Decreased functional brain connectivity in individuals with early-treated phenylketonuria: evidence from resting state fMRI.

Previous histological and neuroimaging studies have documented structural abnormalities in the white matter of the brain in individuals with early-treated phenylketonuria (ETPKU). It remains unclear, however, the extent to which the function of the brain's interconnections are impacted by this condition. Presently, we utilized functional magnetic resonance imaging (fMRI) to evaluate the synchronization of neural signals (i.e., functional connectivity) among brain regions comprising the default mode network (DMN) in a sample of 11 individuals with ETPKU and 11 age- and gender-matched neurologically intact controls. The DMN is a group of interconnected brain regions that are known to be generally more active during rest than during task performance. Data analysis revealed decreased functional connectivity among DMN regions for the ETPKU group compared with the control group. Within the PKU group, we also found a significant relationship between blood phenylalanine (phe) levels and the functional connectivity between select regions of the DMN. In conjunction with findings from another recent fMRI study (Christ, Moffitt et al. 2010), the present results suggest that ETPKU-related deficiencies in functional connectivity are pervasive. The current findings also provide initial evidence that the extent of such impairment may be moderated in part by blood phe levels.