A Neuroimaging Study For The Extreme Male Brain Theory In2to3-year-old Toddlers With Autism Spectrum Disorders

【Objective】To assess total intracranial volume (TIV), global gray matter (GM) and whitematter (WM) volumes, regional GM and WM alterations and the WM tract integritybetween2~3-year-old toddlers with autism spectrum disorders (ASDs) anddevelopmental delays (DDs); to provide neuroanatomical data that support theExtreme Male Brain theory (EMB) of ASDs; to investigate the correlation betweenthe TIV, the global GM and WM volumes and the severity of symptoms,developmental quotient (DQ) and age in children with ASDs.【Methods】Brain images of50toddlers with ASDs and28age-, gender-, and developmentalquotient (DQ)-matched toddlers with DDs (control group) between ages2and3yearswere captured using a combined approach of voxel based morphometry (VBM) andvoxel based analysis (VBA). Structural magnetic resonance imaging (MRI) anddiffusion tensor imaging (DTI) were applied. The TIV, the global GM and WMvolumes, and regional alterations were assessed by VBM. VBA was used toinvestigate the white matter tract integrity. Childhood Autism Rating Scale (CARS)and Autism Diagnostic Interview-Revised (ADI-R) were applied to assess theseverity of symptoms in children with ASDs, and Bayley scales of infantdevelopment (BSID) was used to measure DQ. The correlation research wasconducted between the scores of those three scales and age and the TIV, the globalGM and WM volumes.【Results】(1) Compared with DDs, significant increases were observed in global GM andWM volumes in ASDs (p<0.05). In addition, a trend of greater TIV was seen inASDs (p=0.052). (2) Compared with DDs, significantly more GM volumes were localized inASDs in the right superior temporal gyrus, the right Brodmann area22and the rightBrodmann area38(p<0.001). Conversely, signficantly greater WM volumes wereobserved in ASDs in the right superior temporal gyrus, left middle temporal gyrus,right insula, and right Heschl’s gyrus (p<0.001). Notably no significant decreases inGM and WM volumes were observed in any region between ASDs and control group.(3) Compared with DDs, ASDs strongly exhibited higher FA in the CC,posterior cingulate cortex, and limbic lobe (p<0.001). In addition, ASDs exhibitedlower MD in left CC, posterior cingulate, limbic lobe, and insular cortex (p<0.001).Similarly, no significantly lower FA or higher MD values were observed in ASDs orcontrol group.(4) The TIV in ASDs negatively correlated with social (r=-0.319, p=0.031) andcommunication (r=-0.412，p=0.004) performance measured by ADI-R; the globalGM volumes in ASDs was negatively associated with social (r=-0.345, p=0.019)performance and the global WM volumes significantly associated withcommunication (r=-0.455, p=0.001) performance; but such correlation did not showup in DDs group. Neither of the two groups showed significant relationship betweenthe TIV, the global GM and WM volumes and DQ and age.【Conclusion】These results provide powerful evidence to support the hypothesis of the EMBtheory, confirming that2to3-year-old toddlers with ASDs exhibithyper-masculinization of certain brain regions. These findings provide a link betweenprevious behavioral and neuroendocrine findings, mapping neuroanatomical featuresin a straightforward manner that clearly presents this association. Therefore, thisstudy provides preliminary data that enhances current understanding of relationshipsbetween behavioral, endocrine, and anatomic findings related to ASDsneurophysiology, supporting the EMB theory of ASDs. In addition, the abnormal enlargement of related brain regions significantly associated with clinical symptomsin ASDs.