in animal models.

Differentiated Baroreflex Modulation of Sympathetic Nerve Activity During Deep Brain Stimulation in Humans

Targeted electric deep brain stimulation in midbrain nuclei in humans alters cardiovascular parameters, presumably by modulating autonomic and baroreflex function. Baroreflex modulation of sympathetic outflow is crucial for cardiovascular regulation and is hypothesized to occur at 2 distinct brain locations. The aim of this study was to evaluate sympathetic outflow in humans with deep brain stimulating electrodes during ON and OFF stimulation of specific midbrain nuclei known to regulate cardiovascular function. Multiunit muscle sympathetic nerve activity was recorded in 17 patients undergoing deep brain stimulation for treatment of chronic neuropathic pain (n=7) and Parkinson disease (n=10). Sympathetic outflow was recorded during ON and OFF stimulation. Arterial blood pressure, heart rate, and respiratory frequency were monitored during the recording session, and spontaneous vasomotor and cardiac baroreflex sensitivity were assessed. Head-up tilt testing was performed separately in the patients with Parkinson disease postoperatively. Stimulation of the dorsal most part of the subthalamic nucleus and ventrolateral periaqueductal gray resulted in improved vasomotor baroreflex sensitivity, decreased burst frequency and blood pressure, unchanged burst amplitude distribution, and a reduced fall in blood pressure after tilt. Stimulation of the dorsolateral periaqueductal gray resulted in a shift in burst amplitude distribution toward larger amplitudes, decreased spontaneous beat-to-beat blood pressure variability, and unchanged burst frequency, baroreflex sensitivity, and blood pressure. Our results indicate that a differentiated regulation of sympathetic outflow occurs in the subthalamic nucleus and periaqueductal gray. These results may have implications in our understanding of abnormal sympathetic discharge in cardiovascular disease and provide an opportunity for therapeutic targeting.