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Cameron S Carter

Publications and source records attributed to Cameron S Carter.

At least 19 recordsLinked to original sources

Optimum template selection for atlas-based segmentation.

Atlas-based segmentation of MR brain images typically uses a single atlas (e.g., MNI Colin27) for region identification. Normal individual variations in human brain structures present a significant challenge for atlas selection. Previous researches mainly focused on how to create a specific template for different requirements (e.g., for a certain population). We address atlas selection with a different approach: instead of choosing a fixed brain atlas, we use a family of brain templates for atlas-based segmentation. For each subject and each region, the template selection method automatically chooses the 'best' template with the highest local registration accuracy, based on normalized mutual information. The region classification performances of the template selection method and the single template method were quantified by the overlap ratios (ORs) and intraclass correlation coefficients (ICCs) between the manual tracings and the respective automated labeled results. Two groups of brain images and multiple regions of interest (ROIs), including the right anterior cingulate cortex (ACC) and several subcortical structures, were tested for both methods. We found that the template selection method produced significantly higher ORs than did the single template method across all of the 13 analyzed ROIs (two-tailed paired t-test, right ACC at t(8)=4.353, p=0.0024; right amygdala, matched paired t test t(8)>3.175, p<0.013; for the remaining ROIs, t(8)=4.36, p<0.002). The template selection method also provided more reliable volume estimates than the single template method with increased ICCs. Moreover, the improved accuracy of atlas-based segmentation using optimum templates approaches the accuracy of manual tracing, and thus is valid for automated brain imaging analyses.

Adult↗

Preserved function of the fusiform face area in schizophrenia as revealed by fMRI.

Many lines of evidence suggest that individuals with schizophrenia suffer from face processing deficits. However, the specificity of these deficits and the neural dysfunction underlying them remain unclear. To address these questions, we evaluated the functional status of a critical region for face processing, the fusiform face area (FFA), in subjects with schizophrenia. Fourteen schizophrenia patients and 10 healthy control subjects participated in an fMRI experiment to determine the functional status of the FFA by viewing a series of faces and exemplars of other object categories, while completing a low-level task designed to verify their engagement with the stimuli. Behavioral performance and activation of the FFA were equivalent between groups. Thirteen of 14 patients and all control subjects displayed FFA activation. Furthermore, the degree of FFA activation, as measured by FFA volume and magnitude of activity, was similar between groups. The FFA, a critical region in the neural system subserving the perceptual processing of faces, appears to be intact in schizophrenia. These results call into question the presence of a specific face processing deficit in schizophrenia.

Adult↗

Increased amygdala and decreased dorsolateral prefrontal BOLD responses in unipolar depression: related and independent features.

BACKGROUND: Major depressive disorder is characterized by increased and sustained emotional reactivity, which has been linked to sustained amygdala activity. It is also characterized by disruptions in executive control, linked to abnormal dorsolateral prefrontal cortex (DLPFC) function. These mechanisms have been hypothesized to interact in depression. This study explored relationships between amygdala and DLPFC activity during emotional and cognitive information processing in unipolar depression. METHOD: Twenty-seven unmedicated patients with DSM-IV unipolar major depressive disorder and 25 never-depressed healthy control subjects completed tasks requiring executive control (digit sorting) and emotional information processing (personal relevance rating of words) during event-related functional magnetic resonance imaging (fMRI) assessment. RESULTS: Relative to control subjects, depressed subjects displayed sustained amygdala reactivity on the emotional tasks and decreased DLPFC activity on the digit-sorting task. Decreased relationships between the time-series of amygdala and DLPFC activity were observed within tasks in depression, but different depressed individuals showed each type of bias. CONCLUSIONS: Depression is associated with increased limbic activity in response to emotional information processing and decreased DLPFC activity in response to cognitive tasks though these may reflect separate mechanisms. Depressed individuals also display decreased relationships between amygdala and DLPFC activity, potentially signifying decreased functional relationships among these structures.

Adolescent↗

Automated ROI-based brain parcellation analysis of frontal and temporal brain volumes in schizophrenia.

