Positron Emission Tomography (PET) is a technique used to investigate the functional activity of the brain. The PET technique allows doctors to study the normal biochemical and metabolic processes of the central nervous system of normal individuals and patients with neurologic illnesses without physical / structural damage to the brain. Radioactive water H215O in PET scans permits good visualization of areas of the brain related to speech.

Most of the PET scan studies conducted have concentrated on learning about how language is formed and decoded. Few studies have been conducted on speech production. This study aims to use radioactive water (H215O) and Positron Emission Tomography (PET scan) to measure blood flow to different areas of the brain in order to better understand the mechanisms involved in speech motor control.

When a region of the brain is active, it uses more fuel in the form of oxygen and sugar (glucose). As the brain uses more fuel it produces more waste products, carbon dioxide and water. Blood carries fuel to the brain and waste products away from the brain. As brain activity increases blood flow to and from the area of activity increases also. Knowing these facts, researchers can use radioactive chemicals (H215O) and PET scans to observe what areas of the brain are receiving more blood flow.

Researchers will ask patients to perform tasks that will affect speech, voice, and language. At the same time patients will undergo a PET scan. The tasks are designed to help researchers observe the blood flow to brain areas associated with voicebox (laryngeal) functions, movement of muscles in the jaw, tongue, and mouth, and other aspects of motor speech.

Special studies will be conducted to evaluate how certain therapies and tasks can draw out symptoms in illnesses in which speech and language are affected. Results of these tests will be used in other studies to evaluate the neurologic mechanisms of diseases like Tourette's syndrome and parkinson's disease.

Objective. The primary objective of this protocol is to use multimodal neuroimaging - combining complementary electrophysiological and hemodynamic methods - to characterize brain-language relationships in control subjects and to determine how these relationships are altered in neurological disorders that affect speech and language. A secondary objective is to be able to utilize these findings as endpoints for the evaluation of treatment in future studies.

Study populations. We will focus on three neurological disorders that affect language processing - post-stroke aphasia, traumatic brain injury 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. An overarching interest is to examine the use of language in a real-world, pragmatic context, since it is this context that precipitates symptoms in almost all of these disorders. Focusing on the use of language in an ecologically valid context, we will pay particular attention to relationships between language comprehension and production; the problem of hemispheral lateralization; and the interaction of language with other cognitive domains, focusing on a) motor systems, b) music and c) emotion

The combination of hemodynamic (functional MRI, H2O-15 PET) and electrophysiological (EEG, MEG) modalities capitalizes on the superior spatial resolution of the former and temporal resolution of the latter methods. Whenever possible the same task paradigms are used in both. The majority of studies will utilize fMRI, MEG or EEG methods. H2O-15 PET retains an advantage in studies of continuous overt speech, and will be used as gold standard to compare with MRI methods.

• Communication Disorder
• Healthy
• Stuttering
• Tourette Syndrome
• Voice Disorder

• Alexander GE, DeLong MR, Strick PL. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci. 1986;9:357-81. Review. No abstract available.
• Andrews G, Quinn PT, Sorby WA. Stuttering: an investigation into cerebral dominance for speech. J Neurol Neurosurg Psychiatry. 1972 Jun;35(3):414-8. No abstract available.
• Bartlett EJ, Brown JW, Wolf AP, Brodie JD. Correlations between glucose metabolic rates in brain regions of healthy male adults at rest and during language stimulation. Brain Lang. 1987 Sep;32(1):1-18.

• INCLUSION/EXCLUSION CRITERIA: All subjects, including patients and normal volunteers:

Subjects will be between the ages of 18 and 85 and will not be excluded on the basis of gender or ethnic background.

Premenopausal women will be asked if they are pregnant or might be pregnant on the day of PET or MRI studies. If such a history is negative and a negative urine pregnancy test is obtained on the day of the procedure these patients will be studied; they will otherwise be excluded.

All subjects with a history of major medical or psychiatric illness (DSM-IV criteria), or who have significant abnormalities on the general physical examination unrelated to their primary diagnoses, will be excluded from the study.

We will additionally exclude subjects from MRI studies who have 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.

POST-STROKE APHASIA - We will include only subjects who have experienced sensorimotor and language deficits following ischemic infarcts. Two classes of aphasic patients will be enrolled: subchronic cases, defined as less than one year post-stroke, and chronic cases, more than one year post-stroke. A subset of former will be enrolled in our longitudinal studies. In both groups, the degree of language or sensorimotor impairment will not matter as long as patients are able to cooperate and give informed consent.

