Transcranial Alternating Current Stimulation Research Articles

Non-Invasive Systems Application in Traumatic Brain Injury Rehabilitation.

Traumatic brain injury (TBI) is a significant public health concern, often leading to long-lasting impairments in cognitive, motor and sensory functions. The rapid development of non-invasive systems has revolutionized the field of TBI rehabilitation by offering modern and effective interventions. This narrative review explores the application of non-invasive technologies, including electroencephalography (EEG), quantitative electroencephalography (qEEG), brain-computer interface (BCI), eye tracking, near-infrared spectroscopy (NIRS), functional near-infrared spectroscopy (fNIRS), magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG), and transcranial magnetic stimulation (TMS) in assessing TBI consequences, and repetitive transcranial magnetic stimulation (rTMS), low-level laser therapy (LLLT), neurofeedback, transcranial direct current stimulation (tDCS), transcranial alternative current stimulation (tACS) and virtual reality (VR) as therapeutic approaches for TBI rehabilitation. In pursuit of advancing TBI rehabilitation, this narrative review highlights the promising potential of non-invasive technologies. We emphasize the need for future research and clinical trials to elucidate their mechanisms of action, refine treatment protocols, and ensure their widespread adoption in TBI rehabilitation settings.

On closed-loop brain stimulation systems for improving the quality of life of patients with neurological disorders.

Emerging brain technologies have significantly transformed human life in recent decades. For instance, the closed-loop brain-computer interface (BCI) is an advanced software-hardware system that interprets electrical signals from neurons, allowing communication with and control of the environment. The system then transmits these signals as controlled commands and provides feedback to the brain to execute specific tasks. This paper analyzes and presents the latest research on closed-loop BCI that utilizes electric/magnetic stimulation, optogenetic, and sonogenetic techniques. These techniques have demonstrated great potential in improving the quality of life for patients suffering from neurodegenerative or psychiatric diseases. We provide a comprehensive and systematic review of research on the modalities of closed-loop BCI in recent decades. To achieve this, the authors used a set of defined criteria to shortlist studies from well-known research databases into categories of brain stimulation techniques. These categories include deep brain stimulation, transcranial magnetic stimulation, transcranial direct-current stimulation, transcranial alternating-current stimulation, and optogenetics. These techniques have been useful in treating a wide range of disorders, such as Alzheimer's and Parkinson's disease, dementia, and depression. In total, 76 studies were shortlisted and analyzed to illustrate how closed-loop BCI can considerably improve, enhance, and restore specific brain functions. The analysis revealed that literature in the area has not adequately covered closed-loop BCI in the context of cognitive neural prosthetics and implanted neural devices. However, the authors demonstrate that the applications of closed-loop BCI are highly beneficial, and the technology is continually evolving to improve the lives of individuals with various ailments, including those with sensory-motor issues or cognitive deficiencies. By utilizing emerging techniques of stimulation, closed-loop BCI can safely improve patients' cognitive and affective skills, resulting in better healthcare outcomes.

Standard intensities of transcranial alternating current stimulation over the motor cortex do not entrain corticospinal inputs to motor neurons.

Transcranial alternating current stimulation (TACS) is commonly used to synchronize a cortical area and its outputs to the stimulus waveform, but gathering evidence for this based on brain recordings in humans is challenging. The corticospinal tract transmits beta oscillations (∼21Hz) from the motor cortex to tonically contracted limb muscles linearly. Therefore, muscle activity may be used to measure the level of beta entrainment in the corticospinal tract due to TACS over the motor cortex. Here, we assessed whether TACS is able to modulate the neural inputs to muscles, which would provide indirect evidence for TACS-driven neural entrainment. In the first part of the study, we ran simulations of motor neuron (MN) pools receiving inputs from corticospinal neurons with different levels of beta entrainment. Results suggest that MNs are highly sensitive to changes in corticospinal beta activity. Then, we ran experiments on healthy human subjects (N=10) in which TACS (at 1mA) was delivered over the motor cortex at 21Hz (beta stimulation), or at 7Hz or 40Hz (control conditions) while the abductor digiti minimi or the tibialis anterior muscle were tonically contracted. Muscle activity was measured using high-density electromyography, which allowed us to decompose the activity of pools of motor units innervating the muscles. By analysing motor unit pool activity, we observed that none of the TACS conditions could consistently alter the spectral contents of the common neural inputs received by the muscles. These results suggest that 1mA TACS over the motor cortex given at beta frequencies does not entrain corticospinal activity. KEY POINTS: Transcranial alternating current stimulation (TACS) is commonly used to entrain the communication between brain regions. It is challenging to find direct evidence supporting TACS-driven neural entrainment due to the technical difficulties in recording brain activity during stimulation. Computational simulations of motor neuron pools receiving common inputs in the beta (∼21Hz) band indicate that motor neurons are highly sensitive to corticospinal beta entrainment. Motor unit activity from human muscles does not support TACS-driven corticospinal entrainment.

