Central Mechanisms in Speech Motor Control Studied With H215O PET

Objective

The primary objective of this protocol is to use multimodal neuroimaging combining
complementary electrophysiological and hemodynamic methods to characterize brain-language
relationships in healthy subjects and those with neurological disorders that affect speech
and language. A secondary objective is to utilize these findings to develop evaluation
measures for future treatment studies.

Study Populations

We will focus on four neurological disorders that affect language processing post-stroke
aphasia, traumatic brain injury, epilepsy and developmental stuttering. Each constitutes a
significant clinical problem central to the NIDCD s mission. These disorders can impair
language at several levels - from its elementary perceptual and motor features, the
peripheral building blocks of language, to higher levels of language formulation, including
word, sentence and narrative processing.

Design

We will utilize a set of tasks designed to evaluate language at the levels at which clinical
pathology emerges. We will combine hemodynamic (functional MRI) and electrophysiological
(EEG, MEG) modalities to capitalize on the superior spatial resolution of the former and
temporal resolution of the latter methods. Whenever possible the same task paradigms are used
with both techniques. We will conduct crosssectional sub-studies, addressing specific
questions in each of the disorders of interest; we will also conduct longitudinal sub-studies
of recovery and neuroplastic reorganization in post-stroke aphasia.

Outcome Measures

Outcome measures include speech-language and psychological tests, measures of behavioral
performance during scanning and corresponding MRI, EEG and MEG data. Relationships between
these datasets will be evaluated using statistical analytic packages.

- INCLUSION CRITERIA FOR ALL SUBJECTS:

Ages 18 to 85.

Ability to provide informed consent.

Must be a Native English speaker by age 2

SPECIFIC INCLUSION CRITERIA FOR SELECTED GROUPS OF HEALTHY VOLUNTEERS:

Have had training and experience in creative writing

Have had training and experience in vocal or instrumental music

Have had training and experience in visual arts

SPECIFIC INCLUSION CRITERIA FOR POST-STROKE APHASIA SUBJECTS:

Had sensorimotor and language deficits following ischemic infarcts.

Had stroke at least two weeks ago.

SPECIFIC INCLUSION CRITERIA FOR TRAUMATIC BRAIN INJURY SUBJECTS:

Diagnosis of TBI

At least one month post-injury

SPECIFIC INCLUSION CRITERIA FOR STUTTERING SUBJECTS:

History of developmental stuttering with symptoms of dysfluency presenting before the age
of 13

If recovered, history documented by school or medical records.

SPECIFIC INCLUSION CRITERIA FOR EPILEPSY SUBJECTS:

Ages 18 to 55 years.

Failure of seizures to respond to adequate therapy with at least two standard antiepileptic
drugs.

Willingness to be considered for surgery

Fluency in English. Non-native speakers may be included if their fluency is equivalent to
that of a native speaker.

Must have localization-related epilepsy

Must be currently enrolled in Protocol 08-N-0161 to participate in this study

EXCLUSION CRITERIA FOR ALL SUBJECTS:

Past or present major medical or psychiatric illnesses (DSM-IV criteria) except Post
Traumatic Stress Disorder (PTSD) in TBI subjects an anxiety disorder in stuttering subjects

Significant abnormalities on the general physical examination unrelated to the stroke or
TBI

Unable to undergo MRI studies due to pacemakers, aneurysm clips, cochlear implants,
shrapnel fragments or a significant history of exposure to small metallic objects which
might have become lodged in the tissues of the head or neck or who require hearing aids.

Subjects who are pregnant are excluded from the PET and MRI tests in this study.

Subjects who are lactating are excluded from the PET tests.

Subjects who have or are found to have significant visual agnosia.

Subjects who cannot provide informed consent.

SPECIFIC EXCLUSION CRITERIA FOR POST-STROKE APHASIA SUBJECTS:

More than two prior strokes

Concurrent diagnoses of neurodegenerative disorders or vascular dementia

Comprehension Aphasia Quotient (AQ) of less than 4 on the Western Aphasia Battery (WAB)

SPECIFIC EXCLUSION CRITERIA FOR TRAUMATIC BRAIN INJURY SUBJECTS:

For military subjects: Positive screen for Acinetobacter baumannii-calcoaceticus complex
(ABC) infection or colonization

Severe cognitive impairments as evidenced by scores of less than 7 on the Rancho Los Amigos
Scale of Cognitive Functioning and/or less than 76 on the Galveston Orientation and Amnesia
Test.

For all subjects: Comprehension AQ of less than 4 on the WAB

A diagnosis of PTSD, which is almost always found in TBI subjects recruited from the
military, will not disquality TBI subjects from participation.

SPECIFIC EXCLUSION CRITERIA FOR STUTTERING SUBJECTS:

Structural abnormalities on standard clinical (MPRAGE, T2-weighted) MRI scans studies

A diagnosis of anxiety dirorder will not disqualify stuttering subjects from participation

SPECIFIC EXCLUSION CRITERIA FOR EPILEPSY SUBJECTS:

Claustrophobia or anxiety disorders that could be exacerbated by the MRI Scanner

Subjects with neurological disorders, in addition to epilepsy such as, stroke, Parkinson s
disease), or who have psychiatric diagnoses (, such as, obsessive-compulsive disorder)

Patients on Phenobarbital or chronic Benxodiazepines