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Impairments in frontal cortical gamma synchrony and cognitive control in schizophrenia.

ABSTRACT: A critical component of cognitive impairments in schizophrenia can be characterized as a disturbance in cognitive control, or the ability to guide and adjust cognitive processes and behavior flexibly in accordance with one's intentions and goals. Cognitive control impairments in schizophrenia are consistently linked to specific disturbances in prefrontal cortical functioning, but the underlying neurophysiologic mechanisms are not yet well characterized. Synchronous gamma-band oscillations have been associated with a wide range of perceptual and cognitive processes, raising the possibility that they may also help entrain prefrontal cortical circuits in the service of cognitive control processes. In the present study, we measured induced gamma-band activity during a task that reliably engages cognitive control processes in association with prefrontal cortical activations in imaging studies. We found that higher cognitive control demands were associated with increases in induced gamma-band activity in the prefrontal areas of healthy subjects but that control-related modulation of prefrontal gamma-band activity was absent in schizophrenia subjects. Disturbances in gamma-band activity in patients correlated with illness symptoms, and gamma-band activity correlated positively with performance in control subjects but not in schizophrenia patients. Our findings may provide a link between previously reported postmortem abnormalities in thalamofrontocortical circuitry and alterations in prefrontal activity observed in functional neuroimaging studies. They also suggest that deficits in frontal cortical gamma-band synchrony may contribute to the cognitive control impairments in schizophrenia.

SUBMITTER: Cho RY

PROVIDER: S-EPMC1750867 | biostudies-other | 2006 Dec

REPOSITORIES: biostudies-other

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Impairments in frontal cortical gamma synchrony and cognitive control in schizophrenia.

Cho R Y RY Konecky R O RO Carter C S CS

Proceedings of the National Academy of Sciences of the United States of America 20061214 52

A critical component of cognitive impairments in schizophrenia can be characterized as a disturbance in cognitive control, or the ability to guide and adjust cognitive processes and behavior flexibly in accordance with one's intentions and goals. Cognitive control impairments in schizophrenia are consistently linked to specific disturbances in prefrontal cortical functioning, but the underlying neurophysiologic mechanisms are not yet well characterized. Synchronous gamma-band oscillations have b ...[more]

PMID: 17170134

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Project description:Decision making relies on dynamic interactions of distributed, primarily frontal brain regions. Extensive evidence from functional magnetic resonance imaging (fMRI) studies indicates that the anterior cingulate (ACC) and the lateral prefrontal cortices (latPFC) are essential nodes subserving cognitive control. However, because of its limited temporal resolution, fMRI cannot accurately reflect the timing and nature of their presumed interplay. The present study combines distributed source modeling of the temporally precise magnetoencephalography (MEG) signal with structural MRI in the form of "brain movies" to: (1) estimate the cortical areas involved in cognitive control ("where"), (2) characterize their temporal sequence ("when"), and (3) quantify the oscillatory dynamics of their neural interactions in real time. Stroop interference was associated with greater event-related theta (4 - 7 Hz) power in the ACC during conflict detection followed by sustained sensitivity to cognitive demands in the ACC and latPFC during integration and response preparation. A phase-locking analysis revealed co-oscillatory interactions between these areas indicating their increased neural synchrony in theta band during conflict-inducing incongruous trials. These results confirm that theta oscillations are fundamental to long-range synchronization needed for integrating top-down influences during cognitive control. MEG reflects neural activity directly, which makes it suitable for pharmacological manipulations in contrast to fMRI that is sensitive to vasoactive confounds. In the present study, healthy social drinkers were given a moderate alcohol dose and placebo in a within-subject design. Acute intoxication attenuated theta power to Stroop conflict and dysregulated co-oscillations between the ACC and latPFC, confirming that alcohol is detrimental to neural synchrony subserving cognitive control. It interferes with goal-directed behavior that may result in deficient self-control, contributing to compulsive drinking. In sum, this method can provide insight into real-time interactions during cognitive processing and can characterize the selective sensitivity to pharmacological challenge across relevant neural networks.

