Closing the loop between brain and electrical stimulation: towards precision neuromodulation treatments.

One of the most critical challenges in using noninvasive brain stimulation (NIBS) techniques for the treatment of psychiatric and neurologic disorders is inter- and intra-individual variability in response to NIBS. Response variations in previous findings suggest that the one-size-fits-all approach does not seem the most appropriate option for enhancing stimulation outcomes. While there is a growing body of evidence for the feasibility and effectiveness of individualized NIBS approaches, the optimal way to achieve this is yet to be determined. Transcranial electrical stimulation (tES) is one of the NIBS techniques showing promising results in modulating treatment outcomes in several psychiatric and neurologic disorders, but it faces the same challenge for individual optimization. With new computational and methodological advances, tES can be integrated with real-time functional magnetic resonance imaging (rtfMRI) to establish closed-loop tES-fMRI for individually optimized neuromodulation. Closed-loop tES-fMRI systems aim to optimize stimulation parameters based on minimizing differences between the model of the current brain state and the desired value to maximize the expected clinical outcome. The methodological space to optimize closed-loop tES fMRI for clinical applications includes (1) stimulation vs. data acquisition timing, (2) fMRI context (task-based or resting-state), (3) inherent brain oscillations, (4) dose-response function, (5) brain target trait and state and (6) optimization algorithm. Closed-loop tES-fMRI technology has several advantages over non-individualized or open-loop systems to reshape the future of neuromodulation with objective optimization in a clinically relevant context such as drug cue reactivity for substance use disorder considering both inter and intra-individual variations. Using multi-level brain and behavior measures as input and desired outcomes to individualize stimulation parameters provides a framework for designing personalized tES protocols in precision psychiatry.

The impact of bilateral anodal transcranial direct current stimulation of the premotor and cerebellar cortices on physiological and performance parameters of gymnastic athletes: a randomized, cross-over, sham-controlled study.

Professional sports performance relies critically on the interaction between the brain and muscles during movement. Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique which modulates cortical excitability and can be used to improve motor performance in athletes. The present study aimed to investigate the effect of bilateral anodal tDCS (2 mA, 20 min) over the premotor cortex or cerebellum on motor and physiological functions and peak performance of professional gymnastics athletes. Seventeen professional gymnastics athletes participated in a randomized, sham-controlled, crossover study. In this study, we assessed the efficacy of two anodal tDCS protocols (2 mA, 20 min) with stimulation over the bilateral premotor cortex or cerebellum with the return electrodes placed over the opposite supraorbital areas. Power speed, strength coordination, endurance, static and dynamic strength, static and dynamic flexibility, and rating of perceived exertion were measured before and immediately after tDCS interventions (bilateral anodal tDCS over premotor cortices, anodal tDCS over the cerebellum, and sham tDCS). Additionally, physiological muscle performance parameters, including maximum voluntary isometric contraction (MVIC) of upper body muscles, were assessed during tDCS. Bilateral anodal tDCS over the premotor cortex, compared to anodal tDCS over the cerebellum and sham tDCS conditions, significantly improved power speed, strength coordination, and static and dynamic strength variables of professional gymnastics athletes. Furthermore, bilateral anodal tDCS over the cerebellum, compared to sham tDCS, significantly improved strength coordination. Moreover, bilateral premotor anodal tDCS significantly increased MVIC of all upper body muscles during stimulation, while anodal tDCS over the cerebellum increased MVIC in only some muscles. Bilateral anodal tDCS over the premotor cortex, and to a minor degree over the cerebellum, might be suited to improve some aspects of motor and physiological functions and peak performance levels of professional gymnastics athletes.Clinical Trial Registration ID: IRCT20180724040579N2.

Transferability of cathodal tDCS effects from the primary motor to the prefrontal cortex: A multimodal TMS-EEG study.

