Effects of Prism Adaption and rTMS on Brain Connectivity and Visual Representation

OBJECTIVES:

The ability to efficiently select information from the environment relies on a balanced interaction between the right and left hemispheres. Hemispatial neglect, most frequently following damage to the right hemisphere, has been hypothesized to result from the breakdown of this interhemispheric balance. There is evidence from transcranial stimulation studies that the breakdown of this interhemispheric balance is reflected in fronto-parietal connectivity. The primary goal of this study is to test whether altering the balance between the left and right hemispheres, with repetitive transcranial magnetic stimulation (rTMS) or prism adaptation (PA), will affect functional connectivity measured with functional magnetic resonance imaging (fMRI). We will also explore the relationship between the changes in functional connectivity and behavioral performances.

STUDY POPULATION: Healthy adult volunteers and patients with neglect after a right hemisphere damage.

DESIGN: The study contains three experiments. Experiment 1 is designed to investigate the mechanism of the changes induced by PA in both resting state functional connectivity in neglect patients and healthy volunteers (a two-arm parallel study). Experiment 2 is designed to investigate the mechanism of the changes in resting state functional connectivity induced by lPA, rPA, nPA in healthy volunteers with right dominant eyes and lPA in healthy volunteer with left dominant eye (a four-arm parallel study). Experiment 3 is designed to see if inhibitory rTMS over the right posterior parietal cortex (PPC) can influence functional connectivity and visuospatial bias in healthy volunteers (a crossover study).

OUTCOME MEASURES: For all three experiments the primary outcome measure is the change (or difference) in fronto-parietal resting state connectivity between post and pre PA or rTMS procedure. The secondary outcome measures are the changes in visual field representation and in visuo-motor and cognitive behavior accompanying these manipulations.

• INCLUSION CRITERIA:

Inclusion criteria

for all participants:

All participants must have had a neurological examination by a NINDS physician within the last two years, a clinical MRI within the last year, and be able to read, write and speak English.

Experiment 2 requires 63 healthy volunteers having right dominant eye and 21 volunteers having left dominant eye. Therefore, healthy volunteers with left dominant eye will be recruited until the necessary number is reached. We estimate we will have to screen 150

healthy volunteers. Participants for whom the study was not completed due to technical problems and who did not undergo prism adaptation or TMS will be retested and data from the incomplete session will not be analyzed.

A-Inclusion Criteria for Healthy volunteers/Age-matched Controls

Experiment 1

• Age 18-75 (inclusive; we will try to match this to the stroke group)
• Montreal Cognitive Assessment score greater than or equal to 26
• Absence of neglect at time of testing (Diller test score less than or equal to 2)

Experiments 2 and 3

• Right-handedness
• Age 18-35 (inclusive)
• Twelve or more years of education
• Are able to see a dot of size 0.2 inches at a distance of 22.5 inches without glasses or with contact lenses (only for Experiment 2)

B-Inclusion Criteria for Patients

Experiment 1

• Age 18-75 (inclusive)
• Montreal Cognitive Assessment score greater than or equal to 26
• A right hemisphere stroke or other focal, non-progressive, brain lesion resulting in neglect
• Minimum of 30 days from lesion onset to testing
• Evidence of neglect at time of testing (Diller test score greater than or equal to 5)

Exclusion criteria

A- Exclusion Criteria for Healthy volunteers

• Significant illness affecting the central nervous system
• History of seizure (for Experiment 3)
• Inability to give informed consent
• Concurrent use of sedating medications
• Trained to write in other than left to right direction
• Ferromagnetic metal in the cranial cavity or eye, e.g. aneurysm clip, 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 1.5 hour
• Pregnancy
• Members of the NINDS Behavioral Neurology Unit (BNU)

B- Exclusion Criteria for Patients and Age-matched Controls:

• Significant illness affecting the central nervous system, other than right hemisphere lesion causing neglect in patients
• Inability to give informed consent
• Concurrent use of sedating medications
• Ferromagnetic metal in the cranial cavity or eye, e.g. aneurysm clip, 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 1.5 hour
• Pregnancy
• Members of the NINDS Behavioral Neurology Unit (BNU)