Circuit activity underlying a distinct modulator of prepulse inhibition

Prepulse inhibition (PPI), the diminished eye blink response to a startling pulse induced by a prepulse, is regulated by brainstem, and modulated by cerebral, processes. Attentional modulation by the prepulse (AMP), a potential biomarker of psychotic disorders, differs from other modulatory processes because it only occurs if the interval between the prepulse and pulse exceeds 100 ms (>PP100). Videotaped eye blinks were measured during fMRI scanning in 15 healthy subjects hearing 64 pulse alone, 64 PP60 and 64 PP120 trials in a rapid event-related design. Because attentional influences on PPI vary spontaneously, we posited AMP could be isolated by comparing eye blink and Blood Oxygen Level Dependent covariation during the two PP trial types. Behavioral regressor coefficients reflecting significant covariation covered the insula and auditory cortices during PP120 but not PP60 trials. Clusters within the right anterior insula and auditory cortex were specific to AMP. Functional connections (FCs) between cerebral ROIs implicated in PPI were stronger during PP120 trials. The four FCs that were individually stronger during PP120 trials involved the right insula or auditory cortex and three were not present during PP60 trials. Converging evidence indicates the right insula is the hub of a network underlying AMP.