Locus coeruleus modulation of neurophysiological sensory selectivity differs in autism and other mental health conditions

Sensory symptoms are common in autism and may result from differences in sensory processing. The locus coeruleus-norepinephrine (LC-NE) system modulates sensory processing by increasing selectivity to salience. To specify this mechanism, we manipulated LC-NE activity and explored sensory selectivity in autistic and non-autistic adolescents. We assessed pupillometry and electroencephalography (EEG) in 52 autistic adolescents (ASD), 55 healthy controls (CON), and 43 adolescents with other mental health conditions (MHC) during a passive auditory oddball task. A handgrip exercise manipulated LC-NE activity. Baseline pupil size (BPS) and stimulus-evoked pupillary response (SEPR) measured LC-NE tonic and phasic activity, respectively. Sensory selectivity was estimated with mismatch negativity (MMN) as change detection and P3a as bottom-up attention. Oddballs versus standards elicited increased SEPR, MMN amplitude, and longer MMN and P3a latencies. Increased P3a amplitude was specific to ASD. Across oddballs and standards, the manipulation transiently increased MMN and P3a amplitudes. A manipulation-induced BPS increase was specific to ASD and MHC. Pupillometric measures (BPS, SEPR) modulated sensory selectivity measures (MMN, P3a) differently between clinical groups (ASD, MHC) and CON. Findings indicate biased bottom-up attention in autism. The manipulation did not increase sensory selectivity but temporarily enhanced sensory reactivity to all stimuli with an arousal upregulation in both clinical groups. LC-NE activity differentially modulated sensory selectivity in autism and other mental health conditions. The tonic upregulation is discussed as increased stress susceptibility across autism and other mental health conditions.