Database Registry to Examine Brain Connections and Brain Function in Mental Disorders and Neural Network Biomarkers for Relational Memory and Psychosis in Schizophrenia

Study ID
STU 062010-095

Cancer Related
No

Healthy Volunteers
Yes

Study Sites

  • Clements University Hospital
  • UT Southwestern Ambulatory Services
  • Parkland Health & Hospital System

Contact
Debra Bushong
214/648-4653
debra.bushong@utsouthwestern.edu

Principal Investigator
Carol Tamminga, M.D.

Official Title

Database Registry to Examine Brain Connections and Brain Function in Mental Disorders and Neural Network Biomarkers for Relational Memory and Psychosis in Schizophrenia

Brief Overview


Several observations have been made with magnetic resonance imaging (MRI) that characterize
brain connections and brain function in individuals with schizophrenia and other mental
disorders. For example, research investigating schizophrenia focuses on the dysfunction of
connections within and between the medial temporal lobe and the prefrontal cortex as well as
other pertinent brain regions. This database registry will allow for the collection of
clinical interview data, behavioral data, blood, magnetic resonance imaging (MRI) data, and
functional magnetic resonance imaging (fMRI) data on individuals with and without mental
disorders to better understand how connections in the brain and various brain regions
function differently while volunteers perform various cognitive tasks. This is an
observational study that is being conducted to collect data and place it in a registry for
current and future investigational questions related to imaging in mental disorders.

Summary


The proposed project entails the collection of clinical interview data, behavioral data,
blood, magnetic resonance imaging (MRI) data, and functional magnetic resonance imaging
(fMRI) data from 1000 volunteers, both patient volunteers and healthy normal volunteers.
These data will be used for current and future investigations to better understand how the
brains of those with mental disorders process differently that brains of healthy volunteers.
The volunteers will undergo a series of clinical interviews to determine their diagnosis,
behavioral task training, medical workup, and standard structural and functional magnetic
resonance imaging. No changes will be made to the patient volunteers' medications or
treatment regimes as part of the study. Data will be collected for all volunteer groups
based on their performance on a variety of computer-mediated cognitive tasks. The volunteers
will be trained to criteria on the tasks, at which point they will have the option to
complete the MRI and fMRI portions of the study. Standard and functional MR images of the
entire brain will be acquired while volunteers perform cognitive tasks thought to activate
the medial temporal lobe and other pertinent brain regions. While participating in the task
portion of the fMRI, visual stimulation (images) will be presented via back-projection from
a high-resolution video projector (Epson 7000 series) with adjustable zoom. Volunteers will
be asked to push a button on a handheld button box to record their responses as learned
during training. For the non-task, resting portions of the fMRI, volunteers will be asked to
stay relaxed and alert. In conjunction with one of the fMRI scans we will also conduct a
cerebral blood volume (CBV) MRI to investigate blood perfusion in the medial temporal lobe
of volunteers with mental illness to compare to normal control volunteers.

The proposed project will evaluate brain connectivity during cognitive tasks, including
novelty detection, encoding and retrieval of associations between individual stimuli, and
during other cognitive tasks thought to produce abnormal fMRI activations in volunteers with
mental disorders. One example of a cognitive task is conducted as follows. Volunteers are
shown a series of one-syllable nouns and asked to internally associate a second noun to the
presented word (e.g. "station" to the presented word "train"). They press a response button
when they have made a successful word association. Subsequently, volunteers are presented
with a mixture of the previously encoded words and a new set of one-syllable nouns.
Volunteers press one response button for previously presented words and another button for
novel (new) words. fMRI scans for both parts of this task are acquired in the time between
stimulus presentation and the press of the button. In another example of a cognitive task,
volunteers are shown a novel series of faces paired with names and are instructed to
remember the name for each face. In a subsequent period, volunteers attempt to remember
which name goes to which face. The fMRI scans are acquired during both encoding and
retrieval of the face-name pairs. These two described tasks are representative of the tasks
to be used in terms of their difficulty and the effort required of the volunteers. In
addition, "resting" and "control" tasks will be used to establish a baseline of brain
activity against which we may then compare activity during our task of interest. Volunteers
will receive instructions on task performance and will practice tasks prior to scanning in
order to eliminate the novelty of the task itself as a potential confound. While the
appointment time for a scan may take several hours, the volunteer will be in the scanner
between 60 and 120 minutes depending on the specific memory task that is being administered
at that visit. Any volunteer may receive training and be scanned on more than one task, but
no volunteer will be kept in the scanner for longer than 120 minutes in any given session.
Volunteers may also be asked to undergo one or two 60-minute MR Spectroscopy scans conducted
on the 3Tesla (3T) or 7Tesla (7T) scanner. In this scan we will measure the levels of
different brain compounds, such as neurotransmitters (e.g. glutamate, gamma aminobutyric
acid [GABA]) or endogenous brain metabolites (e.g., N-acetyl -aspartate)in various brain
regions, to non-invasively study tissue biochemistry.

Participant Eligibility


Inclusion Criteria:

Volunteers with Schizophrenia or other mental illness

- Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision
(DSM-IV-TR) diagnosis of Schizophrenia or Schizoaffective disorder

- Competent to give informed consent

- All races and ethnicities

- Eyesight corrected to 20-40 or better

- Able to read, speak, and understand English

Healthy volunteers

- No past or current severe mental illness

- All races and ethnicities

- Eyesight corrected to 20-40 or better

- Able to read, speak, and understand English

Exclusion Criteria:

Volunteers with schizophrenia or other mental illness

- Diagnosis of an organic brain disease

- Diagnosis of DSM-IV-TR alcohol or substance abuse within the last month or DSM-IV-TR
alcohol or substance dependence within the last three months

- Serious, unstable medical illness

- History of serious head injury

- Pregnant women

Healthy volunteers

- History of psychiatric illness

- Current use of psychoactive drugs excluding nicotine and caffeine

- Diagnosis of an organic brain disease

- Serious, unstable medical illness

- History of serious head injury

- Pregnant women