Biomedical subjects

Robert M Bilder

Publications and source records attributed to Robert M Bilder.

At least 19 recordsLinked to original sources

PubMed2006

Asymmetries of cortical shape: Effects of handedness, sex and schizophrenia.

Some evidence suggests that sex, handedness and disease processes associated with schizophrenia affect the magnitude and/or direction of structural brain asymmetries. There are mixed findings, however, on how these factors influence cerebral torque, when torque is assessed with linear or volumetric measurements. We obtained MRI data from 67 healthy (30 males, 10 non-dextrals) and 84 schizophrenia subjects (60 males; 16 non-dextrals) and applied cortical pattern matching to spatially relate and compare differences in the surface morphology of the two cerebral hemispheres at high spatial resolution. Asymmetry indices, computed at thousands of matched hemispheric locations, were used to examine effects of sex, handedness and schizophrenia on hemispheric shape asymmetries while controlling for age and the other factors. Highly significant and discriminative right-frontal and left parietal-occipital surface expansions and protrusions (petalias) were mapped within groups. Although hemispheric shape asymmetries appeared less pronounced within female non-dextrals, asymmetry indices were not shown to differ significantly across sex, hand preference or diagnosis, or to reveal interactions of handedness with sex or diagnosis. Our 3D maps of spatially detailed anterior and posterior hemispheric shape asymmetries reflect subtle geometric distortions in hemispheric surface morphology that cannot be characterized with 2D or volumetric methods. Inter-individual variations in hemispheric torque appear minimally influenced by sex, dextrality or disease status. Biological factors driving language dominance or other lateralized brain functions dissociable from handedness, may more closely relate to hemispheric shape asymmetries, while the lateralization of other discrete brain regions may be more influenced by sexually dimorphic factors or by schizophrenia pathophysiology.

Cerebral Cortex↗

PubMed2006

Increased stress and smaller anterior hippocampal volume.

Animal studies indicate that stress negatively impacts hippocampal structure; little is known, however, regarding the relationship between stress and hippocampal morphology in healthy humans. Twenty-one healthy adults underwent structural magnetic resonance imaging examinations and completed the Derogatis Stress Profile. Greater psychological stress at the time of the scan correlated significantly and more strongly with anterior than posterior hippocampal volume. These findings suggest that psychological stress may be associated with structural alterations in the anterior hippocampal formation and that this relationship may differ along the rostrocaudal axis of the hippocampus. Our results may also have implications for neuropsychiatric disorders that have implicated stress and hippocampal abnormalities in their pathogenesis.

Adult↗

PubMed2006

Relationships between IQ and regional cortical gray matter thickness in healthy adults.

Prior studies show positive correlations between full-scale intelligence quotient (FSIQ) and cerebral gray matter measures. Few imaging studies have addressed whether general intelligence is related to regional variations in brain tissue and the associated influences of sex. Cortical thickness may more closely reflect cytoarchitectural characteristics than gray matter density or volume estimates. To identify possible localized relationships, we examined FSIQ associations with cortical thickness at high spatial resolution across the cortex in healthy young adult (age 17-44 years) men (n = 30) and women (n = 35). Positive relationships were found between FSIQ and intracranial gray and white matter but not cerebrospinal fluid volumes. Significant associations with cortical thickness were evident bilaterally in prefrontal (Brodmann's areas [BAs] 10/11, 47) and posterior temporal cortices (BA 36/37) and proximal regions. Sex influenced regional relationships; women showed correlations in prefrontal and temporal association cortices, whereas men exhibited correlations primarily in temporal-occipital association cortices. In healthy adults, greater intelligence is associated with larger intracranial gray matter and to a lesser extent with white matter. Variations in prefrontal and posterior temporal cortical thickness are particularly linked with intellectual ability. Sex moderates regional relationships that may index dimorphisms in cognitive abilities, overall processing strategies, or differences in structural organization.

Adolescent↗

PubMed2006

Baseline neurocognitive deficits in the CATIE schizophrenia trial.

