Non-invasive Brain Modulation Research Articles

The Role of Non-Invasive Brain Modulation in Identifying Disease Biomarkers for Diagnostic and Therapeutic Purposes in Parkinsonism.

Over the past three decades, substantial advancements have occurred in non-invasive brain stimulation (NIBS). These developments encompass various non-invasive techniques aimed at modulating brain function. Among the most widely utilized methods today are transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES), which include direct- or alternating-current transcranial stimulation (tDCS/tACS). In addition to these established techniques, newer modalities have emerged, broadening the scope of non-invasive neuromodulation approaches available for research and clinical applications in movement disorders, particularly for Parkinson's disease (PD) and, to a lesser extent, atypical Parkinsonism (AP). All NIBS techniques offer the opportunity to explore a wide range of neurophysiological mechanisms and exert influence over distinct brain regions implicated in the pathophysiology of Parkinsonism. This paper's first aim is to provide a brief overview of the historical background and underlying physiological principles of primary NIBS techniques, focusing on their translational relevance. It aims to shed light on the potential identification of biomarkers for diagnostic and therapeutic purposes, by summarising available experimental data on individuals with Parkinsonism. To date, despite promising findings indicating the potential utility of NIBS techniques in Parkinsonism, their integration into clinical routine for diagnostic or therapeutic protocols remains a subject of ongoing investigation and scientific debate. In this context, this paper addresses current unsolved issues and methodological challenges concerning the use of NIBS, focusing on the importance of future research endeavours for maximizing the efficacy and relevance of NIBS strategies for individuals with Parkinsonism.

PP81 Efficacy Of Transcranial Direct Current Stimulation For Depressive Episode Disorders

IntroductionDepression is a general term that describes different depressive disorders which are highly prevalent and disabling, characterized by decreases in quality of life. Transcranial Direct Current Stimulation (tDCS) is a non-invasive brain modulation technique used, among other purposes, for the treatment of chronic pain and headache. In order to clarify the effect of this stimulation on depressive disorders, the objective of this review was to evaluate efficacy and safety of treatment with tDCS for depressive disorders.MethodsA systematic research study was carried out on 30 June 2022 in MEDLINE (by Pubmed), Embase, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), PsycInfo e Global Mental Health databases. Were included systematic reviews (SR) with meta-analysis that selected patients with depression, in use of tDCS, using as comparator sham stimulation (placebo) or any other treatment (pharmacologic or no) or any comparison between pre-and post-intervention.ResultsEight SR with meta-analysis of randomized clinical trials (RCTs) on the efficacy and safety of tDCS in the treatment of depressive disorders were retrieved. Subjects were assessed for clinical response, remission, change in scores on depression scales, occurrence of procedure-related adverse events, and treatment dropout. Three systematic reviews showed results that point to the effectiveness of tDCS for the clinical response outcome and one considering the remission outcome. As for the outcome measured by the change in depression scale scores, all included reviews showed favorable results for tDCS. It is noteworthy that the studies included in the reviews have methodological limitations. With regard to safety, an increased risk treatment-emergent mania or hypomania (TEM) has been observed.ConclusionsThe tDCS association with antidepressants showed favorable results to this technology in a sample with depression and varied clinical characteristics. Regarding safety of this technology, tDCS did not show adverse effects of greater severity, but was verified to have an increased risk of TEM.

Recent advancements in noninvasive brain modulation for individuals with autism spectrum disorder.

Autism spectrum disorder is classified as a spectrum of neurodevelopmental disorders with an unknown definitive etiology. Individuals with autism spectrum disorder show deficits in a variety of areas including cognition, memory, attention, emotion recognition, and social skills. With no definitive treatment or cure, the main interventions for individuals with autism spectrum disorder are based on behavioral modulations. Recently, noninvasive brain modulation techniques including repetitive transcranial magnetic stimulation, intermittent theta burst stimulation, continuous theta burst stimulation, and transcranial direct current stimulation have been studied for their therapeutic properties of modifying neuroplasticity, particularly in individuals with autism spectrum disorder. Preliminary evidence from small cohort studies, pilot studies, and clinical trials suggests that the various noninvasive brain stimulation techniques have therapeutic benefits for treating both behavioral and cognitive manifestations of autism spectrum disorder. However, little data is available for quantifying the clinical significance of these findings as well as the long-term outcomes of individuals with autism spectrum disorder who underwent transcranial stimulation. The objective of this review is to highlight the most recent advancements in the application of noninvasive brain modulation technology in individuals with autism spectrum disorder.

