Changes in sensorimotor inhibition across the menstrual cycle: Implications for neuropsychiatric disorders

doi:10.1016/S0006-3223(96)00065-0

Biological Psychiatry

Volume 41, Issue 4, 15 February 1997, Pages 452-460

https://doi.org/10.1016/S0006-3223(96)00065-0 Get rights and content

The startle reflex is inhibited when the startling noise is preceded 30–500 msec by a weak prepulse. “Prepulse inhibition” (PPI) is reduced in specific neuropsychiatric disorders characterized clinically by impaired inhibition of sensory, motor, or cognitive information. PPI is sexually dimorphic, with men exhibiting significantly more PPI than women. We examined possible neuroendocrine substrates for this sex difference in PPI. The startle reflex, and a measure of visuospatial priming, were measured in 10 men, and in 46 normal women at different points in their menstrual cycle. In women, PPI was significantly reduced in the luteal vs follicular phase of the menstrual cycle. This reduction in PPI was most notable during the period corresponding to midluteal elevations of both estrogen and progesterone. In a task of visuospatial priming, follicular-phase women demonstrated a predominance of inhibition over facilitation, but this pattern reversed across the menstrual cycle.

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Cited by (226)

Effects of total sleep deprivation on sensorimotor gating in humans
2023, Behavioural Brain Research
Sensorimotor gating is a measure of pre-attentional information processing and can be measured by prepulse inhibition (PPI) of the startle reflex. Sleep deprivation has been shown to disrupt PPI in animals and humans, and has been proposed as an early phase 2 model to probe antipsychotic efficacy in heathy humans. To further investigate the reliability and efficacy of sleep deprivation to produce PPI deficits we tested the effects of total sleep deprivation (TSD) on PPI in healthy controls in a highly controlled sleep laboratory environment. Participants spent 4 days and nights in a controlled laboratory environment with their sleep monitored with polysomnography. Participants were randomly assigned to either normal sleep on all 4 nights (N = 17) or 36 h of TSD on the 3rd or 4th night (N = 40). Participants were assessed for sleepiness using the Karolinska Sleepiness Scale (KSS) and underwent a daily PPI task (interstimlulus intervals 30–2000 ms) in the evening. Both within-subject effects (TSD vs. normal sleep in TSD group alone) and between-subject effects (TSD vs. no TSD group) of TSD on PPI were assessed. TSD increased subjective sleepiness measured with the KSS, but did not significantly alter overall startle, habituation or PPI. Sleep measures including duration, rapid eye movement and slow wave sleep duration were also not associated with PPI performance. The current results show that human sensorimotor gating may not be reliably sensitive to sleep deprivation. Further research is required for TSD to be considered a dependable model of PPI disruption for drug discovery in humans.
Negative emotion-conditioned prepulse induces the attentional enhancement of prepulse inhibition in humans
2023, Behavioural Brain Research
Prepulse inhibition (PPI) is a reduction of the acoustic startle reflex (ASR) when the startling stimulus is preceded by a weaker and non-startling stimulus (i.e., prepulse). Previous studies have revealed that PPI can be top-down modulated by selective attention to the fear-conditioned prepulse in animals. However, few researchers have tested this assumption in humans. Thus, in this study, the negative emotional-conditioned prepulse (CS+) was used to explore whether it could improve participants' attention, and further improve the PPI. The results showed that the CS+ prepulse increased the PPI only in females, PPI produced by CS+ prepulse was larger in females than in males, and the perceptual spatial attention further improved the PPI in both females and males. The results suggested that the PPI was affected by emotional, perceptual spatial attention, and sex. These findings highlight an additional method to measure top-down attentional regulation of PPI in humans. Which may offer a useful route to enhance the diagnosis of affective disorders, such as anxiety, depression, and post-traumatic stress disorder.
Disrupted sensorimotor gating in first-episode psychosis patients is not affected by short-term antipsychotic treatment
2021, Schizophrenia Research
Citation Excerpt :
This could, at least in part, be attributable to the relatively small sample size or influence of the menstrual cycle, a factor that was not controlled in this study. Both estrogen and progesterone changes during the menstrual cycle are known to affect PPI (Kumari et al., 2008, 2010; Swerdlow et al., 1997). The effects of antipsychotic treatment on PPI have been extensively studied.
Impaired sensorimotor gating, commonly measured as disrupted prepulse inhibition (PPI) of the acoustic startle response, has been widely observed in psychotic diseases. However, most PPI studies published so far involve patients with long illness duration and different drug treatments. Few studies have investigated untreated patients at their first episode of psychotic symptoms.
PPI is an acoustic startle paradigm (30, 60-, 120-ms interstimulus intervals). Startle reactivity and habituation were succesfully assessed in 49 antipsychotic-naïve first-episode psychosis (FEP) patients and compared with 35 age- and gender-matched healthy control subjects. Mean age of patients was 28 years and 27 for controls. Patients treated with antipsychotics more than 30 days were not included in the study and twenty-three out of forty-nine patients received antipsychotic treatment with a mean treatment time of 13 days.
