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      Transcranial direct current stimulation: a roadmap for research, from mechanism of action to clinical implementation

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          Abstract

          Transcranial direct current stimulation (tDCS) is a promising method for altering the function of neural systems, cognition, and behavior. Evidence is emerging that it can also influence psychiatric symptomatology, including major depression and schizophrenia. However, there are many open questions regarding how the method might have such an effect, and uncertainties surrounding its influence on neural activity, and human cognition and functioning. In the present critical review, we identify key priorities for future research into major depression and schizophrenia, including studies of the mechanism(s) of action of tDCS at the neuronal and systems levels, the establishment of the cognitive impact of tDCS, as well as investigations of the potential clinical efficacy of tDCS. We highlight areas of progress in each of these domains, including data which appears to favor an effect of tDCS on neural oscillations rather than spiking, and findings that tDCS administration to the prefrontal cortex during task training may be an effective way to enhance behavioral performance. Finally, we provide suggestions for further empirical study that will elucidate the impact of tDCS on brain and behavior, and may pave the way for efficacious clinical treatments for psychiatric disorders.

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          Most cited references83

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          Synaptic mechanisms and network dynamics underlying spatial working memory in a cortical network model.

          Single-neuron recordings from behaving primates have established a link between working memory processes and information-specific neuronal persistent activity in the prefrontal cortex. Using a network model endowed with a columnar architecture and based on the physiological properties of cortical neurons and synapses, we have examined the synaptic mechanisms of selective persistent activity underlying spatial working memory in the prefrontal cortex. Our model reproduces the phenomenology of the oculomotor delayed-response experiment of Funahashi et al. (S. Funahashi, C.J. Bruce and P.S. Goldman-Rakic, Mnemonic coding of visual space in the monkey's dorsolateral prefrontal cortex. J Neurophysiol 61:331-349, 1989). To observe stable spontaneous and persistent activity, we find that recurrent synaptic excitation should be primarily mediated by NMDA receptors, and that overall recurrent synaptic interactions should be dominated by inhibition. Isodirectional tuning of adjacent pyramidal cells and interneurons can be accounted for by a structured pyramid-to-interneuron connectivity. Robust memory storage against random drift of the tuned persistent activity and against distractors (intervening stimuli during the delay period) may be enhanced by neuromodulation of recurrent synapses. Experimentally testable predictions concerning the neural basis of working memory are discussed.
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            Is Open Access

            Empirical assessment of published effect sizes and power in the recent cognitive neuroscience and psychology literature

            We have empirically assessed the distribution of published effect sizes and estimated power by analyzing 26,841 statistical records from 3,801 cognitive neuroscience and psychology papers published recently. The reported median effect size was D = 0.93 (interquartile range: 0.64–1.46) for nominally statistically significant results and D = 0.24 (0.11–0.42) for nonsignificant results. Median power to detect small, medium, and large effects was 0.12, 0.44, and 0.73, reflecting no improvement through the past half-century. This is so because sample sizes have remained small. Assuming similar true effect sizes in both disciplines, power was lower in cognitive neuroscience than in psychology. Journal impact factors negatively correlated with power. Assuming a realistic range of prior probabilities for null hypotheses, false report probability is likely to exceed 50% for the whole literature. In light of our findings, the recently reported low replication success in psychology is realistic, and worse performance may be expected for cognitive neuroscience.
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              Frontal midline EEG dynamics during working memory.

              We show that during visual working memory, the electroencephalographic (EEG) process producing 5-7 Hz frontal midline theta (fmtheta) activity exhibits multiple spectral modes involving at least three frequency bands and a wide range of amplitudes. The process accounting for the fmtheta increase during working memory was separated from 71-channel data by clustering on time/frequency transforms of components returned by independent component analysis (ICA). Dipole models of fmtheta component scalp maps were consistent with their generation in or near dorsal anterior cingulate cortex. From trial to trial, theta power of fmtheta components varied widely but correlated moderately with theta power in other frontal and left temporal processes. The weak mean increase in frontal midline theta power with increasing memory load, produced entirely by the fmtheta components, largely reflected progressively stronger theta activity in a relatively small proportion of trials. During presentations of letter series to be memorized or ignored, fmtheta components also exhibited 12-15 Hz low-beta activity that was stronger during memorized than during ignored letter trials, independent of letter duration. The same components produced a brief 3-Hz burst 500 ms after onset of the Probe letter following each letter sequence. A new decomposition method, log spectral ICA, applied to normalized log time/frequency transforms of fmtheta component Memorize-letter trials, showed that their low-beta activity reflected harmonic energy in continuous, sharp-peaked theta wave trains as well as independent low-beta bursts. Possibly, the observed fmtheta process variability may index dynamic adjustments in medial frontal cortex to trial-specific behavioral context and task demands.
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                Author and article information

                Journal
                9607835
                20545
                Mol Psychiatry
                Mol. Psychiatry
                Molecular psychiatry
                1359-4184
                1476-5578
                10 July 2019
                27 August 2019
                February 2020
                27 February 2020
                : 25
                : 2
                : 397-407
                Affiliations
                [1. ]Department of Psychiatry, University of Pittsburgh, Pittsburgh, USA
                [2. ]Department of Psychiatry and Behavioral Sciences, University of California, Davis
                Author notes
                Corresponding Author: Henry Chase; Western Psychiatric Institute and Clinic, Loeffler Building, 121 Meyran Avenue, Pittsburgh, PA, 15213; Tel: 412-383-0113 Fax: 412-383-8336; chaseh@ 123456upmc.edu
                Article
                NIHMS1534163
                10.1038/s41380-019-0499-9
                6981019
                31455860
                ae2ab0ce-ed91-45d9-9f23-bd753e3d0bf3

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                Categories
                Article

                Molecular medicine
                transcranial direct current stimulation,neural mechanism,moderators,psychiatric treatment

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