Publications

OBJECTIVE: Smaller temporal lobe cortical gray matter volumes, including the left superior temporal gyrus, have been reported in magnetic resonance imaging (MRI) studies of patients with chronic schizophrenia and, more recently, in patients with first-episode schizophrenia. However, it remains unknown whether there are progressive decreases in temporal lobe cortical gray matter volumes in patients with first-episode schizophrenia and whether similarly progressive volume decreases are present in patients with affective psychosis. METHOD: High-spatial-resolution MRI scans at initial hospitalization and 1.5 years later were obtained from 13 patients with first-episode schizophrenia, 15 patients with first-episode affective psychosis (mainly manic), and 14 healthy comparison subjects. MRI volumes were calculated for gray matter of superior temporal gyrus and for the amygdala-hippocampal complex.

Several studies suggest that the nonschizophrenic relatives of schizophrenic patients exhibit structural brain abnormalities that may be manifestations of genes that predispose to schizophrenia. In this work, we examine the utility of such measures for linkage analyses. Subjects were 45 nonpsychotic first-degree adult relatives of schizophrenic patients and 48 normal controls. Sixty contiguous 3-mm coronal, T1-weighted 3D magnetic resonance images of the entire brain were acquired on a 1.5-T magnet. We used factor analysis to derive MRI-based phenotypes for analysis. The factor analyses produced three factors that significantly discriminated relatives from controls. We used a linear combination of the three factor scores to derive an MRI phenotype. A receiver operating characteristic (ROC) analysis of this phenotype estimated an area under the curve (AUC) statistic of 0.85. The phenotype also discriminated nonpsychotic relatives having two schizophrenic relatives from those having only one. The nonpsychotic relatives of schizophrenic patients show deviant values on MRI measures of brain structure and the distribution of these deviations among relatives and controls suggests that if these results can be replicated, an MRI-derived phenotype could be useful for genetic linkage and association analyses.

A central question in schizophrenia research is which brain abnormalities are independent of psychosis and which evolve before and after psychosis begins. This question can be addressed by longitudinal neuroimaging studies beginning in the prodrome, but at present there is only one published study. We reviewed the literature on structural brain imaging in persons with chronic and first episode schizophrenia, nonpsychotic persons at genetic high risk, and persons thought to be at risk for imminent psychosis ("prodromal" persons). Medial temporal lobe (MTL), especially hippocampal, volume alterations are among the most robust brain vulnerabilities for schizophrenia. Because verbal declarative memory (VDM) deficits are prominent and the parahippocampal gyrus (PHG) is considered to be centrally involved with the hippocampus in VDM processing, we analyzed PHG data from a family study of schizophrenia. Patients with schizophrenia and nonpsychotic relatives from "multiplex" families (families with multiple persons with schizophrenia) had significantly smaller right parahippocampal anterior (PHa) volumes than controls. Marginally significant findings were observed for the left PHa. Unexpectedly, relatives from "simplex" families (families with only one person with schizophrenia) had significantly larger PH posterior volumes than controls and did not differ from controls on PHa. Results provide some support for the hypothesis that the vulnerability to schizophrenia includes abnormal volumes of the PHG. These data provide additional support for the hypothesis that some MTL abnormalities in schizophrenia are independent of psychosis, at least in families with presumably high genetic loading. Implications of genetic risk studies for prodromal research are discussed.

STUDY OBJECTIVES: While obesity is the most common risk factor for the development of obstructive sleep apnea, the correlation between measures of obesity and apnea severity is only moderate. We thus attempted to identify anatomic and physiologic predictors of apnea severity. DESIGN: We combined a careful assessment of upper airway anatomy, upper airway physiology, and ventilatory control in a group of obese individuals to identify predictors of apnea severity. SETTING: Tertiary care academic medical center. PATIENTS: 14 morbidly obese subjects being evaluated for weight-reduction surgery.

