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The Journal of Head Trauma... Jun 2024We investigated the acoustic startle reflex in recently concussed adolescent athletes compared to healthy controls and those with concussion history (>1 year prior) but...
OBJECTIVES
We investigated the acoustic startle reflex in recently concussed adolescent athletes compared to healthy controls and those with concussion history (>1 year prior) but no current symptoms. We hypothesized that individuals with recent concussion would have a suppressed startle response compared to healthy controls.
METHODS
We conducted a cross-sectional study on 49 adolescent athletes with a recent concussion (n = 20; age: 14.6 ± 1.6 years; 60% female), a concussion history > 1 year prior (n = 16; age: 14.8 ± 2.0 years; 44% female), and healthy controls (n = 13; age: 13.3 ± 2.8 years; 54% female). We measured the eyeblink of the general startle reflex via electromyography activity of the orbicularis oculi muscle using electrodes placed under the right eye. Measurement sessions included twelve 103 decibel acoustic startle probes ~50 milliseconds in duration delivered ~15-25 seconds apart. The primary dependent variable was mean startle magnitude (µV), and group was the primary independent variable. We used a one-way analysis of variance followed by a Tukey post hoc test to compare mean startle magnitude between groups.
RESULTS
Mean startle magnitude significantly differed (F = 5.49, P = .007) among the groups. Mean startle magnitude was significantly suppressed for the concussion (P = .01) and concussion history groups (P = .02) compared to healthy controls. There was no significant difference between the recent concussion and concussion history groups (P = 1.00).
CONCLUSION
Our results provide novel evidence for startle suppression in adolescent athletes following concussion. The concussion history group had an attenuated startle response beyond resolution of their recovery, suggesting there may be lingering physiological dysfunction.
PubMed: 38916433
DOI: 10.1097/HTR.0000000000000979 -
Psychological Medicine Sep 2023Adolescence is a key developmental period for the emergence of psychiatric disorders. However, there is still no consensus on the core mechanisms of dysfunction in...
BACKGROUND
Adolescence is a key developmental period for the emergence of psychiatric disorders. However, there is still no consensus on the core mechanisms of dysfunction in youth. Neurobiological sensitivity to unpredictable threat has been associated with several psychiatric disorders in adults. The present study examined adolescent defensive motivation (startle reflex) and attention (event-related potentials) in anticipation of unpredictable threat in relation to both adolescent and maternal (i.e. familial risk) internalizing and externalizing spectra.
METHODS
The sample included 395 15-year-old adolescents and their biological mothers. Adolescent startle potentiation and probe P300 suppression (indicating increased attention to threat) were measured in anticipation of predictable and unpredictable threat. Adolescent and maternal lifetime history of psychiatric disorders were assessed via semi-structured diagnostic interviews, and confirmatory factor analysis was used to model internalizing and externalizing spectra.
RESULTS
The adolescent internalizing spectrum was positively associated with adolescent startle potentiation and probe P300 suppression to unpredictable threat. Conversely, the adolescent externalizing spectrum was negatively associated with adolescent P300 suppression to unpredictable threat. The maternal internalizing spectrum was positively associated with adolescent startle potentiation to unpredictable threat and P300 suppression to both predictable and unpredictable threat. The maternal externalizing spectrum was negatively associated with adolescent startle potentiation to unpredictable threat and P300 suppression to both predictable and unpredictable threat. Adolescent and maternal internalizing and externalizing spectra were independently related to adolescent startle potentiation and P300 suppression.
CONCLUSIONS
Adolescent neurobiological sensitivity to unpredictable threat is associated with both personal history and familial risk for the internalizing and externalizing spectra.
Topics: Adult; Female; Humans; Adolescent; Genetic Predisposition to Disease; Evoked Potentials; Motivation; Mental Disorders; Reflex, Startle; Mothers
PubMed: 35982518
DOI: 10.1017/S0033291722002434 -
Psychopharmacology Nov 2023Fear conditioning is an important aspect in the pathophysiology of anxiety disorders. The fear-potentiated startle test is based on classical fear conditioning and over... (Meta-Analysis)
Meta-Analysis Review
RATIONALE AND OBJECTIVES
Fear conditioning is an important aspect in the pathophysiology of anxiety disorders. The fear-potentiated startle test is based on classical fear conditioning and over the years, a broad range of drugs have been tested in this test. Synthesis of the available data may further our understanding of the neurotransmitter systems that are involved in the expression of conditioned fear.
