Combined Brain Stimulation Research Articles

Strategies for applying noninvasive brain stimulation techniques to treat psychiatric disorders

With the continuous development of science and technology, medical science, and bioengineering technology, various neuromodulation techniques, such as electrical, magnetic, acoustic, and optical modalities, are rapidly emerging in the therapeutic regime of psychiatric disorders. How to choose the appropriate noninvasive brain stimulation techniques for different psychiatric disorders and their clinical features is becoming a practical dilemma in clinical setting. In this paper, by describing the complex pathogenesis of psychiatric disorders and the limitations of existing therapeutic approaches on psychiatric disorders, combining with the characteristics of different neuromodulation techniques, we propose a new strategy of combined noninvasive brain stimulation to intervene in psychiatric disorders: high-intensity stimulation modulating the whole brain without inducing epilepsy should be as the basic treatment of psychiatric disorders, applying low-intensity stimulation with the advantage of specific targets/brain regions to modulate the residual symptoms or/and single symptom, and for refractory and acute psychiatric disorders, ECT/MECT is preferred for rapid symptom control; different noninvasive brain stimulation techniques can be combined with pharmacological and psychotherapeutic treatments, which will provide a new idea for the future development of this field.

Kinematic Effects of Combined Subthalamic and Dorsolateral Nigral Deep Brain Stimulation in Parkinson's Disease.

Additional stimulation of the substantia nigra (SNr) has been proposed to target axial symptoms and gait impairment in patients with Parkinson's disease (PD). This study aimed to characterize effects of combined deep brain stimulation (DBS) of the subthalamic nucleus (STN) and SNr on gait performance in PD and to map stimulation sites within the SNr. In a double-blinded crossover design, 10 patients with PD and gait impairment underwent clinical examination and kinematic assessment with STN DBS, combined STN+SNr DBS and OFF DBS 30 minutes after reprogramming. To confirm stimulation within the SNr, electrodes, active contacts, and stimulation volumes were modeled in a common space and overlap with atlases of SNr was computed. Overlap of stimulation volumes with dorsolateral SNr was confirmed for all patients. UPDRS III, scoring of freezing during turning and transitioning, stride length, stride velocity, and range of motion of shank, knee, arm, and trunk as well as peak velocities during turning and transitions and turn duration were improved with STN DBS compared to OFF. On cohort level, no further improvement was observed with combined STN+SNr DBS but additive improvement of spatiotemporal gait parameters was observed in individual subjects. Combined high frequency DBS of the STN and dorsolateral SNr did not consistently result in additional short-term kinematic or clinical benefit compared to STN DBS. Stimulation intervals, frequency, and patient selection for target symptoms as well as target region within the SNr need further refinement in future trials.

The effects of combined transcranial brain stimulation and a 4-week visuomotor stepping training on voluntary step initiation in persons with chronic stroke-a pilot study.

Evidence suggests that transcranial direct current stimulation (tDCS) can enhance motor performance and learning of hand tasks in persons with chronic stroke (PCS). However, the effects of tDCS on the locomotor tasks in PCS are unclear. This pilot study aimed to: (1) determine aggregate effects of anodal tDCS combined with step training on improvements of the neural and biomechanical attributes of stepping initiation in a small cohort of persons with chronic stroke (PCS) over a 4-week training program; and (2) assess the feasibility and efficacy of this novel approach for improving voluntary stepping initiation in PCS. A total of 10 PCS were randomly assigned to one of two training groups, consisting of either 12 sessions of VST paired with a-tDCS (n = 6) or sham tDCS (s-tDCS, n = 4) over 4 weeks, with step initiation (SI) tests at pre-training, post-training, 1-week and 1-month follow-ups. Primary outcomes were: baseline vertical ground reaction force (B-vGRF), response time (RT) to initiate anticipatory postural adjustment (APA), and the retention of B-VGRF and RT. a-tDCS paired with a 4-week VST program results in a significant increase in paretic weight loading at 1-week follow up. Furthermore, a-tDCS in combination with VST led to significantly greater retention of paretic BWB compared with the sham group at 1 week post-training. The preliminary findings suggest a 4-week VST results in improved paretic limb weight bearing (WB) during SI in PCS. Furthermore, VST combined with a-tDCS may lead to better retention of gait improvements (NCT04437251) (https://classic.clinicaltrials.gov/ct2/show/NCT04437251).