Neurocognition is moderately to severely impaired in patients with schizophrenia. However, the factor structure of the various neurocognitive deficits, the relationship with symptoms and other variables, and the minimum amount of testing required to determine an adequate composite score has not been determined in typical patients with schizophrenia. An 'all-comer' approach to cognition is needed, as provided by the baseline assessment of an unprecedented number of patients in the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) schizophrenia trial. From academic sites and treatment providers representative of the community, 1493 patients with chronic schizophrenia were entered into the study, including those with medical comorbidity and substance abuse. Eleven neurocognitive tests were administered, resulting in 24 individual scores reduced to nine neurocognitive outcome measures, five domain scores and a composite score. Despite minimal screening procedures, 91.2% of patients provided meaningful neurocognitive data. Exploratory principal components analysis yielded one factor accounting for 45% of the test variance. Confirmatory factor analysis showed that a single-factor model comprised of five domain scores was the best fit. The correlations among the factors were medium to high, and scores on individual factors were very highly correlated with the single composite score. Neurocognitive deficits were modestly correlated with negative symptom severity (r=0.13-0.27), but correlations with positive symptom severity were near zero (r<0.08). Even in an 'all-comer' clinical trial, neurocognitive deficits can be assessed in the overwhelming majority of patients, and the severity of impairment is similar to meta-analytic estimates. Multiple analyses suggested that a broad cognitive deficit characterizes this sample. These deficits are modestly related to negative symptoms and essentially independent of positive symptom severity.

Adult↗

PubMed2006

Cognitive development in schizophrenia: follow-back from the first episode.

Despite consensus that schizophrenia is a neurodevelopmental disorder characterized by cognitive deficits, objective data documenting the course of cognitive development remain sparse. We conducted a follow-back study of patients ascertained at the time of their initial episode of schizophrenia or schizoaffective disorder, and a group of demographically matched healthy volunteers. We obtained school records containing standardized achievement test scores from the 1st through 12th grades, and scholastic aptitude test results from the 11th and 12th grades, and examined the developmental trajectories of cognitive performance with respect to prospective examinations conducted following participants' enrollment in our study. We found significant differences in academic achievement tests as early as the first grade, with scores from participants who would later develop schizophrenia lagging behind their peers by 0.8 to 1.1 grade equivalents. This gap widened resulting in a difference between groups of 1.5 to 1.8 grade equivalents by the 12th grade. In the subset of patients for whom SAT scores were available, we found that WAIS-R Full Scale IQ was 11.5 points lower than predicted from earlier SAT scores, suggesting a substantial decline in cognitive ability accompanying the initial episode of illness. These findings suggest that schizophrenia is marked by substantial cognitive deficits in the first grade, that there may be additional subtle decline preceding the overt onset of psychotic symptoms, and that the initial episode of illness is marked by additional decline. These observations may help advance concepts of premorbid cognitive ability in the schizophrenia syndrome and constrain models of pathophysiology.

Adolescent↗

PubMed2006

Aggression and quantitative MRI measures of caudate in patients with chronic schizophrenia or schizoaffective disorder.

Caudate dysfunction is implicated in schizophrenia. However, little is known about the relationship between aggression and caudate volumes. Forty-nine patients received magnetic resonance imaging scanning in a double-blind treatment study in which aggression was measured. Caudate volumes were computed using a semiautomated method. The authors measured aggression with the Overt Aggression Scale and the Positive and Negative Syndrome Scale. Larger caudate volumes were associated with greater levels of aggression. The relationship between aggression and caudate volumes may be related to the iatrogenic effects of long-term treatment with typical antipsychotic agents or to a direct effect of schizophrenic processes on the caudate.

Adult↗

PubMed2005

Regional specificity of cerebrospinal fluid abnormalities in first episode schizophrenia.

