Inhibitory Reflex Research Articles

Age differences in inhibitory and working memory functioning: limited evidence of system interactions

ABSTRACT Debate persists regarding the nature of age-related deficits in inhibition, and whether inhibitory functioning depends on working memory systems. The current research aimed to measure age-related differences in inhibition and working memory, characterize the relationship between inhibitory functions and working memory performance, and determine how these relationships are affected by age. Toward these ends, we measured performance on a range of established paradigms in 60 young adults (18–30 years) and 60 older adults (60–88 years). Our findings support age-related increases in reflexive inhibition (based on the fixation offset effect and inhibition of return) and age-related decrements in volitional inhibition (based on several paradigms: antisaccade, Stroop, flanker, and Simon). This evidence of stronger reflexive inhibition combined with weaker volitional inhibition suggests that age-related deterioration of cortical structures may allow subcortical structures to operate less controlled. Regarding working memory, older adults had lower backward digit scores and lower forward and backward spatial scores. However, of the 32 analyses (16 in each age group) that tested for dependence of inhibitory functioning on working memory functioning, only one (in young adults) indicated that inhibition performance significantly depended on working memory performance. These results indicate that inhibition and working memory function largely independently in both age groups, and age-related working memory difficulties cannot account for age-related declines in inhibitory control.

The Food-Crushing Reflex and Its Inhibition

Anterior tooth (ANT) contacts induce a short-latency reflex inhibition of the human jaw-closing muscles. The jaw is a rigid class 1 lever for pinpoint targeting muscle force into a single bite point, the pivoting food particle. Seesaw reflex movements around the food particle fulcrum multiply the food-crushing force. Unpredictable jolts of reaction force caused by food crushing are subjected to the rostral ANT and caudally to the two articulate ends of the jaw triangle. The compression/distraction strains of food crushing must be monitored and inhibited by withdrawal reflexes. The mesencephalic ganglion (Vmes), neural myelin sheath, and muscle stretch receptors evolved subsequently to the advent of jaws to improve the velocity of proprioceptive and withdrawal reflexes. In mammalians, the spindles of the taut motor units, stretched by the food fulcrum, send excitatory monosynaptic feedback for the efferent neurons of the respective ipsilateral muscle units via the Vmes. In the Vmes, the spindle-input-mediating afferent neurons are coupled with another source of afferent feedback, which is also excitatory, from the back tooth (BAT) mechanoreceptors. The two sources of excitatory pulses are summated and targeted for the efferent neurons to boost the stretched and taut motor units. Likewise, the afferent feedback from the ANT mechanoreceptors is also coupled in the Vmes with concomitant feedback from spindles. The ANT output, however, is inhibitory to negate the excitatory feedback from the stretched jaw muscle units. The inhibitory feed from the anterior teeth temporarily blocks the excitatory potential of the masticatory motor efferent neurons to protect the anterior teeth and jaw joints from inadvertent strains. The inhibitory inputs from the anterior teeth alternate with the excitatory inputs from the BAT to determine which jaw-closing muscle units are activated or inhibited at any given instant of food crushing. The Vmes exists in all jawed vertebrates, and its evolution was probably motivated by demands for the control of bite force. The monosynaptic unilateral food-crushing excitatory and inhibitory reflexes (UFCRs) override the coexisting bilaterally executed feed for the jaw muscles from the central nervous system. The hypothesis proposed in this study is that the Vmes-mediated UFCRs combine neural inputs from tooth contacts with concomitant feedback from the muscle stretch receptors for the control of the mammalian food-crushing bite force.

Comparing the effects of vitamin A ointment and liposic gel on corneal abrasion prevention during general anesthesia in nonocular surgeries: a double-blind randomized clinical trial

