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Biomedical subjects

Robert M Bilder

Publications and source records attributed to Robert M Bilder.

41 records · Page 3Linked to original sources

Neurodevelopmental aspects of spatial navigation: a virtual reality fMRI study.

Navigation in spatial contexts has been studied in diverse species, yielding insights into underlying neural mechanisms and their phylogenetic progression. Spatial navigation in humans is marked by age-related changes that may carry important implications for understanding cortical development. The emergence of "allocentric" processing, reflecting that ability to use viewer-independent spatial abstractions, represents an important developmental change. We used fMRI to map brain regions engaged during memory-guided navigation in a virtual reality environment in adolescents and adults. Blood oxygen level-dependent (BOLD) signal was monitored in eight adolescents and eight adults in a 1.5-T MRI scanner during three conditions: (1) memory-guided navigation (NAV); (2) arrow-guided navigation (ARROW); and (3) fixation (FIX). We quantified navigation ability during scanning and allocentric memory after scanning, based on subjects' ability to label a previously unseen, aerial view of the town. Adolescents and adults exhibited similar memory-guided navigation ability, but adults exhibited superior allocentric memory ability. Memory-guided navigation ability during scanning correlated with BOLD change between NAV/ARROWS in various regions, including a right frontal and right-anterior medial temporal lobe region. Age group and allocentric memory together explained significant variance in BOLD change in temporoparietal association cortex and the cerebellum, particularly in the left hemisphere. Consistent with developmental models, these findings relate maturation in the coding of spatial information to functional changes in a distributed, left-lateralized neural network.

Adolescent↗

Managing treatment-resistant schizophrenia: evidence from randomized clinical trials.

Clozapine was the first antipsychotic medication to be approved for the indication of treatment-refractory schizophrenia. This followed rigorous testing in patients who retrospectively and prospectively failed treatment trials of relatively high doses of conventional antipsychotics. In the past decade, other atypical antipsychotics have been approved, but they have not been designated specifically for patients with a history of prior poor treatment response. Better tolerated than clozapine, these new agents have been used with varying success in patients who would have otherwise received clozapine. Up until very recently there has not been a head-to-head controlled clinical trial comparing the two most commonly used atypical antipsychotics, risperidone and olanzapine, with clozapine in patients considered to have a suboptimal response to typical antipsychotics. This review summarizes the current advances made in the pharmacological management of these patients by examining recently published randomized controlled clinical trials that have measured psychopathology and cognition.

Journal Article↗

Neuropsychological correlates of hippocampal volumes in patients experiencing a first episode of schizophrenia.

OBJECTIVE: Despite evidence for hippocampal structural abnormalities in patients with schizophrenia, their functional correlates remain largely unknown. This study investigated the neuropsychological correlates of hippocampal volume in 43 men and 32 women experiencing a first episode of schizophrenia. METHOD: Posterior and anterior hippocampal volumes were computed from contiguous 3.1-mm magnetic resonance images and examined in relationship to six domains of neuropsychological functioning. Significant structure-function associations were investigated by examining the correlations between functioning and individual hippocampal slice volumes across the long axis of the hippocampus after interpolation to 10 equally spaced slice positions. RESULTS: Among men, worse executive and motor functioning correlated significantly with smaller anterior, but not posterior, hippocampal volume. The relationship between executive and motor functioning and hippocampal volume was not linear, however, when examined across the long axis of the hippocampus. Anterior hippocampal volume was more strongly correlated with both executive and motor functioning than with either memory or language functioning in men. None of the correlations between either posterior or anterior hippocampal volumes and the neuropsychological domains was significant among women. Anterior hippocampal volume was more strongly correlated with motor functioning in men than in women. CONCLUSIONS: Anterior hippocampal abnormalities associated with deficits on tests considered sensitive to frontal lobe functions implicate a defect in the integrated system linking frontal and mesiotemporal lobe regions. These findings further suggest that there are sex differences in structure-function relations in schizophrenia such that men may have more pronounced frontolimbic system abnormalities.

Adult↗

Neurocognitive effects of clozapine, olanzapine, risperidone, and haloperidol in patients with chronic schizophrenia or schizoaffective disorder.

OBJECTIVE: Newer antipsychotic drugs have shown promise in ameliorating neurocognitive deficits in patients with schizophrenia, but few studies have compared newer antipsychotic drugs with both clozapine and conventional agents, particularly in patients who have had suboptimal response to prior treatments. METHOD: The authors examined the effects of clozapine, olanzapine, risperidone, and haloperidol on 16 measures of neurocognitive functioning in a double-blind, 14-week trial involving 101 patients. A global score was computed along with scores in four neurocognitive domains: memory, attention, motor function, and general executive and perceptual organization. RESULTS: Global neurocognitive function improved with olanzapine and risperidone treatment, and these improvements were superior to those seen with haloperidol. Patients treated with olanzapine exhibited improvement in the general and attention domains but not more than that observed with other treatments. Patients treated with risperidone exhibited improvement in memory that was superior to that of both clozapine and haloperidol. Clozapine yielded improvement in motor function but not more than in other groups. Average effect sizes for change were in the small to medium range. More than half of the patients treated with olanzapine and risperidone experienced "clinically significant" improvement (changes in score of at least one-half standard deviation relative to baseline). These findings did not appear to be mediated by changes in symptoms, side effects, or blood levels of medications. CONCLUSIONS: Patients with a history of suboptimal response to conventional treatments may show cognitive benefits from newer antipsychotic drugs, and there may be differences between atypical antipsychotic drugs in their patterns of cognitive effects.

Adult↗

Neurocognitive correlates of response to treatment in formal thought disorder in patients with first-episode schizophrenia.

OBJECTIVE: To examine the independent contribution of executive versus semantic function to improvement in formal thought disorder after initial stabilization in a first-episode sample. BACKGROUND: Neurocognitive deficits have been suggested to predict treatment response in patients with first-episode schizophrenia. However, studies targeting putative neurocognitive mechanisms to explore improvement in positive psychotic symptoms and especially formal thought disorder are lacking. METHOD: Formal thought disorder symptoms in 81 first-episode patients with schizophrenia or schizoaffective disorder either showed significant improvement (responders > 60% change) or not (nonresponders < 60%) 6 months after initial stabilization of symptoms. These two groups were compared on neuropsychologic (n = 16), clinical (n = 15), and volumetric measures of the frontal and temporal lobes (n = 5) in univariate analyses. The variables that significantly differed between these two groups were used in a forward binary logistic regression analysis. RESULTS: As compared with nonresponders, responders were younger at time of testing, had higher verbal intelligence and reading achievement scores, higher scores on the arithmetic subtest of the Wechsler Adult Intelligence Scale-Revised, and lower number of perseverative responses on the Wisconsin Card Sort Test. Responders also had larger frontal lobe volumes than nonresponders. Only two measures (perseverative responses on the Wisconsin Card Sort Test and age at testing) entered the regression equation. Measures of semantic competency and volumetric measures of the temporal lobes were not associated with formal thought disorder improvement. CONCLUSIONS: Neurocognitive deficits are associated with treatment response in formal thought disorder in first-episode patients with schizophrenia. The improvement in formal thought disorder is more strongly linked to executive than semantic function in this sample, pointing to the salience of frontal systems in treatment response in positive psychotic symptoms.

Adult↗