Measuring the Latency Connectome in the Central Nervous Systems Using Neuroimaging and Neurophysiological Techniques
Condition: Healthy Volunteers
Study type: Observational

Summary: 
      Background:

      Little is known about the time it takes for nerve signals to go from one area of the brain to
      another. Using advanced methods for brain research, researchers want to look at the time it
      takes to send messages between different brain areas. They also want to develop new tests.

      Objectives:

      To develop tests to measure the sizes of nerve fibers in the peripheral nerve system and in
      the brain. Also to find out the different speeds that information travels in nerve fibers.

      Eligibility:

      Healthy, right-handed people ages 18-70

      Design:

      Participants will be screened with medical history and a physical exam.

      Participants will have up to 7 visits depending on the tests they choose. Visits last about
      2-4 hours and may involve the following tests:

        -  Physical exam

        -  Urine tests

        -  Magnetic resonance imaging (MRI). Participants lie on a table that slides into a
           scanner. They will be in the scanner for up to 1 hour. For some scans, sensors are
           placed on the skin. They will get earplugs for loud noises.

        -  Small, sticky pads on the skin will electrically stimulate nerves in the forearm.

        -  Transcranial magnetic stimulation (TMS). A wire coil will be held to the scalp. A brief
           electrical current passes through the coil to affect brain activity.

        -  Electroencephalography. TMS will be given to the brain. Small electrodes on the scalp
           measure brain activity. Participants may do small tasks.

        -  Electrodes on the scalp will send an electrical current to the brain.

        -  A cone with magnetic detectors will be lowered onto the head to record brain activity.
           Participants will perform various tasks.
    

Detailed description: 
      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.
    

Intervention name(s): TMS; MRI
Intervention type(s): Device; Device
Intervention description(s): We will use TMS with paired-pulse technique to activate corticospinal neurons in the primary motor cortex and motorneurons in the brainstem, respectively (Hallett 2007; Ugawa et al. 1991; Ugawa et al.1994). Two stimulations will be separated with various interstimulus intervals to produce collision on nerve fibers with different conduction velocity in the corticospinal tract. The conduction time on nerve fibers in the corticospinal tract with different conduction velocity will be identified and the distribution of these fibers will be calculated.; MRI exams will consist of several sessions including calibration, anatomic, and diffusion MRI scanning (Avram et al. 2013; Avram et al. 2016; Pierpaoli et al. 1996). Data in each exam will be acquired in the left or right forearm (PNS).
Observational model: Case-Only
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Healthy Volunteers
      
Keywords: Transcranial Magnetic Stimulation (TMS); Magnetic Resonance Imaging (MRI); Electroencephalogram (EEG); Magnetoencephalogram; Transcranial Electrical Stimulation (TES)