Deficit of Inhibition as a Marker of Neuroplasticity (DEFINE Study) in Rehabilitation: A Longitudinal Cohort Study Protocol

Abstract

Background: Brain plasticity is an intrinsic property of the nervous system, which is modified during its lifetime. This is one mechanism of recuperation after injuries with an important role in rehabilitation. Evidence suggests that injuries in the nervous system disturb the stability between inhibition and excitability essential for the recuperation process of neuroplasticity. However, the mechanisms involved in this balance are not completely understood and, besides the advancement in the field, the knowledge has had a low impact on the rehabilitation practice. Therefore, the understanding of the relationship between biomarkers and functional disability may help to optimize and individualize treatments and build consistent studies in the future. Methods: This cohort study, the deficit of inhibition as a marker of neuroplasticity study, will follow four groups (stroke, spinal cord injury, limb amputation, and osteoarthritis) to understand the neuroplasticity mechanisms involved in motor rehabilitation. We will recruit 500 subjects (including 100 age- and sex-matched controls). A battery of neurophysiological assessments, transcranial magnetic stimulation, electroencephalography, functional near-infrared spectroscopy, and magnetic resonance imaging, is going to be used to assess plasticity on the motor cortex before and after rehabilitation. One of the main hypotheses in this cohort is that the level of intracortical inhibition is related to functional deficits. We expect to develop a better understanding of the neuroplasticity mechanisms involved in the rehabilitation, and we expect to build neurophysiological "transdiagnostic" biomarkers, especially the markers of inhibition, which will have great relevance in the scientific and therapeutic improvement in rehabilitation. The relationship between neurophysiological and clinical outcomes will be analyzed using linear and logistic regression models. Discussion: By evaluating the reliability of electroencephalography, functional near-infrared spectroscopy, transcranial magnetic stimulation, and magnetic resonance imaging measures as possible biomarkers for neurologic rehabilitation in different neurologic disorders, this study will aid in the understanding of brain plasticity mechanisms in rehabilitation, allowing more effective approaches and screening methods to take place.

Keywords: amputation; biomarkers; brain plasticity; disability; neuronal plasticity; osteoarthritis; spinal cord injury; stroke.