Mindful SensoriMotor Therapy combined with brain modulation for the treatment of pain in individuals with disarticulation or nerve injuries: a single-arm clinical trial

IntroductionNeuropathic pain is a complex and demanding medical condition that is often difficult to treat. Regardless of the cause, the impairment, lesion or damage to the nervous system can lead...

Effect of stimulation frequency on hippocampal electric field induced by deep-brain magnetic stimulation

Deep-brain Magnetic Stimulation (DMS) is a noninvasive brain modulation method that improves hippocampal neural activity. The frequency of DMS has a significant effect on the hippocampal induced electric field. In this paper, we investigate the relationship between stimulation frequency and DMS-induced hippocampal electric field. The frequency sensitivity and distribution uniformity of the hippocampal electric field are calculated to quantify this relationship. The results show that the DMS-induced hippocampal electric field has a frequency-dependent property. The frequency sensitivity of the DMS-induced hippocampal electric field in the high frequency band is lower than that in the low frequency band, which corresponds to the low-pass filtering property of the neuron membrane. The frequency sensitivity of DMS-induced hippocampal electric field is highest in the range of 30–40 Hz. The uniformity of the hippocampal electric field induced by a single coil also reaches the highest in the range of 30–40 Hz, while uniformity of the hippocampal electric field induced by multiple-coil increases with increasing frequency. The frequency-dependent property of the DMS-induced hippocampal electric field is positively correlated with the quantity and size of coils, while negatively correlated with the spacing of the coils. This study is of great help in the selection of DMS frequencies and the design of coils.

Asymptotic Input-Output Relationship Predicts Electric Field Effect on Sublinear Dendritic Integration of AMPA Synapses.

An extracellular electric field (EF) induces transmembrane polarizations on extremely inhomogeneous spaces. Evidence shows that EF-induced somatic polarization in pyramidal cells can modulate the neuronal input-output (I/O) function. However, it remains unclear whether and how dendritic polarization participates in the dendritic integration and contributes to the neuronal I/O function. To this end, we built a computational model of a simplified pyramidal cell with multi-dendritic tufts, one dendritic trunk, and one soma to describe the interactions among EF, dendritic integration, and somatic output, in which the EFs were modeled by inserting inhomogeneous extracellular potentials. We aimed to establish the underlying relationship between dendritic polarization and dendritic integration by analyzing the dynamics of subthreshold membrane potentials in response to AMPA synapses in the presence of constant EFs. The model-based singular perturbation analysis showed that the equilibrium mapping of a fast subsystem can serve as the asymptotic subthreshold I/O relationship for sublinear dendritic integration. This allows us to predict the tendency of EF-mediated dendritic integration by showing how EF changes modify equilibrium mapping. EF-induced hyperpolarization of distal dendrites receiving synapses inputs was found to play a key role in facilitating the AMPA receptor-evoked excitatory postsynaptic potential (EPSP) by enhancing the driving force of synaptic inputs. A significantly higher efficacy of EF modulation effect on global AMPA-type dendritic integration was found compared with local AMPA-type dendritic integration. During the generation of an action potential (AP), the relative contribution of EF-modulated dendritic integration and EF-induced somatic polarization was determined to show their collaboration in promoting or inhibiting the somatic excitability, depending on the EF polarity. These findings are crucial for understanding the EF modulation effect on neuronal computation, which provides insight into the modulation mechanism of noninvasive brain modulation.

Repetitive Transcranial Magnetic Stimulation on the Supplementary Motor Area Changes Brain Connectivity in Functional Dysphagia.

