Neuroimaging of the component white matter connections and structures within the cerebellar-frontal pathway in posterior fossa tumor survivors

Abstract

Introduction In posterior fossa tumor survivors, lower white matter integrity (WMI) in the right cerebellar-left frontal pathway has been well documented and appears to be related to proximity to the cerebellum, radiation treatment, as well as time since treatment in both cranial radiation and surgery-only treatment groups. The current study investigated theories of transneural degeneration following cerebellar tumor resection that may underlie or relate to reductions in WMI and regional brain volumes using correlations. We hypothesized a positive relationship between the volume of the right cerebellum and known white matter output pathways, as well as with the volume of structures that receive cerebellar projections along the pathway. Methods Adult survivors of childhood brain tumors were recruited ( n = 29; age, M = 22 years, SD = 5; 45% female). Age- and gender-matched controls were also included ( n = 29). Participants completed 3 T diffusion-weighted and T1 MPRAGE MRI scans. Brain structure volume relative to intracranial vault served as regional volumetric measures. Fractional anisotropy (FA) and radial diffusivity (RD) served as WMI measures. In the survivor group, partial correlations between WMI and regional volume included controlling for disease severity. Results In posterior fossa tumor survivors, the volumes of the cerebellum, thalamus, and frontal lobe were correlated with WMI of the thalamic-frontal segment of the cerebellar-frontal pathway ( r = 0.41–0.49, p < .05). Cerebellar atrophy was correlated with reduced WMI in the cerebellar-rubral segment (FA, r = −0.32 p > .05; RD, r = 0.53, p < .01). In the no-radiation survivor group, the regional volume of each structure along the pathway was associated with WMI in the cerebellar-rubral segment. In the radiation survivor group, significant correlations were found between the regional brain volume of each structure and the thalamic-frontal segment of the pathway. Discussion The results of this multimodal neuroimaging study provide correlational evidence that the mechanism of injury subsequent to brain tumor treatment may be different depending on type of treatment(s). Without radiation, the primary mechanism of injury is cerebellar tumor growth, resection, and hydrocephalus. Therefore, the most proximal connection to that injury (cerebellar-rubral pathway) was correlated with reductions in volume along the pathway. In contrast, the survivor group treated with radiation may have had possible radiation-induced demyelination of the thalamic-frontal portion of the pathway, based on a strong correlation with volume loss in the cerebellum, red nucleus, thalamus, and frontal lobe.

Double Dissociation of Auditory Attention Span and Visual Attention in Long-Term Survivors of Childhood Cerebellar Tumor: A Deterministic Tractography Study of the Cerebellar-Frontal and the Superior Longitudinal Fasciculus Pathways

“…The white matter pathway connecting the cerebellum and the frontal lobe is commonly studied in the childhood brain tumor population (Ailion et al, 2017(Ailion et al, & 2019. The current study advances the existing literature on this pathway by providing theory-driven evidence about the specific neurocognitive performance that is associated with cerebellar-frontal WMI and provides evidence for a correlational double dissociation that provides specific differential associations for key brain-behavior relationships.…”

“…King #RSGPB-CPPB-114044). Detailed methods and study procedures are described by King et al (2015b) and Ailion et al, (2016Ailion et al, ( & 2019. In brief, survivors either were part of a long-term follow-up of a prior longitudinal study of childhood brain tumors, recruited from a database of brain tumor survivors obtained from Children's Healthcare of Atlanta, or responded to an annual newsletter circulated by the Brain Tumor Foundation of Georgia.…”

“…this sample (Ailion et al, 2019). Global gray and white matter values reported in the tables are based on Voxel-Based Morphometry, with detailed procedures described in Ailion et al (2019). For additional information on how regions of interest were defined, please see the Appendix.…”

“…Deterministic tractography processing is described in detail in Ailion et al (2019) PanTrack was used for network tractography to generate all of the direct connections between the right cerebellum and the left middle frontal gyrus (MFG) as well as the connections between the right MFG and the right parietal lobe. PanTrack output was then viewed in TrackVis.…”

“…However, to date, only one diffusionweighted neuroimaging study on the cerebellar pathways in brain tumor populations has included measures of attention and processing speed (Rueckriegel et al, 2015). We have investigated the segments of the cerebellar-frontal pathway in a prior paper, which provides correlational evidence that type of brain tumor treatment has a differential effect on each structural segment of this pathway (Ailion et al, 2019). The purpose of the current study is to expand on this literature and investigate the neurocognitive contribution of this white matter pathway.…”