Low Current Stimulation Research Articles

Performance and microbial community analysis on nitrate removal in a bioelectrochemical reactor.

In this experiment, we took reflux sludge, sludge from an aeration tank, and soil from roots as microbial inoculating sources for an electrochemical device for denitrification with high-throughput sequencing on cathodic biofilms. The efficiency of nitrate nitrogen removal using different microbial inoculates varied among voltages. The optimal voltages for denitrification of reflux sludge, aeration tank sludge, and root soil were 0.7V, 0.5V, and 0.5V, respectively. Further analysis revealed that the respective voltages had a significant effect upon microbial growth from the respective inoculates. Proteobacteria and Firmicutes were the main denitrifying microbes. With the addition of low current (produced by the applied voltage), the Chao1, Shannon and Simpson indexes of the diversity of microorganisms in soil inoculation sources increased, indicating that low current can increase the diversity and richness of the microorganisms, while the reflux sludge and aeration tank sludge showed different changes. Low-current stimulation decreased microbial diversity to a certain extent. Pseudomonas showed a trend of decline with increasing applied voltage, in which the MEC (microbial electrolysis cell) of rhizosphere soil as inoculates decreased most significantly from 77.05% to 12.58%, while the MEC of Fusibacter showed a significant increase, and the sludge of reflux sludge, aeration tank and rhizosphere soil increased by 31.12%, 18.7% and 34.6%, respectively. The applied voltage also significantly increased the abundance of Azoarcus in communities from the respective inoculates.

Triple‐network‐based conductive polymer hydrogel for soft and elastic bioelectronic interfaces

AbstractConductive polymer hydrogels have greatly improved the compatibility of electronic devices with biological tissues for human–machine interfacing. Hydrogels that possess low Young's modulus, low interfacial impedance, and high tensile properties facilitate high‐quality signal transmission across dynamic biointerfaces. Direct incorporation of elastomers with conductive polymers may result in undesirable mechanical and/or electrical performance. Here, a covalent cross‐linking network and an entanglement‐driven network with conductive poly(3,4‐ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) have been combined. The triple‐network conductive hydrogel shows high stretchability (with fracture strain up to 900%), low impedance (down to 91.2 Ω cm2), and reversible adhesion. Importantly, ultra‐low modulus (down to 6.3 kPa) and strain‐insensitive electrical/electrochemical performance were achieved, which provides a guarantee for low current stimulation. The material design will contribute to the progression of soft and conformal bioelectronic devices, and pave the way to future implantable electronics.

Controlled activation of cortical astrocytes modulates neuropathic pain-like behaviour

Chronic pain is a major public health problem that currently lacks effective treatment options. Here, a method that can modulate chronic pain-like behaviour induced by nerve injury in mice is described. By combining a transient nerve block to inhibit noxious afferent input from injured peripheral nerves, with concurrent activation of astrocytes in the somatosensory cortex (S1) by either low intensity transcranial direct current stimulation (tDCS) or via the chemogenetic DREADD system, we could reverse allodynia-like behaviour previously established by partial sciatic nerve ligation (PSL). Such activation of astrocytes initiated spine plasticity to reduce those synapses formed shortly after PSL. This reversal from allodynia-like behaviour persisted well beyond the active treatment period. Thus, our study demonstrates a robust and potentially translational approach for modulating pain, that capitalizes on the interplay between noxious afferents, sensitized central neuronal circuits, and astrocyte-activation induced synaptic plasticity.