Background: Previous studies arguing that functional dysphagia could be explained by underlying neurobiological mechanisms are insufficient to explain brain regions that functionally interact in patients with functional dysphagia. Therefore, we investigated functional connectivity changes associated with functional dysphagia after applying facilitatory repetitive transcranial magnetic stimulation (rTMS) on the supplementary motor area (SMA). Materials and Methods: A patient with severe long-lasting functional dysphagia and 15 healthy controls participated in this study. A facilitatory 5 Hz rTMS protocol was applied to the patient's SMA. We performed functional magnetic resonance imaging (fMRI) using volitional swallowing tasks to investigate neural network changes before rTMS (pre-rTMS), immediately after rTMS, and 3 months later. Results: The pre-rTMS fMRI results of the patient showed extensive overactivation in the left-lateralized regions related to volitional swallowing compared with the healthy controls. Following rTMS, dysphagia symptoms partially improved. The patient showed positive connectivity with the bilateral cerebellum in the bilateral SMA seeds before rTMS treatment. Furthermore, left-lateralized overactivation was washed out immediately after completion of rTMS, and connectivity between the left SMA and left precentral gyrus recovered 3 months after rTMS treatment. Conclusion: Our findings confirm that functional dysphagia might be a neurobiological manifestation caused by maladaptive functional connectivity changes in brain structures related to swallowing. Furthermore, noninvasive brain modulation with rTMS over the SMA may facilitate functional connectivity changes between the cortical and subcortical regions. Accordingly, these changes will allow control of the movements related to swallowing and may lead to improved clinical symptoms.

Newly discovered neuron-to-glioma communication: new noninvasive therapeutic opportunities on the horizon?

The newly discovered functional integration of glioma cells into brain networks in mouse models provides groundbreaking insight into glioma aggressiveness and resistance to treatments, also suggesting novel potential therapeutic avenues and targets. In the context of such neuron-to-glioma communication, noninvasive brain modulation techniques traditionally applied to modulate neuronal function in neurological and psychiatric diseases (eg, increase/decrease cortical excitability and plasticity) could now be tested in patients with brain tumors to suppress glioma’s activity and its pathological crosstalk with healthy brain tissue.

Neural Stimulation In Vitro and In Vivo by Photoacoustic Nanotransducers

Summary Neuromodulation is an invaluable approach for the study of neural circuits and clinical treatment of neurological diseases. Here, we report semiconducting polymer nanoparticles based photoacoustic nanotransducers (PANs) for neural stimulation in vitro and in vivo. Our PANs strongly absorb the nanosecond pulsed laser in the near-infrared second window (NIR-II) and generate localized acoustic waves. PANs are shown to be surface modified and selectively bind onto neurons. PAN-mediated activation of primary neurons in vitro is achieved with ten 3-ns laser pulses at 1,030 nm over a 3-ms duration. In vivo neural modulation of mouse brain activities and motor activities is demonstrated by PANs directly injected into brain cortex. With submillimeter spatial resolution and negligible heat deposition, PAN stimulation is a new non-genetic method for precise control of neuronal activities, opening up potentials in non-invasive brain modulation.

4009 Magneto-electric nanoparticles (MENs) cobalt ferrite-barrium titanate (CoFe2O4–BaTiO3) for non-invasive neuromodulation

OBJECTIVES/GOALS: Our goal is to develop a non-invasive stimulation technique using magneto-electric nanoparticles (MENs) for inducing and enhancing neuronal activity with high spatial and temporal resolutions and minimal toxicity, which can potentially be used as a more effective approach to brain stimulation. METHODS/STUDY POPULATION: MENs compose of core-shell structures that are attracted to strong external magnetic field (~5000 Gauss) but produces electric currents with weaker magnetic field (~450 Gauss). MENs were IV treated into mice and drawn to the brain cortex with a strong magnetic field. We then stimulate MENs with a weaker magnetic field via electro magnet. With two photon calcium imaging, we investigated both the temporal and spatial effects of MENs on neuronal activity both in vivo and in vitro. We performed mesoscopic whole brain calcium imaging on awake animal to assess the MENs effects. Furthermore, we investigated the temporal profile of MENs in the vasculatures post-treatment and its toxicities to CNS. RESULTS/ANTICIPATED RESULTS: MENs were successfully localized to target cortical regions within 30 minutes of magnetic application. After wirelessly applying ~450 G magnetic field between 10-20 Hz, we observed a dramatic increase of calcium signals (i.e. neuronal excitability) both in vitro cultured neurons and in vivo treated animals. Whole brain imaging of awake mice showed a focal increase in calcium signals at the area where MENs localized and the signals spread to regions further away. We also found MENs stimulatory effects lasted up to 24 hours post treatment. MEN stimulation increases c-Fos expression but resulted in no inflammatory changes, up to one week, by assessing microglial or astrocytes activations. DISCUSSION/SIGNIFICANCE OF IMPACT: Our study shows, through controlling the applied magnetic field, MENs can be focally delivered to specific cortical regions with high efficacy and wirelessly activated neurons with high spatial and temporal resolution. This method shows promising potential to be a new non-invasive brain modulation approach disease studies and treatments.