METHODS
Following a comprehensive search in Medline and Embase, we included 68 research articles that reported on 103 drugs, covering 56 different drug classes. The systematic review was limited to studies using acute, systemic drug administration in naive animals.
RESULTS
Qualitative data synthesis showed that most clinically active anxiolytics, but not serotonin-reuptake inhibitors, reduced cued fear. Anxiogenic drugs increased fear potentiation in 35% of the experiments, reduced fear potentiation in 29% of the experiments, and were without effect in 29% of the experiments. Meta-analyses could be performed for five drug classes and showed that benzodiazepines, buspirone, 5-HT agonists, 5-HT antagonists, and mGluR2,3 agonists reduced cued conditioned fear. The non-cued baseline startle response, which may reflect contextual anxiety, was only significantly reduced by benzodiazepines and 5-HT antagonists. No associations were found between drug effects and methodological characteristics, except for strain.
CONCLUSIONS
The fear-potentiated startle test appears to have moderate to high predictive validity and may serve as a valuable tool for the development of novel anxiolytics. Given the limited available data, the generally low study quality and high heterogeneity additional studies are warranted to corroborate the findings of this review.
Topics: Animals; Anti-Anxiety Agents; Serotonin; Fear; Anxiety; Benzodiazepines; Reflex, Startle
PubMed: 36651922
DOI: 10.1007/s00213-022-06307-1 -
Scientific Reports Oct 2023Acoustic Harassment Devices (AHD) are widely used to deter marine mammals from aquaculture depredation, and from pile driving operations that may otherwise cause hearing...
Acoustic Harassment Devices (AHD) are widely used to deter marine mammals from aquaculture depredation, and from pile driving operations that may otherwise cause hearing damage. However, little is known about the behavioural and physiological effects of these devices. Here, we investigate the physiological and behavioural responses of harbour porpoises (Phocoena phocoena) to a commercial AHD in Danish waters. Six porpoises were tagged with suction-cup-attached DTAGs recording sound, 3D-movement, and GPS (n = 3) or electrocardiogram (n = 2). They were then exposed to AHDs for 15 min, with initial received levels (RL) ranging from 98 to 132 dB re 1 µPa (rms-fast, 125 ms) and initial exposure ranges of 0.9-7 km. All animals reacted by displaying a mixture of acoustic startle responses, fleeing, altered echolocation behaviour, and by demonstrating unusual tachycardia while diving. Moreover, during the 15-min exposures, half of the animals received cumulative sound doses close to published thresholds for temporary auditory threshold shifts. We conclude that AHD exposure at many km can evoke both startle, flight and cardiac responses which may impact blood-gas management, breath-hold capability, energy balance, stress level and risk of by-catch. We posit that current AHDs are too powerful for mitigation use to prevent hearing damage of porpoises from offshore construction.
Topics: Animals; Porpoises; Phocoena; Noise; Reflex, Startle; Sound; Acoustics
PubMed: 37794093
DOI: 10.1038/s41598-023-43453-8 -
Journal of Ethnopharmacology Oct 2023Cynanchum paniculatum (Bunge) Kitag. ex H. Hara (Asclepiadaceae) have been traditionally used in East Asia as analgesic or antiviral agents. Interestingly, some Chinese...
Paeonol, the active component of Cynanchum paniculatum, ameliorated schizophrenia-like behaviors by regulating the PI3K-Akt-GSK3β-NF-κB signalling pathway in MK-801-treated mice.
ETHNOPHARMACOLOGICAL RELEVANCE
Cynanchum paniculatum (Bunge) Kitag. ex H. Hara (Asclepiadaceae) have been traditionally used in East Asia as analgesic or antiviral agents. Interestingly, some Chinese and Korean traditional medicinal books reported that the use of C. paniculatum in the treatment of psychotic symptoms, such as hallucinations and delusions.
AIM OF THE STUDY
In this study, we aimed to investigate whether C. paniculatum could improve sensorimotor gating disruption in mice with MK-801-induced schizophrenia-like behaviors. We also aimed to identify the active component of C. paniculatum that could potentially serve as a treatment for schizophrenia and found that paeonol, the major constituent compound of C. paniculatum, showed potential as a treatment for schizophrenia.