Neurophysiological effects of transcranial direct current stimulation (tDCS) have been extensively studied over the primary motor cortex (M1). Much less is however known about its effects over non-motor areas, such as the prefrontal cortex (PFC), which is the neuronal foundation for many high-level cognitive functions and involved in neuropsychiatric disorders. In this study, we, therefore, explored the transferability of cathodal tDCS effects over M1 to the PFC. Eighteen healthy human participants (11 males and 8 females) were involved in eight randomized sessions per participant, in which four cathodal tDCS dosages, low, medium, and high, as well as sham stimulation, were applied over the left M1 and left PFC. After-effects of tDCS were evaluated via transcranial magnetic stimulation (TMS)-electroencephalography (EEG), and TMS-elicited motor evoked potentials (MEP), for the outcome parameters TMS-evoked potentials (TEP), TMS-evoked oscillations, and MEP amplitude alterations. TEPs were studied both at the regional and global scalp levels. The results indicate a regional dosage-dependent nonlinear neurophysiological effect of M1 tDCS, which is not one-to-one transferable to PFC tDCS. Low and high dosages of M1 tDCS reduced early positive TEP peaks (P30, P60), and MEP amplitudes, while an enhancement was observed for medium dosage M1 tDCS (P30). In contrast, prefrontal low, medium and high dosage tDCS uniformly reduced the early positive TEP peak amplitudes. Furthermore, for both cortical areas, regional tDCS-induced modulatory effects were not observed for late TEP peaks, nor TMS-evoked oscillations. However, at the global scalp level, widespread effects of tDCS were observed for both, TMS-evoked potentials and oscillations. This study provides the first direct physiological comparison of tDCS effects applied over different brain areas and therefore delivers crucial information for future tDCS applications.

Age-dependent non-linear neuroplastic effects of cathodal tDCS in the elderly population: a titration study.

BACKGROUND: Neuromodulatory effects of transcranial direct current stimulation (tDCS) in older humans have shown heterogeneous results, possibly due to sub-optimal stimulation protocols associated with limited knowledge about optimized stimulation parameters in this age group. We systematically explored the association between the stimulation dosage of cathodal tDCS and induced after-effects on motor cortex excitability in the elderly. METHOD: Thirty-nine healthy volunteers in two age groups, namely Pre-Elderly (50-65 years) and Elderly (66-80 years), participated in the study. Ten sessions of cathodal tDCS, with a combination of four intensities (1, 2, 3 mA and sham) and three durations (15, 20, 30 min) were conducted over the M1 in each participant. Cortical excitability changes were monitored with TMS-induced motor evoked potentials (MEPs) for up to 2 h after stimulation. RESULTS: Motor cortex excitability was reduced by cathodal stimulation intensities of 1 and 3 mA in both age groups, in accordance with results observed in the younger age groups of previous studies. For the 2 mA stimulation condition, an age-dependent conversion of plasticity into a stimulation duration-dependent excitability enhancement was observed in the Pre-Elderly group, whereas in the Elderly group, LTD-like plasticity was preserved, or abolished, depending on stimulation duration. CONCLUSION: The LTD-like plasticity effects induced by cathodal tDCS originally described in young adults are also observable in older humans, but non-linearities of the resulting plasticity were partially preserved only in the Pre-Elderly, but not the Elderly group. These results aid in understanding age-dependent plasticity dynamics in humans, and to define more efficient tDCS protocols in the aging brain.

Cognitive functions and underlying parameters of human brain physiology are associated with chronotype.

Circadian rhythms have natural relative variations among humans known as chronotype. Chronotype or being a morning or evening person, has a specific physiological, behavioural, and also genetic manifestation. Whether and how chronotype modulates human brain physiology and cognition is, however, not well understood. Here we examine how cortical excitability, neuroplasticity, and cognition are associated with chronotype in early and late chronotype individuals. We monitor motor cortical excitability, brain stimulation-induced neuroplasticity, and examine motor learning and cognitive functions at circadian-preferred and non-preferred times of day in 32 individuals. Motor learning and cognitive performance (working memory, and attention) along with their electrophysiological components are significantly enhanced at the circadian-preferred, compared to the non-preferred time. This outperformance is associated with enhanced cortical excitability (prominent cortical facilitation, diminished cortical inhibition), and long-term potentiation/depression-like plasticity. Our data show convergent findings of how chronotype can modulate human brain functions from basic physiological mechanisms to behaviour and higher-order cognition.