Cathodal tDCS exerts neuroprotective effect in rat brain after acute ischemic stroke

BackgroundTranscranial direct current stimulation (tDCS) is a non-invasive brain modulation technique that has been proved to exert beneficial effects in the acute phase of stroke. To explore the underlying mechanism, we investigated the neuroprotective effects of cathodal tDCS on brain injury caused by middle cerebral artery occlusion (MCAO).ResultsWe established the MCAO model and sham MCAO model with an epicranial electrode implanted adult male Sprague–Dawley rats, and then they were randomly divided into four groups (MCAO + tDCS, MCAO + sham tDCS (Sham), Control + tDCS and Control + Sham group). In this study, the severity degree of neurological deficit, the morphology of brain damage, the apoptosis, the level of neuron-specific enolase and inflammatory factors, the activation of glial cells was detected. The results showed that cathodal tDCS significantly improved the level of neurological deficit and the brain morphology, reduced the brain damage area and apoptotic index, and increased the number of Nissl body in MCAO rats, compared with MCAO + Sham group. Meanwhile, the high level of NSE, inflammatory factors, Caspase 3 and Bax/Bcl2 ratio in MCAO rats was reduced by cathodal tDCS. Additionally, cathodal tDCS inhibited the activation of astrocyte and microglia induced by MCAO. No difference was found in two Control groups.ConclusionOur results suggested that cathodal tDCS could accelerate the recovery of neurologic deficit and brain damage caused by MCAO. The inhibition of neuroinflammation and apoptosis resulted from cathodal tDCS may be involved in the neuroprotective process.

Transcranial Ultrasound Stimulation Directly Influences the Cortical Excitability of the Motor Cortex in Parkinsonian Mice.

Low-intensity transcranial ultrasound stimulation is a new noninvasive brain modulation method with high spatial resolution and high penetration depth. However, until now, it was unclear whether transcranial ultrasound stimulation has a significant effect on PD. In order to evaluate the effect of transcranial ultrasound stimulation on PD. We used transcranial ultrasound stimulation to modulate parkinsonian-related activity in mice administered MPTP and recorded local field potentials in the motor cortex before and after ultrasound stimulation. We analyzed neuronal oscillatory activity known to be relevant to the pathophysiology of PD. After ultrasound stimulation, mean power intensity in the beta band (13-30 Hz) significantly decreased, and the phase-amplitude coupling strength between the beta and high gamma (55-100 Hz) bands and between the beta and ripple (100-200 Hz) bands also became significantly weaker. This study demonstrates that ultrasonic neuromodulation can significantly decrease parkinsonian-related activity in mice administered MPTP. © 2019 International Parkinson and Movement Disorder Society.

P303 Transcranial direct current stimulation over parietal cortex and associative memory

Background Memory enhancement is one of the most challenging issues in neurorehabilitation. Memory functions are affected by different neurological conditions as well as by normal aging. Recent data suggest that it may be possible to improve performance on some of the memory tests by physiological modulation of the activity within a neural loop which plays crucial role in formation and maintenance of the associative memory and which consists of the hippocampus and the lateral parietal cortex. Aims To check the differential effects of facilitatory and inhibitory noninvasive neuromodulation by transcranial direct current stimulation (TDCS) on associative memory. Methods Nineteen healthy right-handed participants (8 male, age 22–35) were enrolled in a cross-over placebo-controlled study. Following 20-min of either anodal (facilitatory), cathodal (inhibitory) or sham (placebo) TDCS over left lateral parietal cortex (P3 of 10–20 EEG system), in 3 separate sessions with 5–7 days inter-session intervals, participants completed a face-cued word recall test of associative memory. The test consisted of two blocks: (a) learning block, in which random words were paired with unfamiliar faces, and (b) recall block in which participants were asked to identify the target faces and recall the word previously presented together with each face. In each session, participants also completed a verbal fluency task, as a control task. Results The repeated measures ANOVA showed significant main effect of stimulation type ( F ( 2 , 36 ) = 3.71 , p = . 034 , η 2 = . 171 ). Post-hoc tests revealed that participant performed better on the associative memory task after anodal than cathodal stimulation ( p . 05 ), and the same trend was observed between anodal and sham stimulation. No difference was found between sham and cathodal stimulation. No effect of stimulation on verbal fluency task. Conclusions Noninvasive brain modulation has a potential to improve performance on tasks requiring associative memory engagement. The effect may prove to be beneficial for cognitive neurorehabilitation.