PPI was significantly lower in FEP patients, compared to healthy controls. The PPI deficiency found in these patients was not due to antipsychotic treatment since PPI did not differ between treated (n=23) and untreated patients n=(26). By using the latent curve modeling we identified a delayed habituation in patients treated with antipsychotics, suggesting that antipsychotic treatment should be considered as a confound when investigating habituation in schizophrenia.
Our results suggest that acute pharmacological treatment does not normalize PPI in FEP patients but should be considered as a confound when investigating habituation in these patients.
Prepulse inhibition of the acoustic startle reflex and P50 gating in aging and alzheimer's disease
2020, Ageing Research Reviews
Inhibition plays a crucial role in many functional domains, such as cognition, emotion, and actions. Studies on cognitive aging demonstrate changes in inhibitory mechanisms are age- and pathology-related. Prepulse inhibition (PPI) is the suppression of an acoustic startle reflex (ASR) to an intense stimulus when a weak prepulse stimulus precedes the startle stimulus. A reduction of PPI is thought to reflect dysfunction of sensorimotor gating which normally suppresses excessive behavioral responses to disruptive stimuli. Both human and rodent studies show age-dependent alterations of PPI of the ASR that are further compromised in Alzheimer’s disease (AD). The auditory P50 gating, an index of repetition suppression, also is characterized as a putative electrophysiological biomarker of prodromal AD. This review provides the latest evidence of age- and AD-associated impairment of sensorimotor gating based upon both human and rodent studies, as well as the AD-related disruption of P50 gating in humans. It begins with a concise review of neural networks underlying PPI regulation. Then, evidence of age- and AD-related dysfunction of both PPI and P50 gating is discussed. The attentional/ emotional aspects of sensorimotor gating and the neurotransmitter mechanisms underpinning PPI and P50 gating are also reviewed. The review ends with conclusions and research directions.
Hypothalamic-pituitary-adrenal axis responsiveness, startle response, and sensorimotor gating in late pregnancy
2019, Psychoneuroendocrinology
During pregnancy, the hypothalamic-pituitary-adrenal (HPA) axis, the main regulator of the stress response, undergoes dramatic changes. The acoustic startle response (ASR) and the prepulse inhibition (PPI) of the startle response are neurophysiological research tools and objective measures of an individual’s response to an emotional context or stressor. The ASR and PPI are influenced by psychiatric diseases characterized by anxiety symptoms and are sensitive to cortisol. Hence, the ASR and the PPI can be used to investigate the effects of pregnancy-induced endocrine changes and their contribution to affective disorders. The present study sought to investigate the association between measures of HPA-axis responsiveness, startle reactivity and sensorimotor gating during pregnancy that to date remains unknown. The eye-blink component of the ASR, and its prepulse inhibition, were measured in 107 late third trimester pregnant women. Saliva samples were collected to assess the cortisol awakening response (CAR), a measure of HPA-axis activity. Blood was sampled to measure serum levels of cortisol, cortisone and the cortisone to cortisol ratio. Ongoing anxiety disorders, sleep duration, smoking, and age were considered as potential confounders in the statistical analyses. CAR reactivity, measured as area under the curve (AUC) increase and above baseline, was positively associated with baseline startle magnitude [Cohen’s d = 0.27; F (1, 105) = 4.99; p = 0.028, and Cohen’s d = 0.30; F (1, 105) = 6.25; p = 0.014, respectively] as well as PPI at 86 dB [Cohen’s d = 0.29; F (1, 105) = 5.93; p = 0.017; and Cohen’s d = 0.34; F (1, 105) = 8.38; p = 0.005, respectively]. The observed positive correlation between startle magnitude in pregnant women and greater increase in cortisol during the awakening response may be interpreted as heightened neurophysiological reactivity, likely associated with dysregulation of the stress system.
Socio-demographic predictors of prepulse inhibition: A prospective study in children and adolescents from Mexico City
2019, Biological Psychology
Prepulse inhibition (PPI) is a sensorimotor gating mechanism that reduces interfering influences to the neural processing of incoming stimuli, and is associated with several neurodevelopmental disorders. To date, research on PPI and neurodevelopmental disorders has primarily been in cross-sectional, clinical settings. In this prospective, epidemiologic study, we used a data-driven prediction model to identify socio-demographic predictors of PPI in children and adolescents from Mexico City to inform future etiologic studies evaluating PPI. We conducted variable selection and validation using a modified version of the multiple imputation random lasso (MIRL) variable selection algorithm. MIRL identified six predictors of PPI at a stimulus onset asynchrony of 120 ms or 240 ms. Of those six predictors, maternal education, birthweight, and total breastfeeding months were highlighted as previously unstudied variables associated with enhanced PPI. Our findings highlight the potential value of PPI as an adjunct screening tool for identifying children at risk for neurodevelopmental disorders and underscore the relevance for validation research on this topic.

