The goal of our activity is to understand the mechanisms underlying plastic changes in the human central nervous system and to develop novel therapeutic approaches for recovery of function based on these advances. Our work has focused on the human motor system to understand skill acquisition, memory formation, consolidation and reconsolidating. We study cortical reorganization and brain network dynamics underlying behavior in patients with CNS lesions in particular stroke and traumatic brain injury. In healthy volunteers, we study cortical plasticity associated with motor skill learning and memory formation.
We utilize different techniques in the context of exploratory and well defined hypothesis-driven investigations including transcranial magnetic (TMS) and DC (tDCS) stimulation, fMRI, TMS in combination with fMRI, MR spectroscopy, diffusion tensor imaging (DTI), PET scanning and magnetoencephalography (MEG). We are interested in the development of these techniques to help us to understand mechanisms of human plasticity and to modulate human brain processing. Our research protocols in healthy volunteers are geared to identify mechanisms of human neuroplasticity and to develop interventional approaches to enhance them when they play a beneficial role and down-regulate them when they are maladaptive. Advances in this understanding in healthy volunteers are subsequently applied to patients with neurological conditions like stroke in attempts to enhance neurorehabilitative processes. More recently, we started to work on decoding of brain activity spatiotemporal patterns underlying memory of errors, working memory and different forms of consolidation of skill learning. Present activity in the lab includes characterization of replay events in awake humans related to different stages of motor learning.
Our future goals are to improve our understanding of mechanisms underlying plasticity of function in humans. On the basis of these insights, we are engaged in translational efforts to develop rational rehabilitative interventions to improve motor disability after stroke in particular using behavioral as well as open- and closed-loop brain stimulation techniques. In patients with severe hand paralysis, we use an MEG-based brain computer interface to control grasping motions of an orthosis attached to the paralyzed hand.
RECENT RESEARCH
SPATIOTEMPORAL NEURAL DYNAMICS OF THE SELECTION AND MAINTENANCE OF WORKING MEMORY CONTENT AS IT IS MANIPULATED (Journal of Neuroscience. 2019)
Our brain selects and maintains information during short time windows in a way that is essential to reasoning and learning. We applied multivariate analyses to time-resolved MEG brain signals finding that the selection of information relies on sustained oscillatory activity in a network that includes the ventrolateral prefrontal cortex while memory content is transiently replayed in an occipito-temporal network that differs from encoding. These results characterized differentiated spatiotemporal activity underlying encoding, selection, and maintenance of information during working memory.
A RAPID FORM OF CONSOLIDATION IN SKILL LEARNING (Current Biology, 2019)
Here, we looked at the within-seconds time course of early human procedural learning over alternating short periods of practice and rest that constitute a typical early online training session (left hand side). We found that performance did not markedly change over short periods of practice. On the other hand, performance improvements in between practice periods, when subjects were at rest, were significant and accounted for early procedural learning. These offline improvements were more prominent in early training trials when the learning curve was steep and no performance decrements during preceding practice periods were present. At the neural level, simultaneous magnetoencephalographic (MEG) recordings showed an anatomically defined signature of this phenomenon (right hand side). Beta band brain oscillatory activity in a predominantly contralateral fronto-parietal network predicted rest-period performance improvements. Thus, we report a rapid form of offline consolidation that substantially contributes to early skill learning and may extend the concept of consolidation to a time scale in the order of seconds, rather than the hours or days traditionally accepted.
SENSORIMOTOR OSCILLATORY PHASE-POWER INTERACTION GATES RESTING HUMAN CORTICOSPINAL OUTPUT (Cerebral Cortex 2018)
Oscillatory activity within sensorimotor networks is characterized by time-varying changes in phase and power. The influence of interactions between sensorimotor oscillatory phase and power on human motor function, like corticospinal output, is unknown. We addressed this gap in knowledge by delivering transcranial magnetic stimulation (TMS) to the human motor cortex during electroencephalography recordings in 20 healthy participants. Motor evoked potentials, a measure of corticospinal excitability, were categorized offline based on the mu (8–12 Hz) and beta (13–30 Hz) oscillatory phase and power at the time of TMS. Phase-dependency of corticospinal excitability was evaluated across a continuous range of power levels using trial-by-trial linear mixed-effects models. For mu, there was no effect of PHASE or POWER (P > 0.51), but a significant PHASE × POWER interaction (P = 0.002). The direction of phase-dependency reversed with changing mu power levels: corticospinal output was higher during mu troughs versus peaks when mu power was high while the opposite was true when mu power was low. A similar PHASE × POWER interaction was not present for beta oscillations (P > 0.11). We conclude that the interaction between sensorimotor oscillatory phase and power gates human corticospinal output to an extent unexplained by sensorimotor oscillatory phase or power alone.
CLINICAL PROTOCOLS
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Human Cortical Physiology Section Repository Protocol ( 09-N-0156 )
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Screening Protocol for Patients with Stroke ( 10-N-0012 )
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Modulation of motor function by stimulation of the central and peripheral nervous system. ( 07-N-0122 )
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Neural Dynamics and Connectivity in Response Inhibition and Traumatic Brain Injury ( 10-N-0185 )
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Large Scale Online Studies of Motor Responses and Cognition (19-N-0012)
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Influence of Brain Oscillation-Dependent Transcranial Magnetic Stimulation on Motor Function (17-N-0168)
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Neural Basis of Decision Making Deficits in Traumatic Brain Injury (14-N-0083)
GRADUATES
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Christian Gerloff
Joseph Classen
Robert Chen
Cathrin Butefisch
Ulf Ziemann
George Wittenberg
Adriana Conforto
Agnes Floel
Friedhelm Hummel
Pascal Giraux
Pablo Celnik
Nam-Jong Paik
Monica Perez
Janine Reis
Michael Dimyan
Heidi Schambra
Surjo Soekadar
Eran Dayan
Nitzan Censor
Marco Sandrini
Sook-Lei Liew
Olewole Awosika