Narrative, identity and the therapeutic encounter

Summary This article explores the place of narrative in the constitution of selfhood, and through this lens examines its multifaceted role in the clinical encounter. It begins by explaining and critically evaluating the recent view advocated by Schachtman and others that narrative is wholly constitutive of the self. On this view, the role played by narrative is not merely a descriptive one, but serves more fundamentally as the ontological substrate upon which identity is invariably built and sustained. Understood as such, this capacity may distinctively modulate the meanings, motivations, and attitudes individuals adopt in reaction to and in anticipation of happenings in their lives. Acts of self-narrative can serve not only to describe meaningful facts about a person's life, but may also serve to reflexively influence the very states of affairs that they aim to describe. After assessing the theoretical attraction of this view, counter-evidence to this theory is adduced from clinical neuropsychiatric cases wherein lapses of narrative, such as those observed in dementia, dissociative identity disorder, autism and amnestic syndromes, do not entail wholesale losses of selfhood. Analyses of cases such as these reveal that there is more than narrative that is constitutive of selfhood and identity, and further raises the question of whether the absence of conveyed self-narrative ought to be interpreted as evidence of a failure of this capacity versus as evidence that an agent simply is no longer is motivated to express it. Rather than a monotonic construct, it is argued that narrative is one of a cadre of crisscrossing capacities sharing some family resemblance and with characteristically open texture that variably combine to produce selves with no single common denominator, but rather with dynamic clusters of commonalities. Six other symbiotic dimensions are identified that contribute to an intact scaffolding of selfhood, and disturbances within each of which might lead to distinctive pathologies. In particular, the capacities for self-other representation; diachronic unity; synchronic unity; consciousness (in particular, awareness); ecologic embededdness; and cognitive unity are explained and evaluated, along with pathologies that may arise in the setting of disturbances of each. It is contended that avenues of research studying the neural substrates corresponding to these different dimensions of selfhoold, as well as how these varied neuronal systems coalesce to produce a phenomenologically integrated and unified self is much needed. Further clarity with respect to these issues can shed further light on how particular brain lesions may differentially affect elaborations of selfhood. Such research could foreseeably include functional neuroimaging studies, non-invasive brain modulation (e.g., transcranial magnetic stimulation; transcranial direct current stimulation), and targeted neuropsychological testing of individuals with apparent disruptions of self stratified according to the different dimensions elucidated to aid in uncovering the enigmatic neuroanatomy and neurophysiology of selfhood. The cross-disciplinary nature of each of these avenues underscores the profound importance of deep and sustained collaborations among philosophers, ethicists, clinicians and researchers to optimize and advance approaches to the pathologies of the mind and the self. Neuroethical upshots of the account of selfhood developed are discussed, including implications for treatment of individuals with neurodegenerative conditions wherein the self itself is called into question, for the foundation and function living wills, and for approaches to pain management in individuals with disorders of consciousness. While narrative, when elicited, can provide a vital window into patient experience, lapses of narrative may be just as central to the psychoanalysis of the self and to the therapeutic encounter. What is not, and cannot be spoken, is often as vital as the narrative itself.

Feasibility of Non-invasive Brain Modulation for Management of Pain Related to Chemoradiotherapy in Patients with Advanced Head and Neck Cancer.