The timing and regional specificity of cerebrospinal fluid (CSF) enlargements have not been well described in schizophrenia. High-resolution magnetic resonance images and computational image analysis methods were used to localize cross-sectional changes in lateral ventricle and sulcal and subarachnoid CSF in first episode schizophrenia patients (51 males/21 females) and healthy subjects (37 males/41 females). Volumes were obtained for each lateral ventricle horn and regional differences identified by comparing the distances from the ventricular surfaces to the central core at anatomically matched locations. Extra-cortical CSF differences were compared by measuring the proportion of CSF voxels sampled from spatially homologous cortical surface points. Significant extra-cortical CSF enlargements were observed in first episode patients, where regional differences surrounded the temporal, anterior frontal and parietal cortices. Volume and ventricular surface analyses failed to show significant effects of diagnosis. However, interactions indicated dorsal superior horn expansions in female patients compared with same-sex controls. Since ventricular enlargements are widely reported in chronic patients, our observations at first episode suggest ventricular enlargement may progress after disease onset with early changes occurring around the dorsal superior horn. In contrast, sulcal and subarachnoid CSF increases may be manifest near or before the first episode but after brain development is complete, reflecting pronounced reductions in proximal brain tissue.

Adult↗

PubMed2005

Quantitative MRI measures of orbitofrontal cortex in patients with chronic schizophrenia or schizoaffective disorder.

The relationship between orbitofrontal cortex (OFC) volumes and functional domains in treatment-resistant patients with schizophrenia or schizoaffective disorder is poorly understood. OFC dysfunction is implicated in several of the behaviors that are abnormal in schizophrenia. However, little is known about the relationship between these behaviors and OFC volumes. Forty-nine patients received magnetic resonance imaging scanning as part of a double-blind treatment study in which psychiatric symptomatology, neuropsychological function, and aggression were measured. OFC volumes were manually traced on anatomical images. Psychiatric symptomatology was measured with the Positive and Negative Syndrome Scale (PANSS). Aggression was measured with the Overt Aggression Scale (OAS) and with the PANSS. Neuropsychological function was assessed using a comprehensive test battery. Larger right OFC volumes were associated with poorer neuropsychological function. Larger left OFC gray matter volumes and larger OFC white matter volumes bilaterally were associated with greater levels of aggression. These findings are discussed in the context of potential iatrogenic effects.

Adult↗

PubMed2005

Neurocognitive profile in adolescents with early-onset schizophrenia: clinical correlates.

BACKGROUND: Neurocognitive impairments have been documented in adolescents with early-onset schizophrenia (EOS; onset by age 18) and are important treatment targets. Information concerning the severity, pattern, and clinical correlates of these deficits in EOS remains limited. METHODS: Tests assessing motor skills, attention, memory, visuospatial abilities and executive functioning were administered to 54 clinically stabilized adolescents with EOS and 52 age- and sex-matched healthy controls. Childhood-onset patients (onset by age 13) were compared to those with an adolescent onset of illness. Patients' neurocognitive profiles were compared to those of controls. Relationships between neurocognitive deficits and demographic and clinical characteristics were explored. RESULTS: Neurocognitive profiles did not differ between childhood- and adolescent-onset participants. Patients showed a generalized neurocognitive deficit of 2.0 SDs compared to controls, with relative deficit in executive functioning and relative sparing of language and visuospatial abilities. Degree of generalized neurocognitive impairment was associated with premorbid adjustment and negative symptom severity (Adjusted R(2) = .39). CONCLUSIONS: Results document both a significant generalized deficit and a relative deficit of executive functioning in adolescents with EOS. The overall pattern is similar to that observed in severely ill first-episode adult patients. The impairments across multiple neurocognitive domains suggest widespread brain dysfunction in EOS.

Adolescent↗

PubMed2005

Cortical thinning in cingulate and occipital cortices in first episode schizophrenia.

BACKGROUND: Postmortem studies examining discrete regions show reduced cortical thickness in schizophrenia. Computational image analysis methods allow spatially detailed cortical thickness measurements across the entire cortex in 3D, but have not addressed thickness changes in cingulate or other cortices bordering the medial walls of the cerebral hemispheres in first episode schizophrenia. METHODS: Magnetic resonance images and cortical pattern matching methods were used to compare gray matter thickness, measured at sub-voxel resolution at thousands of spatially equivalent locations on the medial hemispheric surfaces, between 72 (51m/21f) first episode schizophrenia patients and 78 (37m/41f) healthy controls similar in age. Group differences were mapped in 3D, and their overall significance was confirmed by permutation testing. RESULTS: Patients with little or no prior antipsychotic medication treatment showed significant cortical thinning within cingulate, occipital and frontopolar cortices with no significant increases in any cortical location. Regional sex differences were observed with pronounced thinning in the left paracentral lobule and right posterior cingulate in male and female patients respectively compared to same sex controls. CONCLUSIONS: Cortical thinning may correspond to cytoarchitectural and neurochemical abnormalities observed in similar anatomic locations and may underlie systems-wise disturbances that include heteromodal association cortices, where cortical thinning has been previously observed in first episode schizophrenia.

