Anodal transcranial direct current stimulation boosts synaptic plasticity and memory in mice via epigenetic regulation of Bdnf expression.
Ontology highlight
ABSTRACT:
SUBMITTER: Podda MV
PROVIDER: S-EPMC4764914 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Slow-wave sleep (SWS) has been shown to promote long-term consolidation of episodic memories in hippocampo-neocortical networks. Previous research has aimed to modulate cortical sleep slow-waves and spindles to facilitate episodic memory consolidation. Here, we instead aimed to modulate hippocampal activity during slow-wave sleep using transcranial direct current stimulation in 18 healthy humans. A pair-associate episodic memory task was used to evaluate sleep-dependent memory consolidation with face-occupation stimuli. Pre- and post-nap retrieval was assessed as a measure of memory performance. Anodal stimulation with 2 mA was applied bilaterally over the lateral temporal cortex, motivated by its particularly extensive connections to the hippocampus. The participants slept in a magnetic resonance (MR)-simulator during the recordings to test the feasibility for a future MR-study. We used a sham-controlled, double-blind, counterbalanced randomized, within-subject crossover design. We show that stimulation vs. sham significantly increased slow-wave density and the temporal coupling of fast spindles and slow-waves. While retention of episodic memories across sleep was not affected across the entire sample of participants, it was impaired in participants with below-average pre-sleep memory performance. Hence, bi-temporal anodal direct current stimulation applied during sleep enhanced sleep parameters that are typically involved in memory consolidation, but it failed to improve memory consolidation and even tended to impair consolidation in poor learners. These findings suggest that artificially enhancing memory-related sleep parameters to improve memory consolidation can actually backfire in those participants who are in most need of memory improvement.
| S-EPMC8064104 | biostudies-literature
Project description:Despite its increasing use in experimental and clinical settings, the cellular and molecular mechanisms underlying transcranial direct current stimulation (tDCS) remain unknown. Anodal tDCS applied to the human motor cortex (M1) improves motor skill learning. Here, we demonstrate in mouse M1 slices that DCS induces a long-lasting synaptic potentiation (DCS-LTP), which is polarity specific, NMDA receptor dependent, and requires coupling of DCS with repetitive low-frequency synaptic activation (LFS). Combined DCS and LFS enhance BDNF-secretion and TrkB activation, and DCS-LTP is absent in BDNF and TrkB mutant mice, suggesting that BDNF is a key mediator of this phenomenon. Moreover, the BDNF val66met polymorphism known to partially affect activity-dependent BDNF secretion impairs motor skill acquisition in humans and mice. Motor learning is enhanced by anodal tDCS, as long as activity-dependent BDNF secretion is in place. We propose that tDCS may improve motor skill learning through augmentation of synaptic plasticity that requires BDNF secretion and TrkB activation within M1.
| S-EPMC2864780 | biostudies-literature
Project description:BackgroundThere is evidence that transcranial direct current stimulation (tDCS) can improve learning performance. Arguably, this effect is related to long term potentiation (LTP), but the precise biophysical mechanisms remain unknown.HypothesisWe propose that direct current stimulation (DCS) causes small changes in postsynaptic membrane potential during ongoing endogenous synaptic activity. The altered voltage dynamics in the postsynaptic neuron then modify synaptic strength via the machinery of endogenous voltage-dependent Hebbian plasticity. This hypothesis predicts that DCS should exhibit Hebbian properties, namely pathway specificity and associativity.MethodsWe studied the effects of DCS applied during the induction of LTP in the CA1 region of rat hippocampal slices and using a biophysical computational model.ResultsDCS enhanced LTP, but only at synapses that were undergoing plasticity, confirming that DCS respects Hebbian pathway specificity. When different synaptic pathways cooperated to produce LTP, DCS enhanced this cooperation, boosting Hebbian associativity. Further slice experiments and computer simulations support a model where polarization of postsynaptic pyramidal neurons drives these plasticity effects through endogenous Hebbian mechanisms. The model is able to reconcile several experimental results by capturing the complex interaction between the induced electric field, neuron morphology, and endogenous neural activity.ConclusionsThese results suggest that tDCS can enhance associative learning. We propose that clinical tDCS should be applied during tasks that induce Hebbian plasticity to harness this phenomenon, and that the effects should be task specific through their interaction with endogenous plasticity mechanisms. Models that incorporate brain state and plasticity mechanisms may help to improve prediction of tDCS outcomes.
