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1.

Background

Transcranial magnetic stimulation (TMS) is a non-invasive method to stimulate localized brain regions. Despite widespread use in motor cortex, TMS is seldom performed in sensory areas due to variable, qualitative metrics.

Objective

Assess the reliability and validity of tracing phosphenes, and to investigate the stimulation parameters necessary to elicit decreased visual cortex excitability with paired-pulse TMS at short inter-stimulus intervals.

Methods

Across two sessions, single and paired-pulse recruitment curves were derived by having participants outline elicited phosphenes and calculating resulting average phosphene sizes.

Results

Phosphene size scaled with stimulus intensity, similar to motor cortex. Paired-pulse recruitment curves demonstrated inhibition at lower conditioning stimulus intensities than observed in motor cortex. Reliability was high across sessions.

Conclusions

TMS-induced phosphenes are a valid and reliable tool for measuring cortical excitability and inhibition in early visual areas. Our results also provide appropriate stimulation parameters for measuring short-latency intracortical inhibition in visual cortex.  相似文献   

2.

Background

Transcutaneous vagus nerve stimulation (tVNS) is a new, non-invasive technique being investigated as an intervention for a variety of clinical disorders, including epilepsy and depression. It is thought to exert its therapeutic effect by increasing central norepinephrine (NE) activity, but the evidence supporting this notion is limited.

Objective

In order to test for an impact of tVNS on psychophysiological and hormonal indices of noradrenergic function, we applied tVNS in concert with assessment of salivary alpha amylase (SAA) and cortisol, pupil size, and electroencephalograph (EEG) recordings.

Methods

Across three experiments, we applied real and sham tVNS to 61 healthy participants while they performed a set of simple stimulus-discrimination tasks. Before and after the task, as well as during one break, participants provided saliva samples and had their pupil size recorded. EEG was recorded throughout the task. The target for tVNS was the cymba conchae, which is heavily innervated by the auricular branch of the vagus nerve. Sham stimulation was applied to the ear lobe.

Results

P3 amplitude was not affected by tVNS (Experiment 1A: N?=?24; Experiment 1B: N?=?20; Bayes factor supporting null model?=?4.53), nor was pupil size (Experiment 2: N?=?16; interaction of treatment and time: p?=?.79). However, tVNS increased SAA (Experiments 1A and 2: N?=?25) and attenuated the decline of salivary cortisol compared to sham (Experiment 2: N?=?17), as indicated by significant interactions involving treatment and time (p?=?.023 and p?=?.040, respectively).

Conclusion

These findings suggest that tVNS modulates hormonal indices but not psychophysiological indices of noradrenergic function.  相似文献   

3.

Background

Repetitive convergent inputs to a single post-synaptic neuron can induce long-term potentiation (LTP) or depression (LTD) of synaptic activity in a spike timing-dependent manner.

Objective

Here we set a protocol of visual paired associative stimulation (vPAS) of the primary visual cortex (V1) in humans to induce persistent changes in the excitatory properties of V1 with a spike timing rule.

Methods

We provided convergent inputs to V1 by coupling transcranial magnetic stimulation (TMS) pulses of the occipital cortex with peripheral visual inputs, at four interstimulus intervals of ?50/-25/+25/+50 ms relative to the visual evoked potential (VEP) P1 latency. We analysed VEP amplitude and delayed habituation before and up to 10 min after each vPAS protocol.

Results

VEP amplitude was reduced after vPAS+25. Delayed VEP habituation was increased after vPAS-25 while it was reduced after vPAS+25.

Conclusions

We provide evidence that associative bidirectional synaptic plasticity is a feature not only of the sensorimotor but also of the human visual system.  相似文献   

4.

Background

Recent studies have shown that neurophysiological outcomes of transcranial direct current stimulation (TDCS) are influenced by current flow in brain regions between the electrodes, and in particular the orientation of current flow relative to the cortical surface.

Objective

We asked whether the directional effects of TDCS on physiological measures in the motor system would also be observed on motor behaviours.

Methods

We applied TDCS during the practice of a ballistic movement task to test whether it affected learning or the retention of learning 48?h later. TDCS electrodes were oriented perpendicular to the central sulcus and two current orientations were used (posterior-anterior, TDCSPA; and anterior-posterior, TDCSAP). Transcranial magnetic stimulation (TMS) was used to assess whether changes in corticospinal excitability reflected any behavioural changes.

