Aberrant Right Temporo-Thalamic Connectivity in ASD an fcMRI and Graph Theory Study

Background: The thalamus is an important subcortical relay structure, through which most sensory information is routed. It plays a crucial role in visual, auditory, and somatosensory functions, as well as attention and motor control. Various lines of evidence have suggested thalamic abnormalities in ASD (e.g., Chugani et al. 1997, Friedman et al. 2003).  Highly specific patterns of thalamocortical connectivity have been demonstrated in typically developing (TD) individuals using functional connectivity MRI (fcMRI; Zhang et al. 2008, 2010; Fair et al. 2010). In a prior study (Nair et al., under review), this thalamocortical pattern of connectivity was replicated for TD children, whereas children with ASD showed mostly reduced connectivity, accompanied by overconnectivity between right temporal lobe and thalamus. However, this study did not examine thalamic connectivity of specialized regions within the temporal lobe.

Objectives: To investigate which specific functional regions within the right temporal lobe drive temporo-thalamic overconnectivity in ASD.

Methods: Resting-state functional MRI data were acquired for 6:10 minutes on a 3T GE scanner for 30 children and adolescents with ASD (ages 8-17 years) and 35 age, sex, IQ, and motion-matched TD participants. Data were preprocessed using AFNI and included motion and field map correction, spatial smoothing, isolation of low frequency fluctuations (.01<f<.1), and normalization to Talairach space. Freesurfer was used to obtain parcellations for: right temporal pole (rTP), superior temporal gyrus (rSTG), middle temporal gyrus (rMTG), inferior temporal gyrus (rITG), fusiform gyrus (rFG), and parahippocampal gyrus (rPHG). A mask was created from the right thalamic overconnectivity cluster detected in our previous study to extract time series and examine connectivity with the Freesurfer regions. As an alternative approach to quantifying connectivity, graph theory was used to compute the functional density ratio of present connections (r>.25) out of all possible ones, between the thalamus and each parcellation of the temporal lobe.

Results: FcMRI results showed overconnectivity (ASD>TD; p<.01 corr.) between right thalamus and rPHG, rIFG, rMTG, posterior rSTG, and rFG. Conversely, significant underconnectivity (ASD<TD; p<.05 corr.) was observed for rTP and anterior rSTG. Graph theory results additionally showed significantly greater functional density connections of rPHG and rITG with the right thalamus in the ASD (compared to the TD) group.

Conclusions: Our findings suggest that right temporo-thalamic overconnectivity in ASD is driven by distributed regions within the thalamus, including medial, inferior, and posterolateral temporal cortices. Anterior portions of the right temporal lobe showed inverse effects (underconnectivity). Further investigations will be needed to determine the functional relevance of this dichotomy, such as potentially compensatory roles of right temporo-thalamic overconnectivity in memory, emotional, auditory, higher visual, or language functions.