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

Abstract

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.

Keywords: Intensity; TMS; Variability; tDCS.

Figure 1

Experimental Procedure. Data were available from studies using four different conditioning protocols: anodal tDCS, cathodal tDCS, PAS 25 stimulation, or PAS 10 stimulation. For each participant, the maximum stimulator output (MSO) was set to elicit baseline MEPs that averaged 1 mV peak-to-peak amplitude. A baseline measure of corticospinal excitability was obtained prior to conditioning protocol and then at multiple time points following conditioning. Three time windows were defined: The Early window included all epochs between 0 and 30 min and the Middle window included epochs between 60 and 120 min. A Late window was composed of epochs obtained after the initial 2-hour session: same evening (se), next morning (nm), next noon (nn), next evening (ne).

Figure 2

MEPs changes at each epoch for the four conditioning protocols. The data are averaged over all participants for a given conditions. In black are shown MEPs changes after tDCS conditioning protocols anodal filled square, cathodal empty circle) and in gray are shown are shown MEPs changes after PAS conditioning protocols (PAS 25 empty square, PAS 10 full circle). Error bars indicate SEMs.

Figure 3

MEPs changes at each epoch for the tDCS (a) and PAS (b) conditioning protocols, with the participants in each condition divided into Low Intensity (fill lines) and High intensity groups (dotted lines). The division was based on a median split defined by the level of TMS stimulation required to elicit 1 mV MEPs prior to the conditioning protocol. Error bars indicate SEMs.

Figure 4

MEPs changes in the Early and Middle time windows for participants in the anodal tDCS protocol, with the participants divided into Low Intensity (black filling) and High intensity (white filling) groups. Error bars indicate SEMs.

Figure 5

Correlation between intensity of TMS stimulation and MEP amplitude change. Data are from the Early time window (0–30 min after intervention) for the anodal (a) and cathodal (b) tDCS groups.