Purpose The aim of this study was to compare the effects of vitamin A ointment and Liposic gel on perioperative corneal abrasion (CA) prevention during nonocular surgeries. Design A double-blind randomized clinical trial. Methods In this double-blind randomized clinical trial 50 eligible candidates for nonocular surgeries were purposively selected from XXX teaching hospital, XXX. One patient eye was randomly allocated to the vitamin A group and the other eye to the Liposic gel group. Immediately after anesthesia induction and blinking reflex suppression, eye care was provided using vitamin A ointment in the vitamin A group and Liposic gel in the Liposic gel group. CA was assessed using the fluorescein eye stain test at the end of general anesthesia, at the end of postoperative recovery, and 24 h after surgery. Eye problems were also assessed 24 h after surgery using an eye problems questionnaire. The SPSS software (v. 23.0) was employed for data analysis through the Wilcoxon’s, paired-sample t, and Friedman’s tests as well as the repeated measures analysis of variance. Findings The prevalence of CA in the vitamin A and the Liposic gel groups was 32 and 50% at the end of general anesthesia (P=0.039), 32 and 52% at the end of postoperative recovery (P = 0.018), and 0 and 0% 24 h after surgery (P = 1.00), respectively. There were no significant between-group differences respecting postoperative eye problems (P > 0.05). Conclusion Vitamin A ointment is more effective than Liposic gel in significantly preventing CA among patients undergoing non-ocular surgeries under general anesthesia.

Repeated low doses of psilocybin increase resilience to stress, lower compulsive actions, and strengthen cortical connections to the paraventricular thalamic nucleus in rats.

Psilocybin (a classic serotonergic psychedelic drug) has received appraisal for use in psychedelic-assisted therapy of several psychiatric disorders. A less explored topic concerns the use of repeated low doses of psychedelics, at a dose that is well below the psychedelic dose used in psychedelic-assisted therapy and often referred to as microdosing. Psilocybin microdose users frequently report increases in mental health, yet such reports are often highly biased and vulnerable to placebo effects. Here we establish and validate a psilocybin microdose-like regimen in rats with repeated low doses of psilocybin administration at a dose derived from occupancy at rat brain 5-HT2A receptors in vivo. The rats tolerated the repeated low doses of psilocybin well and did not manifest signs of anhedonia, anxiety, or altered locomotor activity. There were no deficits in pre-pulse inhibition of the startle reflex, nor did the treatment downregulate or desensitize the 5-HT2A receptors. However, the repeated low doses of psilocybin imparted resilience against the stress of multiple subcutaneous injections, and reduced the frequency of self-grooming, a proxy for human compulsive actions, while also increasing 5-HT7 receptor expression and synaptic density in the paraventricular nucleus of the thalamus. These results establish a well-validated regimen for further experiments probing the effects of repeated low doses of psilocybin. Results further substantiate anecdotal reports of the benefits of psilocybin microdosing as a therapeutic intervention, while pointing to a possible physiological mechanism.

Sampling Reflex as a New Manometric Marker in the Diagnosis of Defecation Disorders - Systematic Review

Abstract Introduction Distension of the rectum wall and subsequent momentary relaxation of the internal anal sphincter (IAS) trigger a reflex called the rectoanal inhibitory reflex (RAIR). This same rectal distension causes a reflex contraction of the external anal sphincter (EAS), responsible for conscious continence called rectoanal excitatory reflex (RAER). This set of reflexes are named sampling reflex. Objectives The sampling reflex is necessary to initiate defecation or flatulence. The objective of this study is to evaluate the sampling reflex and its practical applicability as a manometric marker of the main defecation disorders. Methodology This review followed the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) items. The development method consisted of searching for articles in the research platforms BVS, PubMed, Cochrane Library, SciELO and ScienceDirect and for the selection of articles the Rayyan Platform was used. The articles resulting from the search strategies were added to the platform and five collaborators were invited for the blind selection. Finally, 6 articles were included in the final review. Results An intact sampling reflex allows the individual to facilitate discrimination between flatus and stool and to choose whether to discharge or retain rectal contents. On the other hand, an impaired sampling reflex can predispose an individual to incontinence.Therefore, it was observed that patients with defecation disorders had an impaired sampling reflex, since it was found that constipated patients have incomplete opening of the IAS, lower amplitude of RAIR and increase of RAER. Most incontinent patients present a failure in the recruitment of the EAS, a decrease in the RAER and an increase in the RAIR, in duration and amplitude. Conclusion The improvement of high-resolution anorectal manometric techniques was essential for understanding the pathophysiology of defecation disorders, as well as the physiological understanding and importance of RAIR and RAER.