Dosage-Dependent Impact of Acute Serotonin Enhancement on Transcranial Direct Current Stimulation Effects.

BACKGROUND: The serotonergic system has an important impact on basic physiological and higher brain functions. Acute and chronic enhancement of serotonin levels via selective serotonin reuptake inhibitor administration impacts neuroplasticity in humans, as shown by its effects on cortical excitability alterations induced by non-invasive brain stimulation, including transcranial direct current stimulation (tDCS). Nevertheless, the interaction between serotonin activation and neuroplasticity is not fully understood, particularly considering dose-dependent effects. Our goal was to explore dosage-dependent effects of acute serotonin enhancement on stimulation-induced plasticity in healthy individuals. METHODS: Twelve healthy adults participated in 7 sessions conducted in a crossover, partially double-blinded, randomized, and sham-controlled study design. Anodal and cathodal tDCS was applied to the motor cortex under selective serotonin reuptake inhibitor (20 mg/40 mg citalopram) or placebo medication. Motor cortex excitability was monitored by single-pulse transcranial magnetic stimulation. RESULTS: Under placebo medication, anodal tDCS enhanced, and cathodal tDCS reduced, excitability for approximately 60-120 minutes after the intervention. Citalopram enhanced and prolonged the facilitation induced by anodal tDCS regardless of the dosage while turning cathodal tDCS-induced excitability diminution into facilitation. For the latter, prolonged effects were observed when 40 mg was administrated. CONCLUSIONS: Acute serotonin enhancement modulates tDCS after-effects and has largely similar modulatory effects on motor cortex neuroplasticity regardless of the specific dosage. A minor dosage-dependent effect was observed only for cathodal tDCS. The present findings support the concept of boosting the neuroplastic effects of anodal tDCS by serotonergic enhancement, a potential clinical approach for the treatment of neurological and psychiatric disorders.

Exploring and optimizing the neuroplastic effects of anodal transcranial direct current stimulation over the primary motor cortex of older humans.

BACKGROUND: tDCS modulates cortical plasticity and has shown potential to improve cognitive/motor functions in healthy young humans. However, age-related alterations of brain structure and functions might require an adaptation of tDCS-parameters to achieve a targeted plasticity effect in older humans and conclusions obtained from young adults might not be directly transferable to older adults. Thus, our study aimed to systematically explore the association between tDCS-parameters and induced aftereffects on motor cortical excitability to determine optimal stimulation protocols for older individuals, as well as to investigate age-related differences of motor cortex plasticity in two different age groups of older adults. METHODS: 32 healthy, volunteers from two different age groups of Young-Old (50-65 years, n = 16) and Old-Old (66-80 years, n = 16) participated in this study. Anodal tDCS was applied over the primary motor cortex, with respective combinations of three intensities (1, 2, and 3 mA) and durations (15, 20, and 30 min), in a sham-controlled cross-over design. Cortical excitability alterations were monitored by single-pulse TMS-induced MEPs until the next day morning after stimulation. RESULTS: All active stimulation conditions resulted in a significant enhancement of motor cortical excitability in both age groups. The facilitatory aftereffects of anodal tDCS did not significantly differ between age groups. We observed prolonged plasticity in the late-phase range for two protocols with the highest stimulation intensity (i.e., 3 mA-20 min, 3 mA-30 min). CONCLUSIONS: Our study highlights the role of stimulation dosage in tDCS-induced neuroplastic aftereffects in the motor cortex of healthy older adults and delivers crucial information about optimized tDCS protocols in the domain of the primary motor cortex. Our findings might set the grounds for the development of optimal stimulation protocols to reinstate neuroplasticity in different cortical areas and induce long-lasting, functionally relevant plasticity in normal aging and in pathological conditions, which would require however systematic tDCS titration studies over respective target areas.

