Non-invasive Neurostimulation Research Articles

A Literature Mini-Review of Transcranial Direct Current Stimulation in Schizophrenia.

Transcranial direct current stimulation (tDCS) is a non-invasive neurostimulation method that utilizes the effect of low-current on brain tissue. In recent years, the effect of transcranial direct current stimulation has been investigated as a therapeutic modality in various neuropsychiatric indications, one of them being schizophrenia. This article aims to provide an overview of the potential application and effect of tDCS in treating patients with schizophrenia. A literature search was performed using the PubMed, Web of Science, and Google Scholar databases for relevant research published from any date until December 2021. Eligible studies included those that used randomized controlled parallel-group design and focused on the use of transcranial direct current stimulation for the treatment of positive, negative, or cognitive symptoms of schizophrenia. Studies were divided into groups based on the focus of research and an overview is provided in separate sections and tables in the article. The original database search yielded 705 results out of which 27 randomized controlled trials met the eligibility criteria and were selected and used for the purpose of this article. In a review of the selected trials, transcranial direct current stimulation is a safe and well-tolerated method that appears to have the potential as an effective modality for the treatment of positive and negative schizophrenic symptoms and offers promising results in influencing cognition. However, ongoing research is needed to confirm these conclusions and to further specify distinct application parameters.

Combined Yoga and Transcranial Direct Current Stimulation Increase Functional Connectivity and Synchronization in the Frontal Areas.

Transcranial direct current stimulation (tDCS) is a non-invasive neuro-stimulation technique that can modulate cortical excitability. Similarly, yoga is shown to affect the brain's neural activity and networks. Here, we aimed to investigate the effect of combined yoga and tDCS on brain oscillations and networks using resting-state electroencephalography recordings. In a randomized, cross-over, double-blind design, twenty-two healthy subjects participated in a yoga/active tDCS session (2mA; 20min; anode-F3, cathode F4) or yoga/sham tDCS on 2 separate days. Resting-state EEG data were collected before and after each intervention. Power spectral density (PSD) and functional connectivity, measured by a synchronization measure, phase-locking value, were computed for each condition. There were no significant differences in PSD values among the two interventions. The network-based statistic method was employed for detecting functional connectivity differences between yoga/active and yoga/sham tDCS interventions. Results show that the addition of active tDCS to yoga is associated with increased functional connectivity of the scalp and source EEG data in the frontal area. The changes were widespread, intra-hemispheric, and inter-hemispheric connections, which were mainly between the frontal area to other regions. At the source level, most of the connectivity changes were found in the fronto-parietal network. These findings suggest that combining yoga with tDCS might lead to brain network changes related to the executive and attentional functions.

Individual predictors and electrophysiological signatures of working memory enhancement in aging

A primary goal of translational neuroscience is to identify the neural mechanisms of age-related cognitive decline and develop protocols to maximally improve cognition. Here, we demonstrate how interventions that apply noninvasive neurostimulation to older adults improve working memory (WM). We found that one session of sham-controlled transcranial direct current stimulation (tDCS) selectively improved WM in older adults with more education, extending earlier work and underscoring the importance of identifying individual predictors of tDCS responsivity. Improvements in WM were associated with two distinct electrophysiological signatures. First, a broad enhancement of theta network synchrony tracked improvements in behavioral accuracy, with tDCS effects moderated by education level. Further analysis revealed that accuracy dynamics reflected an anterior-posterior network distribution regardless of cathode placement. Second, specific enhancements of theta-gamma phase-amplitude coupling (PAC) reflecting tDCS current flow tracked improvements in reaction time (RT). RT dynamics further explained inter-individual variability in WM improvement independent of education. These findings illuminate theta network synchrony and theta-gamma PAC as distinct but complementary mechanisms supporting WM in aging. Both mechanisms are amenable to intervention, the effectiveness of which can be predicted by individual demographic factors.

Variability of EEG electrode positions and their underlying brain regions: visualizing gel artifacts from a simultaneous EEG-fMRI dataset.

