Distinct neural mechanisms of social orienting and mentalizing revealed by independent measures of neural and eye movement typicality

Extensive study of typically developing individuals and those on the autism spectrum has identified a large number of brain regions associated with our ability to navigate the social world. Although it is widely appreciated that this so-called “social brain” is composed of distinct, interacting systems, these component parts have yet to be clearly elucidated. Here we used measures of eye movement and neural typicality—based on the degree to which subjects deviated from the norm—while typically developing (N = 62) and individuals with autism (N = 36) watched a large battery of movies depicting social interactions. Our findings provide clear evidence for distinct, but overlapping, neural systems underpinning two major components of the “social brain,” social orienting, and inferring the mental state of others.

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Software and code
Policy information about availability of computer code Data collection MRI data was collected at the Functional Magnetic Resonance Imaging Core Facility on a 32 channel coil GE 3T (GE MR-750 3.0T) magnet and receive-only head coil. Eye movement data was recorded with the Eyelink 1000 Plus.

Data analysis
Post-hoc signal preprocessing was conducted in AFNI (Analysis of Functional Neuro-Images), Version AFNI_19.2.08 'Claudius', and data on the cortical surface were visualized with SUMA (Surface Mapping). Data were also analyzed with in-house software written in MATLAB (version R2016b).
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Data
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Life sciences Behavioural & social sciences Ecological, evolutionary & environmental sciences
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Life sciences study design
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Sample size
Optimal sample size is difficult to estimate in neuroimaging studies. However, the sample size here is comparable to or greater than what is usually reported in fMRI studies.
Data exclusions One TD participant was excluded from the analysis because of an abnormal brain structure scan. 3 ASD participants and 2 TD participants failed to achieve adequate calibration with the eye tracker and were removed from the eye-tracking portion of the analysis

Replication
The reproducibility of the eye movement typicality rating was established through a split halves permutation test. The correlation between eye movement typicality and neural typicality was replicated across the TD and ASD groups Recruitment TD Participants were recruited through listserv announcements. ASD participants were recruited through referrals from Children's National Health Systems.

Ethics oversight
The experiment was approved by the NIMH Institutional Review Board (protocol 10-M-0027). Written informed consent was obtained from all participants or their guardians in the case of minors, in which case written assent was also obtained from the participants themselves Note that full information on the approval of the study protocol must also be provided in the manuscript.

Clinical data
Policy information about clinical studies Noise and artifact removal The first four EPI volumes from each run were removed to ensure remaining volumes were at magnetization steady state, and remaining large transients were removed through a squashing function (AFNI's 3dDespike). Volumes were slice-time corrected and motion parameters were estimated with rigid body transformations (through AFNI's 3dVolreg function). Volumes were co-registered to the anatomical scan. The data were then entered to a Multi-Echo ICA analysis (ME-ICA), as described in Kundu et al. 2013, to further remove nuisance signals (e.g., hardware-induced artifacts, residual head motion). Briefly, this procedure utilizes the physical properties of BOLD and non-BOLD fluctuations, namely the fact that whole signal from BOLD sources increases linearly over echo times, signals from non-BOLD sources remain constant across echoes. This allows the removal of non-BOLD fluctuations (noise). Pearson correlations between neural typicality (the correlation of the time course in each voxel for each participant with the average time course in that voxel across all other participants) was correlated with an independent measure of eye movement typicality (the correlation of the eye movement scan path for that participant with the average scan path across all other participants). Also, group differences in neural typicality between the TD and ASD groups were assessed using a two-tailed t-test.