Functional connectivity abnormalities in Type I Chiari: associations with cognition and pain.

There is initial evidence of microstructural abnormalities in the fibre-tract pathways of the cerebellum and cerebrum of individuals diagnosed with Type I Chiari malformation. However, it is unclear whether abnormal white matter architecture and macro-level morphological deviations that have been observed in Chiari translate to differences in functional connectivity. Furthermore, common symptoms of Chiari include pain and cognitive deficits, but the relationship between these symptoms and functional connectivity has not been explored in this population. Eighteen Type I Chiari patients and 18 age-, sex- and education-matched controls underwent resting-state functional MRI to measure functional connectivity. Participants also completed a neuropsychological battery and completed self-report measures of chronic pain. Group differences in functional connectivity were identified. Subsequently, pathways of significant difference were re-analyzed after controlling for the effects of attention performance and self-reported chronic pain. Chiari patients exhibited functional hypoconnectivity between areas of the cerebellum and cerebrum. Controlling for attention eliminated all deficits with the exception of that from the posterior cerebellar pathway. Similarly, controlling for pain also eliminated deficits except for those from the posterior cerebellar pathway and vermis VII. Patterns of Chiari hyperconnectivity were also found between regions of the cerebellum and cerebrum in Chiari patients. Hyperconnectivity in all regions was eliminated after controlling for attention except between left lobule VIII and the left postcentral gyrus and between vermis IX and the precuneus. Similarly, hyperconnectivity was eliminated after controlling for pain except between the default mode network and globus pallidus, left lobule VIII and the left postcentral gyrus, and Vermis IX and the precuneus. Evidence of both hyper- and hypoconnectivity were identified in Chiari, which is posited to support the hypothesis that the effect of increased pain in Chiari draws on neural resources, requiring an upregulation in inhibitory control mechanisms and resulting in cognitive dysfunction. Areas of hypoconnectivity in Chiari patients also suggest disruption in functional pathways, and potential mechanisms are discussed.