Investigation of Neurofeedback With Real-Time fMRI in Healthy Volunteers and Patients With Hyperkinetic Movement Disorders

Objective:

The objective of this study is to see if healthy volunteers and patients with hyperkinetic movement disorders such as Tic Disorders (TD) including Tourette Syndrome (TS) are able to learn how to alter their brain activity using feedback during functional magnetic resonance imaging (fMRI), and whether such feedback training can lead to improvement in symptoms in TD patients.

Study population:

This study is to be carried out in three phases. In Phase 1 we will study the feedback technique using fMRI with right-handed adult healthy volunteers, in Phase 2 we intend to study if adult patients with TD are also able to learn the feedback technique, and in Phase 3 we intend to study whether feedback training with fMRI leads to improvement in symptoms in TD patients and whether patients were able to retain the ability to alter their brain activity.

Design:

All subjects will have an initial screening visit to consent and assess their eligibility to participate in the current study. All visits are outpatient.

Subjects will have a clinical MRI when required, a series of functional scans, and at least one structural scan for image registration.

Phase 1: Feasibility Studies

Feasibility of fMRI neurofeedback based on activation levels.

Subjects will perform a neurofeedback fMRI visit, where they will attempt at modulating brain activity level based on the observed feedback signal. Task include motor, motor imagery, or mental thoughts. Functional localization of target regions will be done with a motor task or a blink suppression paradigm. Completed.

1. Feasibility of fMRI neurofeedback based on connectivity

   Subjects will perform two fMRI visits, where they will attempt to learn to modulate their own brain connectivity using feedback of connectivity patterns between two motor regions during a real-time fMRI paradigm. Each session will include a performance evaluation. Data acquisition completed.

2. Feasibility of fMRI neurofeedback based on patterns

Subjects will perform one fMRI visit. A blink suppression paradigm will be used to create a personalized model of urge . Using neurofeedback, subjects attempt to modulate the urge pattern. In progress.

Phase 2: Pilot neurofeedback for brain modulation in TD

TD patients will have an evaluation visit, including clinical evaluations, scales and videotaping and an fMRI visit.

In the fMRI visit, the model of urge will be created based on the brain pattern measure before spontaneous tics. Patients will attempt towill be studied to see if they can learn to alter their brain activity to decrease the fitting to the urge model, in a similar way as the healthy volunteers. In progress.

Phase 3: Pilot neurofeedback fMRI for symptoms improvement in TD patients

TD patients will have one evaluation, one scanning, and one follow-up) visit. No visit will last more than 4 hours. The effect of altering brain activity in a specific brain area on symptoms in TD patients will be studied. Patients will be asked to continue to focus their thoughts as they did during feedback scanning any time that they feel an urge prior to a tic or every hour while awake, whichever is more frequent, until a follow-up visit and fMRI scan two or three days later. Require power analysis based on Phase 2.

Outcome measures:

Primary outcomes

Phase 1

1. The difference in connectivity between two ROIs after feedback training compared to a baseline.
2. The difference in neural pattern after feedback training compared to a baseline.

Phase 2

The difference in neural pattern after feedback training compared to a baseline.

Phase 3

The difference in symptoms measured by a TS rating scale before fMRI scanning compared to two or three days after learning the feedback technique.

Secondary outcomes

Phase 1

1. Changes in motor performance on grooved pegboard test
2. Changes in number of blinks after a successful neurofeedback run.

Phase 2 and 3

Changes in number of tics after successful neurofeedback runs compared to baseline.