Functional Connectivity as a Biomarker of rTMS

Background:

Traumatic brain injury (TBI) damages the connections between brain cells. This can lead to problems like memory loss. Repetitive transcranial magnetic stimulation (rTMS) can help improve connections between brain areas in healthy people. Researchers want to see if it can be useful in patients with memory problems after TBI.

Objective:

To see how repetitive transcranial magnetic stimulation can be used to improve the connections between parts of the brain and whether this will lead to changes in memory.

Eligibility:

Adults 18-50 years old with TBI who can speak and write in English.

Healthy volunteers the same age and English ability.

Design:

Participants will be screened with a neurological exam and may have a urine pregnancy test.

Participants with TBI will have 7-15 visits. Healthy volunteers will have 2-8 visits.

At the visits, participants will have all or some of the following:

* MRI for about 1 hour. Participants will lie in a machine that takes pictures in a magnetic field. Participants will do some memory tasks.
* Memory and attention tasks with pictures and with a computer
* Questions about their mental state and well-being
* TMS: A wire coil is held on the scalp and a short electrical current passes through it. Participants will hear a click and feel a pulling or twitch. They may be asked to make simple movements. rTMS is repeated magnetic pulses in short bursts. They will have this for about 20 minutes.

A week after the last visit, some participants will return for a memory test.

Objective: To use resting state functional connectivity (FC) as a biomarker of synaptic modulation by repetitive transcranial magnetic stimulation (rTMS) in paradigms intended to improve memory and learning. Ancillary outcomes include the effects of rTMS on the interaction between the explicit implicit memory systems.

Study population: Healthy adult volunteers

Design: The study contains two experiments. Experiment 1 is designed to establish the number of rTMS sessions required to produce a meaningful change in resting parieto-hippocampal FC in healthy subjects. Experiment 2 will replicate a prior experiment which used rTMS to enhance the explicit memory system in healthy subjects, and look for potential effects on the implicit system. This intervention will be contrasted with a negative control condition (vertex stimulation) in a between-groups design.

Outcome measures: The primary outcome measure is the change in FC produced by serially applied rTMS and improvement in explicit memory. We will explore whether enhancement of the explicit system has effects on resting state connectivity in the implicit system and whether white matter integrity predicts changes in FC in healthy subjects.

Eligibility Criteria:
INCLUSION CRITERIA:

Experiments 1 and 2:

Healthy individuals

Age 18-50 (inclusive)

English speaking and writing

Experiment 3:

Age 18-50 (inclusive)

English speaking and writing

History of mild to moderate TBI

Performance 1 standard deviation below age-adjusted population norms on the

CVLT-2 within the past year from the date of visit.

EXCLUSION CRITERIA:

Any current major neurological or psychiatric disorder such as (but not limited to) stroke, Parkinson disease, Alzheimer disease, schizophrenia or major depression

History of seizure

Medications acting on the central nervous system

Ferromagnetic metal in the cranial cavity or eye, implanted neural stimulator, cochlear implant, or ocular foreign body

Implanted cardiac pacemaker or auto-defibrillator or pump

Non-removable body piercing

Claustrophobia

Inability to lie supine for 1 hour

Pregnancy, nursing, or plans to become pregnant during the study.

Members of the NINDS Behavioral Neurology Unit (BNU)

For Experiment 2: Participation in Experiment 1