Patients with head and neck cancer often experience a significant decrease in their quality of life during chemoradiotherapy (CRT) due to treatment-related pain, which is frequently classified as severe. Transcranial direct current stimulation (tDCS) is a method of non-invasive brain stimulation that has been frequently used in experimental and clinical pain studies. In this pilot study, we investigated the clinical impact and central mechanisms of twenty primary motor cortex (M1) stimulation sessions with tDCS during 7 weeks of CRT for head and neck cancer. From 48 patients screened, seven met the inclusion criteria and were enrolled. Electroencephalography (EEG) data were recorded before and after tDCS stimulation as well as across the trial to monitor short and long-term impact on brain function. The compliance rate during the long trial was extremely high (98.4%), and patients mostly reported mild side effects in line with the literature (e.g., tingling). Compared to a large standard of care study from our institution, our initial results indicate that M1-tDCS stimulation has a pain relief effect during the CRT that resulted in a significant attenuation of weight reduction and dysphagia normally observed in these patients. These results translated to our patient cohort not needing feeding tubes or IV fluids. Power spectra analysis of EEG data indicated significant changes in α, β, and γ bands immediately after tDCS stimulation and, in addition, α, δ, and θ bands over the long term in the seventh stimulation week (p < 0.05). The independent component EEG clustering analysis showed estimated functional brain regions including precuneus and superior frontal gyrus (SFG) in the seventh week of tDCS stimulation. These areas colocalize with our previous positron emission tomography (PET) study where there was activation in the endogenous μ-opioid system during M1-tDCS. This study provides preliminary evidence demonstrating the feasibility and safety of M1-tDCS as a potential adjuvant neuromechanism-driven analgesic therapy for head and neck cancer patients receiving CRT, inducing immediate and long-term changes in the cortical activity and clinical measures, with minimal side-effects.

Noninvasive transcranial focused ultrasonic-magnetic stimulation for modulating brain oscillatory activity

A novel technique, transcranial focused ultrasonic-magnetic stimulation (tFUMS), has been developed for noninvasive brain modulation in vivo. tFUMS has a higher spatial resolution (<2 mm) and a higher penetration depth than other noninvasive neuromodulation methods. The in vivo animal experimental results show that tFUMS can not only increase the power of local field potentials and the firing rate of the neurons, but also enhance the effect of transcranial focused ultrasound stimulation on the neuromodulation. The results demonstrate that tFUMS can modulate brain oscillatory activities by stimulating brain tissues.

Developments of neural effects induced by noninvasive brain modulation

Noninvasive brain modulation (NBM) is such a stimulation technique that uses electric or magnetic fields to non-intrusively stimulate the central nervous system (CNS). Common NBM modalities include transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). TMS usually uses pulsed fields of 1–4 Tesla in intensity with duration less than a millisecond to stimulate brain. Such strong field is sufficient to directly evoke action potentials in relevant neural tissue, which is referred as to suprathreshold field. Unlike TMS, tDCS delivers weak constant current of 0.5–2 mA in intensity to stimulate human cortex by means of a pair of electrode pads placed on the scalp. Such weak stimulus is unable to excite neural tissue to initiate action potentials, which is referred as to subthreshold fields. Nowadays, NBM has become a promising option for the treatment, diagnosis, and rehabilitation of a number of neurologic or psychiatric disorders in clinics, such as, epilepsy, schizophrenia, Alzheimer’s disease, depression, Parkinson’s disease, stroke, as well as pain syndromes. What is more, it is also a common tool used to study brain physiology and function, which has great potentials in exploring cognitive, emotion, memory, attention, learning, perception, language, and plasticity. As a noninvasive method of intervening brain activities, the NBM technique has significantly promoted the developments of cognitive science, neurophysiology, neurology and psychiatry in recent years. Although NBM has been widely and successfully applied in clinics and basic researches, it is still largely unknown how it interacts with CNS and modulates brain function. Such insufficient understanding of the potential mechanisms underlying NBM would delay the design of more effective stimulator as well as limit the development and optimization of stimulation protocols. One common principle for NBM techniques is that they modulate neural activity and ultimately behavior through the generation of extracellular electric fields around the interested brain tissue. According to this principle, two key problems should be considered when we are probing how NBM participates in brain activity and function. One is to determine the characteristics of extracellular fields generated in the brain tissue during stimulation. The common method for addressing this problem is finite element analysis. The other one is to investigate how this induced field modulates neural activity to alter brain function and ultimately behavior. The focus of recent researches associated with this problem is to identify the spiking behaviors of neural system stimulated by electric fields as well as to explore the biophysical basis for their generation. In this paper, we first introduce the application status of NBM in neuroscience and clinics. Then, we review the main findings on the neuromodulation effects of electric field, including electrophysiological experiment and computational modeling simulation. Finally, we raise several key issues that need to be addressed in the future.