Endothelial and Autonomic Assessments in the Management of COVID-19

Background: The goal of this peer review is to outline the benefits of the TM Flow system and Lifeprobes Kiosk assessing the endothelial and autonomic system functions in the management of COVID-19 for triage of the patients at risk and diagnostic of autonomic nervous system dysfunction to understand the long COVID symptoms. Material and Methods: The TM Flow system is a non-invasive medical device that relies on pulse oximetry, blood pressure measurements, and very low electrical current stimulation of the skin via disposable electrodes to provide instantaneous assessments of patients’ vital signs, endothelial function, sudomotor and autonomic nervous system functions, and ankle brachial index measurements. The Lifeprobes Kiosk performs automated pre-consultation patient assessments via an online patient check-in form and medical questionnaire, as well as determines the patient’s vital signs, endothelial function markers and estimated body composition. COVID-19: Current Scientific Data: In the majority of cases, COVID-19 infection will manifest through mild to moderate symptoms (such as cough, runny nose, sore throat, headache, muscle aches, and fever) which would resolve without the need for special treatment or hospitalization. On the other hand, older individuals and those who suffer from underlying medical conditions—such as obesity, diabetes, cardiovascular disease, chronic respiratory disease, and/or cancer—are more susceptible to developing serious illness, often with a fatal outcome. Available evidence further indicates that COVID-19 vaccines reduce the number of new cases, while also lessening the risk of complications that would require hospitalization. However, these findings do not apply to the new delta variant, which leads to more severe complications in younger people than previous variants, even in those who have been vaccinated and/or do not have any underlying medical problems. Research conducted to date indicates that COVID-19 complications result from endothelial dysfunction or damage. In addition, COVID-19 patients are increasingly reporting a wide range of debilitating conditions long after they have tested negative for the presence of the virus, giving rise to the term “Long COVID” which has been attributed to autonomic nervous system dysfunction and small fiber neuropathy. TM Flow markers have been investigated by several clinical studies in the US, India, and Brazil. The clinical studies showed the relevance of the TM Flow endothelial and autonomic nervous markers. Conclusion: Findings yielded by peer-reviewed clinical studies confirm that the TM Flow system and Lifeprobes Kiosk are beneficial and effective non-invasive tools that provide immediate results. Therefore, both should be employed for the triage of COVID-19 patients to expediently identify those at risk of complications, as this would reduce the hospitalization and mortality rates. The TM Flow system is also capable of diagnosing “Long COVID” symptoms related to the autonomic nervous system and small fiber neuropathy.

Ultra-low frequency-transcutaneous electric nerve stimulation for functional border molding and cameo surface recording for enhanced complete denture success: A novel approach

Ultra-low frequency transcutaneous electric nerve stimulation (ULF-TENS) is one of the therapeutic devices used for relaxation of orofacial musculature by the use of low frequency, low current stimulation of the certain branches of trigeminal and facial nerve. Complete denture fabrication is the most widely used modality for rehabilitation of completely edentulous maxillary and mandibular arches. Numerous efforts and techniques have been introduced to improve retention and stability of prosthesis, in order to improve form, function, esthetics, phonetics, and health of the patient. These include modifications in impression making and cameo surface recording to improve the adaptation of the prosthesis. Accurate tracing of functional borders during border molding and recording cameo surface of the prosthesis using ULF-TENS in patients with poor neuromuscular incoordination can play an important role in improving the stability and enhance the performance of the masticatory system. This clinical report describes recording of border molding and cameo surface using ULF-TENS in a completely edentulous patient, resulting in enhanced adaptation with adjacent stomatognathic system.

Values encoded in orbitofrontal cortex are causally related to economic choices.

In the eighteenth century, Daniel Bernoulli, Adam Smith and Jeremy Bentham proposed that economic choices rely on the computation and comparison of subjective values1. This hypothesis continues to inform modern economic theory2 and research in behavioural economics3, but behavioural measures are ultimately not sufficient to verify the proposal4. Consistent with the hypothesis, when agents make choices, neurons in the orbitofrontal cortex (OFC) encode the subjective value of offered and chosen goods5. Value-encoding cells integrate multiple dimensions6-9, variability in the activity of each cell group correlates with variability in choices10,11 and the population dynamics suggests the formation of a decision12. However, it is unclear whether these neural processes are causally related to choices. More generally, the evidence linking economic choices to value signals in the brain13-15 remains correlational16. Here we show that neuronal activity in the OFC is causal to economic choices. We conducted two experiments using electrical stimulation in rhesus monkeys (Macaca mulatta). Low-current stimulation increased the subjective value of individual offers and thus predictably biased choices. Conversely, high-current stimulation disrupted both the computation and the comparison of subjective values, and thus increased choice variability. These results demonstrate a causal chain linking subjective values encoded in OFC to valuation and choice.