Efficacy and safety of combined deep brain stimulation with capsulotomy for comorbid motor and psychiatric symptoms in Tourette’s syndrome: Experience and evidence

ObjectivesTo evaluate the efficacy and safety of combined deep brain stimulation (DBS) with capsulotomy for comorbid motor and psychiatric symptoms in patients with Tourette’s syndrome (TS). MethodsThis retrospective cohort study consecutively enrolled TS patients with comorbid motor and psychiatric symptoms who were treated with combined DBS and anterior capsulotomy at our center. Longitudinal motor, psychiatric, and cognitive outcomes and quality of life were assessed. In addition, a systematic review and meta-analysis were performed to summarize the current experience with the available evidence. ResultsIn total, 5 eligible patients in our cohort and 26 summarized patients in 6 cohorts were included. After a mean 18-month follow-up, our cohort reported that motor symptoms significantly improved by 62.4 % (P = 0.005); psychiatric symptoms of obsessive-compulsive disorder (OCD) and anxiety significantly improved by 87.7 % (P < 0.001) and 78.4 % (P = 0.009); quality of life significantly improved by 61.9 % (P = 0.011); and no significant difference was found in cognitive function (all P > 0.05). Combined surgery resulted in greater improvements in psychiatric outcomes and quality of life than DBS alone. The synthesized findings suggested significant improvements in tics (MD: 57.92, 95 % CI: 41.28–74.56, P < 0.001), OCD (MD: 21.91, 95 % CI: 18.67–25.15, P < 0.001), depression (MD: 18.32, 95 % CI: 13.26–23.38, P < 0.001), anxiety (MD: 13.83, 95 % CI: 11.90–15.76, P < 0.001), and quality of life (MD: 48.22, 95 % CI: 43.68–52.77, P < 0.001). Individual analysis revealed that the pooled treatment effects on motor symptoms, psychiatric symptoms, and quality of life were 78.6 %, 84.5–87.9 %, and 83.0 %, respectively. The overall pooled rate of adverse events was 50.0 %, and all of these adverse events were resolved or alleviated with favorable outcomes. ConclusionsCombined DBS with capsulotomy is effective for relieving motor and psychiatric symptoms in TS patients, and its safety is acceptable. However, the optimal candidate should be considered, and additional experience is still necessary.

Neural substrates of individual differences in learning generalization via combined brain stimulation and multitasking training.

A pervasive limitation in cognition is reflected by the performance costs we experience when attempting to undertake two tasks simultaneously. While training can overcome these multitasking costs, the more elusive objective of training interventions is to induce persistent gains that transfer across tasks. Combined brain stimulation and cognitive training protocols have been employed to improve a range of psychological processes and facilitate such transfer, with consistent gains demonstrated in multitasking and decision-making. Neural activity in frontal, parietal, and subcortical regions has been implicated in multitasking training gains, but how the brain supports training transfer is poorly understood. To investigate this, we combined transcranial direct current stimulation of the prefrontal cortex and multitasking training, with functional magnetic resonance imaging in 178 participants. We observed transfer to a visual search task, following 1mA left or right prefrontal cortex transcranial direct current stimulation and multitasking training. These gains persisted for 1-month post-training. Notably, improvements in visual search performance for the right hemisphere stimulation group were associated with activity changes in the right hemisphere dorsolateral prefrontal cortex, intraparietal sulcus, and cerebellum. Thus, functional dynamics in these task-general regions determine how individuals respond to paired stimulation and training, resulting in enhanced performance on an untrained task.