Results

Directional TDCSAP impaired the retention of learning on the ballistic movement task compared to TDCSPA and a sham condition. Although TDCSPA had no effect on learning or retention, it blocked the typical increase in corticospinal excitability after a period of motor practice.

Conclusions

Our results extend on previous reports of TDCS producing directionally specific changes in neurophysiological outcomes by showing that current direction through a cortical target also impacts upon behavioural outcomes. In addition, changes in corticospinal excitability after a period of motor practice are not causally linked to behavioural learning.  相似文献   

5.

Background

Brain stimulation interventions are increasingly used to reduce craving and consumption in individuals with drug addiction or excessive eating behavior. However, the efficacy of these novel treatments and whether effect sizes are affected by the length of the intervention has not been comprehensively evaluated.

Objective

A meta-analytical approach was employed to evaluate the effectiveness of non-invasive excitatory brain stimulation [transcranial Direct Current Stimulation (tDCS) and high-frequency repetitive Transcranial Magnetic Stimulation (rTMS)] targeted at dorsolateral prefrontal cortex (dlPFC) for reducing craving and consumption levels in drug and eating addiction, including both single- and multi-session protocols.

Methods

After a comprehensive literature search, 48 peer-reviewed studies (1095 participants in total) were included in the current meta-analysis. We computed Hedge's g as a conservative measure for evaluating effect sizes.

Results

Random effects analyses revealed a small effect of neuromodulation interventions on craving and a medium effect on consumption, favoring active over sham stimulation. These effects did not differ across the different populations investigated (alcohol, nicotine, illicit drugs, eating addictions) or by the used technique (rTMS/tDCS, left/right hemisphere). Multi-session protocols showed a larger effect size for reducing craving and consumption than single-session protocols, with a positive linear association between the number of sessions or administered pulses and craving reduction, indicating a dose-response effect.

Conclusions

Our results provide compelling evidence that novel non-invasive brain stimulation targeted at dlPFC reduces craving and consumption levels (providing the first meta-analytical evidence for the latter effect in drug addiction), with larger effects in multi-session as compared to single-session interventions.  相似文献   

6.

Background

Psychiatric conditions currently treated with deep brain stimulation (DBS), such as obsessive-compulsive disorder (OCD), are heterogeneous diseases with different symptomatic dimensions, indicating that fixed neuroanatomical DBS targets for all OCD cases may not be efficacious.

Objective/hypothesis

We tested whether the optimal DBS target for OCD is fixed for all patients or whether it is individualized and related to each patient's symptomatic content. Further, we explored if the optimal target can be predicted by combining functional neuroimaging and structural connectivity.

Methods

In a prospective, randomized, double-blinded study in 7 OCD patients, symptomatic content was characterized pre-operatively by clinical interview and OCD symptom-provocation during functional MRI. DBS electrode implantation followed a trajectory placing 4 contacts along a striatal axis (nucleus accumbens to caudate). Patients underwent three-month stimulation periods for each contact (and sham), followed by clinical evaluation. Probabilistic tractography, applied to diffusion-weighted images acquired pre-operatively, was used to study the overlap between projections from the prefrontal areas activated during symptom provocation and the volume of activated tissue of each electrode contact.

Results

Six patients were classified responders, with median symptomatic reduction of 50% achieved from each patient's best contact. This was located at the caudate in 4 cases and at the accumbens in 2. Critically, the anatomical locus of the best contact (accumbens or caudate) was related to an index derived by combining functional MRI responses to prevailing symptom provocation and prefronto-cortico-striatal projections defined by probabilistic tractography.

Conclusion

Our results therefore represent a step towards personalized, content-specific DBS targets for OCD.  相似文献   

7.
8.

Background

Temporal lobe epilepsy is most prevalent among focal epilepsies, and nearly one-third of patients are refractory to pharmacological intervention. Persistent cognitive and neurobehavioral comorbidities also occur due to the recurrent nature of seizures and medication-related side effects.

Hypothesis

Electrical neuromodulation is an effective strategy to reduce seizures both in animal models and clinically, but its efficacy to modulate cognition remains unclear. We hypothesized that theta frequency stimulation of the medial septum would increase septohippocampal oscillations, increase seizure threshold, and improve spatial learning in a rat model of pilocarpine-induced epilepsy.