MATERIALS AND METHODS
To assess the effect of paeonol on mice with MK-801-induced schizophrenia-like behaviors, we carried out a series of behavioral tests related with symptoms of schizophrenia. In addition, we utilized Western blotting and ELISA techniques to investigate the antipsychotic actions of paeonol.
RESULT
C. paniculatum extract (100 or 300 mg/kg) and paenol (10 or 30 mg/kg) significantly reversed MK-801-induced prepulse deficits in acoustic startle response test. In addition, paeonol (10 or 30 mg/kg) attenuated social novelty preference and novel object recognition memory on MK-801-induced schizophrenia-like behaviour in mice. Furthermore, the phosphorylation levels of PI3K, Akt, GSK3β and NF-κB, as well as related pro-inflammatory cytokine, such as IL-1β and TNF-α, were significantly reversed by the administration of paeonol (10 or 30 mg/kg) in the prefrontal cortex of MK-801-treated mice.
CONCLUSIONS
Collectively, these data show that paeonol can potentially be used as an agent for treating sensorimotor gating deficits, negative symptoms, and cognitive deficits, such as those observed in schizophrenia with few adverse effects.
Topics: Animals; Mice; NF-kappa B; Dizocilpine Maleate; Proto-Oncogene Proteins c-akt; Cynanchum; Phosphatidylinositol 3-Kinases; Reflex, Startle; Schizophrenia; Glycogen Synthase Kinase 3 beta
PubMed: 37164258
DOI: 10.1016/j.jep.2023.116627 -
Neuroscience Oct 2023Fear-potentiated startle (FPS) has been widely used to study fear processing in humans and rodents. Human studies showed higher startle amplitudes and exaggerated fear...
Fear-potentiated startle (FPS) has been widely used to study fear processing in humans and rodents. Human studies showed higher startle amplitudes and exaggerated fear reactivity to unpredictable vs. predictable threats in individuals suffering from post-traumatic stress disorder (PTSD). Although human FPS studies use both sexes, a surprisingly limited number of rodent FPS studies use females. Here we investigate the effects of signal-threat contingency, signal-threat order and threat predictability on FPS in both sexes. We use a classic fear-conditioning protocol (100% contingency of cue and shock pairings, with forward conditioning such that the cue co-terminates with the shock) and compare it to modified fear-conditioning protocols (70% contingency; backward conditioning; or cue and shock un-paired). Although there are no sex differences in the startle amplitudes when corrected for body weight, females consistently demonstrate higher shock reactivity during fear-conditioning. Both sexes and strains demonstrate comparable levels of cued, non-cued, and contextual fear in the classic FPS and FPS following fear-conditioning with 70% contingency or backward order (cue co-starts with shock). However, in the classic FPS, Sprague-Dawley females show reduced proportion between cued fear and cue-elicited vigilant state than males. Lastly, a prominent sex difference is uncovered following unpredictable fear-conditioning (cue and shock un-paired), with Wistar, but not Sprague-Dawley, females showing significantly higher startle overall during the FPS recall, regardless of trial type, and higher contextual fear than males. This striking sex difference in processing unpredictable threats in rodent FPS might help to understand the mechanisms underlying higher incidence of PTSD in women.
Topics: Rats; Humans; Female; Male; Animals; Rats, Sprague-Dawley; Conditioning, Classical; Reflex, Startle; Rats, Wistar; Fear
PubMed: 37640137
DOI: 10.1016/j.neuroscience.2023.08.030 -
International Journal of... Mar 2024Extant literature suggests that many individuals obtain firearms because they perceive the world as unsafe and believe that firearm ownership increases physical...
Extant literature suggests that many individuals obtain firearms because they perceive the world as unsafe and believe that firearm ownership increases physical protection. Converging evidence suggests that firearm owners are vulnerable to uncertainty and experience chronic anticipatory anxiety in daily life; however, biological sex is thought to potentially moderate this association. Studies have yet to examine this hypothesis using objective markers of anticipatory anxiety. The present study therefore examined the impact of handgun ownership and biological sex on psychophysiological reactivity to predictable (P-) and unpredictable (U-) threat (N = 133). Male and female adult participants were classified into two groups: a) individuals who do not currently own any handguns (n = 52), and b) individuals who currently own one or more handguns (n = 81). Startle eyeblink potentiation was recorded as an index of aversive reactivity during a well-validated threat-of-shock paradigm designed to probe anticipatory anxiety (during U-threat) and fear (during P-threat). Results revealed no main effect of group on startle reactivity to P- or U-threat. Females displayed greater startle reactivity to threat (P- and U-) compared with males. The main effect was qualified by a significant group x biological sex interaction. Male handgun owners exhibited greater startle to U-threat, but not P-threat, relative to non-handgun owners. There was no effect of group on startle reactivity in females. Findings revealed that biological sex and threat type influenced threat reactivity. Male handgun owners displayed increased sensitivity to stressors that are uncertain, which may reflect an objective mechanism related to firearm ownership.