Phase-locked transcranial electrical brain stimulation for tremor suppression in dystonic tremor syndromes

ObjectiveTo establish the causal role of the cerebellum and motor cortex in dystonic tremor syndromes, and explore the therapeutic efficacy of phase-locked transcranial alternating current stimulation (TACS). MethodsWe applied phase-locked TACS over the ipsilateral cerebellum (N = 14) and contralateral motor cortex (N = 17) in dystonic tremor syndrome patients, while patients assumed a tremor-evoking posture. We measured tremor power using accelerometery during 30 s stimulation periods at 10 different phase-lags (36-degrees increments) between tremor and TACS for each target. Post-hoc, TACS-effects were related to a key clinical feature: the jerkiness (regularity) of tremor. ResultsCerebellar TACS modulated tremor amplitude in a phase-dependent manner, such that tremor amplitude was suppressed or enhanced at opposite sides of the phase-cycle. This effect was specific for patients with non-jerky (sinusoidal) tremor (n = 10), but absent in patients with jerky (irregular) tremor (n = 4). Phase-locked stimulation over the motor cortex did not modulate tremor amplitude. ConclusionsThis study indicates that the cerebellum plays a causal role in the generation of (non-jerky) dystonic tremor syndrome. Our findings suggest pathophysiologic heterogeneity between patients with dystonic tremor syndrome, which mirrors clinical variability. SignificanceWe show tremor phenotype dependent involvement of the cerebellum in dystonic tremor syndrome. Tremor phenotype may thus guide optimal intervention targets.

Midfrontal Theta Transcranial Alternating Current Stimulation Facilitates Motor Coordination in Dyadic Human-Avatar Interactions.

Synchronous interpersonal motor interactions require moment-to-moment prediction and proactive monitoring of the partner's actions. Neurophysiologically, this is highlighted by an enhancement of midfrontal theta (4-7 Hz) oscillations. In this study, we explored the causal role of midfrontal theta for interpersonal motor interactions using transcranial alternating current stimulation (tACS). We implemented a realistic human-avatar interaction task in immersive virtual reality where participants controlled a virtual arm and hand to press a button synchronously with a virtual partner. Participants completed the task while receiving EEG-informed theta (Experiment 1) or beta (control frequency, Experiment 2) tACS over the frontal midline, as well as sham stimulation as a control. Results showed that midfrontal theta tACS significantly improved behavioral performance (i.e., reduced interpersonal asynchrony) and participants' motor strategies (i.e., increased movement times and reduced RTs), whereas beta tACS had no effect on these measures. These results suggest that theta tACS over frontal areas facilitates action monitoring and motor abilities supporting interpersonal interactions.

Working Memory and Transcranial-Alternating Current Stimulation-State of the Art: Findings, Missing, and Challenges.