| S-EPMC6989352 | biostudies-literature
Project description:Early diagnosis of Alzheimer's disease (AD) supposedly increases the effectiveness of therapeutic interventions. However, presently available diagnostic procedures are either invasive or require complex and expensive technologies, which cannot be applied at a larger scale to screen populations at risk of AD. We were looking for a biomarker allowing to unveil a dysfunction of molecular mechanisms, which underly synaptic plasticity and memory, before the AD phenotype is manifested and investigated the effects of transcranial direct current stimulation (tDCS) in 3×Tg-AD mice, an experimental model of AD which does not exhibit any long-term potentiation (LTP) and memory deficits at the age of 3 months (3×Tg-AD-3M). Our results demonstrated that tDCS differentially affected 3×Tg-AD-3M and age-matched wild-type (WT) mice. While tDCS increased LTP at CA3-CA1 synapses and memory in WT mice, it failed to elicit these effects in 3×Tg-AD-3M mice. Remarkably, 3×Tg-AD-3M mice did not show the tDCS-dependent increases in pCREB Ser133 and pCaMKII Thr286 , which were found in WT mice. Of relevance, tDCS induced a significant increase of plasma BDNF levels in WT mice, which was not found in 3×Tg-AD-3M mice. Collectively, our results showed that plasticity mechanisms are resistant to tDCS effects in the pre-AD stage. In particular, the lack of BDNF responsiveness to tDCS in 3×Tg-AD-3M mice suggests that combining tDCS with dosages of plasma BDNF levels may provide an easy-to-detect and low-cost biomarker of covert impairment of synaptic plasticity mechanisms underlying memory, which could be clinically applicable. Testing proposed here might be useful to identify AD in its preclinical stage, allowing timely and, hopefully, more effective disease-modifying interventions.
| S-EPMC7349675 | biostudies-literature
Project description:BACKGROUND:It is well known that transcranial direct current stimulation (tDCS) is capable of modulating corticomotor excitability. However, a source of growing concern has been the observed inter- and intra-individual variability of tDCS-responses. Recent studies have assessed whether individuals respond in a predictable manner across repeated sessions of anodal tDCS (atDCS). The findings of these investigations have been inconsistent, and their methods have some limitations (i.e. lack of sham condition or testing only one tDCS intensity). OBJECTIVE:To study inter- and intra-individual variability of atDCS effects at two different intensities on primary motor cortex (M1) excitability. METHODS:Twelve subjects participated in a crossover study testing 7-min atDCS over M1 in three separate conditions (2 mA, 1 mA, sham) each repeated three times separated by 48 h. Motor evoked potentials were recorded before and after stimulation (up to 30min). Time of testing was maintained consistent within participants. To estimate the reliability of tDCS effects across sessions, we calculated the Intra-class Correlation Coefficient (ICC). RESULTS:AtDCS at 2 mA, but not 1 mA, significantly increased cortical excitability at the group level in all sessions. The overall ICC revealed fair to high reliability of tDCS effects for multiple sessions. Given that the distribution of responses showed important variability in the sham condition, we established a Sham Variability-Based Threshold to classify responses and to track individual changes across sessions. Using this threshold an intra-individual consistent response pattern was then observed only for the 2 mA condition. CONCLUSION:2 mA anodal tDCS results in consistent intra- and inter-individual increases of M1 excitability.
| S-EPMC5511514 | biostudies-literature
Project description:Collinear flanking stimuli can reduce the detectability of a Gabor target presented in peripheral vision. This phenomenon is called collinear lateral inhibition and it may contribute to crowding in peripheral vision. Perceptual learning can reduce collinear lateral inhibition in peripheral vision, however intensive training is required. Our aim was to assess whether modulation of collinear lateral inhibition can be achieved within a short time-frame using a single 20-minute session of primary visual cortex anodal transcranial direct current stimulation (a-tDCS). Thirteen observers with normal vision performed a 2AFC contrast detection task with collinear flankers positioned at a distance of 2λ from the target (lateral inhibition) or 6λ (control condition). The stimuli were presented 6° to the left of a central cross and fixation was monitored with an infra-red eye tracker. Participants each completed two randomly sequenced, single-masked stimulation sessions; real anodal tDCS and sham tDCS. For the 2λ separation condition, a-tDCS induced a significant reduction in detection threshold (reduced lateral inhibition). Sham stimulation had no effect. No effects of a-tDCS were observed for the 6λ separation condition. This result lays the foundation for future work investigating whether a-tDCS may be useful as a visual rehabilitation tool for individuals with central vision loss who are reliant on peripheral vision.