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: NRS was supported by MH 48381 and MH 42228 and by an award from the National Alliance for Research on Schizophrenia and Depression. Data from 8 women in this study were reported previously (Swerdlow et al 1995b) in a larger study of PPI in normal controls. The visuospatial priming task was created and generously provided by Dr. Gordon Baylis, and was used with the helpful consultation of Dr. Diane Filion. The authors acknowledge outstanding help by Heidi Hartston, Navid Taaid and Dr. Sam Zinner, and helpful discussions with Drs. Barbara Parry, David Braff, Mark Geyer, William Perry, Kristin Cadenhead, Nancy Downs, and Brett Clementz.

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Original articleChanges in sensorimotor inhibition across the menstrual cycle: Implications for neuropsychiatric disorders

Pharmacol Biochem Behav

Behav Brain Res

Brain Res

Eur J Pharmac

Biol Psychiatry

Biol Psychiatry

Biol Psychiatry

Brain Res

Brain Res

Abstr Int Cong Schiz Res

Behav Brain Res

Pharm Biochem Behav

Psychoneuroend

Biol Psychiatry

Biol Psychiatry

Neurosci Biobehav Rev

Direct effect of 17b-estradiol on striatum: Sex differences in dopamine release

Synapse

Hormonal influences on extrapyramidal sensorimotor function and hippocampal plasticity

Individual differences in negative priming: Relations with schizotypal personality traits

Brit J Psychol

Evidence of reduced “cognitive inhibition” in schizophrenia

Brit J Clin Psychol

Sensorimotor gating and schizophrenia: Human and animal model studies

Arch Gen Psychiatry

Gating and habituation of the startle reflex in schizophrenic patients

Arch Gen Psychiatry

Original article
Changes in sensorimotor inhibition across the menstrual cycle: Implications for neuropsychiatric disorders