Methods

Sham and pilocarpine rats were implanted with electrodes in the medial septum, hippocampus and prefrontal cortex. EEG was assessed days prior to and following stimulation. Sham and pilocarpine-treated rats received either no stimulation, continuous (throughout each behavior), or pre-task (one minute prior to each behavior) 7.7?Hz septal stimulation during the Barnes maze spatial navigation test and also during assessment of flurothyl-induced seizures.

Results

Both continuous and pre-task stimulation prevented epilepsy-associated reductions in theta oscillations over time. Additionally, both stimulation paradigms significantly improved spatial navigation in the Barnes maze, reducing latency and improving search strategy. Moreover, stimulation led to significant increases in seizure threshold in pilocarpine-treated rats. There was no evidence of cognitive enhancement or increased seizure threshold in stimulated sham rats.

Conclusion

These findings have profound implications as theta stimulation of the septum represents a single frequency and target that has the potential to both improve cognition and reduce seizures for patients with refractory epilepsy.  相似文献   

9.

Background

When single pulse transcranial magnetic stimulation (TMS) is applied over the primary motor cortex (M1) with sufficient intensity, it evokes muscular contractions (motor-evoked potentials, MEPs) and muscle twitches (TMS-evoked movements). Participants may also report various hand sensations related to TMS, but the perception elicited by TMS and its relationship to MEPs and evoked movements has not been systematically studied.

Objective

The main aim of this work is to evaluate participants' kinesthetic and somatosensory hand perceptions elicited by single-pulse TMS over M1-hand area at different intensities of stimulation and their relation with MEPs and TMS-evoked movements.

Methods

We compared the number of MEPs (measured by electromyography), TMS-evoked movements (measured by an accelerometer) and participants' hand perception (measured by verbal report) elicited by TMS at different intensity of stimulation. This way, we estimated the amplitude of MEPs and the acceleration of TMS-evoked movements sufficient to trigger TMS evoked hand perceptions.

Results

We found that TMS-evoked hand perceptions are induced at 105% of the individual resting motor threshold, a value significantly different from the threshold inducing MEPs (about 100%) and TMS-evoked movements (about 110%). Our data indicate that only MEPs with an amplitude higher than 0.62 mV and TMS-evoked movements with acceleration higher than 0.42 m/s2 were associated with hand perceptions at threshold.

Conclusions

Our data reveal the main features of TMS-evoked hand perception and show that in addition to MEPs and TMS-evoked movements, this is a separate discernible response associated to single-pulse TMS over M1.  相似文献   

10.

Background

Arousal and sleep represent basic domains of behavior, and alterations are of high clinical importance.

Objective/hypothesis

The aim of this study was to further elucidate the neurobiology of insomnia disorder (ID) and the potential for new treatment developments, based on the modulation of cortical activity through the non-invasive brain stimulation technique transcranial direct current stimulation (tDCS). Specifically, we tested the hypotheses that bi-frontal anodal tDCS shortens and cathodal tDCS prolongs total sleep time in patients with ID, compared to sham stimulation. Furthermore, we tested for differences in indices of arousal between ID patients and healthy controls and explored their potential impact on tDCS effects.

Methods

Nineteen ID patients underwent a within-subject repeated-measures sleep laboratory study with adaptation, baseline and three experimental nights. Bifrontal anodal, cathodal and sham tDCS was delivered in a counterbalanced order immediately prior to sleep. Wake EEG was recorded prior to and after tDCS as well as on the following morning. Subsequently, we compared patients with ID to a healthy control group from an earlier dataset.

Results

Against our hypothesis, we did not observe any tDCS effects on sleep continuity or sleep architecture in patients with ID. Further analyses of nights without stimulation demonstrated significantly increased levels of arousal in ID patients compared to healthy controls, as indexed by subjective reports, reduced total sleep time, increased wake after sleep onset and increased high frequency EEG power during wakefulness and NREM sleep. Of note, indices of increased arousal predicted the lack of effect of tDCS in ID patients.

Conclusions

Our study characterizes for the first time differential effects of tDCS on sleep in patients with ID and healthy controls, presumably related to persistent hyperarousal in ID. These findings suggest that adapted tDCS protocols need to be developed to modulate arousal and sleep dependent on baseline arousal levels.  相似文献   

11.