Monopolar tDCS might affect brainstem reflexes: A computational and neurophysiological study

ObjectiveTo assess whether monopolar multi-electrode transcranial direct current stimulation (tDCS) montages might selectively affect deep brain structures through computational predictions and neurophysiological assessment. MethodsElectric field distribution in deep brain structures (i.e., thalamus and midbrain) were estimated through computational models simulating tDCS with two monopolar and two monopolar multi-electrode montages. Monopolar multi-electrode tDCS was then applied to healthy subject, and effects on pontine and medullary circuitries was evaluated studying changes in blink reflex (BR) and masseter inhibitory reflex (MIR). ResultsComputational results suggest that tDCS with monopolar multi-electrode montages might induce electric field intensities in deep brain structure comparable to those in grey matter, while neurophysiological results disclosed that BR and MIR were selectively modulated by tDCS only when cathode was placed over the right deltoid. ConclusionsMulti-electrode tDCS (anodes over motor cortices, cathode over right deltoid) could induce significant electric fields in the thalamus and midbrain, and selectively affect brainstem neural circuits. SignificanceMulti-electrode tDCS (anodes over motor cortices, cathode over right deltoid) might be further explored to affect brainstem activity, also in the context of non-invasive deep brain stimulation.

Clinical utility of anal sphincter relaxation integral in water-perfused and solid-state high-resolution anorectal manometry

We investigated the diagnostic performance of the anal sphincter relaxation integral (ASRI) for infants with Hirschsprung's disease (HD). We performed water-perfused high-resolution anorectal manometry (HRAM) in 18 infants (9 with HD), and solid-state HRAM in another 18 infants (4 with HD). We calculated the ASRI during the rectoanal inhibitory reflex (RAIR) maneuver at pressure cutoffs of <10mmHg (ASRI 10) and <15mmHg (ASRI 15). We investigated the diagnostic performance of the ASRI for HD in infants undergoing water-perfused and solid-state HRAM. HD infants who underwent either water-perfused or solid-state HRAM had significantly lower ASRI 10 and ASRI 15 values, compared with non-HD infants (P<0.05 and P<0.05, respectively). Using the water-perfused HRAM system, ASRI 10 and ASRI 15 values of <7 and<29mmHgs.cm, respectively, exhibited good diagnostic performance for HD (88.89% and 88.89%, respectively). Receiver operating characteristic curve analysis indicated that ASRI 10 and ASRI 15 values of <5.5 and<20mmHgs.cm, respectively, were optimal for the diagnosis of HD infants when using the solid-state HRAM system, with high diagnostic accuracies of 83.33% and 83.33%, respectively. ASRI may assist the diagnosis of HD infants using either water-perfused or solid-state HRAM. These systems require different catheter-specific ASRI cutoffs for the prediction of HD.

A Comparative Review of Vagal Nerve Stimulation Versus Baroreceptor Activation Therapy in Cardiac Diseases.

Sympathetic imbalance coupled with impairment of baroreceptor control is a key factor responsible for hemodynamic abnormalities in congestive heart failure. Vagal nerve stimulation (VNS) and baroreceptor activation therapy (BAT) are two novel interventions for the same. In this paper, we review the role of sympathovagal alterations in cardiac diseases like heart failure, arrhythmia, hypertension (HTN), etc. Studies like neural cardiac therapy for heart failure (NECTAR-HF), autonomic regulation therapy to enhance myocardial function and reduce progression of heart failure (ANTHEM-HF), and baroreflex activation therapy for heart failure (BEAT-HF), which comprise the history, efficacy, limitations, and current protocols, were extensively analyzed in contrast to one another. Vagal nerve stimulation reverses the reflex inhibition of cardiac vagal efferent activity, which is caused as a result of sympathetic overdrive during the course for heart failure. It has shown encouraging results in certain pre-clinical studies; however, there is also a possibility of serious cardiovascular adverse events if given in higher than the recommended dosage. Attenuated baroreflex sensitivity is attributed to cardiac arrhythmogenesis during heart failure. Baroreceptor activation therapy reverses this phenomenon. However, the surgical procedure for baroreceptor stimulation can have unwarranted complications, including worsening heart failure and hypertension. Considering the effectiveness of the given modalities and taking into account the inconclusive evidence of their adverse events, more clinical trials are needed for establishing the future prospects of these interventional approaches.

