PubMed Health⌕ Search

Biomedical subjects

Joseph H Callicott

Publications and source records attributed to Joseph H Callicott.

26 records · Page 2Linked to original sources
PubMed2003

An expanded role for functional neuroimaging in schizophrenia.

Functional magnetic resonance imaging is a surprisingly versatile tool in the quest for disentangling the complexities of mental illnesses such as schizophrenia. Yet, the identification of pathognomonic physiological features of the illness or even a consensus regarding the interpretation of reported findings remain unfulfilled goals, in spite of the increasing sophistication of this technology. Nonetheless, by providing quantification of brain function during various cognitive challenges, functional MRI has been used to leap ahead of these quandaries to identify relationships between genetic variation and brain function. By examining recent findings and efforts to link these findings to genes, this article will review these exciting developments in schizophrenia research.

Brain Mapping↗
PubMed2003

Interindividual differences in functional interactions among prefrontal, parietal and parahippocampal regions during working memory.

To clarify the neural systems deployed by individual subjects during working memory (WM), we collected functional neuroimaging data from healthy subjects, and constructed a model of 2-back WM using structural equation modeling (SEM). A group model was constructed, and models for each subject were validated against it. The group model consisted principally of regions in the prefrontal and parietal cortex, with considerable interindividual variance in the single-subject models. To explore this variance, subjects were split into two groups based on performance. Performance level and self-reported strategy scores were used in a correlation analysis against path weights between nodes of individual models. High performers utilized a left hemisphere sub-network involving inferior parietal lobule and Broca's area, whereas lower performers utilized a right hemisphere sub-network with interactions between inferior parietal lobule and dorsolateral prefrontal cortex. Further, we observed an interaction between the parahippocampal formation and the inferior parietal lobule that was related to the different strategies used by the individuals to perform the task. Strategy and performance level appear to be intricately related in this task, with neural systems supporting verbal processing producing better performance than those associated with spatial processing. These results demonstrate that individual behavioral characteristics are reflected in specific neurofunctional patterns at the system level and that these can be captured by analytical techniques such as SEM.

Adult↗
PubMed2003

Complexity of prefrontal cortical dysfunction in schizophrenia: more than up or down.

OBJECTIVE: Numerous neuroimaging studies have examined the function of the dorsolateral prefrontal cortex in schizophrenia; although abnormalities usually are identified, it is unclear why some studies find too little activation and others too much. The authors' goal was to explore this phenomenon. METHOD: They used the N-back working memory task and functional magnetic resonance imaging at 3 T to examine a group of 14 patients with schizophrenia and a matched comparison group of 14 healthy subjects. RESULTS: Patients' performance was significantly worse on the two-back working memory task than that of healthy subjects. However, there were areas within the dorsolateral prefrontal cortex of the patients that were more active and areas that were less active than those of the healthy subjects. When the groups were subdivided on the basis of performance on the working memory task into healthy subjects and patients with high or low performance, locales of greater prefrontal activation and locales of less activation were found in the high-performing patients but only locales of underactivation were found in the low-performing patients. CONCLUSIONS: These findings suggest that patients with schizophrenia whose performance on the N-back working memory task is similar to that of healthy comparison subjects use greater prefrontal resources but achieve lower accuracy (i.e., inefficiency) and that other patients with schizophrenia fail to sustain the prefrontal network that processes the information, achieving even lower accuracy as a result. These findings add to other evidence that abnormalities of prefrontal cortical function in schizophrenia are not reducible to simply too much or too little activity but, rather, reflect a compromised neural strategy for handling information mediated by the dorsolateral prefrontal cortex.

Achievement↗
PubMed2003

Working memory deficits and levels of N-acetylaspartate in patients with schizophreniform disorder.

OBJECTIVE: The authors used proton magnetic resonance spectroscopic imaging ((1)H-MRSI) to assess potential reductions of N-acetylaspartate (a marker of neuronal integrity) in the hippocampal area and dorsolateral prefrontal cortex of patients with schizophreniform disorder. In addition, they assessed the relationship between N-acetylaspartate levels and working memory deficits. METHOD: Twenty-four patients with DSM-IV schizophreniform disorder and 24 healthy subjects were studied. Subjects underwent (1)H-MRSI and were given the N-back working memory test. RESULTS: The schizophreniform disorder patients had selective reductions of N-acetylaspartate ratios in the hippocampal area and the dorsolateral prefrontal cortex, and a positive correlation was seen between N-acetylaspartate ratios in the dorsolateral prefrontal cortex and performance during the 2-back working memory condition. CONCLUSIONS: Similar to findings reported in schizophrenia studies, N-acetylaspartate reductions in the hippocampal area and the dorsolateral prefrontal cortex were seen in patients with schizophreniform disorder. Moreover, the results support other evidence that neuronal pathology in the dorsolateral prefrontal cortex accounts for a proportion of working memory deficits already present at illness outset.

