Asif Jamil

Systematic evaluation of the impact of stimulation intensity on neuroplastic after-effects induced by transcranial direct current stimulation.

Applications of transcranial direct current stimulation to modulate human neuroplasticity have increased in research and clinical settings. However, the need for longer‐lasting effects, combined with marked inter‐individual variability, necessitates a deeper understanding of the relationship between stimulation parameters and physiological effects. We systematically investigated the full DC intensity range (0.5–2.0 mA) for both anodal and cathodal tDCS in a sham‐controlled repeated measures design, monitoring changes in motor‐cortical excitability via transcranial magnetic stimulation up to 2 h after stimulation. For both tDCS polarities, the excitability after‐effects did not linearly correlate with increasing DC intensity; effects of lower intensities (0.5, 1.0 mA) showed equal, if not greater effects in motor‐cortical excitability. Further, while intra‐individual responses showed good reliability, inter‐individual sensitivity to TMS accounted for a modest percentage of the variance in the early after‐effects of 1.0 mA anodal tDCS, which may be of practical relevance for future optimizations.

Efficacy of Anodal Transcranial Direct Current Stimulation is Related to Sensitivity to Transcranial Magnetic Stimulation

BACKGROUND Transcranial direct current stimulation (tDCS) has become an important non-invasive brain stimulation tool for basic human brain physiology and cognitive neuroscience, with potential applications in cognitive and motor rehabilitation. To date, tDCS studies have employed a fixed stimulation level, without considering the impact of individual anatomy and physiology on the efficacy of the stimulation. This approach contrasts with the standard procedure for transcranial magnetic stimulation (TMS) where stimulation levels are usually tailored on an individual basis. OBJECTIVE/HYPOTHESIS The present study tests whether the efficacy of tDCS-induced changes in corticospinal excitability varies as a function of individual differences in sensitivity to TMS. METHODS We performed an archival review to examine the relationship between the TMS intensity required to induce 1 mV motor-evoked potentials (MEPs) and the efficacy of (fixed-intensity) tDCS over the primary motor cortex (M1). For the latter, we examined tDCS-induced changes in corticospinal excitability, operationalized by comparing MEPs before and after anodal or cathodal tDCS. For comparison, we performed a similar analysis on data sets in which MEPs had been obtained before and after paired associative stimulation (PAS), a non-invasive brain stimulation technique in which the stimulation intensity is adjusted on an individual basis. RESULTS MEPs were enhanced following anodal tDCS. This effect was larger in participants more sensitive to TMS as compared to those less sensitive to TMS, with sensitivity defined as the TMS intensity required to produce MEPs amplitudes of the size of 1 mV. While MEPs were attenuated following cathodal tDCS, the magnitude of this attenuation was not related to TMS sensitivity nor was there a relationship between TMS sensitivity and responsiveness to PAS. CONCLUSION Accounting for variation in individual sensitivity to non-invasive brain stimulation may enhance the utility of tDCS as a tool for understanding brain-behavior interactions and as a method for clinical interventions.

Chronic Enhancement of Serotonin Facilitates Excitatory Transcranial Direct Current Stimulation-Induced Neuroplasticity

Serotonin affects memory formation via modulating long-term potentiation (LTP) and depression (LTD). Accordingly, acute selective serotonin reuptake inhibitor (SSRI) administration enhanced LTP-like plasticity induced by transcranial direct current stimulation (tDCS) in humans. However, it usually takes some time for SSRI to reduce clinical symptoms such as anxiety, negative mood, and related symptoms of depression and anxiety disorders. This might be related to an at least partially different effect of chronic serotonergic enhancement on plasticity, as compared with single-dose medication. Here we explored the impact of chronic application of the SSRI citalopram (CIT) on plasticity induced by tDCS in healthy humans in a partially double-blinded, placebo (PLC)-controlled, randomized crossover study. Furthermore, we explored the dependency of plasticity induction from the glutamatergic system via N-methyl-D-aspartate receptor antagonism. Twelve healthy subjects received PLC medication, combined with anodal or cathodal tDCS of the primary motor cortex. Afterwards, the same subjects took CIT (20 mg/day) consecutively for 35 days. During this period, four additional interventions were performed (CIT and PLC medication with anodal/cathodal tDCS, CIT and dextromethorphan (150 mg) with anodal/cathodal tDCS). Plasticity was monitored by motor-evoked potential amplitudes elicited by transcranial magnetic stimulation. Chronic application of CIT increased and prolonged the LTP-like plasticity induced by anodal tDCS for over 24 h, and converted cathodal tDCS-induced LTD-like plasticity into facilitation. These effects were abolished by dextromethorphan. Chronic serotonergic enhancement results in a strengthening of LTP-like glutamatergic plasticity, which might partially explain the therapeutic impact of SSRIs in depression and other neuropsychiatric diseases.