| S-EPMC7202594 | biostudies-literature
Project description:Most therapeutic candidates for treating attention-deficit hyperactivity disorder (ADHD) have focused on modulating the dopaminergic neurotransmission system with neurotrophic factors. Regulation of this system by transcranial direct current stimulation (tDCS) could contribute to the recovery of cognitive symptoms observed in patients with ADHD. Here, male spontaneously hypertensive rats (SHR) were subjected to consecutive high-definition tDCS (HD-tDCS) (20 min, 50 μA, current density 63.7 A/m2, charge density 76.4 kC/m2) over the prefrontal cortex. This treatment alleviated cognitive deficits, with an increase in tyrosine hydroxylase and vesicular monoamine transporter two and significantly decreased plasma membrane reuptake transporter (DAT). HD-tDCS application increased the expression of several neurotrophic factors, particularly brain-derived neurotrophic factor (BDNF), and activated hippocampal neurogenesis. Our results suggest that anodal HD-tDCS over the prefrontal cortex may ameliorate cognitive dysfunction via regulation of DAT and BDNF in the mesocorticolimbic dopaminergic pathways, and therefore represents a potential adjuvant therapy for ADHD.
| S-EPMC7535928 | biostudies-literature
Project description:Transcranial direct current stimulation (tDCS) paired with exercise training can enhance learning and retention of hand tasks; however, there have been few investigations of the effects of tDCS on leg skill improvements. The purpose of this study was to investigate whether tDCS paired with visuomotor step training can promote skill learning and retention. We hypothesized that pairing step training with anodal tDCS would improve skill learning and retention, evidenced by decreased step reaction times (RTs), both immediately (online skill gains) and 30 min after training (offline skill gains). Twenty healthy adults were randomly assigned to one of two groups, in which 20-min anodal or sham tDCS was applied to the lower limb motor cortex and paired with visuomotor step training. Step RTs were determined across three time points: (1) before brain stimulation (baseline); (2) immediately after brain stimulation (P0); and (3) 30 min after brain stimulation (P3). A continuous decline in RT was observed in the anodal tDCS group at both P0 and P3, with a significant decrease in RT at P3; whereas there were no improvements in RT at P0 and P3 in the sham group. These findings do not support our hypothesis that anodal tDCS enhances online learning, as RT was not decreased significantly immediately after stimulation. Nevertheless, the results indicate that anodal tDCS enhances offline learning, as RT was significantly decreased 30 min after stimulation, likely because of tDCS-induced neural modulation of cortical and subcortical excitability, synaptic efficacy, and spinal neuronal activity.
| S-EPMC7333563 | biostudies-literature
Project description:Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique involving administration of well-tolerated electrical current to the brain through scalp electrodes. TDCS may improve symptoms in neuropsychiatric disorders, but mixed results from recent clinical trials underscore the need to demonstrate that tDCS can modulate clinically relevant brain systems over time in patients. Here, we analyzed longitudinal structural MRI data from a randomized, double-blind, parallel-design clinical trial in depression (NCT03556124, N = 59) to investigate whether serial tDCS individually targeted to the left dorso-lateral prefrontal cortex (DLPFC) can induce neurostructural changes. Significant (FWEc p < 0.05) treatment-related gray matter changes were observed with active high-definition (HD) tDCS relative to sham tDCS within the left DLPFC stimulation target. No changes were observed with active conventional tDCS. A follow-up analysis within individual treatment groups revealed significant gray matter increases with active HD-tDCS in brain regions functionally connected with the stimulation target, including the bilateral DLPFC, bilateral posterior cingulate cortex, subgenual anterior cingulate cortex, and the right hippocampus, thalamus and left caudate brain regions. Integrity of blinding was verified, no significant differences in stimulation-related discomfort were observed between treatment groups, and tDCS treatments were not augmented by any other adjunct treatments. Overall, these results demonstrate that serial HD-tDCS leads to neurostructural changes at a predetermined brain target in depression and suggest that such plasticity effects may propagate over brain networks.
| S-EPMC9938111 | biostudies-literature
Project description:Size and duration of the neuroplastic effects of tDCS depend on stimulation parameters, including stimulation duration and intensity of current. The impact of stimulation parameters on physiological effects is partially non-linear. To improve the utility of this intervention, it is critical to gather information about the impact of stimulation duration and intensity on neuroplasticity, while expanding the parameter space to improve efficacy. Anodal tDCS of 1-3?mA current intensity was applied for 15-30?minutes to study motor cortex plasticity. Sixteen healthy right-handed non-smoking volunteers participated in 10 sessions (intensity-duration pairs) of stimulation in a randomized cross-over design. Transcranial magnetic stimulation (TMS)-induced motor-evoked potentials (MEP) were recorded as outcome measures of tDCS effects until next evening after tDCS. All active stimulation conditions enhanced motor cortex excitability within the first 2?hours after stimulation. We observed no significant differences between the three stimulation intensities and durations on cortical excitability. A trend for larger cortical excitability enhancements was however observed for higher current intensities (1 vs 3?mA). These results add information about intensified tDCS protocols and suggest that the impact of anodal tDCS on neuroplasticity is relatively robust with respect to gradual alterations of stimulation intensity, and duration.
| S-EPMC6890804 | biostudies-literature