Working memory (WM) is a cognitive process that involves maintaining and manipulating information for a short period of time. WM is central to many cognitive processes and declines rapidly with age. Deficits in WM are seen in older adults and in patients with dementia, schizophrenia, major depression, mild cognitive impairment, Alzheimer’s disease, etc. The frontal, parietal, and occipital cortices are significantly involved in WM processing and all brain oscillations are implicated in tackling WM tasks, particularly theta and gamma bands. The theta/gamma neural code hypothesis assumes that retained memory items are recorded via theta-nested gamma cycles. Neuronal oscillations can be manipulated by sensory, invasive- and non-invasive brain stimulations. Transcranial alternating-current stimulation (tACS) and repetitive transcranial magnetic stimulation (rTMS) are frequency-tuned non-invasive brain stimulation (NIBS) techniques that have been used to entrain endogenous oscillations in a frequency-specific manner. Compared to rTMS, tACS demonstrates superior cost, tolerability, portability, and safety profile, making it an attractive potential tool for improving cognitive performance. Although cognitive research with tACS is still in its infancy compared to rTMS, a number of studies have shown a promising WM enhancement effect, especially in the elderly and patients with cognitive deficits. This review focuses on the various methods and outcomes of tACS on WM in healthy and unhealthy human adults and highlights the established findings, unknowns, challenges, and perspectives important for translating laboratory tACS into realistic clinical settings. This will allow researchers to identify gaps in the literature and develop frequency-tuned tACS protocols with promising safety and efficacy outcomes. Therefore, research efforts in this direction should help to consider frequency-tuned tACS as a non-pharmacological tool of cognitive rehabilitation in physiological aging and patients with cognitive deficits.

Transcranial alternating current stimulation and its effects on cognition and the treatment of psychiatric disorders: a systematic review and meta-analysis.

Transcranial alternating current stimulation (TACS) is a non-invasive method of brain stimulation that is hypothesised to alter cortical excitability and brain electrical activity, modulating functional connectivity within the brain. Several trials have demonstrated its potential in treating psychiatric disorders such as depression and schizophrenia. To study the efficacy of TACS in ameliorating symptoms of depression and schizophrenia in patients and its effects on cognition in patients and healthy subjects compared to sham stimulation. Systematic review with meta-analysis. This PROSPERO-registered systematic review (CRD42022331149) is reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, EMBASE, CENTRAL and PsycINFO were searched from inception to March 2022. Only randomised-controlled trials were included. A total of 12 randomised-controlled trials are reviewed for meta-analysis, with three randomised-controlled trials reporting only effects on cognition in psychiatric and cognitively impaired patients, three trials on cognition in healthy subjects, one trial on cognition in both patients and healthy subjects, one trial on only depression, two on both cognition and depression in patients and two on schizophrenia symptoms. No studies were at significant risk of bias. For cognition, TACS showed significant improvement [positive standardised mean differences (SMD) denoting improvement] over sham stimulation in those with psychiatric disorders with an SMD of 0.60 (95% confidence interval [CI]: 0.14, 1.06). Similarly, among patients with depression, an SMD of 1.14 (95% CI: 0.10, 2.18) was found significantly favouring TACS over sham stimulation. Two studies assessed the effect of TACS on schizophrenia symptoms with mixed results. TACS has shown promise in ameliorating symptoms of both schizophrenia and depression in patients. TACS also improves cognition in both patients and healthy subjects. However, these findings are limited by the sample size of included studies, and future studies may be required to better our understanding of the potential of TACS. PROSPERO (CRD42022331149).

The Modulation of Working-Memory Performance Using Gamma-Electroacupuncture and Theta-Electroacupuncture in Healthy Adults.

Working memory (WM), a central component of general cognition, plays an essential role in human beings' daily lives. WM impairments often occur in psychiatric, neurodegenerative, and neurodevelopmental disorders, mainly presenting as loss of high-load WM. In previous research, electroacupuncture (EA) has been shown to be an effective treatment for cognitive impairments. Frequency parameters are an important factor in therapeutic results, but the optimal frequency parameters of EA have not yet been identified. In this study, we chose theta-EA (θ-EA; 6 Hz) and gamma-EA (γ-EA; 40 Hz), corresponding to the transcranial alternating-current stimulation (tACS) frequency parameters at the Baihui (DU20) and Shenting (DU24) acupoints, in order to compare the effects of different EA frequencies on WM. We evaluated WM performance using visual 1-back, 2-back, and 3-back WM tasks involving digits. Each participant (N = 30) attended three different sessions in accordance with a within-subject crossover design. We performed θ-EA, γ-EA, and sham-EA in a counterbalanced order, conducting the WM task both before and after intervention. The results showed that d-prime (d′) under all three stimulation conditions had no significance in the 1-back and 2-back tasks. However, in the 3-back task, there was a significant improvement in d′ after intervention compared to d′ before intervention under θ-EA (F [1, 29] = 22.64; P < 0.001), while we saw no significant difference in the γ-EA and sham-EA groups. Reaction times for hits (RT-hit) under all three stimulation conditions showed decreasing trends in 1-, 2-, and 3-back tasks but without statistically significant differences. These findings suggest that the application of θ-EA might facilitate high-load WM performance.