Adult↗

PubMed2005

Olfactory functions and volumetric measures of orbitofrontal and limbic regions in schizophrenia.

OBJECTIVE: Olfactory deficits in schizophrenia patients have been suggested to reflect medial temporal and/or prefrontal brain abnormalities. In this study, we examined the relationship between different olfactory functions and volumes of the hippocampus-amygdala complex (HAC) and the orbitofrontal brain region using magnetic resonance imaging (MRI). METHODS: Thirty-three young men with schizophrenia (DSM-IV) and 40 healthy controls performed unirhinal olfactory assessment including the main olfactory functions (threshold, discrimination, and identification), and odor judgements (intensity, edibility, familiarity, and pleasantness). Volumes of regions in the medial temporal lobe (hippocampus and amygdala) and the prefrontal region (orbitofrontal gray and white matter) were measured on MRI scans. RESULTS: Compared with controls, patients showed bilaterally impaired thresholds, quality discrimination and identification, as well as edibility judgements. Olfactory deficits were not attributable to smoking, premorbid intelligence, or impaired thresholds. Relative to controls, patients had bilateral reduced hippocampus and amygdala volumes. In patients, smaller hippocampus volumes were associated with poorer olfactory discrimination ability. CONCLUSIONS: Olfactory deficits in schizophrenia appear to be associated with morphometric abnormalities in the medial temporal rather than the orbitofrontal region (OFR). These results indicate that olfactory quality discrimination deficits are related to structural hippocampus abnormalities. Future studies of genetic and behavioral high-risk samples seem warranted.

Adult↗

PubMed2005

White matter abnormalities in obsessive-compulsive disorder: a diffusion tensor imaging study.

CONTEXT: Several neurobiological models of obsessive-compulsive disorder (OCD) posit a primary role for dysfunction of the anterior cingulate gyrus. Both functional and structural neuroimaging studies have implicated anterior cingulate gray matter abnormalities in the pathophysiology of OCD, but there has been little investigation of the anterior cingulate white matter in this disorder. OBJECTIVE: To test the hypothesis that patients with OCD have abnormal white matter microstructure in the anterior cingulate gyrus compared with healthy volunteers as inferred from diffusion tensor imaging. Additional analyses examined group differences in white matter integrity across the entire brain. DESIGN, SETTING, AND PARTICIPANTS: Fifteen patients with a DSM-IV diagnosis of OCD and 15 healthy volunteers matched for age, sex, and handedness underwent diffusion tensor imaging and structural magnetic resonance imaging examinations. Fractional anisotropy (FA), a robust intravoxel measure of water self-diffusion, was compared between groups on a voxel-by-voxel basis in the anterior cingulate white matter after standardization in Talairach space. MAIN OUTCOME MEASURES: Clinical ratings of symptom severity (ie, Yale-Brown Obsessive-Compulsive Scale) and FA. RESULTS: Compared with healthy volunteers, patients demonstrated significantly lower FA bilaterally in 3 areas of the anterior cingulate gyrus white matter. Additional analyses conducted across the rest of the brain white matter revealed lower FA bilaterally in the parietal region (supramarginal gyri), right posterior cingulate gyrus, and left occipital lobe (lingual gyrus). No areas of significantly higher FA were observed in patients compared with healthy volunteers. Lower FA in the parietal region correlated significantly with higher Yale-Brown Obsessive-Compulsive Scale scores. CONCLUSIONS: These preliminary findings provide evidence of an abnormality that involves the anterior cingulate white matter in the pathogenesis of OCD and are consistent with neurobiological models that posit a defect in connectivity in the anterior cingulate basal ganglia-thalamocortical circuit. White matter abnormalities in other brain regions may also be implicated in the neurobiology of OCD.