The impact of individual electrical fields and anatomical factors on the neurophysiological outcomes of tDCS: A TMS-MEP and MRI study.

BACKGROUND: Transcranial direct current stimulation (tDCS), a neuromodulatory non-invasive brain stimulation technique, has shown promising results in basic and clinical studies. The known interindividual variability of the effects, however, limits the efficacy of the technique. Recently we reported neurophysiological effects of tDCS applied over the primary motor cortex at the group level, based on data from twenty-nine participants who received 15min of either sham, 0.5, 1.0, 1.5 or 2.0 mA anodal, or cathodal tDCS. The neurophysiological effects were evaluated via changes in: 1) transcranial magnetic stimulation (TMS)-induced motor evoked potentials (MEP), and 2) cerebral blood flow (CBF) measured by functional magnetic resonance imaging (MRI) via arterial spin labeling (ASL). At the group level, dose-dependent effects of the intervention were obtained, which however displayed interindividual variability. METHOD: In the present study, we investigated the cause of the observed inter-individual variability. To this end, for each participant, a MRI-based realistic head model was designed to 1) calculate anatomical factors and 2) simulate the tDCS- and TMS-induced electrical fields (EFs). We first investigated at the regional level which individual anatomical factors explained the simulated EFs (magnitude and normal component). Then, we explored which specific anatomical and/or EF factors predicted the neurophysiological outcomes of tDCS. RESULTS: The results highlight a significant negative correlation between regional electrode-to-cortex distance (rECD) as well as regional CSF (rCSF) thickness, and the individual EF characteristics. In addition, while both rCSF thickness and rECD anticorrelated with tDCS-induced physiological changes, EFs positively correlated with the effects. CONCLUSION: These results provide novel insights into the dependency of the neuromodulatory effects of tDCS on individual physical factors.

Age-related differences of motor cortex plasticity in adults: A transcranial direct current stimulation study.

BACKGROUND: Cognitive, and motor performance are reduced in aging, especially with respect to acquisition of new knowledge, which is associated with a neural plasticity decline. Animal models show a reduction of long-term potentiation, but not long-term depression, in higher age. Findings in humans are more heterogeneous, with some studies showing respective deficits, but others not, or mixed results, for plasticity induced by non-invasive brain stimulation. One reason for these heterogeneous results might be the inclusion of different age ranges in these studies. In addition, a systematic detailed comparison of the age-dependency of neural plasticity in humans is lacking so far. OBJECTIVE: We aimed to explore age-dependent plasticity alterations in adults systematically by discerning between younger and older participants in our study. METHODS: We recruited three different age groups (Young: 18-30, Pre-Elderly: 50-65, and Elderly: 66-80 years). Anodal, cathodal, or sham transcranial direct current stimulation (tDCS) was applied over the primary motor cortex with 1 mA for 15 min to induce neuroplasticity. Cortical excitability was monitored by single-pulse transcranial magnetic stimulation as an index of plasticity. RESULTS: For anodal tDCS, the results show a significant excitability enhancement, as compared to sham stimulation, for both, Young and the Pre-Elderly groups, while no LTP-like plasticity was obtained in the Elderly group by the applied stimulation protocol. Cathodal tDCS induced significant excitability-diminishing plasticity in all age groups. CONCLUSION: Our study provides further insight in age-related differences of plasticity in healthy humans, which are similar to those obtained in animal models. The decline of LTP-like plasticity in higher age could contribute to cognitive deficits observed in aging.

Ca2+ channel dynamics explain the nonlinear neuroplasticity induction by cathodal transcranial direct current stimulation over the primary motor cortex.

