Leveraging behavioral state to enhance specificity of non-invasive brain stimulation on motor circuits

点击翻译按钮获取中文摘要

Project Summary The last two decades have seen an exponential growth in the use of noninvasive brain stimulation techniques, including repetitive transcranial magnetic stimulation (rTMS), in both basic neuroscience and clinical practice. rTMS holds promise for the study and treatment of neurological disorders. Yet, there is a limited understanding of the effects of rTMS on brain and behavior. We will examine a particular type of rTMS, known as theta burst stimulation (TBS), which induces longer lasting effects than other forms of rTMS, making TBS an important tool for therapeutic applications. While TBS provides relatively focal stimulation, effects on the brain occur through interconnected networks in ways that are poorly understood. Moreover, stimulation is highly state-dependent, and the use of rTMS in most therapeutic settings, such as the treatment of motor disorders, leaves the behavioral state uncontrolled. Augmenting rTMS by pairing it with behavioral interventions is an attractive idea for improving therapeutic rTMS, but its efficacy and mechanisms remain unknown. To address this critical gap, this exploratory R21 proposal will examine the effects of TBS and behavioral state on brain and behavior. Our overall objectives in the proposed work are to (i) elucidate the neural mechanism by which TBS paired with a motor task leads to improvements in hand function and (ii) develop more targeted network-modulatory rTMS interventions to enhance motor function. We will focus on the posterior parietal cortex (PPC), and associated parietal-motor circuits, which subserve skilled grasp control, an ability known to be impaired in stroke, traumatic brain injury, cerebral palsy, and other motor disorders. We will collect functional magnetic resonance imaging (fMRI), electrophysiological measures with TMS, and behavioral measures in the same subjects. Five consecutive daily TBS sessions will be applied to 65 healthy subjects assigned to one of three groups, each followed by two assessments to evaluate the effects of stimulation. In Aim 1, we will demonstrate improvement in action performance by manipulating the behavioral state during PPC stimulation. In Aim 2, we will demonstrate modulation of neurophysiological aftereffects of PPC stimulation by manipulating behavioral state. In Aim 3, we will assess the relationship between brain connectivity, neural plasticity and behavior in response to the behavioral state during brain stimulation. Impact: The methods reported here potentially can be modified to more incisively treat motor disorders after stroke by targeting residual higher motor areas to improve impaired cortical pathways. Results will lay a mechanistic foundation for future studies to show how controlling behavioral state during rTMS can improve therapeutic efficacy after stroke.