Comparison of Bispectral index-guided propofol and etomidate infusion for Supraglottic airway insertion

IntroductionSupraglottic airway devices have become extremely popular for minor therapeutic and surgical procedures. Their insertion requires an adequate depth of anesthesia with suppression of pharyngeal reflexes. Propofol is the most commonly used agent, but has hemodynamic side-effects. Etomidate, although hemodynamically stable, does not suppress pharyngeal reflexes adequately. Moreover, the use of clinical signs to assess the depth of anesthesia has questionable accuracy. Using bispectral index (BIS) monitoring, the hypnotic component of the anesthetic can be measured, with values of 40–60 implying adequate depth of anesthesia. MethodsThis randomized controlled trial included 80 ASA I patients, divided into two groups of 40 patients. Each group received either propofol or etomidate infusion, with BIS monitoring. At BIS 50, infusions were stopped and SGA was inserted. Changes in hemodynamic parameters, time for SGA insertion, number of attempts, and SGA insertion scores were recorded. ResultsWhen BIS reached 50, a statistically significant fall in mean arterial pressure was observed in the propofol group. Time for SGA insertion was less in the propofol group (30.7 ± 8.0 s), with successful SGA insertion observed in 92.5% of patients on the first attempt, compared with 47.9 ± 9.1 s and 32.3% in the etomidate group. ConclusionIn comparison with etomidate, the use of propofol is associated with better conditions for SGA insertion but has the side-effect of hypotension, even with BIS-guided titration of dose for maintaining an adequate depth of anesthesia.

State of the Art Bowel Management for Pediatric Colorectal Problems: Functional Constipation.

Functional constipation (FC) affects up to 32% of the pediatric population, and some of these patients are referred to pediatric surgery units to manage their constipation and/or fecal incontinence. The aim of the current paper is to report the recent updates on the evaluation and management of children with FC as a part of a manuscript series on bowel management in patients with anorectal malformations, Hirschsprung disease, spinal anomalies, and FC. A literature search was performed using Medline/PubMed, Google Scholar, Cochrane, and EMBASE databases and focusing on the manuscripts published within the last 5-10 years. The first step of management of children with FC is to exclude Hirschsprung disease with a contrast study, examination under anesthesia, anorectal manometry (AMAN). If AMAN shows absent rectoanal inhibitory reflex, a rectal biopsy is performed. Internal sphincter achalasia or high resting pressures indicate botulinum toxin injection. Medical management options include laxatives, rectal enemas, transanal irrigations, and antegrade flushes. Those who fail conservative treatment require further assessment of colonic motility and can be candidates for colonic resection. The type of resection (subtotal colonic resection vs. Deloyer's procedure) can be guided with a balloon expulsion test. Most of the patients with FC referred for surgical evaluation can be managed conservatively. Further studies are required to determine an optimal strategy of surgical resection in children unresponsive to medical treatment.

Three dimension high definition manometry evaluated postoperative anal canal functions in children with congenital anorectal malformations.

We aimed to evaluate the function of the reconstructed anal canal in postoperative anorectal malformations (ARMs) patients through three dimension (3D) high-definition anorectal manometry. From January 2015 to December 2019, 3D manometry was performed as a postoperative functional assessment of patients with ARMs divided into age subgroups based on the time of manometry. Manometric parameters, such as the length of the anorectal high-pressure zone (HPZ-length), the mean resting and squeeze pressure of HPZ (HPZ-rest and HPZ-sqze), recto-anal inhibitory reflex (RAIR), and strength distribution of the anal canal, were collected and compared with age-matched controls. Their functional outcomes were analyzed with SPSS 23.0 software for statistical analysis. 171 manometric measurements were performed on 142 postoperative patients (3 months∼15 years). The HPZ-rest in all patients was significantly lower than in age-matched controls (p < 0.05). HPZ-sqze was notably decreased in patients older than 4 years, whereas other age groups were comparable to controls (p < 0.05). The proportions of asymmetric strength distribution and negative RAIR were higher in ARMs patients. The type of anorectal malformations and lower HPZ-rest were the impact factors affecting postoperative functional outcomes. The majority of the ARMs patients had acceptable functional outcomes. 3D manometry can objectively assess the reconstructed anal canal function. The patients with fecal incontinence had a high proportion of extremely low HPZ-rest and HPZ-sqze, negative RAIR, and asymmetric strength distribution. The manometric details will help the clinicians explore the causes of defecation complications and guide further management.