Adult↗

PubMed2005

White matter abnormalities in first-episode schizophrenia or schizoaffective disorder: a diffusion tensor imaging study.

OBJECTIVE: The goal of this study was to investigate brain white matter abnormalities by using diffusion tensor imaging in patients with schizophrenia or schizoaffective disorder close to illness onset. METHOD: Ten patients experiencing a first episode of schizophrenia or schizoaffective disorder and 13 healthy volunteers received diffusion tensor imaging and structural magnetic resonance imaging examinations. Voxel-wise analysis was used to compare fractional anisotropy maps in the white matter of the two groups following intersubject registration to Talairach space. RESULTS: Compared with healthy volunteers, patients demonstrated lower fractional anisotropy in the left internal capsule and left-hemisphere white matter of the middle frontal gyrus and posterior superior temporal gyrus. There were no areas of significantly higher fractional anisotropy in patients compared with healthy volunteers. CONCLUSIONS: These findings suggest that white matter pathology is present early in the course of schizophrenia and may be less pronounced than has been found in previous diffusion tensor imaging studies of patients with chronic illness. Further, these data are consistent with hypotheses regarding frontotemporal dysfunction and the failure of left-hemisphere lateralization in the pathophysiology of schizophrenia.

Adult↗

PubMed2004

Mapping cortical thickness and gray matter concentration in first episode schizophrenia.

We mapped regional changes in cortical thickness and intensity-based cortical gray matter concentration in first episode schizophrenia. High-resolution magnetic resonance images were obtained from 72 (51 male, 21 female) first episode patients and 78 (37 male, 41 female) healthy subjects similar in age. Cortical pattern matching methods allowed comparisons of cortical thickness and gray matter concentration at thousands of homologous cortical locations between subjects in three dimensions. Principal components analyses reduced measures obtained across the cortex to identify global differences in cortical thickness/gray matter concentration. First principal component factor scores showed significant effects of diagnosis, sex and age for both cortical measures. Diagnosis and age effects remained significant after brain size correction. Cortical thickness and gray matter concentration values were highly correlated. Statistical maps showed significant regional gray matter thinning in frontal, temporal and parietal heteromodal association cortices bilaterally in first episode patients. Regional reductions in cortical gray matter concentration were similar but pronounced in the superior temporal lobe. Regional reductions in cortical thickness and gray matter concentration are present at disease onset in brain regions linked with functional disturbances in schizophrenia. Cortical thickness and gray matter concentration mapping produce similar results, although the concentration metric may be influenced by diagnostic differences in extra-cortical cerebrospinal fluid and surface curvature/complexity.

Adult↗

PubMed2004

A developmental examination of gender differences in brain engagement during evaluation of threat.

BACKGROUND: Females appear to be more sensitive and responsive to social cues, including threat signals, than are males. Recent theoretical models suggest that developmental changes in brain functioning play important roles in the emergence of such gender differences. METHODS: We used functional magnetic resonance imaging to examine developmental and gender differences in activation of neural structures thought to mediate attention to emotional faces depicting varying degrees of threat. Analyses focused on the orbitofrontal cortex, amygdala, and anterior cingulate cortex during the evaluation of threat conveyed by faces. Healthy adolescents (n = 17; 53% male) and adults (n = 17; 53% male) were scanned while they rated how threatening pictures of neutral and emotional (angry, fearful, or happy) faces appeared. RESULTS: Results indicate significant interactions among age, gender, and face type for activation during explicit threat monitoring. In particular, adult women activated orbitofrontal cortex and amygdala selectively to unambiguous threat (angry) cues, while adult men showed a less discriminating pattern of activation. No gender differences were evident for adolescents, who as a group resembled adult males. CONCLUSIONS: These findings suggest that there are gender differences in patterns of neural responses to emotional faces that are not fully apparent until adulthood.

