Cortical reorganization and plasticity In the healthy brain

National Institute Of Neurological Disorders And Stroke

Investigators

Linked publications, trials & patents

Abstract

Background: Cortical reorganization occurs in the adult central nervous system, especially during motor skill acquisition. This plasticity contributes to various forms of human behavior including skill 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 to improve skill learning and memory in healthy adults. Findings this year: Memory consolidation is the processes through which the brain strengthens and maintains memories of motor skills acquired through training. Consolidation processes are crucial for maintaining skills over the lifespan and improving recovery outcomes following brain injury or disease. Previously, consolidation has largely been investigated during sleep or over longer rest periods consisting of hour or days between training sessions. Over the past two years, we developed a new line of inquiry that investigated consolidation processes over much shorter rest periods (on the order of several seconds) interspersed within a single training session. This year, we reported in an online study that when humans initially learn a novel motor skill (i.e. - playing a new piece of music on an instrument) performance does not change much while they are actively practicing. Instead, performance improvements are largely limited to short periods of rest between practice, a finding we termed micro-offline learning. However, the brain mechanisms supporting the binding of sequences of discrete action representations into consolidated, temporally precise skills during waking rest remains unknown. Over the past year, we investigated in the lab the role of waking neural replay, the reinstatement during rest of brain activity patterns representing performance of the skill, as a candidate mechanism for these micro-offline gains a form of rapid skill consolidation. We recorded whole-brain MEG while naive participants learned a novel keypress sequence by typing it as fast and accurate as possible over several 10s practice blocks interleaved with 10s rest periods. We developed and trained SVM classifiers on practice MEG to decode individual finger keypresses, and then applied a simple probabilistic model coupled with resampling to search for replay of the practiced sequences over different durations (i.e. - temporal compression factors). Immediately following the onset of practice, we detected on average about 25 replay events of completed practice sequences a 3-fold increase compared to pre-training rest. The modal duration of these replay events was 50ms representing 20x temporal compression of the practiced sequence. Thus, the brain appears to actively and spontaneously exploit the intervening rest periods to amplify the effects of practice and rapidly consolidate the skill memory. Replay of the skill memory was characterized by strong covariations of source power within a network including the sensorimotor cortex, precuneus, entorhinal cortex and hippocampus. The increase in replay appeared to be selective for the practiced sequence, as changes in replay rates were not observed for a control sequence with zero ordinal and transitional overlap. Importantly, the number of replay events were directly related to the magnitude of micro-offline gains observed in individuals, leading us to conclude that waking hippocampo-neocortical replay is a likely binding mechanism supporting rapid skill memory. Over the past year, we also continued to advance an important research initiative aimed at characterizing intra- and inter-individual variability in responses to non-invasive brain stimulation. The rationale for this work is that a more complete understanding of how ongoing endogenous brain activity influences an individuals response to brain stimulation is crucial for the development of novel therapeutic interventions for rehabilitation of individual patients suffering from neurological injury or disease. Endogenous brain activity within sensorimotor networks exhibits dynamic oscillations with time-varying changes in phase (i.e. activity timing) and power (i.e activity magnitude). Based upon our prior work, we know that offline activity in the primary motor cortex (M1) exhibits mu (8-12 Hz) rhythm oscillations defined by excitatory trough and inhibitory peak phases, and that this offline activity crucially supports new skill learning. While we recently showed that the magnitude and direction of neuroplasticity induction within M1 is influenced by mu phase, the relationship between offline mu oscillations and human skill learning has not been investigated. Over the past year, we evaluated the effects of phase-dependent TMS applied during mu peak and trough phases on overnight offline learning of a newly acquired motor skill. This study was conducted in healthy adults over two days. On Day 1, three groups of participants practiced an explicit motor sequence learning task with their non-dominant left hand. Following practice, real phase-dependent TMS was applied to the right M1 during either mu peak (Group 1) or trough (Group 2) phases. An additional group received sham TMS during random mu phases (Group 3). On Day 2, all participants were re-tested on the same task to evaluate overnight offline learning. We found that participants who received phase-dependent TMS during mu trough phases (Group 2) showed increased overnight offline skill learning compared to those who received phase-dependent TMS during mu peak phases (Group 1) or sham TMS during random mu phases (Group 3). Mu trough-phase TMS also elicited stronger whole-brain broadband oscillatory power responses than phase-dependent mu peak-phase TMS. Based upon these findings, we conclude that sensorimotor mu trough phases reflect brief windows of opportunity during which applied TMS can enhance the potentiation of newly acquired skill memories. We have also reported that transcranial direct current stimulation with the anode over the right inferior frontal cortex facilitates response inhibition by modulating neural activity and functional connectivity in the fronto-basal ganglia as well as the right dorsolateral prefrontal cortex and the right inferior parietal cortex as an integral part of the response inhibition network. In collaborative work, we reported that the temporal dynamics of apparently simultaneous learning processes differ. While high-order rule learning is acquired offline, statistical learning is evidenced online.