Structural MRI studies of schizophrenia have yielded a diversity of findings. To help characterize regional gray matter changes in schizophrenia, we used an automated region of interest (ROI)-based approach that targeted frontal and temporal regions in schizophrenia patients. The sample compromised 43 schizophrenia patients (21 chronic patients, 22 unmedicated first episode patients), 20 first episode non-schizophrenia psychosis patients and 47 comparison subjects. Automated regional volume measurement was performed in 22 ROIs, including frontal and temporal cortical subregions and hippocampus. Correlations between volume measures, duration of illness and clinical scores were evaluated. Chronic schizophrenia patients showed gray matter volume differences in left dorsolateral prefrontal cortex (DLPFC) and right supplementary motor area (SMA). First episode psychosis patients presented smaller right anterior cingulate cortex (ACC) and left DLPFC than comparison subjects. Disorganization scores and duration of illness correlated negatively with gray matter volume of DLPFC and SMA in chronic schizophrenia patients. Using an automated ROI-based method, we found volume reductions in lateral and medial frontal regions in both first episode and chronic schizophrenia. The automated ROI-based method can be used as a valid and efficient tool for quantification of regional gray matter volume in schizophrenia in multiple ROIs across the brains of large numbers of subjects.

Adult↗

Functional magnetic resonance imaging study of cognitive control in the healthy relatives of schizophrenia patients.

BACKGROUND: The predisposition, or diathesis, to schizophrenia is highly heritable. The manner in which this genetic diathesis is manifest in the central nervous system is largely unknown, although healthy relatives of schizophrenia patients show executive processing deficits associated with prefrontal cortical impairments. METHODS: The current study evaluated brain activity in 21 healthy relatives of schizophrenia patients and 20 demographically similar control subjects during correct trials on a stimulus-response incompatibility task. During the first part of each trial, participants represented and maintained the instruction for that trial; during the second part, participants used the instruction either to make an automatic response or to overcome this prepotent response. RESULTS: Behaviorally, relatives were slower when overcoming the prepotent response. Analyses focused on the first part of the trial indicated that both groups showed activity in middle frontal (Brodmann areas 46 and 9) and anterior cingulate (Brodmann area 32) gyri. However, control subjects showed significantly greater activity in dorsal prefrontal cortex (Brodmann areas 9, 8, and 6) when preparing to overcome the prepotent response, whereas patients' relatives showed prefrontal activity later, when making the response. CONCLUSIONS: Using an event-related design showed distinct prefrontal brain abnormalities associated with the genetic diathesis to schizophrenia.

Adult↗

Information-processing modules and their relative modality specificity.

This research uses fMRI to understand the role of eight cortical regions in a relatively complex information-processing task. Modality of input (visual versus auditory) and modality of output (manual versus vocal) are manipulated. Two perceptual regions (auditory cortex and fusiform gyrus) only reflected perceptual encoding. Two motor regions were involved in information rehearsal as well as programming of overt actions. Two cortical regions (parietal and prefrontal) performed processing (retrieval and representational change) independent of input and output modality. The final two regions (anterior cingulate and caudate) were involved in control of cognition independent of modality of input or output and content of the material. An information-processing model, based on the ACT-R theory, is described that predicts the BOLD response in these regions. Different modules in the theory vary in the degree to which they are modality-specific and the degree to which they are involved in central versus peripheral cognitive processes.

Adolescent↗

Regionally specific cortical thinning and gray matter abnormalities in the healthy relatives of schizophrenia patients.

Accumulated evidence suggests that schizophrenia is associated with subtle gray matter deficits throughout the cerebral cortex and regional cortical thinning. Although findings are not entirely consistent, healthy relatives of schizophrenia patients also show abnormalities in cortical gray matter volume, suggesting that this may be one aspect of an unexpressed genetic liability to the disorder. Cortical thickness and surface area are additional indicators of cortical cytoarchitectural integrity. To investigate the nature of cortical abnormalities in the healthy relatives of patients, this study used magnetic resonance imaging to evaluate gray matter volume, surface area, and thickness of 13 regions using an automated parcellation methodology. Compared with controls (n = 22), relatives (n = 19) had decreased volume and surface area in the right cingulate gyrus, a bilateral decrease in cingulate thickness, and decreased surface area in the superior temporal lobe. In addition, relatives had a subtle increase in gray matter volume and surface area in the left hemisphere, bilaterally in the parahippocampal gyri, and in the left middle temporal lobe. The results of this study suggest that the cortical regions most affected by the unexpressed genetic liability to schizophrenia may be the cingulate and temporal regions--regions associated with higher level cognitive, affective, and memory functions.

Adult↗

Altered brain activity in women recovered from bulimic-type eating disorders after a glucose challenge: a pilot study.