Transcranial direct current stimulation (tDCS) induces polarity-dependent neuroplasticity: with conventional protocols, anodal tDCS results in excitability enhancement while cathodal stimulation reduces excitability. However, partially non-linear responses are observed with increased stimulation intensity and/or duration. Cathodal tDCS with 2 mA for 20 min reverses the excitability-diminishing plasticity induced by stimulation with 1 mA into excitation, while cathodal tDCS with 3 mA again results in excitability diminution. Since tDCS generates NMDA receptor-dependent neuroplasticity, such non-linearity could be explained by different levels of calcium concentration changes, which have been demonstrated in animal models to control for the directionality of plasticity. In this study, we tested the calcium dependency of non-linear cortical plasticity induced by cathodal tDCS in human subjects in a placebo controlled, double-blind and randomized design. The calcium channel blocker flunarizine was applied in low (2.5 mg), medium (5 mg) or high (10 mg) dosages before 20 min cathodal motor cortex tDCS with 3 mA in 12 young healthy subjects. After-effects of stimulation were monitored with TMS-induced motor evoked potentials (MEPs) until 2 h after stimulation. The results show that motor cortical excitability-diminishing after-effects of stimulation were unchanged, diminished, or converted to excitability enhancement with low, medium and high dosages of flunarizine. These results suggest a calcium-dependency of the directionality of tDCS-induced neuroplasticity, which may have relevant implications for future basic and clinical research.

Transcranial Direct Current Stimulation in ADHD: A Systematic Review of Efficacy, Safety, and Protocol-induced Electrical Field Modeling Results.

Transcranial direct current stimulation (tDCS) is a promising method for altering cortical excitability with clinical implications. It has been increasingly used in neurodevelopmental disorders, especially attention-deficit hyperactivity disorder (ADHD), but its efficacy (based on effect size calculations), safety, and stimulation parameters have not been systematically examined. In this systematic review, we aimed to (1) explore the effectiveness of tDCS on the clinical symptoms and neuropsychological deficits of ADHD patients, (2) evaluate the safety of tDCS application, especially in children with ADHD, (3) model the electrical field intensity in the target regions based on the commonly-applied and effective versus less-effective protocols, and (4) discuss and propose advanced tDCS parameters. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses approach, a literature search identified 14 empirical experiments investigating tDCS effects in ADHD. Partial improving effects of tDCS on cognitive deficits (response inhibition, working memory, attention, and cognitive flexibility) or clinical symptoms (e.g., impulsivity and inattention) are reported in 10 studies. No serious adverse effects are reported in 747 sessions of tDCS. The left and right dorsolateral prefrontal cortex are the regions most often targeted, and anodal tDCS the protocol most often applied. An intensity of 2 mA induced stronger electrical fields than 1 mA in adults with ADHD and was associated with significant behavioral changes. In ADHD children, however, the electrical field induced by 1 mA, which is likely larger than the electrical field induced by 1 mA in adults due to the smaller head size of children, was sufficient to result in significant behavioral change. Overall, tDCS seems to be a promising method for improving ADHD deficits. However, the clinical utility of tDCS in ADHD cannot yet be concluded and requires further systematic investigation in larger sample sizes. Cortical regions involved in ADHD pathophysiology, stimulation parameters (e.g. intensity, duration, polarity, and electrode size), and types of symptom/deficit are potential determinants of tDCS efficacy in ADHD. Developmental aspects of tDCS in childhood ADHD should be considered as well.

Induction of long-term potentiation-like plasticity in the primary motor cortex with repeated anodal transcranial direct current stimulation - Better effects with intensified protocols?