Brain perfusion alterations induced by standalone and combined non-invasive brain stimulation over the dorsolateral prefrontal cortex

Abstract Non-invasive brain stimulation (NIBS) interventions are promising for the treatment of psychiatry disorders. Notwithstanding, the mechanisms of action of NIBS over the dorsolateral prefrontal cortex (DLPFC), a hub that modulates affective and cognitive processes, have not been completely mapped. We aimed to investigate regional cerebral blood flow (rCBF) changes over the DLPFC and the interconnected subgenual anterior cingulate cortex (sgACC) of different NIBS protocols using a Single Photon Emission Computed Tomography (SPECT). Twenty-three healthy subjects were allocated to randomly undergo four sessions of NIBS applied once a week: transcranial direct current stimulation (tDCS), intermittent theta-burst stimulation (iTBS), combined tDCS+iTBS and placebo. The radiotracer 99m-Technetium-ethylene-cysteine-dimer (99m-ECD) was injected intravenously during the NIBS session, and SPECT images were acquired after the session. Results revealed none of the active interventions changing rCBF on the targeted DLPFC, but the combination tDCS+iTBS increased rCBF on the right sgACC. TDCS respectively increased and decreased rCBF on DLPFC sub-regions under the cathode and anode, while iTBS did not show any significant changes compared to placebo. Our findings encourage future clinical trials combining tDCS+iTBS for psychiatric population and mechanistic studies to investigate the effects of tDCS and iTBS over the DLPFC. Research Category and Technology and Methods Basic Research: 9. Transcranial Direct Current Stimulation (tDCS)

Stance Phase Gait Training Post Stroke Using Simultaneous Transcranial Direct Current Stimulation and Motor Learning-Based Virtual Reality-Assisted Therapy: Protocol Development and Initial Testing.

Gait deficits are often persistent after stroke, and current rehabilitation methods do not restore normal gait for everyone. Targeted methods of focused gait therapy that meet the individual needs of each stroke survivor are needed. Our objective was to develop and test a combination protocol of simultaneous brain stimulation and focused stance phase training for people with chronic stroke (>6 months). We combined Transcranial Direct Current Stimulation (tDCS) with targeted stance phase therapy using Virtual Reality (VR)-assisted treadmill training and overground practice. The training was guided by motor learning principles. Five users (>6 months post-stroke with stance phase gait deficits) completed 10 treatment sessions. Each session began with 30 min of VR-assisted treadmill training designed to apply motor learning (ML)-based stance phase targeted practice. During the first 15 min of the treadmill training, bihemispheric tDCS was simultaneously delivered. Immediately after, users completed 30 min of overground (ML)-based gait training. The outcomes included the feasibility of protocol administration, gait speed, Timed Up and Go (TUG), Functional Gait Assessment (FGA), paretic limb stance phase control capability, and the Fugl–Meyer for lower extremity coordination (FMLE). The changes in the outcome measures (except the assessments of stance phase control capability) were calculated as the difference from baseline. Statistically and clinically significant improvements were observed after 10 treatment sessions in gait speed (0.25 ± 0.11 m/s) and FGA (4.55 ± 3.08 points). Statistically significant improvements were observed in TUG (2.36 ± 3.81 s) and FMLE (4.08 ± 1.82 points). A 10-session intervention combining tDCS and ML-based task-specific gait rehabilitation was feasible and produced clinically meaningful improvements in lower limb function in people with chronic gait deficits after stroke. Because only five users tested the new protocol, the results cannot be generalized to the whole population. As a contribution to the field, we developed and tested a protocol combining brain stimulation and ML-based stance phase training for individuals with chronic stance phase deficits after stroke. The protocol was feasible to administer; statistically and/or clinically significant improvements in gait function across an array of gait performance measures were observed with this relatively short treatment protocol.

ДИНАМИКА КЛИНИЧЕСКОГО СОСТОЯНИЯ ПАЦИЕНТОВ С ШИЗОФРЕНИЕЙ С ПОСТПСИХОТИЧЕСКОЙ ДЕПРЕССИЕЙ, С ДУШЕВНОЙ БОЛЬЮ ПОД ВЛИЯНИЕМ БИНАУРАЛЬНОЙ СТИМУЛЯЦИИ ГОЛОВНОГО МОЗГА

