Time course of the induction of homeostatic plasticity generated by repeated transcranial direct current stimulation of the human motor cortex

Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College of London, London, United Kingdom.
Journal of Neurophysiology (Impact Factor: 3.04). 12/2010; 105(3):1141-9. DOI: 10.1152/jn.00608.2009
Source: PubMed

ABSTRACT Several mechanisms have been proposed that control the amount of plasticity in neuronal circuits and guarantee dynamic stability of neuronal networks. Homeostatic plasticity suggests that the ease with which a synaptic connection is facilitated/suppressed depends on the previous amount of network activity. We describe how such homeostatic-like interactions depend on the time interval between two conditioning protocols and on the duration of the preconditioning protocol. We used transcranial direct current stimulation (tDCS) to produce short-lasting plasticity in the motor cortex of healthy humans. In the main experiment, we compared the aftereffect of a single 5-min session of anodal or cathodal tDCS with the effect of a 5-min tDCS session preceded by an identical 5-min conditioning session administered 30, 3, or 0 min beforehand. Five-minute anodal tDCS increases excitability for about 5 min. The same duration of cathodal tDCS reduces excitability. Increasing the duration of tDCS to 10 min prolongs the duration of the effects. If two 5-min periods of tDCS are applied with a 30-min break between them, the effect of the second period of tDCS is identical to that of 5-min stimulation alone. If the break is only 3 min, then the second session has the opposite effect to 5-min tDCS given alone. Control experiments show that these shifts in the direction of plasticity evolve during the 10 min after the first tDCS session and depend on the duration of the first tDCS but not on intracortical inhibition and facilitation. The results are compatible with a time-dependent "homeostatic-like" rule governing the response of the human motor cortex to plasticity probing protocols.