High-Definition and Non-invasive Brain Modulation of Pain andMotor Dysfunction in Chronic TMD.

Temporomandibular disorders (TMD) have a high prevalence and in many patients pain and masticatory dysfunction persist despite a range of treatments. Non-invasive brain neuromodulatory methods, namely transcranial direct current stimulation (tDCS), can provide relatively long-lasting pain relief in chronic pain patients. To define the neuromodulatory effect of five daily 2x2 motor cortex high-definition tDCS (HD-tDCS) sessions on clinical pain and motor measures in chronic TMD patients. It is predicted that M1 HD-tDCS will selectively modulate clinical measures, by showing greater analgesic after-effects compared to placebo, and active treatment will increase pain free jaw movement more than placebo. Twenty-four females with chronic myofascial TMD pain underwent five daily, 20-min sessions of active or sham 2 milliamps (mA) HD-tDCS. Measurable outcomes included pain-free mouth opening, visual analog scale (VAS), sectional sensory-discriminative pain measures tracked by a mobile application, short form of the McGill Pain Questionnaire, and the Positive and Negative Affect Schedule. Follow-up occurred at one-week and four-weeks post-treatment. There were significant improvements for clinical pain and motor measurements in the active HD-tDCS group compared to the placebo group for: responders with pain relief above 50% in the VAS at four-week follow-up (P=0.04); pain-free mouth opening at one-week follow-up (P<0.01); and sectional pain area, intensity and their sum measures contralateral to putative M1 stimulation during the treatment week (P<0.01). No changes in emotional values were shown between groups. Putative M1 stimulation by HD-tDCS selectively improved meaningful clinical sensory-discriminative pain and motor measures during stimulation, and up to four-weeks post-treatment in chronic myofascial TMD pain patients.

Transcranial direct current stimulation: From basic research on psychological processes to rehabilitation

Transcranial direct current stimulation (tDCS) is an “old/new” noninvasive brain modulation technique that has gained increasing popularity and relevance in psychology and neuroscience. The contemporary tDCS procedure is effective and painless. It was shown to modulate motor performance and several sensory and cognitive functions. It can be used to study cortical organization and clarify brain-behavior relationships. Using tDCS for rehabilitation is a promising strategy, and numerous publications suggest that it can be used alone or combined to augment the outcomes of behavioral training and pharmacological interventions. Compared with other brain modulation techniques, it has the advantage of being noninvasive and safe, with easy and effective placebo controls. Its effi cacy, low cost, and ease of use make tDCS a very convenient tool for researchers in developing countries. This review introduces tDCS to a new audience and seeks to inspire future investigations in the fi eld. We highlight work that illustrates the main concepts and applications of tDCS as a basic research and rehabilitation tool.

Exploring action potential initiation in neurons exposed to DC electric fields through dynamical analysis of conductance-based model

Noninvasive direct current (DC) electric stimulation of central nervous system is today a promising therapeutic option to alleviate the symptoms of a number of neurological disorders. Despite widespread use of this noninvasive brain modulation technique, a generalizable explanation of its biophysical basis has not been described which seriously restricts its application and development. This paper investigated the dynamical behaviors of Hodgkin’s three classes of neurons exposed to DC electric field based on a conductance-based neuron model. With phase plane and bifurcation analysis, the different responses of each class of neuron to the same stimulation are shown to derive from distinct spike initiating dynamics. Under the effects of negative DC electric field, class 1 neuron generates repetitive spike through a saddle-node on invariant circle (SNIC) bifurcation, while it ceases this repetitive behavior through a Hopf bifurcation; Class 2 neuron generates repetitive spike through a Hopf bifurcation, meanwhile it ceases this repetitive behavior also by a Hopf bifurcation; Class 3 neuron can generate single spike through a quasi-separatrix-crossing (QSC) at first, then it generates repetitive spike through a Hopf bifurcation, while it ceases this repetitive behavior through a SNIC bifurcation. Furthermore, three classes of neurons’ spiking frequency f–electric field E (f–E) curves all have parabolic shape. Our results highlight the effects of external DC electric field on neuronal activity from the biophysical modeling point of view. It can contribute to the application and development of noninvasive DC brain modulation technique.