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.

Acute and chronic effects of noradrenergic enhancement on transcranial direct current stimulation (tDCS)-induced neuroplasticity in humans

Chronic administration of the selective noradrenaline reuptake inhibitor (NRI) reboxetine (RBX) increased and prolonged the long‐term potentiation‐like plasticity induced by anodal transcranial direct current stimulation (tDCS) for over 24 h. Chronic administration of RBX converted cathodal tDCS‐induced long‐term depression‐like plasticity into facilitation for 120 min. Chronic noradrenergic activity enhancement on plasticity of the human brain might partially explain the delayed therapeutic impact of selective NRIs in depression and other neuropsychiatric diseases.

Acute and Chronic Noradrenergic Effects on Cortical Excitability in Healthy Humans

Abstract Background Noradrenaline is a major neuromodulator in the central nervous system, and it is involved in the pathophysiology of diverse neuropsychiatric diseases. Previous transcranial magnetic stimulation studies suggested that acute application of selective noradrenaline reuptake inhibitors enhances cortical excitability in the human brain. However, other, such like clinical effects, usually require prolonged noradrenaline reuptake inhibitor treatment, which might go along with different physiological effects. Methods The purpose of this study was to investigate the acute and chronic effects of the selective noradrenaline reuptake inhibitor reboxetine on cortical excitability in healthy humans in a double-blind, placebo-controlled, randomized crossover study. Sixteen subjects were assessed with different transcranial magnetic stimulation measurements: motor thresholds, input-output curve, short-latency intracortical inhibition and intracortical facilitation, I-wave facilitation, and short-interval afferent inhibition before and after placebo or reboxetine (8 mg) single-dose administration. Afterwards, the same subjects took reboxetine (8 mg/d) consecutively for 21 days. During this period (subjects underwent 2 experimental sessions with identical transcranial magnetic stimulation measures under placebo or reboxetine), transcranial magnetic stimulation measurements were assessed before and after drug intake. Results Both single-dose and chronic administration of reboxetine increased cortical excitability; increased the slope of the input-output curve, intracortical facilitation, and I-wave facilitation; but decreased short-latency intracortical inhibition and short-interval afferent inhibition. Moreover, chronic reboxetine showed a larger enhancement of intracortical facilitation and I-wave facilitation compared with single-dose application. Conclusions The results show physiological mechanisms of noradrenergic enhancement possibly underlying the functional effects of reboxetine regarding acute and chronic application.

What Effect Does tDCS Have on the Brain? Basic Physiology of tDCS

Purpose of the ReviewTranscranial direct current stimulation (tDCS) can effectively modulate a wide range of clinical and cognitive outcomes by modulating cortical excitability. Here, we summarize the main findings from both animal and human neurophysiology literature, which have revealed mechanistic evidence for the acute and neuroplastic after-effects of tDCS.Recent FindingsInsights into the magnitude and geometric orientation of transcranially induced currents have been provided by the combination of computational modeling of current flow in animal slice preparations and intracranial recordings in humans. In addition to its synaptic effects, stimulation also induces after-effects on the glial and vascular systems, the latter also observed in humans by magnetic resonance imaging. Several studies have also observed non-linear or antagonistic effects of tDCS parameters, which warrants further systematic studies to explore and understand the basic mechanisms.SummarytDCS is a valuable and promising technique across the neurophysiological, cognitive neuroscience, and clinical domains of research. Primary and secondary effects of tDCS still remain to be completely understood. An important challenge for the field is advancing tDCS protocols forward for optimal intervention and treatment strategies.