IntroductionWe investigated the between‐subject variability of EEG (electroencephalography) electrode placement from a simultaneously recorded EEG‐fMRI (functional magnetic resonance imaging) dataset.MethodsNeuro‐navigation software was used to localize electrode positions, made possible by the gel artifacts present in the structural magnetic resonance images. To assess variation in the brain regions directly underneath electrodes we used MNI coordinates, their associated Brodmann areas, and labels from the Harvard‐Oxford Cortical Atlas. We outline this relatively simple pipeline with accompanying analysis code.ResultsIn a sample of 20 participants, the mean standard deviation of electrode placement was 3.94 mm in x, 5.55 mm in y, and 7.17 mm in z, with the largest variation in parietal and occipital electrodes. In addition, the brain regions covered by electrode pairs were not always consistent; for example, the mean location of electrode PO7 was mapped to BA18 (secondary visual cortex), whereas PO8 was closer to BA19 (visual association cortex). Further, electrode C1 was mapped to BA4 (primary motor cortex), whereas C2 was closer to BA6 (premotor cortex).ConclusionsOverall, the results emphasize the variation in electrode positioning that can be found even in a fixed cap. This may be particularly important to consider when using EEG positioning systems to inform non‐invasive neurostimulation.

Physiotherapy interventions may relieve pain in individuals with central neuropathic pain: a systematic review and meta-analysis of randomised controlled trials.

Objectives:To evaluate the effectiveness of any form of physiotherapy intervention for the management of central neuropathic pain (cNeP) due to any underlying cause.Methods:Multiple databases were searched from inception until August 2021. Randomised controlled trials evaluating physiotherapy interventions compared to a control condition on pain among people with cNeP were included. Methodological quality and the quality of evidence were assessed using the Physiotherapy Evidence Database Scale and the Grading of Recommendations, Assessment, Development, and Evaluation tool, respectively.Results:The searches yielded 2661 studies, of which 23 randomised controlled trials met the inclusion criteria and were included in the meta-analyses. Meta-analyses of trials examining non-invasive neurostimulation revealed significant reductions in pain severity due to spinal cord injury (SCI; standardised mean difference (SMD): −0.59 (95% confidence interval [CI]: −1.07, −0.11), p = 0.02) and phantom limb pain (weighted mean difference (WMD): −1.57 (95% CI: −2.85, −0.29), p = 0.02). The pooled analyses of trials utilising acupuncture, transcutaneous electrical nerve stimulation (TENS), and mirror therapy showed significant reductions in pain severity among individuals with stroke (WMD: −1.46 (95% CI: −1.97, −0.94), p < 0.001), multiple sclerosis (SMD: −0.32 (95% CI: −0.57, −0.06), p = 0.01), and phantom limb pain (SMD: −0.74 (95% CI: −1.36, −0.11), p = 0.02), respectively. Exercise was also found to significantly reduce pain among people with multiple sclerosis (SMD: −1.58 (95% CI: −2.85, −0.30), p = 0.02).Conclusion:Evidence supports the use of non-invasive neurostimulation for the treatment of pain secondary to SCI and phantom limb pain. Beneficial pain management outcomes were also identified for acupuncture in stroke, TENS in multiple sclerosis, and mirror therapy in phantom limb pain.

Continuous theta-burst stimulation enhances and sustains neurogenesis following ischemic stroke.

