Preconditioning of low-frequency repetitive transcranial magnetic stimulation with transcranial direct current stimulation: evidence for homeostatic plasticity in the human motor cortex

Abstract

Recent experimental work in animals has emphasized the importance of homeostatic plasticity as a means of stabilizing the properties of neuronal circuits. Here, we report a phenomenon that indicates a homeostatic pattern of cortical plasticity in healthy human subjects. The experiments combined two techniques that can produce long-term effects on the excitability of corticospinal output neurons: transcranial direct current stimulation (TDCS) and repetitive transcranial magnetic stimulation (rTMS) of the left primary motor cortex. "Facilitatory preconditioning" with anodal TDCS caused a subsequent period of 1 Hz rTMS to reduce corticospinal excitability to below baseline levels for >20 min. Conversely, "inhibitory preconditioning" with cathodal TDCS resulted in 1 Hz rTMS increasing corticospinal excitability for at least 20 min. No changes in excitability occurred when 1 Hz rTMS was preceded by sham TDCS. Thus, changing the initial state of the motor cortex by a period of DC polarization reversed the conditioning effects of 1 Hz rTMS. These preconditioning effects of TDCS suggest the existence of a homeostatic mechanism in the human motor cortex that stabilizes corticospinal excitability within a physiologically useful range.

Figures

Figure 1.

Experimental design. a, In the main experiment, a 10 min session of anodal, cathodal, or sham TDCS was given to the left primary motor hand area (M1) on separate days. For anodal TDCS, the anode was placed over the left M1, and the cathode was placed over the right eyebrow. Polarity was reversed for cathodal TDCS. At 10 min after the end of the TDCS session, 900 biphasic pulses of 1 Hz rTMS were given to the left M1 at 85% of resting motor threshold. Corticospinal excitability was probed with single-pulse and paired-pulse TMS over the left M1 before TDCS, after TDCS, and twice after rTMS. b, In the control experiment, the conditioning effects of anodal and cathodal TDCS alone were explored in five subjects (10 min, 1 mA). To control for nonspecific effects of rTMS, real rTMS was replaced by sham rTMS using a specifically designed placebo coil.

Figure 2.

Stimulation-induced changes in motor cortical output to the right first dorsal interosseus muscle. a, In the main experiment, the figure plots the amplitude of a standard test MEP evoked by a single TMS probe stimulus at different times before and after the two types of conditioning. The aftereffects of 1 Hz rTMS were critically dependent on the preconditioning by TDCS over the left M1. A total of 1 Hz rTMS reversed polarity-specific effects induced by anodal or cathodal TDCS. Sham TDCS followed by rTMS had no impact on corticospinal excitability. b, In the first control experiment, TDCS alone induced a polarity-specific shift in the level of corticospinal excitability. Anodal TDCS caused a sustained increase in excitability, whereas cathodal TDCS resulted in a lasting reduction of corticospinal excitability. c, In the second control experiment,when TDCS was administered to the left posterior parietal cortex, TDCS produced no polarity-specific shift in ipsilateral corticospinal excitability and had no preconditioning effect on subsequent administration of 1 Hz rTMS to the left M1. In each panel, the symbols represent the mean MEP amplitude (normalized to the mean MEP amplitude at baseline) after TDCS (first column) and after rTMS (second and third columns). Error bars represent SEM. Both control experiments were conducted in five of the eight subjects who had participated in the main experiment.

Figure 3.

Stimulation-induced effects on various measures of motor cortical excitability. Motor cortical excitability was assessed with single-pulse TMS and paired-pulse TMS at different ISIs using a conditioning-test paradigm (Kujirai et al., 1993). This allowed for assessment of changes in corticospinal excitability (single magnetic pulses) and intracortical excitability of the left M1 (pairs of magnetic pulses). ISIs of 2 and 4 msec probed the magnitude of short-latency intracortical inhibition (SICI), whereas ISIs of 9 and 12 msec were used to assess the strength of short-latency intracortical facilitation (SICF). Changes in paired-pulse excitability paralleled changes in single-pulse excitability. a illustrates the effects of anodal TDCS followed by 1 Hz rTMS. b presents the effects of cathodal TDCS followed by 1 Hz rTMS. Symbols and error bars represent the mean MEP amplitude and SEM, respectively.