OBJECTIVE: It is not known whether individuals with bulimic-type eating disorders have a dysregulation of brain pathways that modulate appetite. Taste plays a role in the regulation of appetite and the purpose of the current study was to determine whether bulimic women have alterations in the physiologic response to the blind administration of glucose. METHOD: To avoid the confounding effects of a current eating disorder, and to assess possibly trait-related disturbances, we studied 10 subjects recovered (> or = 1 year) from a bulimic-type eating disorder and 6 control women. Subjects were administered a solution of glucose or artificial saliva (control solution) in alternating blocks during a functional magnet resonance imaging scan. RESULTS: Individuals who recovered from a bulimic-type eating disorder had significantly lower activation in the right anterior cingulate cortex (ACC; Montreal Neurological Institute [MNI] coordinates x = 8, y = 22, z = 28; cluster size = 18 voxels, T = 5.11, Z-score = 3.78) and in the left cuneus (occipital cortex; MNI coordinates x = -12, y = -78, z = 10; cluster size = 21 voxels, T = 4.27, Z-score = 3.36), when glucose was compared with artificial saliva. CONCLUSION: The ACC plays a role in the anticipation of reward. Individuals with bulimic-type eating disorders may have a reduced reward response to nutrients, and thus may be vulnerable to overeating. However, this is a small sample and the current study will need replication in a larger sample size with investigation of additional regions of interest.

Adult↗

Quantitative comparison of AIR, SPM, and the fully deformable model for atlas-based segmentation of functional and structural MR images.

Typical packages used for coregistration in functional image analyses include automated image registration (AIR) and statistical parametric mapping (SPM). However, both methods have limited-dimension deformation models. A fully deformable model, which combines the piecewise linear registration for coarse alignment with demons algorithm for voxel-level refinement, allows a higher degree of spatial deformation. This leads to a more accurate colocalization of the functional signal from different subjects and therefore can produce a more reliable group average signal. We quantitatively compared the performance of the three different registration approaches through a series of experiments and we found that the fully deformable model consistently produces a more accurate structural segmentation and a more reliable functional signal colocalization than does AIR or SPM.

Adult↗

Reward-related decision-making in pediatric major depressive disorder: an fMRI study.

BACKGROUND: Although reward processing is considered an important part of affective functioning, few studies have investigated reward-related decisions or responses in young people with affective disorders. Depression is postulated to involve decreased activity in reward-related affective systems. METHODS: Using functional magnetic resonance imaging (fMRI), we examined behavioral and neural responses to reward in young people with depressive disorders using a reward decision-making task. The task involved choices about possible rewards involving varying magnitude and probability of reward. The study design allowed the separation of decision/anticipation and outcome phases of reward processing. Participants were 9-17 years old and had diagnoses of major depressive disorder (MDD), anxiety disorders, or no history of psychiatric disorder. RESULTS: Participants with MDD exhibited less neural response than control participants in reward-related brain areas during both phases of the task. Group differences did not appear to be a function of anxiety. Depressive and anxiety symptoms were associated with activation in reward-related brain areas. CONCLUSIONS: Results suggest that depression involves altered reward processing and underscore the need for further investigation of relations among development, affective disorders, and reward processing.

Adolescent↗

Use of FMRI to predict recovery from unipolar depression with cognitive behavior therapy.

OBJECTIVE: In controlled treatment trials, 40%-60% of unmedicated depressed individuals respond to cognitive behavior therapy (CBT). The authors examined whether pretreatment neural reactivity to emotional stimuli accounted for this variation. METHOD: Unmedicated depressed individuals (N=14) and never depressed comparison subjects (N=21) underwent fMRI during performance of a task sensitive to sustained emotional information processing. Afterward, depressed participants completed 16 sessions of CBT. RESULTS: Participants whose sustained reactivity to emotional stimuli was low in the subgenual cingulate cortex (Brodmann's area 25) and high in the amygdala displayed the strongest improvement with CBT. CONCLUSIONS: The presence of emotion regulation disruptions, which are targeted in CBT, may be the key to recovery with this intervention.

Adult↗

Cognitive deficits in unaffected first-degree relatives of schizophrenia patients: a meta-analytic review of putative endophenotypes.

