Cognitive heterogeneity in autism spectrum disorders: Linking complex behavior, function, and neuronal integrity

Progress has been made in characterizing cognitive functioning and the neurological basis of autism spectrum disorders (ASD) disorders, although few studies have directly linked cognitive deficits with neural defects. Complex behavior, brain function, and neuronal integrity were investigated in high-functioning (FSIQ>70) males with ASD. The Color-Word Interference Test, Trail Making Test, Verbal Fluency Test, and Design Fluency Test from the Delis-Kaplan Executive Function System were administered to 12 ASD individuals [age = (26.4(7.7)]. Participants performed below average on the executive function composite ( p = .02). Letter and category switching fluency produced the most consistent deficits (i.e., SS<8); cognitive inhibition and semantic fluency were intact. The neurofunctional basis of intact category and impaired letter fluency was investigated using FMRI. Fourteen ASD [age = 23.8(9.6)] and 14 controls [age = 22.4(8.7)] participated. The ASD group had greater right prefrontal and temporal activation in letter fluency (p < .05, corrected for multiple comparisons). In category fluency, controls demonstrated greater left middle frontal activation (p < .05, corrected). An asymmetry index [(L-R)/(0.5(L+R))] of positive activation in right and left prefrontal cortices (p < .05, one-tailed, corrected) was computed for each participant. Controls showed greater leftward lateralization in letter fluency ( M control = 1.62, M ASD = 0.38; p < .001). Twelve of 14 ASD participants evidenced right, bilateral, absent, or weak left lateralized patterns of activation. No lateralization differences in category fluency were found (M control = .6 59, M ASD = .323; p > .05). The relationship between FMRI letter fluency activation and neuronal integrity was investigated using proton magnetic resonance spectroscopy. N-acetyl-aspartate was reduced in left prefrontal cortex in ASD (p = .043) and correlated to functional activation in left prefrontal cortex in ASD (rs = .794, p = .006). Diminished hemispheric specialization for complex language in ASD was demonstrated, with greater impairment observed in tasks which are strongly lateralized in healthy individuals. Atypical functional lateralization likely reflects primary neuronal dysfunction in addition to hypothesized aberrant connectivity, and may be a consequence of early, rapid overgrowth of frontal and temporal lobes and subsequent arrested development recently reported in autism. Such growth dysregulation may disrupt the protracted process by which the left hemisphere becomes dominant for language, and may subsequently contribute to language impairments seen in autism.