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.

Changes in the amplitude and timing of the hemodynamic response associated with prepulse inhibition of acoustic startle.

Disruption of the early stages of information processing in limbic brain circuits may underlie symptoms of severe neuropsychiatric disorders. Prepulse inhibition of acoustic startle (PPI) is diminished in many of these disorders and may reflect the disruption of this CNS function. PPI is associated with brain activity in many of the same regions in humans as it is in laboratory animals, suggesting that neuroimaging studies in humans may help localize deficits that can then be elucidated in animal models. In this article, we employed a rapid presentation event-related design during continuous EPI BOLD scanning to examine hemodynamic response functions (HRFs) associated with PPI. Fourteen healthy participants listened to 100 pulse alone and 100 prepulse combined with pulse (prepulse-pulse) trials. PPI is the normalized difference in the startle response to the two trial types. Following the prepulse-pulse trials, the amplitudes of the HRFs in auditory cortices and in the anterior insula were increased, while in the cerebellum, thalamus and anterior cingulate, they were decreased, relative to the pulse alone trials. In addition, the timing of the prepulse-pulse responses was delayed in the auditory cortices, anterior insula and cerebellum. Finally, PPI measured outside the scanner was predicted by the difference in BOLD responses between trial types in the anterior insula and in the cerebellum. The results suggest that prepulse inhibition, and by extension early stages of information processing, modulate both the amplitude as well as timing of neural activity.