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    • "These lasting effects cannot be explained as persistent network activity in the absence of some adaptive process since in our previous work gamma power returned to baseline activity within 100 ms after short-lasting DC field stimulation (Reato et al. 2010). Importantly, the afterstimulation effect was consistent with the acute effect, reminiscent of Hebbian or activitydependent plasticity and contrary to homeostatic plasticity (Fricke et al. 2011; Reato et al. 2013). "
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    ABSTRACT: Transcranial Direct Current Stimulation (tDCS) is emerging as a versatile tool to affect brain function. While acute neurophysiological effects of stimulation are well understood, little is know about the long term effects. One hypothesis is that stimulation modulates ongoing neural activity which then translates into lasting effects via physiological plasticity. Here we used carbachol-induced gamma oscillations in hippocampal rat slices to establish whether prolonged constant current stimulation has a lasting effect on endogenous neural activity. During 10 minutes of stimulation, power and frequency of gamma oscillations, as well as multi-unit activity were modulated in a polarity specific manner. Remarkably, the effects on power and multi-unit activity persisted for more than 10 minutes after stimulation terminated. Using a computational model we propose that altered synaptic efficacy in excitatory and inhibitory pathways could be the source of these lasting effects. Future experimental studies using this novel in-vitro preparation may be able to confirm or refute the proposed hypothesis. Copyright © 2014, Journal of Neurophysiology.
    Journal of Neurophysiology 12/2014; 113(5):jn.00208.2014. DOI:10.1152/jn.00208.2014 · 3.04 Impact Factor
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    • "In particular, NMDA and AMPA receptors are essential for synaptic plasticity by influencing long-term potentiation and depression (LTP and LTD) across structurally-connected brain regions (Bliss and Collingridge, 1993). These synaptic and neuronal pathways consolidate into stable and long-lasting functional brain networks (Fricke et al., 2011; Venkatakrishnan et al., 2011; Venkatakrishnan and Sandrini, 2012). However, the effects of tDCS on glutamate levels and its relation to largescale network connectivity have yet to be fully elucidated; that is, there must be a better understanding of how tDCS interacts across different scales within the brain's neural architecture by combining different, yet complementary, imaging modalities (see Hunter et al., 2013 for a review), which was the primary objective of the present study. "
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    ABSTRACT: Transcranial direct current stimulation (tDCS) modulates glutamatergic neurotransmission and can be utilized as a novel treatment intervention for a multitude of populations. However, the exact mechanism by which tDCS modulates the brain’s neural architecture, from the micro to macro scales, have yet to be illuminated. Using a within-subjects design, resting-state functional magnetic resonance imaging (rs-fMRI) and proton magnetic resonance spectroscopy (1H-MRS) were performed immediately before and after the administration of anodal tDCS over right parietal cortex. Group independent component analysis (ICA) was used to decompose fMRI scans into 75 brain networks, from which 12 resting-state networks were identified that had significant voxel-wise functional connectivity to anatomical regions of interest. 1H-MRS was used to obtain estimates of combined glutamate and glutamine (Glx) concentrations from bilateral intraparietal sulcus. Paired sample t-tests showed significantly increased Glx under the anodal electrode, but not in homologous regions of the contralateral hemisphere. Increases of within-network connectivity were observed within the superior parietal, inferior parietal, left frontal-parietal, salience and cerebellar intrinsic networks, and decreases in connectivity were observed in the anterior cingulate and the basal ganglia (p<0.05, FDR-corrected). Individual differences in Glx concentrations predicted network connectivity in most of these networks. The observed relationships between glutamatergic neurotransmission and network connectivity may be used to guide future tDCS protocols that aim to target and alter neuroplastic mechanisms in healthy individuals as well as those with psychiatric and neurologic disorders.
    Brain Research 12/2014; 1594(2015):92-107. DOI:10.1016/j.brainres.2014.09.066 · 2.83 Impact Factor
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    • "A second possible explanation at the local level could be based on metaplasticity phenomena, i.e., activity-dependent mechanisms in which the neural activity at one point in time can modulate the induction of plasticity in a following point in time [46]. These mechanisms, such as homeostatic plasticity, have been previously shown to alter the induction of plasticity by non-invasive brain stimulation techniques, even after a few minutes of stimulation [10] [47]. Nevertheless, a crucial aspect of homeostatic plasticity refers to compensatory mechanisms that develop with intense and prolonged plasticity-inducing protocols rather than being instantaneous [9]. "
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    ABSTRACT: Anodal transcranial direct current stimulation (A-tDCS) is a non-invasive technique in which cortical polarization can be used to increase excitability and facilitate learning through the modulation of neuroplasticity. Although the facilitatory effects of A-tDCS are well documented, there is evidence that they are not always present and may even be reversed during task execution.Objective In this study, we explore the interaction between A-tDCS and task execution. We aimed to test how the excitability induced by the task interacts with the excitability induced by A-tDCS and determines the behavioral outcome.Methods We performed an experiment in which A-tDCS or a control stimulation (Ctrl) were combined with one of two motor practices (MP), one inducing learning and increasing cortical excitability (F-MP) and the other neither inducing learning nor changing cortical excitability (S-MP). Six blocks of MP were performed while the primary motor cortex was stimulated. Moreover, one block of F-MP was performed before the stimulation (baseline) and one after. In an additional experiment, motor evoked potentials (MEPs) were recorded before the baseline block (TMS-pre) and after the MP (TMS-post).ResultsWe observed that A-tDCS reduced learning when participants performed the F-MP and facilitated learning for the S-MP. MEPs data paralleled behavioral results, confirming that the effects generated by A-tDCS depend on the excitability changes induced by the task. Conclusions: Our results demonstrate that tDCS-induced plasticity is task-dependent, and the concurrent combination of A-tDCS with another excitability-increasing event, e.g., motor practice, may trigger non-additive mechanisms, hindering neuroplasticity.
    Brain Stimulation 11/2014; 8(2). DOI:10.1016/j.brs.2014.11.006 · 5.43 Impact Factor
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