Investigating Nuisance Effects Induced in EEG During tACS Application.

Transcranial alternating-current stimulation (tACS) in the frequency range of 1–100 Hz has come to be used routinely in electroencephalogram (EEG) studies of brain function through entrainment of neuronal oscillations. It turned out, however, to be highly non-trivial to remove the strong stimulation signal, including its harmonic and non-harmonic distortions, as well as various induced higher-order artifacts from the EEG data recorded during the stimulation. In this paper, we discuss some of the problems encountered and present methodological approaches aimed at overcoming them. To illustrate the mechanisms of artifact induction and the proposed removal strategies, we use data obtained with the help of a schematic demonstrator setup as well as human-subject data.

Region-Specific Effects of 10-Hz Transcranial Alternate Current Stimulation Over the Left Posterior Parietal Cortex and Primary Somatosensory Area on Tactile Two-Point Discrimination Threshold.

Changes in α-band cortical oscillatory activity (8–13 Hz) affect perception; however, how these changes in the left posterior parietal cortex (PPC) and primary somatosensory cortex (S1), which play different roles in determining the two-point discrimination (TPD) threshold, affect TPD threshold remains unelucidated. Therefore, to determine TPD threshold, we aimed to investigate the function of the left PPC and S1 by applying α-band transcranial alternating current stimulation (α-tACS; 10 Hz). TPD threshold was examined at the pad of the right index finger, contralateral to the stimulation site, in 17 healthy adults using a custom-made, computer-controlled, two-point tactile stimulation device, with random application of either active or sham α-tACS over the left PPC (Experiment 1) and left S1 (Experiment 2). Then, 50% TPD threshold was obtained in the active and sham conditions via logistic regression analysis. Afterward, we compared the difference between the active and sham conditions at 50% TPD threshold in each region and found that α-tACS reduced TPD threshold when applied over the left PPC (P = 0.010); however, its effect was insignificant when applied over the left S1 (P = 0.74). Moreover, a comparison of the change in 50% TPD threshold among the regions revealed that α-tACS applied over the left PPC significantly reduced TPD threshold compared with that applied over the left S1 (P = 0.003). Although we did not reveal the actual changes in cortical activity induced by α-tACS, this is the first empirical evidence that α-tACS applied over the left PPC and left S1 exerts region-specific effects on determining TPD threshold assessed in the contralateral index finger pad by stimulation.

Comparing the Effectiveness of the Transcranial Alternating Current Stimulation (TACS) and Ritalin on Symptoms of Attention Deficit Hyperactivity Disorder in 7-14-Year-Old Children

Several studies have been conducted on the effect of transcranial direct current stimulation on adult patients. But, in recent years, only a few studies have been carried out in children and teenagers because the aim of the present study was to compare the effectiveness of TACS and Ritalin in the treatment of attention deficit hyperactivity disorder (ADHD) symptoms. This interventional clinical trial study was performed on 62 children with ADHD who were referred to the private psychiatric clinic of children in Tehran. The children were randomly assigned to two coded groups based on a lottery so that they were enrolled in the TACS or the Ritalin group. A questionnaire child syndrome inventory (parental form) and integrated visual and auditory (IVA) test with a pretest and posttest design was used in this study. TACS therapy protocol was employed (3 days a week for eight weeks using alternating current stimulation at 10 Hz over two points on the prefrontal cortex: the anode centered over F3 [the left dorsolateral prefrontal cortex] and the cathode over F4[the right dorsolateral prefrontal cortex]). Results showed that the posttest scores of the TACS-treated group were higher than those of the Ritalin-treated group, and there was a significant difference between the areas of visual attention (visual vigilance, visual focus, Sustained attention visual) and response control visual and auditory prudence (P&lt;0.05). Results indicated that TACS was more effective and more durable compared to Ritalin in reducing attention deficit, hyperactivity, and impulsivity.