Adult↗
PubMed2003

Abnormal fMRI response of the dorsolateral prefrontal cortex in cognitively intact siblings of patients with schizophrenia.

OBJECTIVE: The identification of neurobiological intermediate phenotypes may hasten the search for susceptibility genes in complex psychiatric disorders such as schizophrenia. Earlier family studies have suggested that deficits in executive cognition and working memory may be related to genetic susceptibility for schizophrenia, but the biological basis for this behavioral phenotype has not been identified. METHOD: The authors used functional magnetic resonance imaging (fMRI) during performance of the N-back working memory task to assess working memory-related cortical physiology in nonschizophrenic, cognitively intact siblings of patients with schizophrenia. They compared 23 unaffected siblings of schizophrenic patients to 18 matched comparison subjects. As a planned replication, they studied another 25 unaffected siblings and 15 comparison subjects. RESULTS: In both cohorts, there were no group differences in working memory performance. Nevertheless, both groups of siblings showed an exaggerated physiological response in the right dorsolateral prefrontal cortex that was qualitatively similar to results of earlier fMRI studies of patients with schizophrenia. CONCLUSIONS: These fMRI data provide direct evidence of a primary physiological abnormality in dorsolateral prefrontal cortex function in individuals at greater genetic risk for schizophrenia, even in the absence of a manifest cognitive abnormality. This exaggerated fMRI response implicates inefficient processing of memory information at the level of intrinsic prefrontal circuitry, similar to earlier findings in patients with schizophrenia. These data predict that inheritance of alleles that contribute to inefficient prefrontal information processing will increase risk for schizophrenia.

Adult↗
PubMed2002

Dopaminergic modulation of cortical function in patients with Parkinson's disease.

Patients with idiopathic Parkinson's disease suffer not only from classic motor symptoms, but from deficits in cognitive function, primarily those subserved by the prefrontal cortex as well. The aim of the current study was to investigate the modulatory effects of dopaminergic therapy on neural systems subserving working memory and motor function in patients with Parkinson's disease. Ten patients with stage I and II Parkinson's disease were studied with functional magnetic resonance imaging, during a relatively hypodopaminergic state (ie, 12 hours after a last dose of dopamimetic treatment), and again during a dopamine-replete state. Functional magnetic resonance imaging was performed under three conditions: a working memory task, a cued sensorimotor task and rest. Consistent with prior data, the cortical motor regions activated during the motor task showed greater activation during the dopamine-replete state; however, the cortical regions subserving working memory displayed greater activation during the hypodopaminergic state. Interestingly, the increase in cortical activation during the working memory task in the hypodopaminergic state positively correlated with errors in task performance, and the increased activation in the cortical motor regions during the dopamine-replete state was positively correlated with improvement in motor function. These results support evidence from basic research that dopamine modulates cortical networks subserving working memory and motor function via two distinct mechanisms: nigrostriatal projections facilitate motor function indirectly via thalamic projections to motor cortices, whereas the mesocortical dopaminergic system facilitates working memory function via direct inputs to prefrontal cortex. The results are also consistent with evidence that the hypodopaminergic state is associated with decreased efficiency of prefrontal cortical information processing and that dopaminergic therapy improves the physiological efficiency of this region.

Brain Chemistry↗
PubMed2002

Cortical systems associated with covert music rehearsal.

Musical representation and overt music production are necessarily complex cognitive phenomena. While overt musical performance may be observed and studied, the act of performance itself necessarily skews results toward the importance of primary sensorimotor and auditory cortices. However, imagined musical performance (IMP) represents a complex behavioral task involving components suited to exploring the physiological underpinnings of musical cognition in music performance without the sensorimotor and auditory confounds of overt performance. We mapped the blood oxygenation level-dependent fMRI activation response associated with IMP in experienced musicians independent of the piece imagined. IMP consistently activated supplementary motor and premotor areas, right superior parietal lobule, right inferior frontal gyrus, bilateral mid-frontal gyri, and bilateral lateral cerebellum in contrast with rest, in a manner distinct from fingertapping versus rest and passive listening to the same piece versus rest. These data implicate an associative network independent of primary sensorimotor and auditory activity, likely representing the cortical elements most intimately linked to music production.

Adult↗