Publications by Year: 2002

OBJECTIVES: It is controversial whether a semantic processing bias for strong associates is present in schizophrenia, and unknown whether the language abnormalities observed in schizophrenia can be attributed to dysfunctions early or late in cognitive processing. Combined behavioral and event-related potential (ERP) data can indicate the nature and timing of such abnormalities. METHODS: Sensibility judgements of dominant and subordinate homograph sentences were measured in 12 schizophrenia patients and 13 normal controls. ERPs were recorded to the disambiguating sentence-ending word. RESULTS: All subjects showed greatest misinterpretation of subordinate homograph sentences, but schizophrenia patients particularly misinterpreted these sentence types. For control subjects, subordinate homograph sentences that were classified as nonsensical showed greater N400 than those classified as sensible. By contrast, the N400 of patients was large, regardless of the sensibility judgement—patients’ brains initially responded to all subordinate sentences as if nonsensical. These data are consonant with a semantic bias. However, the patients’ N400 to dominant homograph sentence endings was also larger than that of controls, a finding not consonant with a semantic bias. CONCLUSIONS: The behavioral results indicate a selective comprehension abnormality in schizophrenia dependent on the content of verbal memory. The ERP results suggest a pervasive contextual memory failure. A semantic activation decay model is proposed to explain these results.

OBJECTIVE: "Cognitive" circuits anatomically link the frontal lobe to subcortical structures; therefore, pathology in any of the core components of these circuits, such as in the caudate nucleus, may result in neurobehavioral syndromes similar to those of the frontal lobe. Neuroleptic medication, however, affects the size of the caudate nucleus. For this reason, individuals diagnosed with schizotypal personality disorder offer an ideal group for the measurement of the caudate nucleus because they may be genetically related to individuals with schizophrenia but do not require neuroleptic treatment because of their less severe symptoms. METHOD: Magnetic resonance imagining (MRI) scans obtained on a 1.5-T magnet with 1.5-mm contiguous slices were used to measure the caudate nucleus and lateral ventricles in 15 right-handed male subjects with schizotypal personality disorder who had no previous neuroleptic exposure and in 14 normal comparison subjects. Subjects were group matched for parental socioeconomic status, handedness, and gender. RESULTS: First, the authors found significantly lower left and right absolute (13.1%, 13.2%) and relative (9.1%, 9.2%) caudate nucleus volumes in never-medicated subjects with schizotypal personality disorder than in normal subjects. Second, they found significant, inverse correlations between caudate nucleus volume and the severity of perseveration in two distinct working memory tasks in these neuroleptic-naive subjects with schizotypal personality disorder. CONCLUSIONS: These data are consistent with the findings of reduced caudate nucleus volume reported in studies of neuroleptic-naive patients experiencing their first episode of schizophrenia and support the association of intrinsic pathology in the caudate nucleus with abnormalities in working memory in the schizophrenia spectrum.

BACKGROUND: Mismatch negativity (MMN) is an event-related brain potential that is sensitive to stimulus deviation from a repetitive pattern. The MMN is thought primarily to reflect the activity of sensory memory, with, at most, moderate influences of higher-level cognitive processes, such as attention. The MMN is reported to be reduced in patients with chronic schizophrenia. However, it is unknown whether MMN is reduced in patients with first-episode schizophrenia (at first hospitalization).

A technique for detecting neural activity in functional MRI data is introduced. It is based on a novel framework termed maximum correlation modeling. The method employs a spatial filtering approach that adapts to the local activity patterns, which results in an improved detection sensitivity combined with good specificity. A spatially varying hemodynamic response is simultaneously modelled by a sum of two gamma functions. Comparisons to traditional analysis methods are made using both synthetic and real data. The results indicate that the maximum correlation modeling approach is a strong alternative for analyzing fMRI data.

A novel and computationally efficient method for exploratory analysis of functional MRI data is presented. The basic idea is to reveal underlying components in the fMRI data that have maximum autocorrelation. The tool for accomplishing this task is Canonical Correlation Analysis. The relation to Principal Component Analysis and Independent Component Analysis is discussed and the performance of the methods is compared using both simulated and real data.