Bilateral Gamma/Delta Transcranial Alternating Current Stimulation Affects Interhemispheric Speech Sound Integration

Perceiving speech requires the integration of different speech cues, that is, formants. When the speech signal is split so that different cues are presented to the right and left ear (dichotic listening), comprehension requires the integration of binaural information. Based on prior electrophysiological evidence, we hypothesized that the integration of dichotically presented speech cues is enabled by interhemispheric phase synchronization between primary and secondary auditory cortex in the gamma frequency band. We tested this hypothesis by applying transcranial alternating current stimulation (TACS) bilaterally above the superior temporal lobe to induce or disrupt interhemispheric gamma-phase coupling. In contrast to initial predictions, we found that gamma TACS applied in-phase above the two hemispheres (interhemispheric lag 0°) perturbs interhemispheric integration of speech cues, possibly because the applied stimulation perturbs an inherent phase lag between the left and right auditory cortex. We also observed this disruptive effect when applying antiphasic delta TACS (interhemispheric lag 180°). We conclude that interhemispheric phase coupling plays a functional role in interhemispheric speech integration. The direction of this effect may depend on the stimulation frequency.

Effect of Theta Transcranial Alternating Current Stimulation and Phase-Locked Transcranial Pulsed Current Stimulation on Learning and Cognitive Control.

Non-invasive brain stimulation (NIBS) is emerging as a robust treatment alternative for major depressive disorder, with a potential for achieving higher remission rates by providing targeted stimulation to underlying brain networks, such as the salience network (SN). Growing evidence suggests that these therapeutic effects are dependent on the frequency and phase synchrony between SN oscillations and stimulation as well as the task-specific state of the SN during stimulation. However, the development of phase-synchronized non-invasive stimulation has proved challenging until recently. Here, we use a phase-locked pulsed brain stimulation approach to study the effects of two NIBS methods: transcranial alternating current stimulation (tACS) versus phase-locked transcranial pulsed current stimulation (tPCS), on the SN during an SN activating task. 20 healthy volunteers participated in the study. Each volunteer partook in four sessions, receiving one stimulation type at random (theta-tACS, peak tPCS, trough tPCS or sham) while undergoing a learning game, followed by an unstimulated test based on learned material. Each session lasted approximately 1.5 h, with an interval of at least 2 days to allow for washout and to avoid cross-over effects. Our results showed no statistically significant effect of stimulation on the event related potential (ERP) recordings, resting electroencephalogram (EEG), and the performance of the volunteers. While stimulation effects were not apparent in this study, the nominal performance of the phase-locking algorithm offers a technical foundation for further research in determining effective stimulation paradigms and conditions. Specifically, future work should investigate stronger stimulation and true task-specific stimulation of SN nodes responsible for the task as well as their recording. If refined, NIBS could offer an effective, homebased treatment option.

Human Sensation of Transcranial Electric Stimulation

Noninvasive transcranial electric stimulation is increasingly being used as an advantageous therapy alternative that may activate deep tissues while avoiding drug side-effects. However, not only is there limited evidence for activation of deep tissues by transcranial electric stimulation, its evoked human sensation is understudied and often dismissed as a placebo or secondary effect. By systematically characterizing the human sensation evoked by transcranial alternating-current stimulation, we observed not only stimulus frequency and electrode position dependencies specific for auditory and visual sensation but also a broader presence of somatic sensation ranging from touch and vibration to pain and pressure. We found generally monotonic input-output functions at suprathreshold levels, and often multiple types of sensation occurring simultaneously in response to the same electric stimulation. We further used a recording circuit embedded in a cochlear implant to directly and objectively measure the amount of transcranial electric stimulation reaching the auditory nerve, a deep intercranial target located in the densest bone of the skull. We found an optimal configuration using an ear canal electrode and low-frequency (<300 Hz) sinusoids that delivered maximally ~1% of the transcranial current to the auditory nerve, which was sufficient to produce sound sensation even in deafened ears. Our results suggest that frequency resonance due to neuronal intrinsic electric properties need to be explored for targeted deep brain stimulation and novel brain-computer interfaces.

