The influence of stimulus onset asynchrony, task order, sex and hormonal contraception on prepulse inhibition and prepulse facilitation: Methodological considerations for drug and imaging research

Abstract

Background: Prepulse-induced startle modulation occurs when a weak sensory stimulus (‘prepulse’) is presented before a startling sensory stimulus (‘pulse’), producing an inhibited (Prepulse Inhibition, PPI) or facilitated (Prepulse Facilitation, PPF) startle response. We recently identified several gaps and outlined future lines of enquiry to enable a fuller understanding of the neurobiology of PPI and PPF in healthy and clinical populations. However, before embarking on these studies, it is important to consider how task and population characteristics affect these phenomena in healthy humans. Methods: We examined PPI and PPF in separate tasks, with counterbalanced task order across participants in one session, using a range of stimulus onset asynchronies (SOAs), in 48 healthy adults (23 men, 25 women; 10 hormonal contraceptive users) to determine which SOAs produce the strongest PPI and PPF and also explored how sex and hormonal contraception might influence PPI and PPF under these experimental conditions. Results: Both PPI and PPF were affected by SOA, with greatest PPI observed at 60 and 120 ms, and greatest PPF at 4500 and 6000 ms. PPI was influenced by sex (more PPI in men than women) and hormonal contraception, whereas PPF was affected by task order (greater PPF when the PPF task followed, rather than preceded, the PPI task). Conclusions: Our findings indicate that studies of PPI and PPF need to consider, not only sex and hormonal status of study participants, but also task characteristics and presentation order to reduce variance and increase replicability across studies.

Elucidation of the mechanism underlying impaired sensorimotor gating in patients with primary blepharospasm using prepulse inhibition

“…In contrast, the present study reported a smaller PPI of about 40%. Additionally, previous studies have shown that PPI is most pronounced at 120 ms in healthy populations ( 26 , 27 ), but in our research, PPI size appeared to be greater at 200 ms. The differences in ethnicity may contribute to the discrepancy of results, in addition to age and gender structures ( 27 , 32 , 33 ).…”

“…Additionally, previous studies have shown that PPI is most pronounced at 120 ms in healthy populations ( 26 , 27 ), but in our research, PPI size appeared to be greater at 200 ms. The differences in ethnicity may contribute to the discrepancy of results, in addition to age and gender structures ( 27 , 32 , 33 ). Furthermore, we found that impaired PPI in BSP patients also occurred at ISIs of 200 and 300 ms, and the R 1 amplitude facilitation and bilateral R 2 latencies prolongation were absent in BSP patients, which above was not explored in previous studies ( 25 , 34 ).…”

“…In recent years, PPI impairment has also been observed in movement disorders such as Parkinson's disease ( 23 ), cervical dystonia ( 24 ), and BSP ( 25 ). Previous studies have shown that PPI is most pronounced at 120 ms in healthy populations ( 26 , 27 ), but no studies have been conducted in healthy populations and patients with dystonia in China or Asia.…”

Age-related changes in prepulse inhibition of the startle response

“…Previous studies have shown that menstrual cycle, for example, is a factor that impacts PPI levels ( 44 ). Another recent study investigating sex differences on PPI and contraceptive use revealed higher PPI in men than in women who do not use contraceptives; however, no significant differences were found between women who use and women who do not use contraceptives ( 17 ). According to previous studies, lower PPI of older adults would not be explained by this factor, since the older women had already gone through the menopause period and only the pre-menopause period had been associated with lower PPI level ( 45 ).…”

“…The phenomenon of prepulse inhibition is mediated by several neural pathways, from structures of the auditory system, the limbic system, and superior cortical areas ( 41 ). A recent systematic review has shown that thalamic, striatal, and frontal lobe are the most evidenced (9 studies) areas activated in healthy populations during PPI ( 17 ). Aging, in general, is associated with physiological changes that can affect the normal functioning of some of these structures, and this may be related to many of the results we found in our study.…”