Cortical reorganization occurs in the adult central nervous system, especially during motor skill acquisition. Plasticity contributes to various forms of human behavior including motor learning and memory formation, consolidation, reconsolidation and short- and long-term retention. It is very important to understand the role of these different behavioral processes and of the mechanisms underlying these various forms of human plasticity during skill acquisition. Findings this year: Previous work using transcranial magnetic stimulation (TMS) has demonstrated that the pre-supplementary motor area (preSMA), an important node within the fronto-basal-ganglia network, plays a critical role in the inhibition of motor responses. However, the fact that TMS influences are known to be network-based, and involve interactions between interconnected regions, raises the possibility that motor response inhibition is a function of both local preSMA activity and ongoing functional connectivity within the fronto-basal-ganglia network. To understand this relationship, we applied single-pulse TMS to the pre-SMA during functional MRI while participants were at rest.Using this experimental design, we were able to investigate the relationship between simultaneous changes in local pre-SMA activity, and functional connectivity within the fronto-basal-ganglia network in relation to response inhibition efficiency as evaluated by a stop-signal task. The results showed that TMS applied to the pre-SMA resulted in increased activation within the right inferior-frontal cortex (rIFC) and basal ganglia, as well as augmentation of their task-free functional connectivity. Both the TMS-induced changes in resting-state basal ganglia activity and functional connectivity changes between rIFC and left striatum, and within the overall network correlated with the efficiency of response inhibition.These functional changes were also directly related to inter-individual differences between white-matter microstructure along the preSMA-rIFC pathway. These results suggest that the task-free functional and structural connectivity between the rIFCop and basal ganglia are critical factors in response inhibition behavior. In a related study, we found that foreknowledge prior to the task is sufficient to influence neural activity associated with the primary response and modulate inhibition efficiency, irrespective of whether stopping an overt response is required. Sequence learning, a basic component of complex motor skill learning, relies on the formation of both unconscious and conscious memories that are transitional and ordinal in nature, respectively. It is not known how practice structure influences the relative contribution these types of memories make to overall learning, and what the systems-level neural substrates of these memory types are. In this study, participants were randomly assigned to two groups where practice structure was either varied or grouped (mixing or grouping sequences during training, respectively). Learning was assessed 30 min and 1 week later, and decomposed into transitional and ordinal memory types. We found that varied practice improved transitional memory.Furthermore, greater transitional memory changes were associated with enhanced interactions within a network consisting of the dorsal premotor cortex, thalamus, cerebellum, and lingual and cingulate regions. This result suggests that practice structure significantly influences unconscious transitional memory formation, and identifies a cortico-subcortical network linked to premotor cortex that support these memories at the systems level. It is known that episodic memory, an important component of motor memory formation and recall, displays the largest degree of age-related decline, and is a process that becomes accelerated in several pathological neurological conditions. Previous studies have shown that the left lateral prefrontal cortex (PFC) contributes to the encoding of episodic memories along the life span. In collaboration with a group in Brescia, Italy, we used a controlled, double-blind study design to assess whether anodal trascranial direct current stimulation (tDCS) applied over the left lateral PFC during the learning of verbal episodic memories would enhance delayed recall observed in elderly individuals. Older adults learned a list of words while receiving anodal or placebo (sham) tDCS. Memory recall was tested 48 hours and 1 month later. The results showed that anodal tDCS strengthened episodic memories as observed through greater delayed recall (48 hours) performance compared to placebo stimulation.Thus, enhancement of verbal episodic memory in the elderly by PFC-tDCS suggests that this intervention could be used in neurorehabilitation protocols designed to target to neurological conditions displaying episodic memory impairments. Voluntary modulation of brain sensorimotor rhythms (SMR), which are 8-15 Hz oscillations associated with successful motor performance, imagery, and imitation, can be used to control brain-machine interfaces (BMI) in the absence of any physical movements. The mechanisms underlying acquisition of such skill remain unknown. Here, we investigated the causal relationship between primary motor cortex (M1) function and successful acquisition of and control over SMR modulatory skill. We trained thirty healthy participants over 5 consecutive days to control SMR oscillations. Participants were randomly assigned to one of 3 groups that received either 20 min of anodal, cathodal, or sham transcranial direct current stimulation (tDCS) over M1. Learning SMR control across training days was superior in the anodal tDCS group relative to the cathodal and sham tDCS groups. The newly acquired skill remained superior in the anodal tDCS group up to one month later. Thus, anodal tDCS appears to facilitate acquisition and retention of SMR modulatory skill. Several international collaborative projects resulted in additional findings over the past year. One study done in collaboration with a group from the University of Tubingen assessed the impact of transcranial direct current stimulation (tDCS), which has previously been shown to influence cognitive, affective or motor brain functions (as described in the above), on whole-brain oscillatory activity measured concurrently with magnetoencephalography (MEG). We were able to show for the first time that tDCS has an immediate impact on slow cortical magnetic fields (SCF, 0-4Hz) within task-related brain regions spatially homologous to regions showing similar changes in hemodynamic response measured with functional MRI. There was also a polarity-dependent (anodal versus cathodal) effect of the stimulation, as there was a differential effect on reaction time and slow cortical magnetic field modulation in both primary sensorimotor and medial parietal regions.This study provided the proof-of-concept, that experimental paradigms combining tDCS and whole-head MEG provide a powerful approach to investigate the direct effects of transcranial electric currents on ongoing neuromagnetic source activity, brain function and behavior.