Possible involvement of brain hydrogen sulphide in the inhibition of the rat micturition reflex induced by activation of brain alpha7 nicotinic acetylcholine receptors

We previously reported that brain α7 nicotinic acetylcholine receptors inhibited the rat micturition reflex. To elucidate the mechanisms underlying this inhibition, we focused on the relationship between α7 nicotinic acetylcholine receptors and hydrogen sulphide (H2S) because we found that H2S also inhibits the rat micturition reflex in the brain. Therefore, we investigated whether H2S is involved in the inhibition of the micturition reflex induced by the activation of α7 nicotinic acetylcholine receptors in the brain. Cystometry was performed in male Wistar rats under urethane anesthesia (0.8 g/kg, ip) to examine the effects of icv pre-treated GYY4137 (H2S donor, 1 or 3 nmol/rat) or aminooxyacetic acid (AOAA; non-selective H2S synthesis inhibitor, 3 or 10 μg/rat) on PHA568487 (α7 nicotinic acetylcholine receptor agonist, icv)-induced prolongation of intercontraction intervals. PHA568487 administration at a lower dose (0.3 nmol/rat, icv) had no significant effect on intercontraction intervals, while under pre-treatment with GYY4137 (3 nmol/rat icv), PHA568487 (0.3 nmol/rat, icv) significantly prolonged intercontraction intervals. PHA568487 at a higher dose (1 nmol/rat, icv) induced intercontraction interval prolongation, and the PHA568487-induced prolongation was significantly suppressed by AOAA (10 μg/rat, icv). The AOAA-induced suppression of the PHA568487-induced intercontraction interval prolongation was negated by supplementing H2S via GYY4137 at a lower dose (1 nmol/rat, icv) in the brain. GYY4137 or AOAA alone showed no significant effect on intercontraction intervals at each dose used in this study. These findings suggest a possible involvement of brain H2S in inhibiting the rat micturition reflex induced by activation of brain α7 nicotinic acetylcholine receptors.

Effect of a psychoeducational intervention on motor and perceptual-visual development through the inhibition of primitive reflexes in schoolchildren aged 4 to 7 years old

The efficacy of the Assessing Neuromotor Readiness for Learning (Blythe, 2012) on primitive reflex inhibition is described. The sample consisted of 25 girls and 21 boys aged 4–7 years (M = 4.84, SD = 1.10). For the sake of evaluating the efficacy of the intervention, the Developmental Screening by the Chester Institute of Neurophysiological Psychology, INPP (Blythe, 2012), was used by means of a pretest-posttest design with a control group. The statistical analyses performed were ANCOVA and factorial ANOVA—depending on the fulfilment of the assumptions. The main findings refer to the existence of active primitive reflexes in the sample, and how these primitive reflexes are sensitive to the psychoeducational intervention of reflex inhibition through movement. Besides, the involvement of primitive reflex inhibition in the improvement of motor development—but not in perceptual-visual development—has been proved.

Different outcomes of neonatal and adult Zika virus infection on startle reflex and prepulse inhibition in mice

Zika virus (ZIKV) infection causes severe neurological consequences in both gestationally-exposed infants and adults. Sensorial gating deficits strongly correlate to the motor, sensorial and cognitive impairments observed in ZIKV-infected patients. However, no startle response or prepulse inhibition (PPI) assessment has been made in patients or animal models. In this study, we identified different outcomes according to the age of infection and sex in mice: neonatally infected animals presented an increase in PPI and delayed startle latency. However, adult-infected male mice presented lower startle amplitude, while a PPI impairment was observed 14 days after infection in both sexes. Our data further the understanding of the functional impacts of ZIKV on the developing and mature nervous system, which could help explain other behavioral and cognitive alterations caused by the virus. With this study, we support the startle reflex testing in ZIKV-exposed patients, especially infants, allowing for early detection of functional neuromotor damage and early intervention.