In some cases, in the depressive symptoms of schizophrenia, the phenomenon of mental pain or «vital melancholy» is traced, which often has an obsessive nature and proceeds with suicidal intentions. The low effect of existing methods of therapy of this condition with the help of psychopharmacotherapy is noted. In this study, the authors attempted to additionally influence this symptom complex using binaural stimulation of the brain, along with psychopharmacotherapy. The authors used Th e Psychach e Scal e t o asses s mental pain and measure it numerically, and the PANSS scale to diagnose the clinical symptoms of schizophrenia. In the main group of patients receiving binaural brain stimulation, it was possible to achieve better treatment results for a number of symptoms related to the negative cluster, the cluster of general symptoms and one more additional symptom: emotional lability than in the control group that did not receive this specific additional treatment. The use of binaural brain stimulation in combination with drug therapy has significantly reduced the severity of mental pain in patients with schizophrenia.

A causal role for the right frontal eye fields in value comparison.

Recent studies have suggested close functional links between overt visual attention and decision making. This suggests that the corresponding mechanisms may interface in brain regions known to be crucial for guiding visual attention - such as the frontal eye field (FEF). Here, we combined brain stimulation, eye tracking, and computational approaches to explore this possibility. We show that inhibitory transcranial magnetic stimulation (TMS) over the right FEF has a causal impact on decision making, reducing the effect of gaze dwell time on choice while also increasing reaction times. We computationally characterize this putative mechanism by using the attentional drift diffusion model (aDDM), which reveals that FEF inhibition reduces the relative discounting of the non-fixated option in the comparison process. Our findings establish an important causal role of the right FEF in choice, elucidate the underlying mechanism, and provide support for one of the key causal hypotheses associated with the aDDM.

Brain Circuits Involved in the Development of Chronic Musculoskeletal Pain: Evidence From Non-invasive Brain Stimulation.

It has been well-documented that the brain changes in states of chronic pain. Less is known about changes in the brain that predict the transition from acute to chronic pain. Evidence from neuroimaging studies suggests a shift from brain regions involved in nociceptive processing to corticostriatal brain regions that are instrumental in the processing of reward and emotional learning in the transition to the chronic state. In addition, dysfunction in descending pain modulatory circuits encompassing the periaqueductal gray and the rostral anterior cingulate cortex may also be a key risk factor for pain chronicity. Although longitudinal imaging studies have revealed potential predictors of pain chronicity, their causal role has not yet been determined. Here we review evidence from studies that involve non-invasive brain stimulation to elucidate to what extent they may help to elucidate the brain circuits involved in pain chronicity. Especially, we focus on studies using non-invasive brain stimulation techniques [e.g., transcranial magnetic stimulation (TMS), particularly its repetitive form (rTMS), transcranial alternating current stimulation (tACS), and transcranial direct current stimulation (tDCS)] in the context of musculoskeletal pain chronicity. We focus on the role of the motor cortex because of its known contribution to sensory components of pain via thalamic inhibition, and the role of the dorsolateral prefrontal cortex because of its role on cognitive and affective processing of pain. We will also discuss findings from studies using experimentally induced prolonged pain and studies implicating the DLPFC, which may shed light on the earliest transition phase to chronicity. We propose that combined brain stimulation and imaging studies might further advance mechanistic models of the chronicity process and involved brain circuits. Implications and challenges for translating the research on mechanistic models of the development of chronic pain to clinical practice will also be addressed.

Disability and functional outcomes following STN, VC/VS, and combined deep brain stimulation in obsessive compulsive disorder