Background

Transcranial direct current stimulation (tDCS) modulates neuronal activity and is a potential therapeutic tool for many neurological diseases. However, its beneficial effects on post cardiac arrest syndrome remains uncertain.

Objective/hypothesis

We investigated the effects of repetitive anodal tDCS on neurological outcome and survival in a ventricular fibrillation (VF) cardiac arrest rat model.

Methods

Cardiopulmonary resuscitation was initiated after 6?min of VF in 36 Sprague-Dawley rats. The animals were randomized into three groups immediately after resuscitation (n?=?12 each): no-treatment control (NTC) group, targeted temperature management (TTM) group, and tDCS group. For tDCS, 1?mA anodal tDCS was applied on the dorsal scalp for 0.5?h. The stimulation was repeated for four sessions with 1-h resting interval under normothermia. Post-resuscitation hemodynamic, cerebral, and myocardial injuries, 96-h neurological outcome, and survival were evaluated.

Results

Compared with the NTC group, post-resuscitation serum astroglial protein S100 beta and cardiac troponin T levels and 96-h neuronal and myocardial damage scores were markedly reduced in the tDCS and TTM groups. Myocardial ejection fraction, neurological deficit score, and 96-h survival rate were also significantly better for the tDCS and TTM groups. The period of post-resuscitation arrhythmia with hemodynamic instability was considerably shorter in the tDCS group, but no differences were observed in neurological outcome and survival between the tDCS and TTM groups.

Conclusions

In this cardiac arrest rat model, repeated anodal tDCS commenced after resuscitation improves 96-h neurological outcome and survival to an extent comparable to TTM by attenuating post-resuscitation cerebral and cardiac injuries.  相似文献   

12.

Background

Transcranial direct current stimulation (tDCS) has been used to improve exercise performance, though the protocols used, and results found are mixed.

Objective

We aimed to analyze the effect of tDCS on improving exercise performance.

Methods

A systematic search was performed on the following databases, until December 2017: PubMed/MEDLINE, Embase, Web of Science, SCOPUS, and SportDiscus. Full-text articles that used tDCS for exercise performance improvement in adults were included. We compared the effect of anodal (anode near nominal target) and cathodal (cathode near nominal target) tDCS to a sham/control condition on the outcome measure (performance in isometric, isokinetic or dynamic strength exercise and whole-body exercise).

Results

22 studies (393 participants) were included in the qualitative synthesis and 11 studies (236 participants) in the meta-analysis. The primary motor cortex (M1) was the main nominal tDCS target (n?=?16; 72.5%). A significant effect favoring anodal tDCS (a-tDCS) applied before exercise over M1 was found on cycling time to exhaustion (mean difference?=?93.41?s; 95%CI?=?27.39?s–159.43?s) but this result was strongly influenced by one study (weight?=?84%), no effect was found for cathodal tDCS (c-tDCS). No significant effect was found for a-tDCS applied on M1 before or during exercise on isometric muscle strength of the upper or lower limbs. Studies regarding a-tDCS over M1 on isokinetic muscle strength presented mixed results. Individual results of studies using a-tDCS applied over the prefrontal and motor cortices either before or during dynamic muscle strength testing showed positive results, but performing meta-analysis was not possible.

Conclusion

For the protocols tested, a-tDCS but not c-tDCS vs. sham over M1 improved exercise performance in cycling only. However, this result was driven by a single study, which when removed was no longer significant. Further well-controlled studies with larger sample sizes and broader exploration of the tDCS montages and doses are warranted.  相似文献   

13.

Introduction

Staging preclinical Alzheimer disease (AD) by the expected years to symptom onset (EYO) in autosomal dominant AD (ADAD) through biomarker correlations is important.

Methods

We estimated the correlation matrix between EYO/cognition and imaging/CSF biomarkers, and searched for the EYO cutoff where a change in the correlations occurred before and after the cutoff among the asymptomatic mutation carriers of ADAD. We then estimated the longitudinal rate of change for biomarkers/cognition within each preclinical stage defined by the EYO.

Results

Based on the change in the correlations, the preclinical ADAD was divided by EYOs ?7 and ?13 years. Mutation carriers demonstrated a temporal ordering of biomarker/cognition changes across the three preclinical stages.

