Table 5.
Significant findings of investigations of sex/gender-by-diagnosis interactions and sex/gender-stratified analysis of autism-control differences in brain activation and neural responses to tasks (task fMRI).
| Study | Country of origin for study sample | Method (‘sex’ or ‘gender’ is based on the term used in the study) | Metrics/Outcome measure | Sample size (M:F) | Age range | Covariates in analysis | Notable results (‘sex’ or ‘gender’ is based on the term used in the study) |
|---|---|---|---|---|---|---|---|
|
Beacher et al., 2012a |
United Kingdom |
task fMRI (whole-brain) sex*dx |
brain activation during performance of mental rotation and verbal fluency tasks |
29 autism (15:14) 32 TD (16:16) |
no range; AS 32.8 ± 9.1 yr TD 30.4 ± 7.7 yr |
realignment movement, proxy measure of intelligence (NART) |
significant sex*dx interaction across occipital, temporal, parietal, middle frontal regions (left precuneus, left middle occipital gyrus, left inferior temporal gyrus, right middle occipital gyrus) with greater activation in males with AS compared to females with AS and TD males |
|
Schneider et al., 2013 |
Germany |
task fMRI (whole-brain) gender stratified |
empathic responses and task-relevant neural activation patterns |
28 autism (15:13) 28 TD (15:13) |
all participants 18–55 yr |
realignment parameters, TAS-20 (Toronto Alexithymia Scores) |
autistic females had decreased activation in the midbrain, limbic regions (left amygdala), right PAG (ASD < TD); no significant difference in male groups |
|
Holt et al., 2014 (CFSA) |
United Kingdom |
task fMRI (whole-brain) sex*dx + sex stratified |
performance/ neural response on Eyes task |
49 autism (33:16) 40 unaffected siblings (12:28) 40 TD (20:20) |
all participants 12–18 yr |
age, verbal IQ |
no significant sex*dx interaction effects autistic females and unaffected female siblings both had decreased activation in the left dorsal anterior ACC, anterior PFC, inferior prefrontal gyrus, DLPFC, retrosubicular area – suggesting neuro-endophenotype in females; sex stratified analysis in males did not show evidence of neuro-endophenotype in male groups |
|
Kirkovski et al., 2016a |
Australia |
task fMRI (whole-brain + ROIs: medial PFC, right TPJ – including STS) sex stratified |
performance/ neural response in social under-standing task |
27 autism (13:14) 23 TD (11:12) |
all participants 19–56 yr |
motion realignment parameters (not specified), handedness |
males - right posterior superior temporal sulcus (ASD < TD); no significant difference in female groups |
|
Lai et al., 2019b (MRC-AIMS) |
United Kingdom |
task fMRI (ROIs: VMPFC, right TPJ) sex*dx |
neural response during mentalizing and self-referential cognition |
57 autism (29:28) 62 TD (33:29) |
all participants 18–45 yr |
age, FSIQ |
males – right TPJ and VMPFC (ASD < TD); no significant difference in female groups |
|
Lawrence et al., 2020b(GENDAAR) |
United States |
task fMRI (whole-brain limited to gray matter voxels and bilateral NAcc ROI) sex*dx + sex stratified |
social reward processing during instrumental implicit learning task |
82 autism (43:39) 72 TD (39:33) |
all participants 8–17 yr |
site/scanner, age, pubertal development, general cognitive ability |
ROI analyses: compared to same-sex TD counterparts, autistic males and females showed no significant differences in NAcc activity whole-brain analyses: autistic females showed greater neural activity (ASD > TD) to social rewards in lateral frontal regions (VLPFC, OFC, anterior insula, and other frontal and temporal regions); autistic males did not significantly differ from TD males no significant sex*dx interaction in NAcc ROI or whole-brain analyses |
Abbreviations: ACC, anterior cingulate cortex; AS, Asperger syndrome; CFSA, Cambridge Family Study of Autism; DLPFC, dorsolateral prefrontal cortex; FSIQ, full scale intelligence quotient; GENDAAR, Gender Exploration of Neurogenetics and Development to Advance Autism Research; MRC-AIMS, Medical Research Council Autism Imaging Multicentre Study; NART, National Adult Reading Test; NAcc, nucleus accumbens; OFC, orbitofrontal cortex; PAG, periaqueductal gray; PFC, prefrontal cortex; ROI, region-of-interest; STS, superior temporal sulcus; TPJ, temporo-parietal junction; VLPFC, ventrolateral prefrontal cortex; VMPFC, ventromedial prefrontal cortex.