Cognitive deficits may index genetic liability for schizophrenia and are candidate endophenotypes for the illness. In order to compare the degree of sensitivity among cognitive tasks to group differences between healthy relatives and controls and the influence of moderator variables, this review reports mean effect sizes for 43 cognitive test scores from 58 studies of cognitive performance in the unaffected adult relatives of schizophrenia patients. Results indicate reliable relative-control differences, in the small to medium effect size range, over a diverse array of tasks, with the largest effect sizes seen in complex versions of continuous performance tasks, auditory verbal learning, design copy tests, and category fluency. Three study design features were found to have significant effects on overall effect size magnitude: groups unmatched on education, groups unmatched on age, and asymmetric psychiatric exclusion criteria. After excluding studies with the latter 2 design features, reliable performance differences were still observed over a smaller subset of cognitive test variables, with the largest effect sizes seen in Trails B (d = 0.50) and performance measures from both simple (d = 0.56) and complex (d = 0.60-0.66) versions of continuous performance tasks. Four of the 6 largest effect sizes reflect tasks with high executive control demands in common, such as working memory demands, set shifting, and inhibition of prepotent responses. Cognitive deficits, particularly those tapping such executive control functions, should continue to prove valuable as endophenotypes of interest in the search for specific genetic factors related to schizophrenia.

Cognition Disorders↗

Functional neuroimaging and electrophysiology biomarkers for clinical trials for cognition in schizophrenia.

"Measurement and Treatment Research to Improve Cognition in Schizophrenia" or MATRICS is a National Institute of Mental Health (NIMH)--sponsored research effort to drive novel drug development for the treatment of cognitive impairments in schizophrenia. On September 9-10, 2004, MATRICS convened representatives from NIMH, academia, and industry for the final of a series of consensus-oriented conferences, with this meeting entitled "New Approaches to Assessing and Improving Cognition in Schizophrenia." In this article, we present a summary of the discussions that focused on functional neuroimaging and electrophysiology biomarkers, outlining the research priorities, which included developing further consensus regarding the cognitive processes that are critical to examine in schizophrenia and the paradigms to examine them, resolving issues of test-retest reliability and discrepant findings in the literature, and additional basic research regarding the methods before fully implementing these paradigms in drug trials. Also summarized are the relative advantages and disadvantages of the different approaches and varying perspectives among the participants regarding these tools. Our hope is that this report will help guide and further stimulate coordinated efforts among researchers, industry, and funding agencies in meeting the urgent need for novel pharmacotherapeutics for cognitive impairments in schizophrenia and useful neurobiological indexes for tracking the resulting improvements in cognitive function.

Cognition Disorders↗

Amphetamine improves cognitive function in medicated individuals with schizophrenia and in healthy volunteers.

BACKGROUND: Recent research on schizophrenia indicates that cognitive deficits in this illness are important predictors of functional outcome, highlighting the need for treatments that have a positive impact on cognitive function. Here we explore the hypothesis that acute administration of d-amphetamine can improve cognitive function in individuals with schizophrenia who are well-treated with typical antipsychotics, as well as in healthy controls performing under dual task conditions designed to elicit performance deficits analogous to those found in schizophrenia. METHODS: Ten individuals with schizophrenia taking haldol or prolixin and 22 healthy controls performed spatial working memory, language production, and Stroop tasks under both placebo and 0.25 mg/kg of D-amphetamine. RESULTS: D-Amphetamine improved reactions times on the spatial working memory and Stroop tasks for both individuals with schizophrenia and controls, and improved working memory accuracy in schizophrenia. In addition, D-amphetamine improved language production for both individuals with schizophrenia and controls. CONCLUSIONS: These results provide support for the hypothesis that the adjunctive administration of dopamine agonist can improve cognitive in individuals with schizophrenia taking typical antipsychotics. The results are discussed in terms of their implications for understanding the nature of working memory deficits in schizophrenia, and potential future avenues for cognitive enhancement in this illness.

Adult↗

Applying new approaches from cognitive neuroscience to enhance drug development for the treatment of impaired cognition in schizophrenia.

New approaches to the measurement of cognition in schizophrenia include the use of tasks from experimental cognitive psychology to examine the integrity of specific cognitive systems and the application of these tasks in noninvasive neuroimaging (e.g., functional magnetic resonance imaging [fMRI]) studies that directly measure the effects of drugs on cognition-related brain activity. These approaches offer many advantages, including the isolation of specific cognitive systems that may be conserved across species; controlling for the confounding effects of generalized performance deficits such as poor motivation, sedation, and so on; and providing a direct translational bridge from studies using animal models of cognition to patient-based research using fMRI. These developments have the potential to transform the early human phases of drug development and streamline the decision making at this critical point in the process. As was the case for the Measurement and Treatment Research to Improve Cognition in Schizophrenia initiative, optimizing the application of cognitive neuroscience to new drug development will require a major commitment by multiple investigators to task development and a thorough psychometric evaluation of both behavioral and neuroimaging measures.

Animals↗