Rationale: Previous work has indicated that continuous theta-burst stimulation (cTBS), a modality of transcranial magnetic stimulation (TMS), may provide neuroprotection and improve neurological function after stroke by preserving the blood-brain barrier, altering glial polarization phenotypes, and supporting peri-infarct angiogenesis. The present study was performed to examine whether cTBS, a noninvasive neurostimulation technique, promotes neurogenesis in a photothrombotic (PT) stroke rat model and contributes to functional recovery.Methods: Beginning 3 h or 1 week after the induction of PT stroke, once-daily 5-min cTBS treatments were applied to the infarcted hemisphere for 6 days. Samples were collected 6 days, 22 days, and 35 days after PT stroke. Fluorescent labeling, Western blotting, and behavioral tests were performed accordingly.Results: We found that cTBS therapy significantly expanded the pool of neural progenitor cells (NPCs) and newly generated immature neurons in the cortical peri-infarct region after PT stroke. Likewise, the amount of DCX-positive immature neurons in the peri-infarct area was markedly elevated by cTBS. Application of cTBS strikingly diminished the PT-induced loss of NPCs and newly-formed neurons. In addition, the amount of newly generated mature neurons in the peri-infarct zone was significantly promoted by cTBS. Intriguingly, cTBS reduced reactive gliogenesis significantly while promoting oligodendrogenesis and preserving myelination. Mechanistic studies uncovered that cTBS upregulated brain-derived neurotrophic factor (BDNF) and fibroblast growth factor 2 (FGF2). Finally, cTBS-treated animals displayed improved motor functions. To be noted, temozolomide (TMZ), a drug that has been previously used to suppress neurogenesis, could reverse the beneficial effects of cTBS.Conclusions: Our findings provide new insight into the mechanism by which cTBS promotes functional recovery from stroke. We demonstrated that cTBS effectively enhances and sustains neurogenesis after PT stroke. Both early and delayed cTBS treatment could improve the survival of newly generated neurons and functional recovery, and inhibition of neurogenesis could reverse these therapeutic benefits. Mechanistically, cTBS was effective in upregulating the release of neurotrophic factors, protecting NPC and immature neurons, as well as suppressing excessive gliogenesis.

The LC-NE system as a potential target for neuromodulation to ameliorate non-motor symptoms in Parkinson's disease.

Parkinson's disease (PD) is associated with severe motor symptoms but also with several non-motor symptoms (NMS). A substantial reduction of norepinephrine (NE) levels in various brain regions reflecting an extensive loss of innervation from the LC has been assumed as causal for the development of NMS and specifically of attentional impairments in PD. Transcutaneous auricular vagus nerve stimulation (taVNS) is a new, non-invasive neurostimulation method supposed to modulate the LC-NE system in humans. In the current opinion paper, we introduce taVNS as a systemic approach to directly affect NE neurotransmission in healthy as well as clinical populations and discuss its potential as therapeutic option for the treatment of NMS, specifically attentional deficits, in patients with PD. Here, we first describe the LC-NE system and discuss how LC-NE dysfunction might affects cognition in PD before detailing the mode of action of taVNS and proposing its use to modulate cognitive deficits in these patients.

A computational model to guide the functional decoupling of two brain regions with transcranial alternating current stimulation

Abstract Recent research has shown that cortical hyper-synchronization between frontoparietal areas in resting state could be an early biomarker of Alzheimer’s disease (AD). It is expected that reducing this synchronization could slow down the development of AD typical symptoms. In this sense, non-invasive neurostimulation techniques are candidate tools to desynchronize distant regions of the brain. In specific, transcranial Alternating Current Stimulation (tACS) can influence the oscillatory dynamics of neuronal groups in the brain specially modifying signals’ frequency and amplitude. Here we explore the possibility of using tACS to desynchronize frontoparietal brain regions: would this be possible? What frequencies would be the most suitable to minimize synchronization? Thus, we built ten personalized brain models in The Virtual Brain from magnetic resonance imaging and magnetoencephalography recordings. They are built of a structural connectivity network linking brain regions (from AAL2 atlas) and neural mass models per region to simulate electrophysiological dynamics. We applied tACS to stimulate those virtual brains areas on the parietal cortex (P3, P4 positions), using ROAST to calculate a current propagation model that determines how much electric field reaches each part of the brain. Our results show that it is possible to reduce cortical synchronization between two regions with tACS applying frequencies around the natural (i.e. in resting state) oscillation frequency of the stimulated region. These results could lead the experimental search of brain desynchronization with tACS on real subjects. Additionally, they strengthen the possibility of using that technique as an early intervention in Alzheimer’s disease. Keywords: Simulation, The virtual brain, Magnetoencephalography, tACS

The Involvement of the Posterior Cerebellum in Reconstructing and Predicting Social Action Sequences.