Safety Aspects, Tolerability and Modeling of Retinofugal Alternating Current Stimulation.

BackgroundWhile alternating current stimulation (ACS) is gaining relevance as a tool in research and approaching clinical applications, its mechanisms of action remain unclear. A review by Schutter and colleagues argues for a retinal origin of transcranial ACS’ neuromodulatory effects. Interestingly, there is an alternative application form of ACS specifically targeting α-oscillations in the visual cortex via periorbital electrodes (retinofugal alternating current stimulation, rACS). To further compare these two methods and investigate retinal effects of ACS, we first aim to establish the safety and tolerability of rACS.ObjectiveThe goal of our research was to evaluate the safety of rACS via finite-element modeling, theoretical safety limits and subjective report.Methods20 healthy subjects were stimulated with rACS as well as photic stimulation and reported adverse events following stimulation. We analyzed stimulation parameters at electrode level as well as distributed metric estimates from an ultra-high spatial resolution magnetic resonance imaging (MRI)-derived finite element human head model and compared them to existing safety limits.ResultsTopographical modeling revealed the highest current densities in the anterior visual pathway, particularly retina and optic nerve. Stimulation parameters and finite element modeling estimates of rACS were found to be well below existing safety limits. No serious adverse events occurred.ConclusionOur findings are in line with existing safety guidelines for retinal and neural damage and establish the tolerability and feasibility of rACS. In comparison to tACS, retinofugal stimulation of the visual cortex provides an anatomically circumscribed model to systematically study the mechanisms of action of ACS.

Therapeutic Effects of Transcranial Alternative Current Stimulation (tACS) in Chronic Post Stroke Hemianopia

Therapeutic Effects of Transcranial Alternative Current Stimulation (tACS) in Chronic Post Stroke Hemianopia

Theta band high definition transcranial alternating current stimulation, but not transcranial direct current stimulation, improves associative memory performance

Associative memory (AM) deficits are common in neurodegenerative disease and novel therapies aimed at improving these faculties are needed. Theta band oscillations within AM networks have been shown to be important for successful memory encoding and modulating these rhythms represents a promising strategy for cognitive enhancement. Transcranial alternating current stimulation (TACS) has been hypothesized to entrain and increase power of endogenous brain rhythms. For this reason, we hypothesized that focal delivery of theta band electrical current, using high-definition TACS, would result in improved AM performance compared to sham stimulation or transcranial direct current stimulation (TDCS). In this pilot study, 60 healthy subjects were randomized to receive high definition TACS, high definition TDCS, or sham stimulation delivered to the right fusiform cortex during encoding of visual associations. Consistent with our hypothesis, improved AM performance was observed in the TACS group, while TDCS had no effect. However, TACS also resulted in improved correct rejection of never seen items, reduced false memory, and reduced forgetting, suggesting the effect may not be specific for AM processes. Overall, this work informs strategies for improving associative memory and suggests alternating current is more effective than direct current stimulation in some contexts.

Ameliorative Effects of Different Transcranial Electrical Stimulation Paradigms on the Novel Object Recognition Task in a Rat Model of Alzheimer Disease

Background: Treatment of Alzheimer as a disease that is associated with cognitive impairment has been associated with some restrictions. Recently, researchers have focused on non-pharmacological treatments, including non-invasive stimulation of the brain by transcranial electrical stimulation (tES). Four main paradigms of transcranial electrical current include transcranial direct current stimulation (tDCS), transcranial alternative current stimulation (tACS), transcranial random noise stimulation (tRNS), transcranial pulse current stimulation (tPCS). The tDCS is a possible new therapeutic option for patients with cognitive impairment, including Alzheimer disease. Materials and Methods: The study was done on Sprague-Dawley male rats weighing 250-270 g. to develop Alzheimer’s model, the cannula was implanted bilaterally into the hippocampus. Aβ 25-35 (5μg/ 2.5µl/day) was microinjected bilaterally for 4 days. Then, an electrical stimulation paradigm was applied to the animal for 6 days. Animal cognitive capacity was evaluated on day 11 and 12 by novel object recognition (NOR) test. Results: Our results showed that application of tDCS; tACS; tRNS and tPCS reversed beta-amyloid-induced impairment (P&lt;0.05). The tRNS Group spent total exploration time around the objects compared to other groups (P&lt;0.05). There was no significant difference between the four different paradigms in discrimination ratio and the percentage of total exploration time. Conclusion: The results of this study showed that the use of multiple sessions of different tES paradigms could improve Aβ-induced memory impairment in the NOR test. Therefore, based on evidence, it can be expected that in addition to using tDCS, other stimulatory paradigms may also be considered in the treatment of AD. [GMJ.2019;8:e1440]

