Interhemispheric Functional Connectivity Change Is Linked to Callosal Fiber Integrity Change over a 1-Year Follow-up in Chronic Alcoholics

Abstract

Chronic alcoholism has deleterious long-term effects on the integrity of callosal white matter fibers connecting the two cerebral hemispheres. We tested whether microstructural fiber changes relate to resting-state functional connectivity changes in alcoholics who have maintained sobriety during a one-year interval, and whether these changes are beyond those potentially exhibited by controls. 12 (7w, 5m) alcoholics (ALC) and 13 (7w, 6m) age-matched controls (CTL) underwent MR diffusion tensor imaging and functional MR imaging at baseline and 1-year follow-up. In ALC, age at alcoholism onset was on average 37 years (range 15-56 years); the average time since last drink before study entry was 3½ months for ALC. Within the 1-year follow-up period, 6 ALC remained sober and 6 resumed drinking at social levels. We examined effects of group (CTL, ALC) and time (baseline, 1 year) on fractional anisotropy (FA) and mean diffusivity (MD) of fiber tufts of the whole corpus callosum and of 7 callosal sectors quantified with fiber tracking. Functional connectivity between the left and right hemisphere was tested for group and time, for 8 bilaterally homologous cortical areas: anterior, dorsolateral, and medial prefrontal, motor, parietal, occipital, medial and lateral temporal. Alcoholics showed poorer callosal fiber integrity (lower FA, higher MD) than CTL, with 3-way interactions for FA and MD indicating continued microstructural decline over the year in ALC relative to CTL that was more pronounced in anterior than posterior callosal sectors. Overall, groups did not differ in interhemispheric functional connectivity strength; a group-by-time interaction indexed a connectivity decline over the year between lateral temporal cortices in ALC relative to CTL. Higher amounts of lifetime alcohol consumption correlated with continued decline in callosal FA and with change to weaker interhemispheric connectivity between motor regions in ALC and between temporal regions over both groups. Within alcoholics, 1-year change to weaker functional connectivity between left and right medial frontal, motor, medial temporal and occipital regions was associated with continued decline in callosal white matter (FA, MD). To the extent that callosal fibers support interhemispheric cortico-cortical functional connectivity, these data suggest that continued fiber degradation is accompanied by decline in interhemispheric functional connectivity strength. Thus, continued decline in callosal fiber integrity occurs in alcoholism despite sobriety and relates to weaker interhemispheric functional connections in ALC, specifically in those with heavier past lifetime drinking.