Recent advances in social neuroscience have highlighted the critical role of the cerebellum and especially the posterior cerebellar Crus in social mentalizing (i.e., theory of mind). Research in the past 5years has provided growing evidence supporting the view that the posterior cerebellum builds internal action models of our social interactions to predict how other people's actions will be executed, and what our most likely responses to these actions will be. This paper presents an overview of a series of fMRI experiments on novel tasks involving a combination of (a) the learning or generation of chronological sequences of social actions either in an explicit or implicit manner, which (b) require social mentalizing on another person's mental state such as goals, beliefs, and implied traits. Together, the results strongly confirm the central role of the posterior cerebellar Crus in identifying and automatizing action sequencing during social mentalizing, and in predicting future action sequences based on social mentalizing inferences about others. This research program has important implications: It provides for the first time (a) fruitful starting points for diagnosing and investigating social sequencing dysfunctions in a variety of mental disorders which have also been related to cerebellar dysfunctions, (b) provides the necessary tools for testing whether non-invasive neurostimulation targeting the posterior cerebellum has a causal effect on social functioning, and (c) whether these stimulation techniques and training programs guided by novel cerebellar social sequencing insights, can be exploited to increase posterior cerebellar plasticity in order to alleviate social impairments in mental disorders.

Non-invasive neurostimulation modulates processing of spatial frequency information in rapid perception of faces.

This study used high-frequency transcranial random noise stimulation (tRNS) to examine how low and high spatial frequency filtered faces are processed. Response times were measured in a task where healthy young adults categorised spatially filtered hybrid faces, presented at foveal and peripheral blocks, while sham and high-frequency random noise was applied to a lateral occipito-temporal location on their scalp. Both the Frequentist and Bayesian approaches show that in contrast to sham, active stimulation significantly reduced response times to peripherally presented low spatial frequency information. This finding points to a possible plasticity in targeted regions induced by non-invasive neuromodulation of spatial frequency information in rapid perception of faces.

The Role of the Posterior Cerebellum in Dysfunctional Social Sequencing.

Recent advances in social neuroscience have highlighted the critical role of the cerebellum in social cognition, and especially the posterior cerebellum. Studies have supported the view that the posterior cerebellum builds internal action models of our social interactions to predict how other people's actions will be executed and what our most likely responses are to these actions. This mechanism allows to better anticipate action sequences during social interactions in an automatic and intuitive way and to fine-tune these anticipations, making it easier to understand other's social behaviors and mental states (e.g., beliefs, intentions, traits). In this paper, we argue that the central role of the posterior cerebellum in identifying and automatizing social action sequencing provides a fruitful starting point for investigating social dysfunctions in a variety of clinical pathologies, such as autism, obsessive-compulsive and bipolar disorder, depression, and addiction. Our key hypothesis is that dysfunctions of the posterior cerebellum lead to under- or overuse of inflexible social routines and lack of plasticity for learning new, more adaptive, social automatisms. We briefly review past research supporting this view and propose a program of research to test our hypothesis. This approach might alleviate a variety of mental problems of individuals who suffer from inflexible automatizations that stand in the way of adjustable and intuitive social behavior, by increasing posterior cerebellar plasticity using noninvasive neurostimulation or neuro-guided training programs.

Brain regions that support accurate speech production after damage to Broca's area.