Problems with the continued proliferation of unsubstantiated psychophysiological techniques being promulgated and sold for clinical use

This journal is dedicated to publishing studies and reviews which assist our readers to recognize psychophysiological techniques, assessments, and interventions likely to be useful in a wide range of situations. Sadly, this includes informing readers when psychophysiological techniques are being promulgated and sold without sufficient evidence to support their claims of efficacy. This is crucially important because it is all too easy for most of us to mistake sales pitches supposedly supported by poor and non-existent research, testimonials, and the like for actual evidence of efficacy. Thus, readers can’t easily determine whether the technique in question has sufficient support to warrant its use. The journal will begin publishing thorough reviews of such techniques in the next few issues beginning with a review of low current and audiovisual stimulation techniques. An example of a technique which may well be effective but is being promulgated with claims far beyond the research demonstrating its efficacy is the LENS system currently being sold to treat a wide variety of clinical problems.
 This journal is dedicated to publishing studies and reviews which assist our readers to recognize psychophysiological techniques, assessments, and interventions likely to be useful in a wide range of situations. Sadly, this includes informing readers when psychophysiological techniques are being promulgated and sold without sufficient evidence to support their claims of efficacy. This is crucially important because it is all too easy for most of us to mistake sales pitches supposedly supported by poor and non-existent research, testimonials, and the like for actual evidence of efficacy. Thus, readers can’t easily determine whether the technique in question has sufficient support to warrant its use. The journal will begin publishing thorough reviews of such techniques in the next few issues beginning with a review of low current and audiovisual stimulation techniques. An example of a technique which may well be effective but is being promulgated with claims far beyond the research demonstrating its efficacy is the LENS system currently being sold to treat a wide variety of clinical problems.

Randomized Controlled Study Evaluating Efficiency of Low Intensity Transcranial Direct Current Stimulation (tDCS) for Dyspnea Relief in Mechanically Ventilated COVID-19 Patients in ICU: The tDCS-DYSP-COVID Protocol.

The severe respiratory distress syndrome linked to the new coronavirus disease (COVID-19) includes unbearable dyspneic suffering which contributes to the deterioration of the prognosis of patients in intensive care unit (ICU). Patients are put on mechanical ventilation to reduce respiratory suffering and preserve life. Despite this mechanical ventilation, most patients continue to suffer from dyspnea. Dyspnea is a major source of suffering in intensive care and one of the main factors that affect the prognosis of patients. The development of innovative methods for its management, especially non-drug management is more than necessary. In recent years, numerous studies have shown that transcranial direct current stimulation (tDCS) could modulate the perception of acute or chronic pain. In the other hand, it has been shown that the brain zones activated during pain and dyspnea are close and/or superimposed, suggesting that brain structures involved in the integration of aversive emotional component are shared by these two complex sensory experiences. Therefore, it can be hypothesized that stimulation by tDCS with regard to the areas which, in the case of pain have activated one or more of these brain structures, may also have an effect on dyspnea. In addition, our team recently demonstrated that the application of tDCS on the primary cortical motor area can modulate the excitability of the respiratory neurological pathways. Indeed, tDCS in anodal or cathodal modality reduced the excitability of the diaphragmatic cortico-spinal pathways in healthy subjects. We therefore hypothesized that tDCS could relieve dyspnea in COVID-19 patients under mechanical ventilation in ICU. This study was designed to evaluate effects of two modalities of tDCS (anodal and cathodal) vs. placebo, on the relief of dyspnea in COVID-19 patients requiring mechanical ventilation in ICU.Trial Registration: This protocol is derived from the tDCS-DYSP-REA project registered on ClinicalTrials.gov NCT03640455. It will however be registered under its own NCT number.

Low-intensity current (LIC) stimulation of subcutaneous adipose derived stem cells (ADSCs) – A missing link in the course of LIC based wound healing

