We hypothesized that compared with sham stimulation, AtDCS over M1 will enhance online and offline learning of the implicit motor sequence. In contrast, because PMd is known to be engaged in explicit knowledge of motor sequences, upregulating PMd with AtDCS during practice will attenuate online and offline learning of the implicit motor sequence. Thirteen right-handed healthy adults consented to participate

in the experimental protocol approved by the Institutional Review Board of the Northwestern University. None of the participants had any history of neurological, psychiatric illness or any contraindications to transcranial magnetic stimulation (TMS) or tDCS. All participants used their non-dominant (left) hand for practice of the sequences. Sirolimus mouse Each participant attended three experimental sessions separated

by at least 8 days (Fig. 1). Each experimental session consisted of two consecutive days. On day 1 of each experimental session, selleck inhibitor TMS was used to identify the hotspot for the first dorsal interosseous (FDI) muscle (see below for details). Participants were then tested for baseline performance on the motor sequence. Following baseline assessment, the participants received AtDCS over PMd or M1 or sham AtDCS. Once the participants were comfortable with tDCS (∼2 min later), motor sequence practice was begun. The order of PMd, M1 and sham tDCS was counterbalanced across the three experimental sessions and across participants. On day 2 of each session, the participants returned for a test of retention of the learned motor sequence. A modified version of the serial reaction time task (SRTT) (Nissen & Bullemer, 1987) was used for implicit or procedural learning. Stimuli were presented in a horizontal array at one of the four locations on a computer screen. Each of the positions on the screen corresponded to four keys (V, B, N, M) on the keyboard. Participants sat comfortably in front of the computer with fingers (little, ring, middle and index) of the left hand on the four keys (V,

B, N, M), respectively. For each trial, when a cue appeared on the screen, the participants responded as quickly as possible by pressing the corresponding Galeterone key. The stimulus remained on the screen until the correct response was made. Unbeknown to the participant a ten-item sequence was repeatedly presented. This allowed them to acquire the sequence in an implicit manner. At each experimental session, participants practiced one of the three ten-item implicit sequences (4-1-2-4-3-2-1-4-1-3; 3-2-4-3-1-4-2-3-4-1; 2-1-3-2-4-3-1-3-2-4) of comparable difficulty and with minimal carryover between sequences. A different sequence was practiced at each experimental session and the order of the sequences was counterbalanced across the 13 subjects.