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Published August 3, 2012 | Published
Journal Article Open

The Role of Corpus Callosum Development in Functional Connectivity and Cognitive Processing

Abstract

The corpus callosum is hypothesized to play a fundamental role in integrating information and mediating complex behaviors. Here, we demonstrate that lack of normal callosal development can lead to deficits in functional connectivity that are related to impairments in specific cognitive domains. We examined resting-state functional connectivity in individuals with agenesis of the corpus callosum (AgCC) and matched controls using magnetoencephalographic imaging (MEG-I) of coherence in the alpha (8–12 Hz), beta (12–30 Hz) and gamma (30–55 Hz) bands. Global connectivity (GC) was defined as synchronization between a region and the rest of the brain. In AgCC individuals, alpha band GC was significantly reduced in the dorsolateral pre-frontal (DLPFC), posterior parietal (PPC) and parieto-occipital cortices (PO). No significant differences in GC were seen in either the beta or gamma bands. We also explored the hypothesis that, in AgCC, this regional reduction in functional connectivity is explained primarily by a specific reduction in interhemispheric connectivity. However, our data suggest that reduced connectivity in these regions is driven by faulty coupling in both inter- and intrahemispheric connectivity. We also assessed whether the degree of connectivity correlated with behavioral performance, focusing on cognitive measures known to be impaired in AgCC individuals. Neuropsychological measures of verbal processing speed were significantly correlated with resting-state functional connectivity of the left medial and superior temporal lobe in AgCC participants. Connectivity of DLPFC correlated strongly with performance on the Tower of London in the AgCC cohort. These findings indicate that the abnormal callosal development produces salient but selective (alpha band only) resting-state functional connectivity disruptions that correlate with cognitive impairment. Understanding the relationship between impoverished functional connectivity and cognition is a key step in identifying the neural mechanisms of language and executive dysfunction in common neurodevelopmental and psychiatric disorders where disruptions of callosal development are consistently identified.

Additional Information

© 2012 Hinkley et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received November 4, 2011; Accepted May 29, 2012; Published August 3, 2012. This work was supported in part by National Institutes of Health (NIH) grants R01 DC004855, DC006435, DC010145, NS067962, NS64060, and by National Science Foundation grant BCS-0926196 to SSN, NIH grant K23 MH083890 to EJM, K02 NS052192 to EHS, KL2 RR024130 to EJM, EHS), the Sandler Program for Breakthrough Biomedical Research (EHS), the Simons Foundation (LKP), National Alliance for Research on Schizophrenia and Depression (LKP) and the Dystonia Medical Research Foundation (LBNH). This project was supported by the National Institutes of Health/National Center for Research Resources (NIH/NCRR) UCSF-Clinical and Translational Science Institute (CTSI) grant no. UL1 RR024131. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study. The authors have declared that no competing interests exist. This project is made possible primarily through the efforts of our participants and their families. We would like to thank Jacqueline Gold and Susana Hill, as they were instrumental in the project coordination and participant evaluation process, and Drs. William Seeley and Elizabeth Disbrow for helpful comments on the manuscript. Author Contributions: Conceived and designed the experiments: SSN EHS LBNH EJM. Performed the experiments: AMF RJJ SH LKP. Analyzed the data: LBNH AMF. Contributed reagents/materials/analysis tools: RJJ LKP WSB AJB MW ZS PM PB. Wrote the paper: LBNH EJM SSN EHS LKP WSB PM.

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August 19, 2023
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