Broca’s area in the posterior half of the left inferior frontal gyrus has traditionally been considered an important node in the speech production network. Nevertheless, recovery of speech production has been reported, to different degrees, within a few months of damage to Broca’s area. Importantly, contemporary evidence suggests that, within Broca’s area, its posterior part (i.e. pars opercularis) plays a more prominent role in speech production than its anterior part (i.e. pars triangularis). In this study, we therefore investigated the brain activation patterns that underlie accurate speech production following stroke damage to the opercular part of Broca’s area. By combining functional MRI and 13 tasks that place varying demands on speech production, brain activation was compared in (i) seven patients of interest with damage to the opercular part of Broca’s area; (ii) 55 neurologically intact controls; and (iii) 28 patient controls with left-hemisphere damage that spared Broca’s area. When producing accurate overt speech responses, the patients with damage to the left pars opercularis activated a substantial portion of the normal bilaterally distributed system. Within this system, there was a lesion-site-dependent effect in a specific part of the right cerebellar Crus I where activation was significantly higher in the patients with damage to the left pars opercularis compared to both neurologically intact and patient controls. In addition, activation in the right pars opercularis was significantly higher in the patients with damage to the left pars opercularis relative to neurologically intact controls but not patient controls (after adjusting for differences in lesion size). By further examining how right Crus I and right pars opercularis responded across a range of conditions in the neurologically intact controls, we suggest that these regions play distinct roles in domain-general cognitive control. Finally, we show that enhanced activation in the right pars opercularis cannot be explained by release from an inhibitory relationship with the left pars opercularis (i.e. dis-inhibition) because right pars opercularis activation was positively related to left pars opercularis activation in neurologically intact controls. Our findings motivate and guide future studies to investigate (i) how exactly right Crus I and right pars opercularis support accurate speech production after damage to the opercular part of Broca’s area and (ii) whether non-invasive neurostimulation to one or both of these regions boosts speech production recovery after damage to the opercular part of Broca’s area.

Complex Regional Pain Syndrome. A Comprehensive Review on Neuroplastic Changes Supporting the Use of Non-invasive Neurostimulation in Clinical Settings.

Background: Complex regional pain syndrome (CRPS) is a rare debilitating disorder characterized by severe pain affecting one or more limbs. CRPS presents a complex multifactorial physiopathology. The peripheral and sensorimotor abnormalities reflect maladaptive changes of the central nervous system. These changes of volume, connectivity, activation, metabolism, etc., could be the keys to understand chronicization, refractoriness to conventional treatment, and developing more efficient treatments.Objective: This review discusses the use of non-pharmacological, non-invasive neurostimulation techniques in CRPS, with regard to the CRPS physiopathology, brain changes underlying chronicization, conventional approaches to treat CRPS, current evidence, and mechanisms of action of peripheral and brain stimulation.Conclusion: Future work is warranted to foster the evidence of the efficacy of non-invasive neurostimulation in CRPS. It seems that the approach has to be individualized owing to the integrity of the brain and corticospinal function. Non-invasive neurostimulation of the brain or of nerve/muscles/spinal roots, alone or in combination with conventional therapy, represents a fertile ground to develop more efficient approaches for pain management in CRPS.

Theta-Burst Stimulation of Forearm Muscles in Patients With Complex Regional Pain Syndrome: Influence on Brain and Clinical Outcomes.

Objective: Complex regional pain syndrome (CRPS) is a common pain condition characterized by the changes in the brain that are not yet addressed by conventional treatment regimens. Repetitive peripheral magnetic stimulation (rPMS) of muscles is painless and non-invasive and can influence these changes (the induction of brain plasticity) to reduce pain and improve motricity. In patients with CRPS, this open-label pilot study tested rPMS after-effects on the pain intensity and sensorimotor control of the upper limb along with the excitability changes of the primary motor cortex (M1).Methods: Eight patients with CRPS were enrolled in a single-session program. Patients were tested at pre- and post-rPMS over the flexor digitorum superficialis (FDS) muscle. The clinical outcomes were pain intensity, proprioception, active range of motion (ROM), and grip strength. M1 excitability was tested using the single- and paired-pulse transcranial magnetic stimulation (TMS) of M1.Results: In our small sample study, rPMS reduced instant and week pain, improved proprioception and ROM, and reduced the hemispheric imbalance of several TMS outcomes. The more M1 contralateral to the CRPS side was hyperactivated at baseline, the more pain was reduced.Discussion: This open-label pilot study provided promising findings for the use of rPMS in CRPS with a focus on M1 plastic changes. Future randomized, placebo-controlled clinical trials should confirm the existence of a causal relationship between the TMS outcomes and post-rPMS decrease of pain. This will favor the development of personalized treatments of peripheral non-invasive neurostimulation in CRPS.

