Physiology of Interregional Connectivity in the Human Brain
Overview
- Phase
- N/A
- Intervention
- Not specified
- Conditions
- Healthy
- Sponsor
- Shirley Ryan AbilityLab
- Enrollment
- 76
- Locations
- 1
- Primary Endpoint
- Changes in EEG effective connectivity
- Last Updated
- 7 years ago
Overview
Brief Summary
The purpose of this study is to understand the physiology of connectivity between cortical regions in the human brain in healthy participants and in patients with white matter lesions. Specifically, the investigators will examine the effects of paired associative stimulation (PAS) which consists in delivering brief (< 1 ms) current pulses separated by a short millisecond-level time interval ("asynchrony") to two cortical areas. The used techniques are all non-invasive and considered safe in humans: transcranial magnetic stimulation (TMS), electroencephalography (EEG), magnetic resonance imaging (MRI), and functional MRI (fMRI). Based on prior literature in animals and human studies, it is hypothesized that PAS may increase or decrease effective connectivity between the stimulated areas depending on the asynchrony value. The main outcome measure is source-resolved EEG responses evoked by single-pulse TMS; this is a more direct measure of neuronal changes occurring at the targeted cortical area than motor evoked potentials (MEPs) or sensor-level EEG responses used in previous studies.
Detailed Description
This study consists of two experiments. In Experiment A, healthy participants without disorders or medications influencing brain function (N=24) will be recruited. A range of negative and positive asynchronies (from minus 50 to + 50 ms) will be tested. To allow comparison with prior studies that used MEPs as outcome measures, in 12 participants the primary motor cortex in the left and right hemisphere will be targeted. In another 12 participants, two cortical areas within the same hemisphere will be stimulated. In Experiment B, participants with stroke, traumatic brain injury (TBI), or multiple sclerosis (MS) (total maximum N across all such participants is 52) will be recruited. These participants are required to have one or more subcortical white matter lesions, which would be expected to result in cortico-cortical disconnections. Here, the investigators will only test PAS with positive asynchronies, with the goal of testing if the findings observed in healthy participants are similar in participants with white matter lesions. It will also be examined if the PAS-induced connectivity changes persist beyond the stimulation sessions if PAS is given repeatedly over several days. PAS will be applied to two cortical targets that have been disconnected from each other. The rationale for including more than one disorder in Experiment B is that the disconnections are in all cases caused by white matter lesions and the results may therefore be similar. To detect possible differences between disorders, the data from the three groups will also be analyzed separately.
Investigators
Tommi Raij
Research Scientist, Brain Stimulation Director
Shirley Ryan AbilityLab
Eligibility Criteria
Inclusion Criteria
- •Inclusion Criteria for Healthy Participants:
- •Age from 18 to 85 years
- •Right-handed
- •Normal hearing and (corrected) vision
- •Able to understand and give informed consent
- •English speaker
- •Inclusion Criteria for Patients:
- •Age from 18 to 85 years
- •Stroke (ischemic subcortical, intermediate level, chronic phase 3 weeks or more from lesion)
- •TBI (closed-skull, intermediate level, chronic phase 3 weeks or more from lesion)
Exclusion Criteria
- •Exclusion Criteria for Healthy Participants:
- •Cardiac pacemaker or pacemaker wires; neurostimulators; implanted pumps
- •Metal in the body (rods, plates, screws, shrapnel, dentures, IUD) or metallic particles in the eye
- •Surgical clips in the head or previous neurosurgery
- •Any magnetic particles in the body
- •Cochlear implants
- •Prosthetic heart valves
- •Epilepsy or any other type of seizure history
- •Any neurological diagnoses or medications influencing brain function
- •History of significant head trauma (i.e., extended loss of consciousness, neurological sequelae)
Outcomes
Primary Outcomes
Changes in EEG effective connectivity
Time Frame: Experiment A: Within-session (before versus after PAS at 1 and 60 minutes). Experiment B: Within-session (before versus after PAS at 1 and 60 minutes). Across-sessions (persistence of changes up to 1 month after last PAS session).
EEG will be recorded with a 64-channel whole-head TMS-compatible device (NeurOne, Bittium, Kuopio, Finland). Data will be collected before (Pre-PAS) and at 1 minute (Post-PAS T1) and at 60 minutes (Post-PAS T60) after PAS. To record spTMS-evoked EEG responses the investigators will deliver 80 single TMS pulses to the two areas receiving PAS, one target after the other in separate runs. Effective connectivity will be measured by comparing the source-resolved EEG evoked response waveforms before (Pre-PAS) and at 1 (Post-PAS T1) and at 60 minutes after PAS (Post-PAS T60).
Changes in resting-state EEG coherence
Time Frame: Experiment A: Within-session (before versus after PAS at 1 and 60 minutes). Experiment B: Within-session (before versus after PAS at 1 and 60 minutes). Across-sessions (persistence of changes up to 1 month after last PAS session).
Resting-state EEG will be recorded with a 64-channel whole-head device (NeurOne, Bittium, Kuopio, Finland). Data will be collected before (Pre-PAS) and at 1 minute (Post-PAS T1) and at 60 minutes (Post-PAS T60) after PAS. Resting-state EEG coherence will be computed in the source space for the two areas receiving PAS from 1 to 100 Hz.
Secondary Outcomes
- Motor evoked potentials (MEPs)(Experiment A: Within-session (before versus after PAS at 1 and 60 minutes). Experiment B: Done only in patients where the M1 was targeted with PAS.)
- MRI functional connectivity(Experiment A: Baseline. Experiment B: Baseline to 1 month after the last PAS session.)
- MRI structural connectivity(Experiment A: Baseline. Experiment B: Baseline to 1 month after the last PAS session.)