Frontal lobe dysfunction underlies the differential word retrieval impairment in adolescents with high-functioning autism.

There is substantial evidence of word retrieval impairment as indicated by poor performance on the category fluency test in autism spectrum disorder (ASD). However, little is known about the neural mechanisms underlying this impairment. Functional neuroimaging studies have shown that the lateral frontal cortex plays a key role in flexible word retrieval. Thus, we examined whether individuals with ASD exhibited altered frontal processing during the category fluency test using functional near-infrared spectroscopy (fNIRS). Twenty-two adolescents with high-functioning ASD (20 males) and 22 typically developing (TD) adolescents (16 males) aged 11-18 years were recruited. All underwent a category fluency paradigm, which required production of animal or means of transportation words for 1 min each although their frontal hemodynamic changes were recorded with fNIRS. We found that adolescents with ASD produced fewer animal but not transportation words (group-by-category interaction: P = 0.003), suggesting differential word retrieval impairment. In addition, unlike TD adolescents who exhibited activation primarily in lateral frontal regions during word production, adolescents with ASD had comparable activation across lateral and medial frontal regions. More importantly, this lack of lateral-medial distinction of activation, which was associated with poor word retrieval, differed significantly between groups only in the animal category (group-by-category interaction: P = 0.018). Thus, our findings implicate frontal lobe dysfunction in the impairment of differential word retrieval in adolescents with ASD. The relatively greater involvement of the medial frontopolar cortex might reflect the use of nonspecialized brain regions to compensate for the category-dependent difficulties with word retrieval in ASD. Autism Res 2019, 12: 600-613.