Neural Connectivity in Young Adults with ASD: A Comparison of Brain Function During Theory of Mind and Resting State

Background: The measurement of ‘resting state’ during fMRI has led to the identification of a ‘default mode network’ (DMN) of brain regions, which are active at rest but which consistently show relative deactivations during cognitively demanding tasks. Decreased functional connectivity in this network is found in ASD, compared to neurotypical controls. The DMN overlaps with brain areas activated by theory of mind tasks. No previous study has attempted to study how functional connectivity in adults with ASD differs from typical controls by contrasting potential mechanisms during both resting state and a theory of mind paradigm.

Objectives: Our first objective was to contrast neural activity in the DMN during rest in high functioning autistic and control subjects with activation during a complex task demanding high -order theory of mind abilities. Our second objective was to examine the functional connectivity of the DMN in a number of different ways, in order to identify whether evidence for decreased functional ‘connectivity’ of the DMN in ASD is driven by neuronal fluctuations that are unrelated to task effects.

Methods: We recruited 25 adults with high-functioning autism and 25 IQ matched controls. Clinical group was defined by consensual diagnosis according to DSM-IV-TR criteria, and ADOS examination. None was medicated. Mean FSIQ of the control group was 123 (SD 21) and for the ASD group 132(SD 18). Subjects had their neural activity measured using BOLD contrast, both at rest and during a theory of mind task, by acquiring T2*-weighted echoplanar images on a 1.5T Siemens Avanto MR scanner. Resting state activity was measured whilst subjects lay still with their eyes looking at a fixed point. Theory of mind processing was measured by requiring subjects to make judgements on a variant of the ‘Mind in the Eyes’ task (Baron-Cohen et al 2001). fMRI and connectivity data were analysed using SPM 8 (MatLab); resting state activity utilised REST state package (YF Zang) and the DTI data  utilised FSL software.

Results: During the resting state, activity within the DMN was greater in controls in the posterior cingulate cortex, angular and supramarginal gyrus of the parietal lobe, relative to the ASD group. During the theory of mind task, the ASD group had relatively lower activity in the inferior frontal cortex (IFG), insular, anterior cingulate cortex (ACC), ventral medial prefrontal cortex (VMPFC), bilateral superior temporal gyrus (STG), temporal pole (TP), and precuneus.

Conclusions: Neural activity in the DMN and other social brain regions during rest is lower in ASD than controls. There is reduced activity in the same areas during a theory of mind task, based on reading ‘The Mind in the Eyes’. Measures of functional and structural connectivity are currently being analysed. Fluctuations in task related signals will be contrasted with spontaneous fluctuations at rest, in order to address the question, is any difference in ‘connectivity’ between key brain regions of the DMN driven by task, or are there residual differences in spontaneous neuronal activity in ASD?