Role of Ayurveda in Managing Tinnitus

Tinnitus is one of the annoying disorders which can significantly impair patient’s quality of life and productivity. Although it is not a life threatening disease, but it results into emotional distress, cognitive distress, intrusiveness, auditory and perceptual difficulties, sleep disturbances, and various somatic complaints. Its incidence and prevalence are enhancing day by day. Various pharmacological agents including anticonvulsants, anxiolytics, antidepressants, muscle relaxants etc. are presently used or trialed for its pacification, but there is little evidence of their benefit over harm. The role of invasive and non-invasive Neurostimulation treatments, supposed to be very effective, are also little known. The introduction of Hearing aids and cochlear implantation are also not very much conclusive. No evidence of a significant change in the subjective loudness of tinnitus has been noticed with Cognitive behavioural treatment. In this way, there is a need for making an availability of uniformly accepted, broadly effective treatments capable of drastically decreasing the loudness and impact of tinnitus and withstanding systematic replication. This article is for serving the very purpose. Here, an effort has been made to present the remedial procedures and regimen for the alleviation of tinnitus described in Ayurveda, an ancient healing science of India. In Ayurveda, tinnitus has been delineated in the name of Karnanada. The article also brings about several case studies and clinical studies on tinnitus carried out at different centres/Institutes of Ayurveda.

Rapid whole-brain electric field mapping in transcranial magnetic stimulation using deep learning.

Transcranial magnetic stimulation (TMS) is a non-invasive neurostimulation technique that is increasingly used in the treatment of neuropsychiatric disorders and neuroscience research. Due to the complex structure of the brain and the electrical conductivity variation across subjects, identification of subject-specific brain regions for TMS is important to improve the treatment efficacy and understand the mechanism of treatment response. Numerical computations have been used to estimate the stimulated electric field (E-field) by TMS in brain tissue. But the relative long computation time limits the application of this approach. In this paper, we propose a deep-neural-network based approach to expedite the estimation of whole-brain E-field by using a neural network architecture, named 3D-MSResUnet and multimodal imaging data. The 3D-MSResUnet network integrates the 3D U-net architecture, residual modules and a mechanism to combine multi-scale feature maps. It is trained using a large dataset with finite element method (FEM) based E-field and diffusion magnetic resonance imaging (MRI) based anisotropic volume conductivity or anatomical images. The performance of 3D-MSResUnet is evaluated using several evaluation metrics and different combinations of imaging modalities and coils. The experimental results show that the output E-field of 3D-MSResUnet provides reliable estimation of the E-field estimated by the state-of-the-art FEM method with significant reduction in prediction time to about 0.24 second. Thus, this study demonstrates that neural networks are potentially useful tools to accelerate the prediction of E-field for TMS targeting.

Non-Invasive Neurostimulation Methods for Acute and Preventive Migraine Treatment-A Narrative Review.

Neurostimulation methods have now been studied for more than 20 years in migraine treatment. They can be divided into invasive and non-invasive methods. In this narrative review, the non-invasive methods are presented. The most commonly studied and used methods are vagal nerve stimulation, electric peripheral nerve stimulation, transcranial magnetic stimulation, and transcranial direct current stimulation. Other stimulation techniques, including mechanical stimulation, play only a minor role. Nearly all methods have been studied for acute attack treatment and for the prophylactic treatment of migraine. The evidence of efficacy is poor for most procedures, since no stimulation device is based on consistently positive, blinded, controlled trials with a sufficient number of patients. In addition, most studies on these devices enrolled patients who did not respond sufficiently to oral drug treatment, and so the role of neurostimulation in an average population of migraine patients is unknown. In the future, it is very important to conduct large, properly blinded and controlled trials performed by independent researchers. Otherwise, neurostimulation methods will only play a very minor role in the treatment of migraine.

Therapeutic Neurostimulation in Obsessive-Compulsive and Related Disorders: A Systematic Review.