Millions of people die as a result of fatal injuries accounting for 9% of the total global annual deaths. Non fatal injuries generally result in variety of wounds. The normal wound healing process is slow and takes weeks to months, depending on the type of wound. In last two decades, electrotherapy called low-intensity currents (LIC) for the treatment became popular for faster wound healing, as well as in management of nonresponding and ulcerative wounds. It was reported that LIC mimics 'the current of injury' which is generated by body on wounding and helps in faster wound healing. Researchers have also studied the migration of localized cell and other bio-molecules under the influence of LIC helping the wound to heal faster. Literature review has also suggested that, electrical stimulation of isolated adipose tissue derived stem cells (ADSCs) releases growth factors and differentiates in to specialized cells like fibroblasts and keratinocytes in laboratory conditions. These research areas are well explored and emerged as independent state-of-the-arts therapies and technologies.Considering the fact, that adipose tissue (along with ADSCs) is present subcutaneously, a new hypothesis is proposed which states that 'low intensity current (LIC) stimulation of wound stimulates subcutaneous adipose tissue containing ADSCs which releases different growth factors and also differentiates into certain cells like fibroblasts, neurons and keratinocytes. These cells easily migrate to wound site due to lipolysis and loosening of fat tissue, resulting in faster wound healing'. Thus this hypothesis provides a missing link between two state of the art technologies; first one is 'LIC based electrotherapy' and second one is 'in-vitro LIC stimulation of ADCSs' where role and significance of in-situ ADCSs were never studied.

Pre-treatment attentional processing speed and antidepressant response to transcranial direct current stimulation: Results from an international randomized controlled trial

BackgroundTranscranial direct current stimulation (tDCS) has promising antidepressant effects, however, clinical trials have shown variable efficacy. Pre-treatment neurocognitive functioning has previously been identified as an inter-individual predictor of tDCS antidepressant efficacy. ObjectiveIn this international multicentre, sham-controlled study, we investigated this relationship while also assessing the influence of clinical and genotype (BDNF Val66Met and COMT Val158Met polymorphisms) factors as predictors of response to active tDCS. MethodsThe study was a triple-masked, parallel, randomized, controlled design across 6 international academic medical centers. Participants were randomized to active (2.5 mA) or sham (34 μA) tDCS for 30 min each session for 20 sessions. The anode was centered over the left dorsolateral prefrontal cortex at F3 (10/20 EEG system) and the cathode over the lateral right frontal area at F8. ResultsBetter pre-treatment attentional processing speed on the Ruff 2 & 7 Selective Attention Test (Total Speed: β = 0.25, p < .05) and concurrent antidepressant medication use (β = 0.31, p < .05) predicted antidepressant efficacy with active tDCS. Genotype differences in the BDNF Val66Metand COMT Val158Met polymorphisms were not associated with antidepressant effects. Secondary analyses revealed that only participants in the highest performing Ruff 2 & 7 Total Speed group at pre-treatment in both active and sham tDCS conditions showed significantly greater antidepressant response compared to those with lower performance at both the 2 and 4 week treatment time points (p < .05). ConclusionsThese results suggest that high pre-treatment attentional processing speed may be relevant for identifying participants more likely to show better tDCS antidepressant response to both high (2.5 mA) and very low (34 μA) current intensity stimulation. Clinical trials registrationwww.clinicaltrials.gov, NCT01562184.

Chronic Electrical Stimulation Promotes the Excitability and Plasticity of ESC-derived Neurons following Glutamate-induced Inhibition In vitro

Functional electrical stimulation (FES) is rapidly gaining traction as a therapeutic tool for mediating the repair and recovery of the injured central nervous system (CNS). However, the underlying mechanisms and impact of these stimulation paradigms at a molecular, cellular and network level remain largely unknown. In this study, we used embryonic stem cell (ESC)-derived neuron and glial co-cultures to investigate network maturation following acute administration of L-glutamate, which is a known mediator of excitotoxicity following CNS injury. We then modulated network maturation using chronic low frequency stimulation (LFS) and direct current stimulation (DCS) protocols. We demonstrated that L-glutamate impaired the rate of maturation of ESC-derived neurons and glia immediately and over a week following acute treatment. The administration of chronic LFS and DCS protocols individually following L-glutamate infusion significantly promoted the excitability of neurons as well as network synchrony, while the combination of LFS/DCS did not. qRT-PCR analysis revealed that LFS and DCS alone significantly up-regulated the expression of excitability and plasticity-related transcripts encoding N-methyl-D-aspartate (NMDA) receptor subunit (NR2A), brain-derived neurotrophic factor (BDNF) and Ras-related protein (RAB3A). In contrast, the simultaneous administration of LFS/DCS down-regulated BDNF and RAB3A expression. Our results demonstrate that LFS and DCS stimulation can modulate network maturation excitability and synchrony following the acute administration of an inhibitory dose of L-glutamate, and upregulate NR2A, BDNF and RAB3A gene expression. Our study also provides a novel framework for investigating the effects of electrical stimulation on neuronal responses and network formation and repair after traumatic brain injury.