PURPOSE: Rasmussen encephalitis is a progressive inflammatory process with difficult-to-control focal or lateralized seizure activity, leading to hemispheric dysfunction and atrophy in advanced stages. Anatomic changes of atrophy may be subtle in earlier phases of the disease, and progressive changes on serial scans may be difficult to detect. We report a case of early-stage Rasmussen encephalitis with a relatively stable clinical course in whom we performed magnetic resonance imaging (MRI)-based volumetric analysis over an interval of 1 year, to assess for volumetric changes. METHODS: Volumetric analysis was performed on two successive MRI scans obtained at age 5 and 6 years, by using the CARDVIEWS program (J Cogn Neurosci, 1996). The images were segmented into gray- and white-matter structures according to signal intensity of their borders semiautomatically, with manual corrections. The cerebral cortex was further subdivided into smaller parcellation units according to anatomic landmarks identifiable on MRI. RESULTS: Stable left cerebral hemispheric atrophy and progressive atrophy in the left precentral gyrus, left inferior frontal gyrus, and left cerebellar atrophy were detected over the 1-year interval. CONCLUSIONS: Volumetric analysis enables early detection and quantification of anatomic changes, identification of focal involvement, and assists in determining the severity of disease and timing for surgical interventions such as hemispherectomy.

Morphometric magnetic resonance imaging (MRI) was used to compare regional brain volumes in eight women with body dysmorphic disorder (BDD) and eight healthy comparison subjects. The BDD group exhibited a relative leftward shift in caudate asymmetry and greater total white matter vs. the comparison group. Findings with respect to the caudate nucleus are consistent with both the conceptualization of BDD as an obsessive-compulsive spectrum disorder, and the ’striatal topography model’ of obsessive-compulsive disorders.

Different subterritories of anterior cingulate cortex (ACC) and adjacent ventromedial frontal cortex have been shown to serve distinct functions. This scheme has influenced contemporary pathophysiologic models of psychiatric disorders. Prevailing neurocircuitry models of post-traumatic stress disorder (PTSD) implicate dysfunction within pregenual ACC and subcallosal cortex (SC), as well as amygdala and hippocampus. In the current study, cortical parcellation of magnetic resonance imaging data was performed to test for volumetric differences in pregenual ACC and SC, between women with PTSD and trauma-exposed women without PTSD. The PTSD group exhibited selectively decreased pregenual ACC and SC volumes. These results are consistent with contemporary schemes regarding functional and structural dissection of frontal cortex, and suggest specific regional cortical pathology in PTSD.

Cytokinins, or plant growth hormones, bind with very high affinity to cytokinin-specific binding proteins (CSBPs). Recombinant mung bean CSBP has been overexpressed in Escherichia coli and crystallized in complex with zeatin, a natural plant growth hormone. The crystals belong to the hexagonal system, space group P6(2) or P6(4), with unit-cell parameters a = 113.62, c = 86.85 A, contain two to five copies of the protein in the asymmetric unit and diffract X-rays to 1.25 A resolution.

We describe a system of surface-assisted parcellation (SAP) of the human cerebellar cortex derived from neural systems functional and behavioral anatomy. This system is based on MRI and preserves the unique morphologic and topographic features of the individual cerebellum. All major fissures of the cerebellum were identified and traced in the flattened representation of the cerebellar cortex using the program "FreeSurfer." Parcellation of the cerebellar cortex followed using the fissure information in conjunction with landmarks using the program "Cardviews" to create 64 gyral-based cerebellar parcellation units. Computer-assisted algorithms enable the execution of the cerebellar parcellation procedure as well as volumetric measurements and topographic localization. The SAP technique makes it possible to represent multimodal structural and functional imaging data on the flattened surface of the cerebellar cortex as illustrated in one functional MRI experiment.

Magnetic resonance diffusion tensor imaging (DTI) is a new technique that can be used to visualize and measure the diffusion of water in brain tissue; it is particularly useful for evaluating white matter abnormalities. In this paper, we review research studies that have applied DTI for the purpose of understanding neuropsychiatric disorders. We begin with a discussion of the principles involved in DTI, followed by a historical overview of magnetic resonance diffusion-weighted imaging and DTI and a brief description of several different methods of image acquisition and quantitative analysis. We then review the application of this technique to clinical populations. We include all studies published in English from January 1996 through March 2002 on this topic, located by searching PubMed and Medline on the key words "diffusion tensor imaging" and "MRI." Finally, we consider potential future uses of DTI, including fiber tracking and surgical planning and follow-up.