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: We continue to make progress in the development and refinement of brain-state-dependent stimulation protocols that aim to dramatically improve the magnitude of neuromodulatory effects of brain stimulation techniques such as transcranial magnetic stimulation (TMS). Progress along these lines is critical for translating our basic research work into new therapies for treating motor deficits caused by brain injury or disease such as stroke. Along these lines, we published a study during the past year in the Journal of Clinical Neurophysiology that investigated the electroencephalography (EEG) signatures directly related to activation of corticospinal neurons in the primary motor cortex (M1). M1 is the functional region of the brain that directly connects to neurons in the spinal cord that control voluntary muscle contraction. Thus, M1 is area of the brain most directly in control of generating voluntary movement. EEG is a non-invasive neuroimaging technique used in clinical settings that indirectly measures brain activity via recordings of very small electrical potentials measured on the scalp. Better understanding of EEG signatures related to motor output of the brain and how they relate to the direction of induced current within the brain generated by TMS will improve precise characterization of the brain biomarkers used for stimulation patterns designed to improve neuromodulatory effects, and ultimately clinical outcomes. In this study, we investigated the EEG signatures of cortical evoked potentials with different components induced by TMS in 10 healthy volunteers. The TMS was applied in a manner that induced either posterior-anterior or anterior-posterior current directions EEG signatures with P25 (i.e. - positive peak at 25ms following stimulation) and N45 (i.e. - negative peak at 45ms following stimulation) components recorded at the electrode over the left M1 (i.e. - electrode C3 in the international 10-20 system) with induced posterior-anterior current directions were larger than those with induced anterior-posterior currents, while the signatures with P180 and N280 components recorded at the FC1 electrode (anterior and lateral to C3, and overlying the junction of M1 and premotor cortex) were more prominent for induced anterior-posterior current directions than induced posterior-anterior currents in M1. Source localization analysis, which directly models the electrical currents measured at the scalp as a function of the underlying neuronal activity, revealed that the source of the evoked EEG signature when TMS induced an anterior-posterior current was distributed across both M1 and premotor cortex while the signature with induced posterior-anterior current direction was centered within M1 only. Based upon these results, we concluded that activation of corticospinal pyramidal neurons in M1 is the result of local intracortical circuit interactions within M1 that is modified by inputs from premotor cortex with different sensitivities to TMS in opposite current directions. We also made advances over the past year in our research work related to the COVID-19 epidemic. Early in the Covid pandemic, reports started to emerge of patients with lingering symptoms following recovery from acute infection, often referred to as Long Covid. Despite the high prevalence of neurological symptoms like brain fog and memory dysfunction in Long Covid, most research has relied on surveys or clinical tools typically used to assess declarative memory. No prior studies have examined Long Covid patients ability to learn and consolidate a procedural motor skill. We are addressing this question in a group of patients with Long Covid and age- and sex-matched controls.