BackgroundOCD severity scores mostly convey information within the domain of clinical conceptualisations. To capture the full impact of any new intervention it is crucial to measure its impact on disability. For this purpose we captured prospective data on changes in disability, function and impairments with multiple tools throughout the UCL-MRC trial of Deep brain stimulation (DBS) for Obsessive Compulsive Disorder (OCD) between 2013-2017. The clinical and cognitive outcomes from the trial have already been reported in 2019. We hypothesized a concomitant improvement in perceived and observed indicators of disability with clinical improvement in OCD symptoms. This is a preliminary report of the disability outcome data from the trial.MethodSix patients with severe treatment resistant OCD were recruited for this study from the NHS England OCD Specialist Service. Eligible participants were offered lesion surgery (anterior cingulotomy) or entry to the DBS trial. OCD medication was kept constant throughout the trial. We tested the effects of DBS by comparing baseline, VC/VS, STN, both sites and CBT stages of trial on the following three assessments of function: GAF, SDS and CAOIC. An impairment focussed interview was done to quantify changes in function specific to OCD. Friedman's test was used to test for DBS effects during the double-blind crossover phases comparing baseline, amSTN and VC/VS. Post-hoc pair-wise Conover tests for significant effects were used with FDR corrections. All significant results are reported at P &lt; 0.05.ResultDBS had a significant effect across all phases for all above mentioned clinical measures. For all three measures of disability, there were significant improvements after both amSTN and VC/VS DBS. For all three measures of disability the effect of VC/VS DBS was significantly better that amSTN DBS. For all three measures of disability there was a non-significant trend (p = 0.058) for stimulation at both sites to have a better effect than stimulation of one site alone. For all three measures of disability, there were no significant difference between DBS alone and DBS and CBT.ConclusionThis study is the first to have directly compared differential effects of STN versus VC/VS DBS stimulation in OCD patients whilst testing clinical, cognitive and disability outcomes. The results of this study indicate that although both sites are equally effective in reducing OCD, stimulating VC/VS leads to a significantly greater improvement on disability scores in severe OCD.

Staging and Combining Brain Stimulation Interventions: Vagus Nerve Stimulation and Electroconvulsive Therapy.

Staging and Combining Brain Stimulation Interventions: Vagus Nerve Stimulation and Electroconvulsive Therapy.

Unraveling the Temporal Dynamics of Reward Signals in Music-Induced Pleasure with TMS.

Music's ability to induce feelings of pleasure has been the subject of intense neuroscientific research lately. Prior neuroimaging studies have shown that music-induced pleasure engages cortico-striatal circuits related to the anticipation and receipt of biologically relevant rewards/incentives, but these reports are necessarily correlational. Here, we studied both the causal role of this circuitry and its temporal dynamics by applying transcranial magnetic stimulation (TMS) over the left dorsolateral PFC combined with fMRI in 17 male and female participants. Behaviorally, we found that, in accord with previous findings, excitation of fronto-striatal pathways enhanced subjective reports of music-induced pleasure and motivation, whereas inhibition of the same circuitry led to the reduction of both. fMRI activity patterns indicated that these behavioral changes were driven by bidirectional TMS-induced alteration of fronto-striatal function. Specifically, changes in activity in the NAcc predicted modulation of both hedonic and motivational responses, with a dissociation between pre-experiential versus experiential components of musical reward. In addition, TMS-induced changes in the fMRI functional connectivity between the NAcc and frontal and auditory cortices predicted the degree of modulation of hedonic responses. These results indicate that the engagement of cortico-striatal pathways and the NAcc, in particular, is indispensable to experience rewarding feelings from music.SIGNIFICANCE STATEMENT Neuroimaging studies have shown that music-induced pleasure engages cortico-striatal circuits involved in the processing of biologically relevant rewards. Yet, these reports are necessarily correlational. Here, we studied both the causal role of this circuitry and its temporal dynamics by combining brain stimulation over the frontal cortex with functional imaging. Behaviorally, we found that excitation and inhibition of fronto-striatal pathways enhanced and disrupted, respectively, subjective reports of music-induced pleasure and motivation. These changes were associated with changes in NAcc activity and NAcc coupling with frontal and auditory cortices, dissociating between pre-experimental versus experiential components of musical reward. These results indicate that the engagement of cortico-striatal pathways, and the NAcc in particular, is indispensable to experience rewarding feeling from music.

Combined Brain and Hand Stimulation to Improve Hand Function in Individuals With Moderate to Severe Chronic Stroke: A Pilot Randomized Controlled Trial

Abstract Date Presented 03/26/20 We conducted a phase I pilot randomized controlled trial examining the preliminary efficacy of combining brain and hand stimulation to improve hand function in individuals with moderate to severe chronic stroke. Our findings suggest that the combined brain and hand stimulation shows promise in improving hand movement, function, and participation in daily tasks in this population. Future studies are warranted to examine the efficacy of this intervention. Primary Author and Speaker: Amit Sethi Contributing Authors: Alvaro Pascual-Leone, Emiliano Santarnecchi

Implicit Motor Imagery and the Lateral Occipitotemporal Cortex: Hints for Tailoring Non-Invasive Brain Stimulation.