Modulating functional connectivity with non-invasive brain stimulation for the investigation and alleviation of age-associated declines in response inhibition: A narrative review

&NA; Response inhibition, the ability to withhold a dominant and prepotent response following a change in circumstance or sensory stimuli, declines with advancing age. While non‐invasive brain stimulation (NiBS) has shown promise in alleviating some cognitive and motor functions in healthy older individuals, NiBS research focusing on response inhibition has mostly been conducted on younger adults. These extant studies have primarily focused on modulating the activity of distinct neural regions known to be critical for response inhibition, including the right inferior frontal gyrus (rIFG) and the pre‐supplementary motor area (pre‐SMA). However, given that changes in structural and functional connectivity have been associated with healthy aging, this review proposes that NiBS protocols aimed at modulating the functional connectivity between the rIFG and pre‐SMA may be the most efficacious approach to investigate—and perhaps even alleviate—age‐related deficits in inhibitory control. HighlightsStructural and functional changes within the fronto‐basal‐ganglia network likely mediate declined inhibition in elderly.Non‐invasive brain stimulation can provide mechanistic insight into how executive functions deteriorate with advancing age.Non‐invasive brain stimulation modulating inter‐regional network activity may alleviate age‐related deficits in inhibition.

S181. Optimizing the neuroplastic effects of cathodal transcranial direct current stimulation (tDCS) over the primary motor cortex

Introduction Transcranial direct current stimulation (tDCS) can non-invasively induce polarity-dependent excitability alterations in the human motor cortex lasting more than an hour after stimulation. Clinical application with encouraging results have been reported in several pilot studies, but the optimal stimulation protocols remain to be determined. Methods We systemically explored the association between tDCS parameters (intensity, duration) and induced after-effects on motor cortex excitability. Cathodal tDCS was applied in three different intensities (1, 2 and 3 mA) and durations (15, 20 and 30mins) on 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 revealed nonlinear after-effects, which might be caused by calcium dynamics relevant for long term depression and potentiation induction. Results The results revealed that 1 mA −15 min, 1 mA −30 min and 3 mA −20 min induced LTD-like plasticity, while LTP-like plasticity was observed after 2 mA stimulation for 20 min. It was shown that there is a nonlinear modulatory effect of stimulation intensity/duration on neuroplasticity, which might be caused by calcium dynamics relevant for long-term depression and potentiation induction. Conclusion Our study thus provides further insights on the dependency of tDCS-induced neuroplasticity on the stimulation parameters, and therefore delivers crucial information for future clinical applications.

S149. Improved bimanual control in elderly after motor cortex stimulation

Introduction Accompanying the natural advancing of age is a decline in cognitive and motor functions, which may be the result of altered neuroplasticity, due to changes in synaptic function and neurotransmission. Successful performance of routine, but complex motor tasks such as bimanual movements may require optimal synchronization of motor cortical areas, which decline with ageing. On the other hand, recent work has shown that transcranial direct current stimulation (tDCS) may be a useful tool to restitute these altered mechanisms, and improve performance of motor skills. Presently, we address the question of identifying physiological markers of age-related differences during acquisition of new bimanual motor control tasks, based on induced oscillatory changes, using EEG. Second, we assess whether performance of complex bimanual skills can be improved in the elderly using tDCS. Methods Experiment 1 : 43 healthy subjects (21 elderly) performed the bimanual tracking task (BTT), which is a complex task requiring multiple cognitive domains, as well as the skilled use of in-phase and anti-phase movements, at various frequencies. Three blocks of the task were performed (180 total trials) while EEG was recorded to measure task-induced power changes. Experiment 2 : An additional 40 subjects (20 elderly) were recruited for evaluating whether right M1 anodal tDCS (1.0 mA, 20 min) may improve performance in the task, particularly in the non-dominant left hand. The study was double-blinded, sham-controlled, and employed a randomized crossover design in order to assess tDCS-induced performance and task-induced synchronization differences between young and elderly groups. Results Experiment 1: Overall task performance in younger subjects was more accurate than in elderly. Younger subjects showed significantly stronger desynchronization in the mu and beta band, whereas older subjects showed greater gamma band activity in motor cortical areas. In addition, these patterns were also found to correlate inter-individually with accurate performance in the task. Experiment 2: ANOVA revealed a main effect of stimulation, which was significant between active and sham tDCS conditions in the elderly but not in young. Further exploratory analyses revealed significant improvements in both left and right hand coordination in active stimulation conditions for both groups of subjects, with the greatest improvement found in left-hand dominant motor movements in the elderly group. Conclusion We show that both task-induced oscillatory synchronization and inter-limb kinematics underlying bimanual motor coordination are different between the young and elderly. Further, a single session of tDCS applied to the motor cortex could significantly improve bimanual performance in the elderly. Although further studies are needed to optimize tDCS parameters for enhanced and prolonged effects, tDCS may be a viable tool in restituting the learning of complex motor functions in the aging or other vulnerable populations.