Neural mapping of prepulse-induced startle reflex modulation as indices of sensory information processing in healthy and clinical populations: A systematic review.

Startle reflex is modulated when a weaker sensory stimulus ("prepulse") precedes a startling stimulus ("pulse"). Prepulse Inhibition (PPI) is the attenuation of the startle reflex (prepulse precedes pulse by 30-500 ms), whereas Prepulse Facilitation (PPF) is the enhancement of the startle reflex (prepulse precedes pulse by 500-6000 ms). Here, we critically appraise human studies using functional neuroimaging to establish brain regions associated with PPI and PPF. Of 10 studies, nine studies revealed thalamic, striatal and frontal lobe activation during PPI in healthy groups, and activation deficits in the cortico-striato-pallido-thalamic circuitry in schizophrenia (three studies) and Tourette Syndrome (two studies). One study revealed a shared network for PPI and PPF in frontal regions and cerebellum, with PPF networks recruiting superior medial gyrus and cingulate cortex. The main gaps in the literature are (i) limited PPF research and whether PPI and PPF operate on separate/shared networks, (ii) no data on sex differences in neural underpinnings of PPI and PPF, and (iii) no data on neural underpinnings of PPI and PPF in other clinical disorders.

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.

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.