Whole-brain morphometric study of schizophrenia revealing a spatially complex set of focal abnormalities.

CONTEXT: Neuroanatomic abnormalities in schizophrenia may underlie behavioral manifestations. Characterization of such abnormalities is required for interpreting functional data. Frontotemporal abnormalities have been documented by using predetermined region-of-interest approaches, but deformation-based morphometry permits examination of the entire brain. OBJECTIVES: To perform whole-brain analyses of structural differences between patients with schizophrenia and controls, to examine sex and medication effects, and to apply a high-dimensional nonlinear pattern classification technique to quantify the degree of separation between patients and controls, thereby testing the potential of this new technique as an aid to diagnostic procedures. DESIGN: Whole-brain morphologic analysis using high-dimensional shape transformations. SETTING: Schizophrenia Research Center, University of Pennsylvania Medical Center. PARTICIPANTS: Neuroleptic-naïve and previously treated patients with DSM-IV schizophrenia (n = 69) and sociodemographically matched controls (n = 79). MAIN OUTCOME MEASURES: Gray matter, white matter, and ventricular cerebrospinal fluid volumes in the brain. RESULTS: Magnetic resonance images showed reduced gray matter and increased ventricular cerebrospinal fluid volumes in patients with schizophrenia in the whole brain and in specific foci: the hippocampus and adjacent white matter, the cingulate and orbitofrontal cortex, the frontotemporal and parietotemporal areas, and the occipital areas near the lingual gyrus. The classifier had a mean classification accuracy of 81.1% for men and women combined (82% for women and 85% for men, when each group was treated separately), determined via cross-validation. CONCLUSIONS: This study confirms previous findings of reduced frontotemporal volumes and suggests new hypotheses, especially involving occipital association and speech production areas. It also suggests finer localization of volume reduction in the hippocampus and other limbic structures and in the frontal lobe. Pattern classification showed high sensitivity and specificity for the diagnosis of schizophrenia, suggesting the potential utility of magnetic resonance imaging as a diagnostic aid.

Organization of semantic category exemplars in schizophrenia.

Semantic memory was investigated in 27 individuals with schizophrenia and 30 healthy controls using an animal similarity judgment and organization test with reduced retrieval demands. Participants arranged 12 common animal names according to similarity on a computer screen and provided verbal descriptions of organizational strategies. Distance between each animal pair was compared to the number of shared semantic attributes between the pairs (e.g., size, diet, habitat). The three primary organizational strategies included single animals not related to other exemplars, isolated clusters of animals that shared a single strategic relationship (e.g., pets), and overlapping clusters that combined more than one strategic relationship (e.g., cats and mammals). A strong negative correlation was observed between distance ratings and number of shared semantic attributes, confirming that semantic features related to visual distances in both groups. Animal pairs that shared few semantic attributes were placed in closer proximity in the schizophrenia group, whereas the groups placed animal pairs sharing more features equidistantly. Analyses of clustering strategies revealed a double dissociation, with patients relying on isolated, non-overlapping clusters and controls producing more overlapping semantic clusters. Results suggest that performance differences on semantic tasks with limited retrieval demands in schizophrenia relate to difficulties utilizing higher-order categorization strategies.

A method for obtaining 3-dimensional facial expressions and its standardization for use in neurocognitive studies.

Facial expressions of emotion are increasingly being used in neuroscience as probes for functional imaging and as stimuli for studying hemispheric specialization for face and emotion processing. Available facial stimuli are 2-dimensional and therefore, their orientation is fixed and poorly suited for examining asymmetries, they are often obtained under poorly specified conditions, usually posed, lack ethnic diversity, and are of restricted age range. We describe a method for accurately acquiring and reconstructing the geometry of the human face and for display of this reconstruction in a 3-dimensional format. We applied the method in a sample of 70 actors and 69 actresses expressing happiness, sadness, anger, fear and disgust, as well as neutral expressions. Each emotion was expressed under three levels of intensity and under both posed and evoked conditions. Resulting images are of high technical quality and are accurately identified by raters. The stimuli can be downloaded in digital form as 'movies' where angle and orientation can be manipulated for inclusion in functional imaging probes or in tests that can be administered as measures of individual differences in facial emotion processing. The database of emotional expressions can also be used as a standard for comparison with clinical populations.

A cognitive neuroscience-based computerized battery for efficient measurement of individual differences: standardization and initial construct validation.

There is increased need for efficient computerized methods to collect reliable data on a range of cognitive domains that can be linked to specific brain systems. Such need arises in functional neuroimaging studies, where individual differences in cognitive performance are variables of interest or serve as confounds. In genetic studies of complex behavior, which require particularly large samples, such trait measures can serve as endophenotypes. Traditional neuropsychological tests, based on clinical pathological correlations, are protracted, require extensive training in administration and scoring, and leave lengthy paper trails (double-entry for analysis). We present a computerized battery that takes an average of 1h and provides measures of accuracy and speed on 9 neurocognitive domains. They are cognitive neuroscience-based in that they have been linked experimentally to specific brain systems with functional neuroimaging studies. We describe the process of translating tasks used in functional neuroimaging to tests for assessing individual differences. Data are presented on each test with samples ranging from 139 (81 female) to 536 (311 female) of carefully screened healthy individuals ranging in age from 18 to 84. Item consistency was established with acceptable to high Cronbach alpha coefficients. Inter-item correlations were moderate to high within domain and low to nil across domains, indicating construct validity. Initial criterion validity was demonstrated by sensitivity to sex differences and the effects of age, education and parental education. These results encourage the use of this battery in studies needing an efficient assessment of major neurocognitive domains such as multi-site genetic studies and clinical trials.

The other-race effect in face processing among African American and Caucasian individuals with schizophrenia.

OBJECTIVE: Studies of emotion recognition abilities in schizophrenia show greater impairment for non-Caucasians with schizophrenia compared with Caucasians. These studies, however, included only Caucasian faces as stimuli. There is evidence from healthy individuals for a performance disadvantage on face memory and emotion recognition when processing faces from a different ethnicity. The authors sought to measure the "other-race effect" in schizophrenia, which could account for previous findings and provide information about sensitivity to such social cues in patients. METHOD: The study included 540 participants from four groups: African Americans with schizophrenia (N=135), Caucasians with schizophrenia (N=135), African American community comparison subjects (N=135), and Caucasian community comparison subjects (N=135). All participants completed face recognition and facial emotion identification tasks that included both Caucasian and African American faces as stimuli. RESULTS: Although comparison participants performed better than individuals with schizophrenia across all tasks, both comparison participants and participants with schizophrenia exhibited a strong and significant other-race effect for face memory and emotion recognition. The magnitude of the other-race effect did not differ between these two groups. CONCLUSIONS: These findings reveal an intact other-race effect in patients with schizophrenia and highlight a methodological concern in the measurement of face processing abilities in schizophrenia, namely, that findings of greater impairment in African American patients are spurious when Caucasian faces are used as stimuli. Despite overall impairments in face memory and emotion recognition, the presence of a normative other-race effect in schizophrenia may reflect typical experiences with faces during development.