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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 (MEP) 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 MEP 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 baseline stimulation may enhance the utility of tDCS as a tool for understanding brain-behavior interactions and a method for clinical interventions.

The neuromodulator dopamine plays an important role in synaptic plasticity. The effects are determined by receptor subtype specificity, concentration level, and the kind of neuroplasticity induced. D1-like receptors have been proposed to be involved in cognitive processes via their impact on plasticity. Cognitive studies in humans and animals revealed a dosage-dependent effect of D1-like receptor activation on task performance. In humans, D1-like receptor activation re-establishes plasticity under D2 receptor block. However, a dosagedependent effect has not been explored so far. To determine the impact of the amount of D1-like receptor activation on neuroplasticity in humans, we combined sulpiride, a selective D2 receptor antagonist, with the dopamine precursor L-DOPA (25, 100, and 200 mg) or applied placebo medication. The impact on plasticity induced by anodal and cathodal transcranial direct current stimulation (tDCS) was compared with the impact on plasticity induced by excitatory and inhibitory paired associative stimulation (PAS) at the primary motor cortex of healthy humans. Stimulation-generated cortical excitability alterations were monitored by transcranial magnetic stimulation-induced motor-evoked potential amplitudes. D1-like receptor activation produced an inverted U-shaped dose-response curve on plasticity induced by both facilitatory tDCS and PAS. For excitability-diminishing tDCS and PAS, aftereffects were abolished or converted trendwise into facilitation. These data extend findings of dose-dependent inverted U-shaped effects of D1 receptor activation on neuroplasticity of the motor cortex.

The neuromodulator dopamine plays an important role in synaptic plasticity. The effects depend on receptor subtypes, affinity, concentration level, and the kind of neuroplasticity induced. In animal experiments, dopamine D 2 -like receptor stimulation revealed partially antagonistic effects on plasticity, which might be explained by dosage dependency. In humans, D 2 receptor block abolishes plasticity, and the D 2 /D 3 , but predominantly D 3 , receptor agonist ropinirol has a dosage-dependent nonlinear affect on plasticity. Here we aimed to determine the specific affect of D 2 receptor activation on neuroplasticity in humans, because physiological effects of D 2 and D 3 receptors might differ. Therefore, we combined application of the selective D 2 receptor agonist bromocriptine (2.5, 10, and 20 mg or placebo medication) with anodal and cathodal transcranial direct current stimulation (tDCS), which induces nonfocal plasticity, and with paired associative stimulation (PAS) generating a more focal kind of plasticity in the motor cortex of healthy humans. Plasticity was monitored by transcranial magnetic stimulation-induced motor-evoked potential amplitudes. For facilitatory tDCS, bromocriptine prevented plasticity induction independent from drug dosage. However, its application resulted in an inverted U-shaped dose-response curve on inhibitory tDCS, excitability-diminishing PAS, and to a minor degree on excitability-enhancing PAS. These data support the assumption that modulation of D 2 -like receptor activity exerts a nonlinear dose-dependent effect on neuroplasticity in the human motor cortex that differs from predominantly D 3 receptor activation and that the kind of plasticity-induction procedure is relevant for its specific impact.

Transcranial alternating current stimulation (tACS) can modulate brain oscillations, cortical excitability and behaviour. In aging, the decrease in EEG alpha activity (8–12 Hz) in the parieto-occipital and mu rhythm in the motor cortex are correlated with the decline in cognitive and motor functions, respectively. Increasing alpha activity using tACS might therefore improve cognitive and motor function in the elderly. The present study explored the influence of tACS on cortical excitability in young and old healthy adults. We applied tACS at individual alpha peak frequency for 10 min (1.5 mA) to the left motor cortex. Transcranial magnetic stimulation was used to assess the changes in cortical excitability as measured by motor-evoked potentials at rest, before and after stimulation. TACS increased cortical excitability in both groups. However, our results also suggest that the mechanism behind the effects was different, as we observed an increase and decrease in intracortical inhibition in the old group and young group, respectively. Our results indicate that both groups profited similarly from the stimulation. There was no indication that tACS was more effective in conditions of low alpha power, that is, in the elderly.Electronic supplementary materialThe online version of this article (10.1007/s00221-018-5314-3) contains supplementary material, which is available to authorized users.