Ideal post-stroke aphasia patients will have single infarcts. We will exclude patients with a history of more than two prior strokes. We will also exclude patients with concurrent diagnoses of neurodegenerative disorders or vascular dementia. Subjects with a comprehension AQ of less than 4 on the Western Aphasia Battery will be considered to have receptive aphasic symptoms severe enough to interfere with the ability to provide informed consent and will be excluded from the study. Subjects will be excluded from experiments that use speech stimuli if they demonstrate greater than 40-dBHL reduction in more than two audiologic thresholds between 25 Hz and 2 KHz on audiometric examination

INCLUSION CRITERIA: FOR POST-STROKE APHASIA (all of the following must be present)

Between the ages of 18 and 85

History of ischemic cerebral infarction with residual sensorimotor and/or language deficits.

EXCLUSION CRITERIA: FOR POST-STROKE APHASIA (exclude individual if one or more of the following is present)

History of major medical illness unrelated to primary diagnosis of stroke

Significant abnormalities on general physical and neurological examination unrelated to primary diagnosis

Concurrent diagnoses of neurodegenerative disorder or vascular dementia.

Premenopausal women pregnant or nursing

Presence of 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.

Major psychiatric illness (DSM-IV criteria)

Comprehension AQ of 4 or greater on the WAB

Greater than 40 dBHL reduction in more than two audiologic thresholds between 25 Hz and 2 KHz on audiometric examination for experiments that use speech stimuli.

TRAUMATIC BRAIN INJURY - Inclusion criteria entail the diagnosis of TBI, based on medical records with confirmatory diagnostic assessment by referring physicians, in the case of military personnel, from the theater and field hospital to which the combat casualties are transferred. Subjects will be at least one month post-injury.

Specific exclusion criteria for TBI patients overlap with general exclusion criteria for MRI studies. We thus exclude patients with the presence of shrapnel or other metal inclusions (determined by CT or MRI screening studies at collaborating institutions).

TBI patients who have served in Iraq or Afghanistan will be screened for Acinetobacter baumannii-calcoaceticus complex (ABC) infection or colonization or will have been screened at collaborating military institutions. Patients who are positive will be excluded from the study and referred for treatment.

As with stroke patients, TBI patients with a comprehension AQ of less than 4 on the Western Aphasia Battery will be excluded from the study. Subjects will be excluded from experiments that use speech stimuli if they demonstrate greater than 40-dBHL reduction in more than two audiologic thresholds between 25 Hz and 2 KHz on audiometric examination.

Pre-screening at collaborating military institutions will exclude patients with 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.

INCLUSION CRITERIA: FOR TRAUMATIC BRAIN INJURY(all of the following must be present)

Between the ages of 18 and 85

Diagnosis of TBI, based on medical records with confirmatory diagnostic assessment by referring physician from theatre/field hospital to which combat casualties are transferred

At least one month post-injury

EXCLUSION CRITERIA: FOR TRAUMATIC BRAIN INJURY (exclude individual if one or more of the following is present)

History of major medical illness unrelated to primary diagnosis of traumatic brain injury

Significant abnormalities on general physical and neurological examination unrelated to the primary diagnosis

Positive screen for Acinetobacter baumannii-calcoaceticus complex (ABC) infection or colonization.

Premenopausal women pregnant or nursing

Presence of 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.

Major psychiatric illness (DSM-IV criteria)

Comprehension AQ of 4 or greater on the WAB

Greater than 40 dBHL reduction in more than two audiologic thresholds between 25 Hz and 2 KHz on audiometric examination for experiments that use speech stimuli.

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 (administered at collaborating military institutions).

DEVELOPMENTAL STUTTERING - We will include two classes of patients, both of whom must carry the diagnosis of developmental stuttering, having presented with typical dysfluent symptoms in childhood (before the age of 13). One group will have evidence of current stuttering, another will have evidence of childhood stuttering (documented by school or medical records) but will be currently symptom-free.

We will exclude patients with evidence of pathological structural abnormalities on brain imaging studies and subjects who are not native English speakers. We will also exclude subjects with positive findings on neurological examination other than those related to the primary diagnosis of developmental stuttering.

INCLUSION CRITERIA: FOR DEVELOPMENTAL STUTTERING (all of the following must be present)

Between the ages of 18 and 85

History of developmental stuttering with symptoms of dysfluency presenting in childhood (before the age of 13)

If recovered, history documented by school or medical records.

EXCLUSION CRITERIA: FOR DEVELOPMENTAL STUTTERING (exclude individual if one or more of the following is present)

History of major medical illness unrelated to primary diagnosis of developmental stuttering

Significant abnormalities on general physical and neurological examination unrelated to primary diagnosis

Premenopausal women pregnant or nursing

Evidence of pathological structural abnormalities on brain imaging studies

English not acquired as a native language (around the age of 2)

Presence of 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.

Major psychiatric illness (DSM-IV criteria)