BACKGROUND: A single session of anodal tDCS induces LTP-like plasticity which lasts for about 1 h, while repetition of stimulation within a time interval of 30 min results in late-phase effects lasting for at least 24 h with standard stimulation protocols. OBJECTIVE: In this pilot study, we explored if the after-effects of a recently developed intensified single session stimulation protocol are relevantly prolonged in the motor cortex by repetition of this intervention. METHODS: 16 healthy right-handed subjects participated in this study. The effects of an intensified (3 mA-20min) and a standard anodal tDCS protocol (1 mA-15min) with short (20 min) and long (3 h) repetition intervals were compared with the effects of respective single session tDCS protocols (3 mA-20min, 1 mA-15min, and Sham). Cortical excitability alterations were monitored by single-pulse TMS-elicited MEPs. RESULTS: Compared to sham, both single session tDCS protocols (1 mA-15min, and 3 mA-20min) resulted in cortical excitability enhancements lasting for about 30 min after stimulation. The short repetition interval (20 min) resulted in a prolongation of after-effects for the standard protocol, which lasted for more than 24 h after stimulation. For the intensified protocol, the prolongation of after-effects was limited to 120 min after stimulation. The long repetition interval (3 h) resulted in no excitability-enhancing after-effects for the intensified, and only minor excitability enhancement within the first 30 min after the intervention for the standard protocol. CONCLUSION: These results suggest a non-linearity of late-phase LTP-like plasticity induction, which was dependent not only on the interval of intervention repetition, but also on other protocol characteristics, including intensity, and duration of tDCS. Further studies in larger samples are needed to confirm these results.

Repeated stimulation of the dorsolateral-prefrontal cortex improves executive dysfunctions and craving in drug addiction: A randomized, double-blind, parallel-group study.

BACKGROUND: According to the neurocognitive model of addiction, the development and maintenance of drug addiction is associated with cognitive control deficits, as well as decreased activity of prefrontal regions, especially the dorsolateral prefrontal cortex (DLPFC). This study investigated how improving executive functions (EFs) impacts methamphetamine-use disorder, which has been less explored compared to craving, but might be a central aspect for the therapeutic efficacy of DLPFC stimulation in drug addiction. METHODS: We assessed the efficacy of 10 repeated sessions of transcranial direct current stimulation (tDCS) over the DLPFC on executive dysfunctions in methamphetamine-use disorder, and its association with craving alterations. 39 of 50 initially recruited individuals with methamphetamine-use disorder who were in the abstinent-course treatment were randomly assigned to "active" and "sham" stimulation groups in a randomized, double-blind parallel-group study. They received active (2 mA, 20 min) or sham tDCS for 10 sessions over 5 weeks. Performance on major EF tasks (e.g., working memory, inhibitory control, cognitive flexibility, and risk-taking behaviour) and craving were measured before, immediately after, and 1 month following the intervention. Participants reported abstinence from drug consumption throughout the experiment, verified by regular urine tests during the course of the study up to the follow-up measurement. RESULTS: The group which received active DLPFC tDCS showed significantly improved task performance across all EFs immediately after and 1 month following the intervention, when compared to both pre-stimulation baseline and individuals who received sham tDCS. Similarly, a significant reduction in craving was observed immediately after and 1 month following the intervention in the active, but not sham stimulation group. A significant correlation between cognitive control improvement and craving reduction was found as well. CONCLUSIONS: Improvement of cognitive control functions is closely associated with reduced craving. Repeated DLPFC stimulation in order to improve executive control could be a promising approach for therapeutic interventions in drug addiction. However, the observed findings require further confirmation by studies that measure relapse/consumption of the respective substances over longer follow-up measurements.

Probing the relevance of repeated cathodal transcranial direct current stimulation over the primary motor cortex for prolongation of after-effects.

