Cortical reorganization and plasticity In the healthy brain

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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 ones lifespan and improving recovery outcomes following brain injury or disease. Previously, consolidation has only 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. Last year, we reported 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. Over the past year, we advanced this research program in a large crowdsourcing study conducted online (cumulative N over all experiments=951). First, our original lab-based findings were successfully replicated demonstrating generalizability to participants learning the same task on their own computers at home (N=389). Second, by varying the length of the practice period, we showed that micro-offline improvements are equivalent across different practice period durations (N=118). This finding confirmed that micro-offline learning is not trivially related to simple recovery from performance fatigue but is instead the result of memory strengthening that occurs during these short intervening rest periods. Third, retroactive interference resulting from having participants switch to practicing a different variant of the skill immediately following practice of the target skill reduced the learning rate relative to the simple passage of time (N=373), confirming that micro-offline learning is likely the result of stabilization of the motor memory over a timescale of several seconds. In summary, these combined results support the role of a novel form of memory consolidation occurring on the timescale of several seconds in early skill learning in humans. A future direction of this work is to develop non-invasive brain stimulation interventions aimed at enhancing fast micro-scale consolidation and learning in healthy humans and improving therapeutic outcomes in neurological patients. 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). Last year, we found that motor evoked potentials (MEPs), a measure of communication strength between the brain and spinal cord important for generating movements, could be predicted by an interaction between the oscillatory phase and power of the sensorimotor brain rhythm. Communication strength between the brain and spinal cord was higher during sensorimotor rhythm troughs versus peaks when power was high while the opposite was true when power was low. This past year, in a follow-up to this work we sought to understand how non-sustained rhythmic signals in the brain influence brain and spinal cord communication. Short-lasting beta (15-30Hz) oscillations displaying only 1-2 cycles is a prominent signal of sensorimotor cortical activity. We evaluated the relationship between beta event characteristics and corticospinal excitability in healthy adults. Results show that the number, amplitude, and timing of beta events preceding transcranial magnetic stimulation (TMS) each significantly predicted motor-evoked potential (MEP) amplitudes, providing initial evidence that short-lasting endogenous beta oscillatory events shape human corticospinal excitability. These findings provide an important possible biomarker for elucidating the pathophysiology of motor deficits following stroke.