Electrical Stimulation of Afferent Pathways for the Suppression of Pathological Tremor.

Pathological tremors are involuntary oscillatory movements which cannot be fully attenuated using conventional treatments. For this reason, several studies have investigated the use of neuromuscular electrical stimulation for tremor suppression. In a recent study, however, we found that electrical stimulation below the motor threshold also suppressed tremor, indicating involvement of afferent pathways. In this study, we further explored this possibility by systematically investigating how tremor suppression by afferent stimulation depends on the stimulation settings. In this way, we aimed at identifying the optimal stimulation strategy, as well as to elucidate the underlying physiological mechanisms of tremor suppression. Stimulation strategies varying the stimulation intensity and pulse timing were tested in nine tremor patients using either intramuscular or surface stimulation. Significant tremor suppression was observed in six patients (tremor suppression > 75% was observed in three patients) and the average optimal suppression level observed across all subjects was 52%. The efficiency for each stimulation setting, however, varied substantially across patients and it was not possible to identify a single set of stimulation parameters that yielded positive results in all patients. For example, tremor suppression was achieved both with stimulation delivered in an out-of-phase pattern with respect to the tremor, and with random timing of the stimulation. Overall, these results indicate that low-current stimulation of afferent fibers is a promising approach for tremor suppression, but that further research is required to identify how the effect can be maximized in the individual patient.

Effect of Muscle Length on Fatigue Induced by Low Frequency Current Stimulation in Human Medial Gastrocnemius Muscle

Effect of Muscle Length on Fatigue Induced by Low Frequency Current Stimulation in Human Medial Gastrocnemius Muscle

Enhancing statistical calculation with transcranial direct current stimulation (tDCS) to the left intra-parietal sulcus (IPS)

Researchers have focused only minimally on cognitive enhancement using low current brain stimulation, transcranial direct current stimulation (tDCS), in attempting to improve math performance. In this study we administered the low current brain stimulation followed by instruction.Thirty-two participants completed the study, the participants were randomly assigned to one of three groups: control, 1mA, or 2mA. The experimental group participants received low current brain stimulation, tDCS for 20min. After administration of the tDCS each group viewed an instructional video showing calculations for a non-parametric statistics, Kruskal–Wallis. Upon completion of viewing the video participants completed calculation of a problem requiring using a Kruskal–Wallis. We found that both experimental groups performed significantly better than the control group on calculating the statistic, Kruskal–Wallis. We used time spent completing the calculation as a covariate. The use of low current brain stimulation combined with instruction show promise in enhancing math/statistics performance.

Asynchronous recruitment of low-threshold motor units during repetitive, low-current stimulation of the human tibial nerve.

Motoneurons receive a barrage of inputs from descending and reflex pathways. Much of our understanding about how these inputs are transformed into motor output in humans has come from recordings of single motor units during voluntary contractions. This approach, however, is limited because the input is ill-defined. Herein, we quantify the discharge of soleus motor units in response to well-defined trains of afferent input delivered at physiologically-relevant frequencies. Constant frequency stimulation of the tibial nerve (10–100 Hz for 30 s), below threshold for eliciting M-waves or H-reflexes with a single pulse, recruited motor units in 7/9 subjects. All 25 motor units recruited during stimulation were also recruited during weak (<10% MVC) voluntary contractions. Higher frequencies recruited more units (n = 3/25 at 10 Hz; n = 25/25 at 100 Hz) at shorter latencies (19.4 ± 9.4 s at 10 Hz; 4.1 ± 4.0 s at 100 Hz) than lower frequencies. When a second unit was recruited, the discharge of the already active unit did not change, suggesting that recruitment was not due to increased synaptic drive. After recruitment, mean discharge rate during stimulation at 20 Hz (7.8 Hz) was lower than during 30 Hz (8.6 Hz) and 40 Hz (8.4 Hz) stimulation. Discharge was largely asynchronous from the stimulus pulses with “time-locked” discharge occurring at an H-reflex latency with only a 24% probability. Motor units continued to discharge after cessation of the stimulation in 89% of trials, although at a lower rate (5.8 Hz) than during the stimulation (7.9 Hz). This work supports the idea that the afferent volley evoked by repetitive stimulation recruits motor units through the integration of synaptic drive and intrinsic properties of motoneurons, resulting in “physiological” recruitment which adheres to Henneman’s size principle and results in relatively low discharge rates and asynchronous firing.

