Measuring the Latency Connectome in the Central Nervous Systems Using Neuroimaging and Neurophysiological Techniques

Objectives: We are proposing the development and assessment of an MRI and neurophysiology-based experimental and theoretical framework to measure peripheral and intercortical latencies and latency distributions in the living human. This entails combining and integrating neurophysiological and neuroimaging so that we can eventually generate latency and latency distribution matrices for central nervous systems (CNS) using neuroimaging techniques. Neuroimaging and neurophysiological studies in the peripheral nerve system (PNS) will provide essential data for proof-of-concept and for validating this approach. Study Population: We intend to study up to 40 healthy volunteers. Each subject will complete 1 to 8 visits involving various measurements with different neuroimaging and neurophysiological techniques. Design: This is an exploratory study that consists of different measurements using multimodal neurophysiological and neuroimaging techniques. Diffusion magnetic resonance imaging (MRI), mean apparent propagator (MAP)-MRI, AxCaliber MRI, multiple pulsed field gradient MRI, and resting-state functional MRI will be performed in 1 to 2 visits. In another 1 to 5 visits, we will use neurophysiological techniques including peripheral electrical stimulation, transcranial magnetic stimulation (TMS), electroencephalography (EEG) and magnetoencephalography (MEG) with various experimental paradigms to correlate with the latency and latency distribution matrices generated by neuroimaging techniques. All these techniques are exploratory and success or failure of one of them does not have immediate implications for the others. Outcome Measures: We will measure average axon diameter (AAD) and axon diameter distributions (ADD), as well as compute white matter pathway trajectories using diffusion MRI and MAP-MRI data, and use resting-state functional MRI to measure blood oxygenation level-dependent signal to identify salient cortical regions in which many of these tracts terminate. For proof-of-concept measurements in the PNS, compound muscle action potential or surface compound nerve action potential on the skin will be measured following peripheral nerve stimulation. For TMS , we will measure motor evoked potential (MEP) amplitude. Cortical evoked potential in different cortical areas induced by TMS will be measured in EEG recordings. We will study millisecond coupling delays between different cortical areas with MEG. We will measure time and phase delays as computed from whole-head signals in the subject. Coherence analysis for cortical activity with EEG and MEG recordings between different cortical areas will be performed. We will attempt to correlate MRI measurements with the individual physiological measurements.