Discussion

Duration of each preclinical stage can be estimated in ADAD, facilitating better planning of prevention trials with the EYO cutoffs under the recently released FDA guidance. The generalization of these results to sporadic AD warrants further investigation.  相似文献   

14.

Objective

The present work aims to evaluate the significance of sleep disturbance and electroencephalogram (EEG) alteration in the early stage of Alzheimer's disease (AD).

Background and Rationale

Sleep disturbance is common in patients with AD. It is not known if it can occur at the early stage of AD and if EEG recording may help identify the early sign of the disease.

Historical Evolution

Sleep disturbance in AD has generally been considered as late consequence of the neurodegenerative process. A growing body of evidence has suggested that the sleep disturbance may occur at the early stage of AD.

Updated Hypothesis

Based on the previous epidemiologic studies and our recent findings, we propose that sleep disturbance may play an important role in the development of AD. Sleep EEG changes may serve as a valuable early sign for AD in the prepathological stage.

Early Experimental Data

Our data suggested that AβPPswe/PS1ΔE9 transgenic AD mice at preplaque stage (3 and 4 months of age) exhibited different profile of sleep architecture and sleep EEG, which preceded the cognitive deficit and AD neuropathology.

Future Experiments and Validation Studies

Future experiments should focus on sleep EEG changes in patients with mild cognitive impairment and early stage of AD. Follow-up studies in high-risk population of the elderly are equally important. In addition, the exact molecular mechanism underlying the sleep disturbance should be thoroughly investigated.

Major Challenges for the Hypothesis

Studies on human participants with early stage of AD, especially the follow-up studies on the presymptomatic elderly in a large population, are difficult and time-consuming.

Linkage to Other Major Theories

Our hypothesis may link previous theories to establish a bidirectional relationship between sleep disorders and AD, which may finally form a new schematic mechanism to understand the disease pathogenesis and disease progression.  相似文献   

15.

Background

Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulatory technique that has broad diagnostic and therapeutic potential across a range of neurological and psychiatric diseases.

Objective

This study utilises a bibliometric approach to systematically and comprehensively evaluate the literature on TMS from the last three decades.

Methods

The Scopus citation database was used to identify all peer-reviewed journal articles concerning TMS over the period 1988–2017. Frequency-distribution, cross-tabulation and keyword analyses were performed to determine the most prolific researchers, institutions, nations, journals and the foremost studied disease entities within the TMS field. Given recent heightened awareness of gender bias across many fields of biomedicine, female representation among the most prolific authors was determined. Open-access publication rates and types of study design utilised were also quantified.

Results

17,492 TMS-related articles were published during the study period 1988–2017. The annual TMS research output has increased dramatically over this time, despite a recent levelling-off of publications per year. The most prolific institutions were based in the United Kingdom, the United States and Canada. The top disease entities studied were stroke, depression and Parkinson's disease. Only 4/52 of the most productive researchers during the study period were female. A minority (4.81%) of publications were published as gold open-access.

Conclusion

This study implemented a systematic, bibliometric approach to quantitively assess the breadth of the TMS literature base and identify temporal publication and authorship trends. Drawing on these insights may aid understanding of historical progress in TMS over the last 30 years and help identify into unmet needs and opportunities to improve scientific and publishing practices to contribute to the future health of the field. These findings are likely to be relevant to researchers, clinicians, funders, industry collaborators and other stakeholders.  相似文献   

16.

Introduction

Little is known about dementia incidence in diverse populations of oldest-old, the age group with highest dementia incidence.

Methods

Incident dementia diagnoses from 1/1/2010 to 9/30/2015 were abstracted from medical records for 2350 members of an integrated health care system in California (n = 1702 whites, n = 375 blacks, n = 105 Latinos, n = 168 Asians) aged ≥90 in 2010. We estimated race/ethnicity-specific age-adjusted dementia incidence rates and implemented Cox proportional hazards models and Fine and Gray competing risk of death models adjusted for demographics and comorbidities in midlife and late-life.

Results

Dementia incidence rates (n = 771 cases) were lowest among Asians (89.9/1000 person-years), followed by whites (96.9/1000 person-years), Latinos (105.8/1000 person-years), and blacks (121.5/1000 person-years). Cox regression and competing risk models estimated 28% and 36% higher dementia risk for blacks versus whites adjusting for demographics and comorbidities.