Topics: Adult; Humans; Male; Female; Ownership; Anxiety; Fear; Mental Disorders; Reflex, Startle
PubMed: 38185419
DOI: 10.1016/j.ijpsycho.2024.112297 -
Schizophrenia Research Jul 202422q11.2 deletion syndrome (22q11DS) is one of the most robust genetic predictors of psychosis and other psychiatric illnesses. In this study, we examined 22q11DS...
BACKGROUND
22q11.2 deletion syndrome (22q11DS) is one of the most robust genetic predictors of psychosis and other psychiatric illnesses. In this study, we examined 22q11DS subjects' acoustic startle responses (ASRs), which putatively index psychosis risk. Latency of the ASR is a presumptive marker of neural processing speed and is prolonged (slower) in schizophrenia. ASR measures correlate with increased psychosis risk, depend on glutamate and dopamine receptor signaling, and could serve as translational biomarkers in interventions for groups at high psychosis risk.
METHODS
Startle magnitude, latency, and prepulse inhibition were assessed with a standard acoustic startle paradigm in 31 individuals with 22q11.2DS and 32 healthy comparison (HC) subjects. Surface electrodes placed on participants' orbicularis oculi recorded the electromyographic signal in ASR eyeblinks. Individuals without measurable startle blinks in the initial habituation block were classified as non-startlers.
RESULTS
Across the startle session, the ASR magnitude was significantly lower in 22q11DS subjects than HCs because a significantly higher proportion of 22q11DS subjects were non-startlers. Latency of the ASR to pulse-alone stimuli was significantly slower in 22q11DS than HC subjects. Due to the overall lower 22q11DS startle response frequency and magnitudes prepulse inhibition could not be analyzed.
CONCLUSIONS
Reduced magnitude and slow latency of 22q11DS subjects' responses suggest reduced central nervous system and neuronal responsiveness. These findings are consistent with significant cognitive impairments observed in 22q11DS subjects. Further research is needed to untangle the connections among basic neurotransmission dysfunction, psychophysiological responsiveness, and cognitive impairment.
Topics: Humans; Male; Female; Reflex, Startle; Adult; Adolescent; Young Adult; DiGeorge Syndrome; Prepulse Inhibition; Blinking; Reaction Time; Electromyography; Acoustic Stimulation
PubMed: 38703519
DOI: 10.1016/j.schres.2024.04.022 -
Behavioural Brain Research Jul 2023Sensorimotor gating is a measure of pre-attentional information processing and can be measured by prepulse inhibition (PPI) of the startle reflex. Sleep deprivation has... (Randomized Controlled Trial)
Randomized Controlled Trial
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.
Topics: Animals; Humans; Sleep Deprivation; Sleepiness; Reproducibility of Results; Attention; Sleep; Sensory Gating; Reflex, Startle
PubMed: 37169130
DOI: 10.1016/j.bbr.2023.114487 -
Methods in Molecular Biology (Clifton,... 2024Prepulse inhibition (PPI) is a measure of sensorimotor gating which is widely used in rodents to study information processing and attention dysfunction. PPI is commonly...
Prepulse inhibition (PPI) is a measure of sensorimotor gating which is widely used in rodents to study information processing and attention dysfunction. PPI is commonly measured in rats and mice using automated equipment. Here, we present details of a PPI testing protocol extensively used in previous studies. The protocol includes a set pulse-alone startle level and prepulse-pulse combinations with varying interval and intensity. Variations of this protocol can be used depending on the experimental aim or equipment and software version.
Topics: Rats; Mice; Animals; Prepulse Inhibition; Reflex, Startle; Rodentia; Acoustic Stimulation; Acoustics
PubMed: 38070085
DOI: 10.1007/978-1-0716-3585-8_10