Prefrontal activation and connectivity during verbal fluency in autism Spectrum disorder: an fNIRS study

The neural mechanisms behind varying cognitive ability in children with Autism Spectrum Disorder (ASD) remain unclear. This study compared cortical activation and brain connectivity across ASD subgroups stratified by Full-Scale Intelligence Quotient (FSIQ).

Sixty-four children with ASD were divided into two groups based on their FSIQ scores: Group 1 (n = 30, FSIQ ≥ 70) and Group 2 (n = 34, FSIQ < 70). Using a 19-channel functional near-infrared spectroscopy (fNIRS) system, we assessed cortical activation and functional connectivity in both groups during a Verbal Fluency Task (VFT) by monitoring changes in oxyhemoglobin (Oxy-Hb) concentration. Inter-group differences in brain activation and connectivity were compared, and correlations between cortical activation levels and clinical indices (FSIQ, verbal production) were examined.

Compared to Group 2, Group 1 showed significantly stronger cortical activation in channels 1 and 2 [corresponding to the inferior frontal gyrus (IFG)] (U = 212.000, Z = -4.009, FDR-corrected p < 0.001; U = 160.000, Z = -4.709, FDR-corrected p < 0.001). Global functional connectivity was also greater in Group 1 (mean = 0.586, SD = 0.521) relative to Group 2 (mean = 0.413, SD = 0.521) (permutation statistic = 4.82, FDR-corrected p < 0.001). Moreover, Oxy-Hb changes in channels 1 (r_s  = 0.304, p < 0.05), 2 (r_s  = 0.405, p < 0.01), and 10 (r_s  = 0.253, p < 0.05) were positively correlated with FSIQ scores. Activation in channels 1 (r_s  = 0.529, p < 0.001), 2 (r_s  = 0.569, p < 0.001) and 10 (r_s  = 0.290, p < 0.05) were also significantly correlated with verbal production.

Our findings provide neurofunctional evidence for the association between cognitive resource capacity and verbal-executive processing in ASD. ASD children with lower FSIQ exhibited lower prefrontal activation and lower functional connectivity during the VFT, particularly within the IFG, frontopolar cortex (FPC), and dorsolateral prefrontal cortex (DLPFC). These results underscore the utility of fNIRS in delineating distinct neurocognitive profiles within ASD and highlight the IFG as a key region where neural activity correlates with both cognitive ability and language output, offering a potential target for mechanism-based intervention strategies.