Adolescent↗

PubMed2004

Abnormal gyral complexity in first-episode schizophrenia.

BACKGROUND: Abnormalities in the patterns and frequency of cortical folding might help identify temporal and regionally specific disturbances in normal neurodevelopmental processes that occur in association with schizophrenia. Few studies, however, have investigated gyral complexity in schizophrenia. METHODS: High-resolution magnetic resonance images were used to examine differences in gyral complexity, measured three-dimensionally in five separate hemispheric regions covering the entire cortical surface, in patients with first-episode schizophrenia (n = 50) compared with demographically matched healthy comparison subjects (n = 50). The modulating effects of gender and hemisphere were also examined. RESULTS: Significant increases in cortical folding were observed in the right superior frontal cortex in male schizophrenic patients compared with male control subjects, but not between female diagnostic groups. Significant main effects of hemisphere were found in frontal, parietal, and occipital regions in directions complementary to cerebral torques. CONCLUSIONS: Results support previous findings of right frontal hypergyria in male schizophrenic patients and suggest that these abnormalities predate illness onset and are of neurodevelopmental origin. Therefore, in schizophrenia, sexually dimorphic developmental processes and differences in hemispheric connectivity, which have been shown to influence the organization and/or frequency of cortical folding, seem to be disturbed during gyral formation in utero.

Adult↗

PubMed2004

Investigation of unirhinal olfactory identification in antipsychotic-free patients experiencing a first-episode schizophrenia.

Although olfactory deficits have been reported in patients with schizophrenia, few studies have examined whether these deficits are lateralized or investigated their possible clinical correlates. In this study, we administered the University of Pennsylvania Smell Identification Test (UPSIT) unirhinally (one nostril at a time) to 15 patients experiencing a first-episode of schizophrenia and 17 healthy comparison subjects. Clinical and olfactory assessments were conducted on the same day in patients while they were antipsychotic drug-free. Patients performed more poorly compared to healthy volunteers in their ability to identify odors across both nostrils, but there were no group differences in right and left nostril impairment. Among patients, greater deficits in grooming and hygiene correlated significantly and more strongly with poorer ability in identifying odors presented to the left compared to the right nostril. Our findings suggest that deficits in grooming and hygiene, including poor body odor, observed in patients experiencing a first-episode of schizophrenia are associated with an impairment in left nostril, and possibly left hemisphere, olfactory processing.

Adolescent↗

PubMed2004

Regional specificity of hippocampal volume reductions in first-episode schizophrenia.

Hippocampal volume reductions are widely observed in schizophrenia. Some studies suggest anterior hippocampal regions are more susceptible and associated with frontal lobe dysfunctions, while others implicate posterior regions. Using high-resolution MR images and novel computational image analysis methods, we identified the hippocampal subregions most vulnerable to disease processes in 62 (45 m/17 f) first-episode schizophrenia patients compared to 60 (30 m/30 f) healthy controls, similar in age. The hippocampi were traced on coronal brain slices and hemispheric volumes were compared between diagnostic groups. Regional structural abnormalities were identified by comparing distances, measured from homologous hippocampal surface points to the central core of each individual's hippocampal surface model, between groups in 3D. CSF concentrations were also compared statistically at homologous hippocampal surface points to localize corresponding gray matter reductions. Significant bilateral hippocampal volume reductions were observed in schizophrenia irrespective of brain size corrections. Statistical mapping results, confirmed by permutation testing, showed pronounced left hemisphere shape differences in anterior and midbody CA1 and CA2 regions in patients. Significant CSF increases surrounding the hippocampus were observed in a similar spatial pattern in schizophrenia. Results confirm that hippocampal volume reductions are a robust neuroanatomical correlate of schizophrenia and are present by first episode. Mid- to antero-lateral hippocampal regions show pronounced volume changes and complementary increases in peri-hippocampal CSF, suggesting that these hippocampal regions are more susceptible to disease processes in schizophrenia. Targeting regional hippocampal abnormalities may help dissociate schizophrenia patients from other groups exhibiting global hippocampal volume changes, and better focus systems-level pathophysiological hypotheses.

Adolescent↗