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.