Background: Recent evidence has converged in showing that the lateral occipitotemporal cortex is over-recruited during implicit motor imagery in elderly and in patients with neurodegenerative disorders, such as Parkinson’s disease. These data suggest that when automatically imaging movements, individuals exploit neural resources in the visual areas to compensate for the decline in activating motor representations. Thus, the occipitotemporal cortex could represent a cortical target of non-invasive brain stimulation combined with cognitive training to enhance motor imagery performance. Here, we aimed at shedding light on the role of the left and right lateral occipitotemporal cortex in implicit motor imagery. Methods: We applied online, high-frequency, repetitive transcranial magnetic stimulation (rTMS) over the left and right lateral occipitotemporal cortex while healthy right-handers judged the laterality of hand images. Results: With respect to the sham condition, left hemisphere stimulation specifically reduced accuracy in judging the laterality of right-hand images. Instead, the hallmark of motor simulation, i.e., the biomechanical effect, was never influenced by rTMS. Conclusions: The lateral occipitotemporal cortex seems to be involved in mental representation of the dominant hand, at least in right-handers, but not in reactivating sensorimotor information during simulation. These findings provide useful hints for developing combined brain stimulation and behavioural trainings to improve motor imagery.

Design and Rationale of the PACt-MD Randomized Clinical Trial: Prevention of Alzheimer's dementia with Cognitive remediation plus transcranial direct current stimulation in Mild cognitive impairment and Depression.

By the time Alzheimer's disease and related disorders (ADRD) are diagnosed, efficacy of treatments is limited. Preventive interventions are urgently needed. To design a randomized controlled trial to assess a novel intervention that aims to prevent ADRD in high-risk groups. We report on the rationale and describe the design of a multisite randomized controlled trial that aims to prevent ADRD in older persons with: (1) mild cognitive impairment (MCI); (2) remitted major depressive disorder (MDD) without MCI; or (3) remitted MDD with MCI. PACt-MD (Prevention of Alzheimer's dementia with Cognitive remediation plus transcranial direct current stimulation in Mild cognitive impairment and Depression) is a trial that randomized 375 older participants with MCI, MDD, or MCI + MDD to cognitive remediation (CR) plus transcranial direct current stimulation (tDCS) or sham-CR + sham-tDCS for 5 days/week for 8 weeks followed by boosters for 5 days/week once every 6 months until participants progress to MCI or ADRD, or the end of the study. Between boosters, participants are asked to train on CR daily. At baseline, end of 8 weeks, and yearly from baseline, participants undergo clinical, cognitive, and functional assessments. The primary aims are to compare the efficacy of CR + tDCS versus sham + sham in preventing: 1) long-term cognitive decline; and 2) incidence of ADRD or MCI. The secondary aim is to assess for cognitive improvement after the 8-week course. We will also explore the moderating and mediating effects of several biomarkers collected from the participants. PACt-MD is unique in combining brain stimulation and a psychosocial intervention to prevent ADRD. PACt-MD is also a platform for studying multi-domain biomarkers that will advance our understanding of the relationships among MCI, MDD, and ADRD.

A Systematic Review of the Effectiveness of Non-Invasive Brain Stimulation Techniques to Reduce Violence Proneness by Interfering in Anger and Irritability.