Discussion

Patterns of racial/ethnic disparities in dementia seen in younger older adults continue after the age of 90 years, though smaller in magnitude.  相似文献   

17.

Background

Accounts of cognitive processes in judgment and decision-making are frequently based on a dual-process framework, which reflects two qualitatively different types of processing: intuitive (Type 1) and analytical (Type 2) processes.

Objective

The present study investigated the effects of bilateral transcranial direct current stimulation (tDCS) to the dorsolateral prefrontal cortex (DLPFC) on judgment and decision-making performance.

Methods

Participants received anodal tDCS stimulation to the right DLPFC, left DLPFC or sham. There were 3 tasks: vignettes measuring heuristic thinking, belief bias syllogisms, and the cognitive reflection test (CRT), a measure of the ability to inhibit automatic responses to reach a correct solution. Fifty-four participants (mean age?=?24.63?±?4.46 years; 29 females) were recruited.

Results

Results showed that anodal tDCS to the right DLPFC was associated with an increase in cognitive reflection performance (Type 2 processing) as compared to left DLPFC and to sham. Logic thinking was reduced following anodal tDCS to the left DLPFC.

Conclusion

These findings are broadly consistent with a dual process framework, and cannot be explained by differences in cognitive ability and thinking style. The results demonstrate the involvement of the right DLPFC in cognitive reflection, and suggest the possibility of improving cognitive performance through tDCS.  相似文献   

18.

Introduction

Psychogenic non-epileptic seizures (PNES) are paroxysms of either altered subjective or objective manifestations that may mimic epileptic seizures (ES), without abnormal neuronal epileptiform activity. In this report, we present the case of a 39-year-old woman with PNES and functional movement disorders, who was successfully treated with neuro-guided transcranial direct current stimulation (tDCS).

Methods

We used a PET-guided tDCS approach, as a hypometabolism of the frontal region was revealed by FDG TEP scan. TDCs was performed 5 days/week, 2 times/day, during 3 weeks. All clinical manifestations were reported in a seizure diary. We also assessed dissociation, depression, alexithymia, psychotraumatic scales, and involuntary movements.

Results

The treatment was followed by a decrease of both psychogenic involuntary movements and PNES at 5 weeks. At the same time, PTSD symptoms, dissociative symptoms, depression and alexithymia improved.

Conclusion

PET-scan and tDCS seems to be promising tools for the evaluation and treatment of PNES in clinical practice, and may have a specific role on dissociative symptoms.  相似文献   

19.
20.

Background

Deep brain stimulation (DBS) is an emerging treatment for severe obsessive-compulsive disorder (OCD). We compared the efficacy of ventral capsule/ventral striatal (VC/VS) and anteromedial subthalamic nucleus (amSTN) DBS in the same patients and tested for mechanistic differences on mood and cognitive flexibility and associated neural circuitry. The possible synergistic benefit of DBS at both sites and cognitive behavioral therapy was explored.

Methods

Six patients with treatment-refractory OCD (5 men; Yale-Brown Obsessive Compulsive Scale score >32) entered double-blind counterbalanced phases of 12-week amSTN or VC/VS DBS, followed by 12-week open phases when amSTN and VC/VS were stimulated together, in which optimal stimulation parameters were achieved and adjunctive inpatient cognitive behavioral therapy was delivered. OCD and mood were assessed with standardized scales and cognitive flexibility with the Cambridge Neuropsychological Test Automated Battery Intra-Extra Dimensional Set-Shift task. Diffusion-weighted and intraoperative magnetic resonance imaging scans were performed for tractography from optimally activated electrode contacts.

Results

DBS at each site significantly and equivalently reduced OCD symptoms with little additional gain following combined stimulation. amSTN but not VC/VS DBS significantly improved cognitive flexibility, whereas VC/VS DBS had a greater effect on mood. The VC/VS effective site was within the VC. VC DBS connected primarily to the medial orbitofrontal cortex, and amSTN DBS to the lateral orbitofrontal cortex, dorsal anterior cingulate cortex, and dorsolateral prefrontal cortex. No further improvement followed cognitive behavioral therapy, reflecting a floor effect of DBS on OCD.

Conclusions

Both the VC/VS and amSTN are effective targets for severe treatment-refractory OCD. Differential improvements in mood and cognitive flexibility and their associated connectivity suggest that DBS at these sites modulates distinct brain networks.  相似文献   

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