Efecto de una intervención psicoeducativa en el desarrollo motor y perceptivo-visual a través de la inhibición de los reflejos primitivos en escolares de 4 a 7 años

The efficacy of the Assessing Neuromotor Readiness for Learning program (Blythe, 2012) on inhibition of primitive reflexes is presented. The sample is made up of 25 girls and 21 boys aged four to seven years old (M=4.84, SD=1.10). The Developmental Screening of the Institute of Neurophysiological Psychology of Chester, INPP (Blythe, 2012) has been used to evaluate the efficacy of the intervention through a pretest-postest design with control group. ANCOVA and Factorial ANOVA have been used for statistical analysis, depending on the fulfillment of assumptions. The main findings of this study refers to the existence of active primitive reflexes in a sample of schoolchildren and how these primitive reflexes are sensitive to psychoeducational intervention on reflex inhibition through a movement program. In addition, the involvement of inhibition of primitive reflexes in improving motor development has been highlighted but except for visual perception skills.

Adolescent exposure to the Spice/K2 cannabinoid JWH-018 impairs sensorimotor gating and alters cortical perineuronal nets in a sex-dependent manner

The consumption of synthetic cannabinoids during adolescence is reported to be a risk factor for the appearance of psychiatric disorders later in life. JWH-018 was identified as one of the primary psychoactive components present in Spice/K2 preparations. This study evaluated the short- and long-term consequences of exposure to JWH-018 during the adolescence in anxiety-like behavior, fear extinction, and sensorimotor gating in male and female mice. Alterations in anxiety varied depending on the time interval between treatment and behavioral analysis along with sex, while no changes were observed in the extinction of fear memory. A decrease in prepulse inhibition of the startle reflex was revealed in male, but not female, mice at short- and long-term. This behavioral disturbance was associated with a reduction in the number of perineuronal nets in the prelimbic and infralimbic regions of the prefrontal cortex in the short-term. Furthermore, adolescent exposure to JWH-018 induced an activation of microglia and astrocytes in the prefrontal cortex of male mice at both time intervals. A transitory decrease in the expression of GAD67 and CB2 cannabinoid receptors in the prefrontal cortex was also found in male mice exposed to JWH-018. These data reveal that the treatment with JWH-018 during the adolescence leads to long-lasting neurobiological changes related to psychotic-like symptoms, which were sex-dependent.

N°203 – Prepulse Inhibition of the blink reflex in psychogenic sensory loss

N°203 – Prepulse Inhibition of the blink reflex in psychogenic sensory loss

N°47 – Prepulse inhibition of the blink reflex – The role of prepulse stimulus intensity versus prepulse-induced blink reflex size

N°47 – Prepulse inhibition of the blink reflex – The role of prepulse stimulus intensity versus prepulse-induced blink reflex size

Functional constipation refractory to medical management: The anal sphincters are the problem

AimMost patients with functional constipation (FC) improve with medical treatment. For those with refractory symptoms, we propose a comprehensive and multidisciplinary work-up and decision-making approach to therapy. MethodsWe retrospectively reviewed patients referred to our center between 2019-2022 with suspected FC who had failed medical management. All patients underwent a contrast enema, anorectal manometry, examination under anesthesia, rectal biopsy (if needed), and botulinum toxin injection (as indicated). Results54 patients were evaluated using our algorithm. One was found to have anal stenosis on exam. The rectoanal inhibitory reflex (RAIR) was normal in 41(76%) patients and unable to be elicited in 12(22%). Two (17%) patients without a RAIR had Hirschsprung Disease (HD) and underwent a pull-through. 10(83%) with no RAIR had normal biopsies and were managed successfully with laxatives. Of the 41 patients with a normal RAIR, 14(34%) had high resting pressures (external sphincters) or non-relaxing (internal) sphincters and received botulinum toxin. 8(57%) of them were emptying well after one month. 24 patients failed laxatives (with or without botulinum toxin injections) and then underwent a Malone procedure. 23(96%) of these patients improved with antegrade flushes. One patient (1/21, 4.1%) did not undergo Malone and instead underwent colonic manometry and a sigmoid resection, after which he emptied well. ConclusionWe propose a systematic multidisciplinary approach for constipated patients who failed medical management starting with assessment of anal sphincters. This allows for targeted adjustment of laxative regimen, use of botulinum toxin to the internal and/or external anal sphincter and antegrade flushes via a Malone. Level of evidence levelIV

Effects of total sleep deprivation on sensorimotor gating in humans

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.