The field of neurocriminology has proposed several treatments (e.g., pharmacological, brain surgery, androgen-deprivation therapy, neurofeedback) to reduce violence proneness, but unfortunately, their effectiveness has been limited due to their side-effects. Therefore, it is necessary to explore alternative techniques to improve patients’ behavioural regulation with minimal undesirable effects. In this regard, non-invasive brain stimulation techniques, which are based on applying changing magnetic fields or electric currents to interfere with cortical excitability, have revealed their usefulness in alleviating the symptomatology of several mental disorders. However, to our knowledge, there are no reviews that assess whether these techniques are useful for reducing violence proneness. Therefore, we conducted a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria using the following databases: PsycINFO, PubMed, Dialnet, Psicodoc, Web of Knowledge, and the Cochrane Library. We initially identified 3746 entries, and eventually included 56 publications. Most of the studies were unanimous in concluding that the application of these techniques over the prefrontal cortex (PFC) was not sufficient to promote anger and irritability reductions in euthymic individuals of both genders. Nevertheless, the application of non-invasive brain stimulation techniques, especially transcranial direct current stimulation, over the right PFC seemed to reduce violent reactions in these individuals by interfering with the interpretation of the unfavourable situations (e.g., threating signals) or inner states that evoked anger. In antisocial and pathological populations, the conclusions were provided by a few pilot studies with important methodological weaknesses. The main conclusion of these studies was that bilateral stimulation of the PFC satisfactorily reduced anger and irritability only in inmates, patients with autism spectrum disorders (ASD), people who suffered a closed-head injury, and agitated patients with Alzheimer’s disease. Moreover, combining these techniques with risperidone considerably reduced aggressiveness in these patients. Therefore, it is necessary to be cautious about the benefits of these techniques to control anger, due the methodological weaknesses of these studies. Nonetheless, they offer valuable opportunities to prevent violence by designing new treatments combining brain stimulation with current strategies, such as psychotherapy and psychopharmacology, in order to promote lasting changes.

(Invited) Using Fast Scan Cyclic Voltammetry to elucidate the mechanism of action of Deep Brain Stimulation

Deep Brain Stimulation (DBS) is now an established neurosurgical therapy for variety of neurologic and psychiatric disorders. Investigations into the mechanism of action of DBS, using electrochemical recording techniques such as Fast Scan Cyclic Voltammetry (FSCV), has now demonstrated that DBS evokes release of neurotransmitter, including dopamine and adenosine depending on sites of stimulation. FSCV has been an established method for investigating neurochemical changes in animal models and is emerging as a potential method for monitoring neurotransmitter systems in humans undergoing DBS. At the Mayo Clinic, we have developed the WINCS (Wireless Instantaneous Neurotransmitter Concentration Sensing) system and its successor WINCS-Harmoni, a next generation device capable of combining brain stimulation with real-time neurochemical recording in vivo. Recently, we have also developed a novel technique termed multiple cyclic square wave voltammetry (M-CSWV) for quantifying tonic DA concentrations in vivo, which uses cyclic square wave voltammetric waveforms in conjunction with a delayed holding potential period to control adsorption. Here, a review of the technology development of WINCS and the use FSCV for elucidating the mechanism of action of DBS will be presented.

The benefits of combined brain stimulation and cognitive training: a pilot study

The benefits of combined brain stimulation and cognitive training: a pilot study

Stochastic resonance enhances the rate of evidence accumulation during combined brain stimulation and perceptual decision-making.

Perceptual decision-making relies on the gradual accumulation of noisy sensory evidence. It is often assumed that such decisions are degraded by adding noise to a stimulus, or to the neural systems involved in the decision making process itself. But it has been suggested that adding an optimal amount of noise can, under appropriate conditions, enhance the quality of subthreshold signals in nonlinear systems, a phenomenon known as stochastic resonance. Here we asked whether perceptual decisions made by human observers obey these stochastic resonance principles, by adding noise directly to the visual cortex using transcranial random noise stimulation (tRNS) while participants judged the direction of coherent motion in random-dot kinematograms presented at the fovea. We found that adding tRNS bilaterally to visual cortex enhanced decision-making when stimuli were just below perceptual threshold, but not when they were well below or above threshold. We modelled the data under a drift diffusion framework, and showed that bilateral tRNS selectively increased the drift rate parameter, which indexes the rate of evidence accumulation. Our study is the first to provide causal evidence that perceptual decision-making is susceptible to a stochastic resonance effect induced by tRNS, and to show that this effect arises from selective enhancement of the rate of evidence accumulation for sub-threshold sensory events.