Ameliorative Effects of Different Transcranial Electrical Stimulation Paradigms on the Novel Object Recognition Task in a Rat Model of Alzheimer Disease

Background: Treatment of Alzheimer as a disease that is associated with cognitive impairment has been associated with some restrictions. Recently, researchers have focused on non-pharmacological treatments, including non-invasive stimulation of the brain by transcranial electrical stimulation (tES). Four main paradigms of transcranial electrical current include transcranial direct current stimulation (tDCS), transcranial alternative current stimulation (tACS), transcranial random noise stimulation (tRNS), transcranial pulse current stimulation (tPCS). The tDCS is a possible new therapeutic option for patients with cognitive impairment, including Alzheimer disease. Materials and Methods: The study was done on Sprague-Dawley male rats weighing 250-270 g. to develop Alzheimer's model, the cannula was implanted bilaterally into the hippocampus. Aβ 25-35 (5μg/ 2.5µl/day) was microinjected bilaterally for 4 days. Then, an electrical stimulation paradigm was applied to the animal for 6 days. Animal cognitive capacity was evaluated on day 11 and 12 by novel object recognition (NOR) test. Results: Our results showed that application of tDCS; tACS; tRNS and tPCS reversed beta-amyloid-induced impairment (P&lt;0.05). The tRNS Group spent total exploration time around the objects compared to other groups (P&lt;0.05). There was no significant difference between the four different paradigms in discrimination ratio and the percentage of total exploration time. Conclusion: The results of this study showed that the use of multiple sessions of different tES paradigms could improve Aβ-induced memory impairment in the NOR test. Therefore, based on evidence, it can be expected that in addition to using tDCS, other stimulatory paradigms may also be considered in the treatment of AD. [GMJ. 2019;inpress:e1440]

Ameliorative Effects of Different Transcranial Electrical Stimulation Paradigms on the Novel Object Recognition Task in a Rat Model of Alzheimer Disease.

Background: Treatment of Alzheimer as a disease that is associated with cognitive impairment has been associated with some restrictions. Recently, researchers have focused on non-pharmacological treatments, including non-invasive stimulation of the brain by transcranial electrical stimulation (tES). Four main paradigms of transcranial electrical current include transcranial direct current stimulation (tDCS), transcranial alternative current stimulation (tACS), transcranial random noise stimulation (tRNS), transcranial pulse current stimulation (tPCS). The tDCS is a possible new therapeutic option for patients with cognitive impairment, including Alzheimer disease. Materials and Methods: The study was done on Sprague-Dawley male rats weighing 250-270 g. to develop Alzheimer’s model, the cannula was implanted bilaterally into the hippocampus. Aβ 25-35 (5μg/ 2.5µl/day) was microinjected bilaterally for 4 days. Then, an electrical stimulation paradigm was applied to the animal for 6 days. Animal cognitive capacity was evaluated on day 11 and 12 by novel object recognition (NOR) test. Results: Our results showed that application of tDCS; tACS; tRNS and tPCS reversed beta-amyloid-induced impairment (P<0.05). The tRNS Group spent total exploration time around the objects compared to other groups (P<0.05). There was no significant difference between the four different paradigms in discrimination ratio and the percentage of total exploration time. Conclusion: The results of this study showed that the use of multiple sessions of different tES paradigms could improve Aβ-induced memory impairment in the NOR test. Therefore, based on evidence, it can be expected that in addition to using tDCS, other stimulatory paradigms may also be considered in the treatment of AD.