Induction of self awareness in dreams through frontal low current stimulation of gamma activity.

Recent findings link fronto-temporal gamma electroencephalographic (EEG) activity to conscious awareness in dreams, but a causal relationship has not yet been established. We found that current stimulation in the lower gamma band during REM sleep influences ongoing brain activity and induces self-reflective awareness in dreams. Other stimulation frequencies were not effective, suggesting that higher order consciousness is indeed related to synchronous oscillations around 25 and 40 Hz.

Transcranial direct current stimulation of the frontal-parietal-temporal area attenuates smoking behavior

Many brain regions are involved in smoking addiction (e.g. insula, ventral tegmental area, prefrontal cortex and hippocampus), and the manipulation of the activity of these brain regions can show a modification of smoking behavior. Low current transcranial direct current stimulation (tDCS) is a noninvasive way to manipulate cortical excitability, and thus brain function and associated behaviors. In this study, we examined the effects of inhibiting the frontal-parietal-temporal association area (FPT) on attention bias to smoking-related cues and smoking behavior in tobacco users. This inhibition is induced by cathodal tDCS stimulation. We tested three stimulation conditions: 1) bilateral cathodal over both sides of FPT; 2) cathodal over right FPT; and 3) sham-tDCS. Visual attention bias to smoking-related cues was evaluated using an eye tracking system. The measurement for smoking behavior was the number of daily cigarettes consumed before and after tDCS treatment. We found that, after bilateral cathodal stimulation of the FPT area, while the attention to smoking-related cues showed a decreased trend, the effects were not significantly different from sham stimulation. The daily cigarette consumption was reduced to a significant level. These effects were not seen under single cathodal tDCS or sham-tDCS. Our results show that low current tDCS of FPT area attenuates smoking cue-related attention and smoking behavior. This non-invasive brain stimulation technique, targeted at FPT areas, might be a promising method for treating smoking behavior.