Studies of schizotypal personality disorder (SPD) are important because the condition is genetically related to schizophrenia and because data accumulating to confirm its biological underpinnings are challenging some traditional views about the nature of per-sonality disorders. This review of 17 structural imaging studies in SPD indicates that individuals with this disorder show brain abnormalities in the superior temporal gyrus, parahippocampus, temporal horn region of the lateral ventricles, corpus callosum, thalamus, and septum pellucidum, as well as in total cerebrospinal fluid volume, similar to those seen in persons with schizophrenia. Differences between SPD and schizophrenia include lack of abnormalities in the medial temporal lobes and lateral ventricles in SPD. Whether the normal volume, and possibly normal functioning, of the medial temporal lobes in individuals with SPD may help to suppress psychosis in this disorder remains an intriguing but still unresolved question. Such speculation must be tempered due to a paucity of studies, and additional work is needed to confirm these preliminary findings. The imaging findings do suggest, however, that SPD probably represents a milder form of disease along the schizophrenia continuum. With further clarification of the neuroanatomy of SPD, researchers may be able to identify which neuroanatomical abnormalities are associated with the frank psychosis seen in schizophrenia.

BACKGROUND: In chronic schizophrenia, the P300 is broadly reduced and shows a localized left temporal deficit specifically associated with reduced gray matter volume of the left posterior superior temporal gyrus (STG). In first-episode patients, a similar left temporal P300 deficit is present in schizophrenia, but not in affective psychosis. The present study investigated whether the left temporal P300-left posterior STG volume association is selectively present in first-episode schizophrenia.

The self-diffusion coefficients of water in casein solutions and gels were measured using a pulsed-gradient spin-echo nuclear magnetic resonance technique (PGSE NMR). The dependence of the self-diffusion coefficient of water on the concentration and structure of casein is reported. The results were analyzed using a cell model. It was found that the water self-diffusion coefficient is insensitive to the structure of the casein in solution or in a gelled state. The influence of casein concentration on the water self-diffusion coefficient could be explained by obstruction from the casein molecule. Assuming a simple model with two water regions, each characterized by a specific water concentration and value of the water diffusion coefficient, the water mobility reduction induced by the casein can be rationalized.

We applied partial least squares (PLS) as a novel multivariate statistical technique to examine neuropsychological correlates of magnetic resonance imaging (MRI) measures of brain volumes in a well studied sample of 15 male patients with chronic schizophrenia. In the current study, because the total number of measures far surpassed the total number of subjects, extant multivariate techniques such as canonical correlation could not be used to examine relationships among simultaneous measures of MRI and neuropsychology. Moreover, because MRI measures were expected to be highly inter-correlated, as would be neuropsychological test scores, extant multivariate statistical techniques would be substantially limited because they typically assume statistical independence among sets of measures. PLS, on the other hand, proved to be especially well suited to examining the relationships among function and anatomy measures in this sample, where statistically significant relationships were demonstrated that were entirely consistent with prior studies using univariate correlation techniques. In particular, statistically significant relationships emerged among sets of MRI temporal lobe measures and neuropsychological tests of verbal memory and categorization as well as among MRI frontal measures and neuropsychological tests of working memory.

Magnetic resonance (MR) diffusion tensor imaging (DTI) can resolve the white matter fiber orientation within a voxel provided that the fibers are strongly aligned. However, a given voxel may contain a distribution of fiber orientations due to, for example, intravoxel fiber crossing. The present study sought to test whether a geodesic, high b-value diffusion gradient sampling scheme could resolve multiple fiber orientations within a single voxel. In regions of fiber crossing the diffusion signal exhibited multiple local maxima/minima as a function of diffusion gradient orientation, indicating the presence of multiple intravoxel fiber orientations. The multimodality of the observed diffusion signal precluded the standard tensor reconstruction, so instead the diffusion signal was modeled as arising from a discrete mixture of Gaussian diffusion processes in slow exchange, and the underlying mixture of tensors was solved for using a gradient descent scheme. The multitensor reconstruction resolved multiple intravoxel fiber populations corresponding to known fiber anatomy. Ma