Disrupted network connectivity in pediatric brain tumor survivors is a signature of injury

Abstract

Cognition is compromised in pediatric brain tumor survivors but the neurophysiological basis of this compromise remains unclear. We hypothesized that reduced neural synchronization across brain networks is involved. To test this, we evaluated group differences using a retrospective cohort comparison design between 24 pediatric brain tumor survivors [11.81 ± 3.27)] and 24 age matched healthy children [12.04 ± 3.28)] in functional connectivity within a cerebellar network to examine local effects of the tumor, a whole brain network to examine diffuse effects of treatment (i.e., chemotherapy and radiation), and across multiple intrinsic connectivity networks. Neural activity was recorded during magnetoencephalography scanning while participants were at rest and functional connectivity within networks was measured using the phase lag index. We corroborated our findings using a computational model representing the local tumor effects on neural synchrony. Compared to healthy children, pediatric brain tumor survivors show increased functional connectivity for theta and beta frequency bands within the cerebellar network and increased functional connectivity for the theta band within the whole brain network that again localized to the cerebellum. Computational modeling showed that increased synchrony in the theta bad is observed following local clustering as well as sparse interarea brain connectivity. We also observed increased functional connectivity for the alpha frequency band in the ventral attention network and decreased functional connectivity within the gamma frequency band in the motor network within paedatric brain tumor survivors versus healthy children. Notably, increased gamma functional connectivity within the motor network predicted decreased reaction time on behavioral tasks in pediatric brain tumor survivors. Disrupted network synchrony may be a signature of neurological injury and disease.

Reduced Fusiform Gyrus Activation During Face Processing in Pediatric Brain Tumor Survivors

“…These findings suggest neurobiological similarities in specialized face processing areas between PBTS and youth with other neurodevelopmental conditions with social difficulties, such as ASD, despite differing etiologies. Additionally, our findings are consistent with broader disturbances across both structural (e.g., white matter) and functional brain networks in PBTS that have been documented in prior neuroimaging studies with survivors (Dockstader, Wang, Bouffet, & Mabbott, 2014;Gauvreau et al, 2019;Scantlebury et al, 2016) and could impact face processing networks. The importance of white matter connectivity to face processing brain areas has been established in TD individuals (Gschwind, Pourtois, Schwartz, Van De Ville, & Vuilleumier, 2012) and related to social processing and behavioral impairments in youth with ASD (Ameis & Catani, 2015;Fitzgerald, Gallagher, & McGrath, 2016).…”

Networking of the Human Cerebellum: From Anatomo-Functional Development to Neurosurgical Implications

“…Functional-MRI studies contributed to further characterizing these aspects. A recent study found that cognitive disturbances in pediatric infra-tentorial tumor survivors were related to abnormalities in regional neural synchrony, leading to reorganization of network topology and, consequently, to disconnection of damaged regions and multiple extracerebellar functional brain networks (195). In the largest lesion mapping study to date, the cognitive and affective symptoms following pediatric cerebellar tumor resection were evaluated in 195 pediatric patients.…”

Cross-translational models of late-onset cognitive sequelae and their treatment in pediatric brain tumor survivors

“…In addition to structural and diffusion abnormalities, altered functional network organization and local neural activity is often detected in pediatric brain tumor survivors using functional neuroimaging techniques. The impact of injury on resting-state functional networks indicate that abnormalities are not limited to the tumor region and that they are associated with deficits in multiple cognitive domains (Gauvreau et al, 2019). Magnetoencephalography (MEG) and functional MRI (fMRI) analyses can detect aberrant regional activation and related cognitive dysfunction in patients during performance of specific tasks.…”