Spike Synchronization in Hippocampal Cultures Using Hebbian Learning

Event Abstract Back to Event Spike Synchronization in Hippocampal Cultures Using Hebbian Learning Víctor Lorente Sánchez1*, Jose Manuel Ferrández Vicente1, Felix De La Paz2 and Eduardo Fernández3 1 Universidad Politécnica de Cartagena, Spain 2 UNED, Departamento de Inteligencia Artificial, Spain 3 Universidad Miguel Hernández, Instituto de Bioingeniería, Spain The use of dissociated cortical neurons cultured onto microelectrode arrays represents a useful experimental model to characterize both the spontaneous behaviour of neuronal populations and their activity in response to electrical and pharmacological changes. Learning is a natural process that needs the creation and modulation of sets of associations between stimuli and responses. Many different stimulation protocols have been used to induced changes in the electrophysiological activity of neural cultures looking for achieve learning [1-11] and low-frequency stimulation has brought good results to researchers enhancing bursting activity in cortical cultures [8,9]. Hebbian learning describes a basic mechanism for synaptic plasticity wherein an increase in synaptic efficacy arises from the presynaptic cell's repeated and persistent stimulation of the postsynaptic cell. The theory is commonly evoked to explain some types of associative learning in which simultaneous activation of cells leads to pronounced increases in synaptic strength. Basically the efficiency of a synaptic connection is increased when presynaptic activity is synchronous with post-synaptic activity. In this work, we use different stimulation protocols following Hebb’s Law to create adjacent physical or logical connections between adjacent electrodes in the connectivity graphs. The connected electrodes show synchronized activity before and after a new stimulation is applied. Dissociated cultures of hippocampal CA1-CA3 neurons were prepared from E17.5 sibling embryos. Microelectrode arrays (Multichannel systems, MCS) consisted of 60 TiN/SiN planar round electrodes (200 μm electrode spacing, 30 μm electrode diameter) arrange in a 8x8 grid were used. A total of 24 cultures were used in five experiments of 2-3 weeks duration. In every experiment 4-5 cultures were stimulated with a specific electrical stimulation protocol. Low frequency current stimulation and tetanization voltage stimulation were the main protocols used in this study. Experiments were started when neural cultures had 14 Days in Vitro (DIV) and were carried out during 2-3 weeks. In every experiment, the electrophysiological activity of the cultures was previously analysed and connectivity diagrams based on cross-correlation were obtained for each culture. Two pairs of electrodes with an acceptable spiking activity and no logical connections between them were selected for stimulation. Low-frequency current stimulation and tetanic stimulation had both an impact on the electrophysiological responses of the cultures. Raster plots showed that all of the stimulations provided induce changes in the firing frequency of the cultures. Instantaneous firing frequency graphs shows that stimulated electrodes start firing in more separated period of times after stimulation but each firing period last longer. In addition, interspike intervals show the same results observed in the spiking periods but also it can be seen analytically the ISI decrease both in value and dispersion. Both effects are related to the neural stimulation, which modulates the firing capabilities of the cultures. Connectivity diagrams based on cross-correlation between electrodes showed some kind of connections reorganization after stimulations, concentrating them in a few electrodes. Furthermore, adjacent physical or logical connections in the connectivity graph following Hebb’s law appeared in some pairs of stimulated electrodes. Electrodes with created connections between them can distinctly be detected with the instantaneous firing frequencies graphs (Figure 1). The firing periods of the electrodes from the connected pairs follow exactly each other, whereas the firing periods of the not connected pairs of electrodes do not match. Furthermore, the electrodes of connected pairs change both the firing periods after stimulation. This features indicates that there exits a strong connection between them. Low-frequency stimulation induces permanent changes in most experiments using different values of current amplitude and stimulation patterns. Persistent and synchronous stimulation of relevant adjacent electrodes may be used for strengthen the efficiency of their connectivity graph. These processes may be used for imposing a desired behaviour over the network dynamics. Figure 1 Acknowledgements This work is being funded by grant 12361/FPI/09 from Séneca Foundation, Science and Technology Agency from the region of Murcia and by the project 2010V/PUNED/0011 from Universidad Nacional de Educación a Distancia.

Time-course changes in motor cortical excitability following low level constant transcranial direct current stimulation

Time-course changes in motor cortical excitability following low level constant transcranial direct current stimulation

Investigating the Neurophysiological Effects of Direct Current Stimulation (IN6-1.005)

Objective: To create a mouse model of direct current stimulation. Background Although transcranial direct current stimulation (tDCS) and deep brain stimulation(DBS) are currently being used as investigative tools in neuroscience and as potential therapies for a variety of neurological conditions, their neurophysiologic mechanisms remain poorly understood. Importantly, no animal studies to date have directly measured physiological changes associated with direct, low-current brain stimulation. Design/Methods: Twenty-four mice were assigned to anodal, cathodal, and sham groups and were implanted with electrodes in left auditory cortex. Mice underwent direct current stimulation for 20min at 20microAmps. Auditory evoked potentials were recorded pre-stimulation, 1hr, 1wk, and 2wk post-stimulation. EEG was analyzed for amplitude/latency of P1, N1, and P2 signals. We assessed EEG power and intertrial coherence using event-related spectral perturbations. Results: In the anodal condition there was significant reduction in delta, theta, and alpha power that persisted through the two-week timepoint. In the cathodal condition there was significant reduction in delta that persisted through the one-week timepoint and reduction in theta and alpha power observed only at the one-hour timepoint (all p values Conclusions: Observed reductions in low frequency power bands after direct current stimulation were consistent with recent clinical studies using tDCS and extracranial EEG recordings (Keeser et al., 2010). In humans, attenuation of low frequency power may be associated with improved cognitive function and increased BOLD signal changes (Hlinka et al., 2010). Our approach may thus provide a means examine the use of direct current stimulation relevant to tDCS and DBS to improve brain function in animal models. Supported by: Summer Research Scholarship, American Academy of Neurology, 2011 and T32 Brain Injury Training Grant, NINDS, 2011. Disclosure: Dr. Rojas has nothing to disclose. Dr. Hamilton has nothing to disclose. Dr. Luminais has nothing to disclose. Dr. Siegel has nothing to disclose.