Double Dissociation in Amygdala and Insula to an Auditory “Looming” Threat Task

Background: Understanding the mechanisms that underlie anxiety in autism is a critical task for experimental and clinical research. Previous studies have shown atypical fear conditioning response in autistic samples. However, because fear conditioning requires learning, other processes potentially complicate the interpretation of results. Neuroimaging studies of auditory “looming” have shown amygdala activation in response to sounds that appear to be coming “toward” the person in contrast to neutral or to “receding” sounds. We proposed using a looming task to investigate neural fear response without the need for any contingency learning.

Objectives: A multi-method study of auditory looming and receding in young autistic adults. We hypothesized typical fear response (e.g., amygdala and insula) in the autism sample compared to neurotypical young adults, suggesting that other factors underlie atypical fear conditioning and elevated anxiety in autism.

Methods: 25 AUT and 31 age and ability matched neurotypical (NT) young adults listened to sounds that get progressively louder (looming) or quieter (receding) while undergoing fMRI scans. The auditory stimuli consisted of pulsed tones of 2000ms duration and a 1kHz carrier frequency that were amplitude-modulated with a smoothed square wave envelope of 5Hz. The 2000ms sound sweeps were multiplied with an exponential function to obtain sound pressure level changes of 15dB (rising intensity sound, 70-85dB; falling intensity sound, 85-70dB; constant intensity sound, 77dB). Stimuli were presented bilaterally. All analyses were corrected for multiple comparisons using family-wise error correction.

Results: There was a main effect for group in left amygdala activation, NT>AUT (F=14.35; p=0.008) but no main effect for sound condition or group x condition interaction. There was a main effect for condition in bilateral insula, looming > receding (right: F=58.19; p=0.000; left: F=51.55; p=0.000) and a main effect for group for right insula, in the opposite direction, AUT > NT (F=39.53; p=0.000), but no group x condition interaction.

Conclusions: While we initially hypothesized that task response would not differ between groups, these and other data coming into our lab suggest a story of “physiological inflexibility” in which a restricted range of psychophysiological response in autism may contribute to frequent outbursts, meltdowns, or crippling anxiety. The neural response to threat differs between autism and neurotypical samples even when no learning is required, and may contribute to higher-order symptoms of anxiety that are so frequent in autism.