Sustained Neural Processing of Personally Relevant Negative Emotional Stimuli in Youth with ASD: A Possible Mechanistic Explanation for Poor Emotion Regulation

Background: There is increasing evidence that individuals with autism spectrum disorder (ASD) have poor emotion regulation, but the underlying neural processes are not well understood. In depressed samples, functional neuroimaging has revealed sustained neural processing of emotional stimuli (Erk et al., 2010). This may also occur in ASD given observations that emotional reactions are often characterized by a perseverative quality and prolonged negative affect (Mazefsky, Pelphrey, & Dahl, 2012).

Objectives: This study investigated differences in blood oxygen level dependent (BOLD) signal activation in youth with ASD during an event-related task that alternated between emotional processing and non-emotional processing conditions. Using a priori criteria, the objective was to identify brain regions with sustained activity following the presentation of personally-relevant negatively valenced stimuli.

Methods: Youth (12-17 years old) with ADOS- and ADI-confirmed ASD without intellectual disability (n= 25) and an IQ-, age-, and gender-matched control sample (n= 23) completed a task in a Siemens Verio 3T Magnetic Resonance Imaging (MRI) Scanner with a 32-channel head coil. The participants, together with their parents, created a list of 12 words that had a negative connotation to them prior to the participant being scanned. Each of the imaging trials alternated between an emotional processing condition, which consisted either of the personally-relevant negative words or normed neutral words, and a non-emotional simple memory task. Analyses were conducted using the Analysis of Functional NeuroImages (AFNI). A feature conjunction analysis was conducted to identify regions that satisfied the following a priori criteria in support of the hypothesis: 1) ASD group had greater activity than controls during the emotional portion of the task; 2) ASD group had greater activity during the entire trial (into the memory task), following the presentation of negative words: 3) ASD group was more reactive to negative versus neutral words; 4) changes in activity represented an increase from baseline. All regions included were greater than 30 voxels and had an effect size that was medium or greater (d > .5) and p <.05.

Results: Regions satisfying all a priori criteria were the left insula (89 vox), right pulvinar (67 vox), left dorsolateral prefrontal cortex (62 vox), and right insula (45 vox) (Figure 1). Time course plots of activity in these brain regions provided further support for increased and sustained processing across the trial after the personally relevant negative words in the ASD group (Figure 2). In the ASD group, correlations between heightened and sustained activity in the identified regions and poorer cognitive control and greater irritability were moderate and approaching significance.

Conclusions: fMRI findings indicate a heightened and sustained response to negative stimuli in youth with ASD in brain regions related to salience evaluations and cognitive control. This may provide a potential neural mechanism to explain poor emotion regulation in ASD. Prolonged processing