KEY POINTS: To explore the capability of cathodal transcranial direct current stimulation (tDCS) to induce late-phase long-term depression (LTD) via repeated stimulation. Conventional (1 mA for 15 min) and intensified (3 mA for 20 min) protocols with short (20 min) and long (24 h) intervals were tested. Late-phase plasticity was not induced by a single repetition of stimulation. Repetition reduced the efficacy of stimulation protocols with higher intensities. ABSTRACT: Transcranial direct current stimulation (tDCS) has shown promising results in pilot studies as a therapeutic intervention in disorders of the central nervous system, but more sustained effects are required for clinical application. To address this issue, one possible solution is the use of repeated stimulation protocols. Previous studies indicated the possibility of extending the after-effects of single intervention cathodal tDCS by repeating the tDCS, with relatively short intervals between repetitions being most effective. In this study, we thus investigated the effects of repeated stimulation protocols at short and long intervals, for a conventional tDCS protocol (1 mA for 15 min) and a newly developed optimized protocol (3 mA for 20 min). In 16 healthy participants, we compared single interventions of conventional and optimized protocols, repeated application of these protocols at intervals of 20 min and 24 h, and a sham tDCS session. tDCS-induced neuroplastic after-effects were then monitored with transcranial magnetic stimulation (TMS)-induced motor evoked potentials (MEPs) until the following evening after stimulation. The results revealed that the duration of the after-effects of repeated conventional and optimized protocols with short intervals remained nearly unchanged compared to the respective single intervention protocols. For the long-interval (24 h) protocol, stimulation with the conventional protocol did not significantly alter respective after-effects, while it reduced the efficacy of the optimized protocol, compared with respective single interventions. Thus late-phase plasticity could not be induced by a single repetition of stimulation in this study, but repetition reduced the efficacy of stimulation protocols with higher intensities. This study provides further insights into the dependency of tDCS-induced neuroplasticity on stimulation parameters, and therefore delivers crucial information for future tDCS applications.

Expanding the parameter space of anodal transcranial direct current stimulation of the primary motor cortex.

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.

Titrating the neuroplastic effects of cathodal transcranial direct current stimulation (tDCS) over the primary motor cortex.

Transcranial direct current stimulation (tDCS) non-invasively induces polarity-dependent excitability alterations in the human motor cortex lasting for more than an hour after stimulation. Clinical applications with encouraging results have been reported in several pilot studies, but the optimal stimulation protocols remain to be determined. This is also important because the efficacy and directionality of tDCS effects follow non-linear rules regarding neuroplastic effects for the stimulation parameters duration and intensity. In this study, we systemically explored the association between tDCS, these parameters and induced after-effects on motor cortex excitability. Cathodal tDCS was applied in four different intensities (sham, 1, 2 and 3 mA) and three durations (15, 20 and 30 mins) in 16 young healthy subjects and the after-effects were monitored with TMS-induced motor evoked potentials (MEP) until the next day evening after stimulation. The results of the repeated measures ANOVA conducted to disentangle the effects of tDCS intensity and duration show a main effect of intensity in which 1 mA and 3 mA stimulation induced a reduction of MEP amplitudes, but 2 mA resulted in excitability enhancement. The results of a secondary ANOVA conducted to compare if active stimulation effects differ from those of sham stimulation revealed a significant main effect of tDCS condition in which 1 mA-15 min, 1 mA-30 min and 3 mA-20 min cathodal tDCS induced LTD-like plasticity, while LTP-like plasticity was observed after 2 mA-20 min stimulation. Our study thus provides further insights on the dependency of tDCS -induced neuroplasticity from the stimulation parameters, and therefore delivers crucial information for future applications.

Basic and functional effects of transcranial Electrical Stimulation (tES)-An introduction.

Non-invasive brain stimulation (NIBS) has been gaining increased popularity in human neuroscience research during the last years. Among the emerging NIBS tools is transcranial electrical stimulation (tES), whose main modalities are transcranial direct, and alternating current stimulation (tDCS, tACS). In tES, a small current (usually less than 3mA) is delivered through the scalp. Depending on its shape, density, and duration, the applied current induces acute or long-lasting effects on excitability and activity of cerebral regions, and brain networks. tES is increasingly applied in different domains to (a) explore human brain physiology with regard to plasticity, and brain oscillations, (b) explore the impact of brain physiology on cognitive processes, and (c) treat clinical symptoms in neurological and psychiatric diseases. In this review, we give a broad overview of the main mechanisms and applications of these brain stimulation tools.