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.

Differences in brain morphology and working memory capacity across childhood

“…Differences in corpus callosum anatomy such as reduced volume or reduced microstructural integrity are related to lower lateralization of function in typical participants and patient groups (Hinkley et al., 2016; Just, Cherkassky, Keller, Kana, & Minshew, 2007; Persson et al., 2006). In turn, lower lateralization is associated with lower performance on cognitive tasks, including executive function tasks (Hinkley et al., 2012; Just et al., 2007; Nagel, Herting, Maxwell, Bruno, & Fair, 2013). Similarly, posterior temporal white matter may provide connections for integration between specialized regions of temporal lobe for verbal and visuospatial working memory with the posterior parietal executive attention network.…”

Abnormal interhemispheric motor interactions in patients with callosal agenesis

“…The healthy and adult human population consists of 90% right-handed and 10% left-handed or ambidextrous individuals [55,56]. In adults with complete AgCC, this distribution is different in that only 70% are right-handed and 30% are left-handed or ambidextrous [57][58][59][60]. One significant factor for this shift in handedness distribution in AgCC patients could be the absence of transcallosal suppression during the final preparation phase of hand control.…”

Resting-State Networks and the Functional Connectome of the Human Brain in Agenesis of the Corpus Callosum

“…In addition, at the low temporal resolution of fMRI (2 sec per brain volume in this study), it is not possible to differentiate neural information transmission via single versus multiple synaptic pathways. In an magnetoencephalography (MEG) resting-state connectivity study of partial and complete AgCC patients (Hinkley et al, 2012), both inter-and intra-hemispheric connectivity was diminished in the alpha-band (8-12 Hz) in frontal, parietal, and occipital regions in AgCC. MEG has a temporal resolution in the order of a millisecond and is exceedingly more sensitive to discrepancies in timing than fMRI.…”