Invasive and noninvasive neurostimulation therapies for obsessive-compulsive and related disorders (OCRD) were systematically reviewed with the aim of assessing clinical characteristics, methodologies, neuroanatomical substrates, and varied stimulation parameters. Previous reviews have focused on a narrow scope, statistical rather than clinical significance, grouped together heterogenous protocols, and proposed inconclusive outcomes and directions. Herein, a comprehensive and transdiagnostic evaluation of all clinically relevant determinants is presented with translational clinical recommendations and novel response rates. Electroconvulsive therapy (ECT) studies were limited in number and quality but demonstrated greater efficacy than previously identified. Targeting the pre-SMA/SMA is recommended for transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS). TMS yielded superior outcomes, although polarity findings were conflicting, and refinement of frontal/cognitive control protocols may optimize outcomes. For both techniques, standardization of polarity, more treatment sessions (20), and targeting multiple structures are encouraged. A deep brain stimulation (DBS) ‘sweet spot’ of the striatum for OCD was proposed, and CBT is strongly encouraged. Tourette’s patients showed less variance and reliance on treatment optimization. Several DBS targets achieved consistent, rapid, and sustained clinical response. Analysis of fiber connectivity, as opposed to precise neural regions, should be implemented for target selection. Standardization of protocols is necessary to achieve translational outcomes.

Transcutaneous auricular VNS applied to experimental pain: A paired behavioral and EEG study using thermonociceptive CO2 laser.

BackgroundTranscutaneous auricular Vagal Nerve Stimulation (taVNS) is a non-invasive neurostimulation technique with potential analgesic effects. Several studies based on subjective behavioral responses suggest that taVNS modulates nociception differently with either pro-nociceptive or anti-nociceptive effects.ObjectiveThis study aimed to characterize how taVNS alters pain perception, by investigating its effects on event-related potentials (ERPs) elicited by different types of spinothalamic and lemniscal somatosensory stimuli, combined with quantitative sensory testing (detection threshold and intensity ratings).MethodsWe performed 3 experiments designed to study the time-dependent effects of taVNS and compare with standard cervical VNS (cVNS). In Experiment 1, we assessed the effects of taVNS after 3 hours of stimulation. In Experiment 2, we focused on the immediate effects of the duty cycle (OFF vs. ON phases). Experiments 1 and 2 included 22 and 15 healthy participants respectively. Both experiments consisted of a 2-day cross-over protocol, in which subjects received taVNS and sham stimulation sequentially. In addition, subjects received a set of nociceptive (thermonociceptive CO2 laser, mechanical pinprick) and non-nociceptive (vibrotactile, cool) stimuli, for which we recorded detection thresholds, intensity of perception and ERPs. Finally, in Experiment 3, we tested 13 epileptic patients with an implanted cVNS by comparing OFF vs. ON cycles, using a similar experimental procedure.ResultsNeither taVNS nor cVNS appeared to modulate the cerebral and behavioral aspects of somatosensory perception.ConclusionThe potential effect of taVNS on nociception requires a cautious interpretation, as we found no objective change in behavioral and cerebral responses to spinothalamic and lemniscal somatosensory stimulations.

Perinatal stroke: mapping and modulating developmental plasticity.

Most cases of hemiparetic cerebral palsy are caused by perinatal stroke, resulting in lifelong disability for millions of people. However, our understanding of how the motor system develops following such early unilateral brain injury is increasing. Tools such as neuroimaging and brain stimulation are generating informed maps of the unique motor networks that emerge following perinatal stroke. As a focal injury of defined timing in an otherwise healthy brain, perinatal stroke represents an ideal human model of developmental plasticity. Here, we provide an introduction to perinatal stroke epidemiology and outcomes, before reviewing models of developmental plasticity after perinatal stroke. We then examine existing therapeutic approaches, including constraint, bimanual and other occupational therapies, and their potential synergy with non-invasive neurostimulation. We end by discussing the promise of exciting new therapies, including novel neurostimulation, brain-computer interfaces and robotics, all focused on improving outcomes after perinatal stroke.