Fronto-cerebellar connections are thought to be involved in higher-order cognitive functioning. It is suspected that damage to this network may contribute to cognitive deficits in chronic alcoholics. However, it remains to be elucidated if fronto-cerebellar circuitry is altered in high-risk individuals even prior to alcohol use onset. The current study used functional connectivity MRI (fcMRI) to examine fronto-cerebellar circuitry in 13 alcohol-naïve, at-risk youth with a family history of alcoholism (FH+) and 14 age-matched controls. In addition, we examined how white matter microstructure, as evidenced by fractional anisotropy (FA), related to fcMRI. FH+. youth showed significantly reduced functional connectivity between bilateral anterior prefrontal cortices and contralateral cerebellar seed regions compared to controls. We found that this reduction in connectivity significantly correlated with reduced FA in the anterior limb of the internal capsule and the superior longitudinal fasciculus. Taken together, our findings reflect associated aberrant functional and structural connectivity in substance-naïve FH+. adolescents, perhaps suggesting an identifiable neurophenotypic precursor to substance use. Given the role of frontal and cerebellar brain regions in subserving executive functioning, the presence of premorbid abnormalities in fronto-cerebellar circuitry may heighten the risk for developing an alcohol use disorder in FH+. youth through atypical control processing.
Bibliographical noteFunding Information:
This research was supported by the National Institute on Alcohol Abuse and Alcoholism ( T32AA007468 – Herting; R01 AA017664 – Nagel), pilot funds from the Portland Alcohol Research Center ( P60 AA010760 – Nagel), the Oregon Clinical and Translational Research Institute (Fair), Medical Research Foundation (Fair), UNCF Merck postdoctoral fellowship (Fair), Ford Foundation (Fair), the National Institute of Neurological Disorders and Stroke ( K08 NS52147 – Nagel) and the Oregon Clinical and Translational Research Institute ( UL1 RR024140 ). A special thanks to Emily Maxwell for her assistance in data collection, and to Michael Blythe for his assistance with data pre-processing and analyses.
- Functional connectivity