Altered Extended Locus Coeruleus and Ventral Tegmental Area Networks in Boys with Autism Spectrum Disorders: A Resting-State Functional Connectivity Study

Introduction: Previous studies have suggested that cerebral projections of the norepinephr-ine (NE) and dopamine (DA) systems have important etiology and treatment implications for autism spectrum disorder (ASD). Methods: We used functional magnetic resonance imaging to evaluate spontaneous resting state functional connectivity in boys aged 7?15 years with ASD (n=86) and age-, intelligence quotient-matched typically developing boys (TD, n=118). Specifically, we investigated functional connectivity of the locus coeruleus (LC) and ventral tegmental area (VTA), the main source projection of neurotransmitters NE and DA, respectively. Results: 1) Both the LC and VTA showed reduced connectivity with the postcentral gyrus (PoCG) in boys with ASD, reflecting the potential roles of NE and DA in modulating the function of the somatosensory cortex in boys with ASD. 2) The VTA had increased connectivity with bilateral thalamus in ASD; this alteration was correlated with repetitive and restrictive features. 3) Altered functional connectivity of both the LC and VTA with brain regions such as the angular gyrus (AG), middle temporal gyrus visual area (MT/V5), and occipital face area (OFA) in ASD group. Discussion: Our findings implicate the role of LC-NE and VTA-DA systems from the perspective of functional neuroimaging and may shed light on pharmacological studies targeting NE and DA for the treatment of autism in the future.