Project description:Objective: Age of onset is one of the heterogeneous factors in schizophrenia, and an earlier onset of the disease indicated a worse prognosis. The left superior frontal gyrus (SFG) is involved in numerous cognitive and motor control tasks. Hence, we explored the relationship between abnormal changes in SFG resting-state functional connectivity (rsFC) and cognitive function in the peak age of incidence to understand better the pathophysiological mechanism in youth-onset drug-naïve schizophrenia to search for reliable biomarkers. Methods: About 66 youth-onset drug-naïve schizophrenia patients and 59 healthy controls (HCs) were included in this study. Abnormal connectivity changes in the left SFG and whole brain were measured using the region of interest (ROI) rsFC analysis method. The cognitive function was assessed using the MATRICS Consensus Cognitive Battery (MCCB), and the severity of the clinical symptoms was evaluated by positive and negative syndrome scale (PANSS). Furthermore, we analyzed the relationships among abnormal FC values, cognition scores, and clinical symptoms. Results: We found decreased FC between left SFG and bilateral precuneus (PCUN), right hippocampus, right parahippocampal gyrus, left thalamus, left caudate, insula, and right superior parietal lobule (SPL), whereas increased FC was seen between the left SFG and right middle frontal gyrus (MFG) in the youth-onset drug-naïve schizophrenia group, compared with HCs. Meanwhile, the T-scores were lower in each cognitive domain than HCs. Moreover, in the youth-onset drug-naive schizophrenia group, the insula was negatively correlated with processing speed. No significant correlations were found between the FC-value and PANSS score. Conclusions: Our findings suggest widespread FC network abnormalities in the left SFG and widespread cognitive impairments in the early stages of schizophrenia. The dysfunctional connectivity of the left SFG may be a potential pathophysiological mechanism in youth-onset drug-naïve schizophrenia.

Project description:Cognitive deficits contribute to functional disability in patients with schizophrenia and may be related to altered functional networks that serve cognition. We evaluated the integrity of major functional networks and assessed their role in supporting two cognitive functions affected in schizophrenia: processing speed (PS) and working memory (WM). Resting-state functional magnetic resonance imaging (rsfMRI) data, N = 261 patients and 327 controls, were aggregated from three independent cohorts and evaluated using Enhancing NeuroImaging Genetics through Meta Analysis rsfMRI analysis pipeline. Meta- and mega-analyses were used to evaluate patient-control differences in functional connectivity (FC) measures. Canonical correlation analysis was used to study the association between cognitive deficits and FC measures. Patients showed consistent patterns of cognitive and resting-state FC (rsFC) deficits across three cohorts. Patient-control differences in rsFC calculated using seed-based and dual-regression approaches were consistent (Cohen's d: 0.31?±?0.09 and 0.29?±?0.08, p?<?10-4 ). RsFC measures explained 12-17% of the individual variations in PS and WM in the full sample and in patients and controls separately, with the strongest correlations found in salience, auditory, somatosensory, and default-mode networks. The pattern of association between rsFC (within-network) and PS (r = .45, p = .07) and WM (r = .36, p = .16), and rsFC (between-network) and PS (r = .52, p = 8.4?×?10-3 ) and WM (r = .47, p = .02), derived from multiple networks was related to effect size of patient-control differences in the functional networks. No association was detected between rsFC and current medication dose or psychosis ratings. Patients demonstrated significant reduction in several FC networks that may partially underlie some of the core neurocognitive deficits in schizophrenia. The strength of connectivity-cognition relationships in different networks was strongly associated with network's vulnerability to schizophrenia.

Dataset Information

Impairments in frontal cortical gamma synchrony and cognitive control in schizophrenia.

Publications

Impairments in frontal cortical gamma synchrony and cognitive control in schizophrenia.

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