Experiment 1 examined whether tDCS enhances rapid frequency discrimination

learning. Human subjects were trained on a frequency discrimination task for 2 days with anodal tDCS applied during the first day with the second day used to assess effects of stimulation on retention. This revealed that tDCS did not affect learning but did degrade frequency discrimination during both days. Follow-up testing 2–3 months after stimulation showed no long-term effects. Following the unexpected results, two additional experiments Rapamycin concentration examined the effects of tDCS on the underlying mechanisms of frequency discrimination, place and temporal coding. Place coding underlies frequency selectivity and was measured using psychophysical tuning curves with broader curves indicating poorer frequency selectivity. Temporal

coding is determined by measuring the ability to discriminate sounds with different fine temporal structure. We found that tDCS does not broaden frequency selectivity but instead degraded the ability to discriminate tones with different fine temporal structure. The overall results suggest anodal tDCS applied over auditory cortex degrades frequency discrimination by affecting temporal, but not place, coding mechanisms. Perceptual learning is the improvement in perceptual performance with training ITF2357 in vivo not due to familiarity with the task. In audition, learning is specific to the trained stimulus and does not generalize widely to tasks with the same procedure but different stimuli (Wright et al., 1997; Wright & Fitzgerald, 2005). In particular, frequency discrimination learning is specific to the trained frequencies (Demany, CHIR-99021 mouse 1985; Irvine et al., 2000; Demany & Semal, 2002), with evidence showing that the rapid improvements within the first hour of training are due to genuine perceptual learning rather than procedural familiarity (Hawkey et al., 2004; Ortiz & Wright, 2009). This is consistent with neurophysiological evidence showing frequency

discrimination learning is associated with frequency-specific plastic changes in tonotopic maps (Recanzone et al., 1993; Menning et al., 2000; Jäncke et al., 2001; Polley et al., 2006). In humans, rapid auditory learning is associated with neuroplastic changes in auditory cortex (Alain et al., 2007, 2010). These changes underlie learning as greater long-term potentiation-mediated neuroplastic change is associated with increased learning (Rutkowski & Weinberger, 2005) and is independent of task familiarity (Reed et al., 2011). Transcranial direct current stimulation (tDCS) is a relatively new non-invasive technique for manipulating cortical excitability in humans. Anodal tDCS increases local cortical excitability (Miranda et al., 2006) by decreasing membrane potential of stimulated neurons (Nitsche et al., 2003a; Stagg & Nitsche, 2011), as shown by changes in corticospinal excitability and cortical hemodynamic response (Nitsche & Paulus, 2000, 2001; Lang et al.