Effects of combined exposure to pyridostigmine bromide and shaker stress on acoustic startle response, pre-pulse inhibition and open field behavior in mice.

PubMed

Dubovicky, M; Paton, S; Morris, M; Mach, M; Lucot, J B

2007-01-01

The present study investigated the effect of combined exposure of pyridostigmine bromide (PB) and chronic shaker stress on acoustic startle responses (ASR), pre-pulse inhibition (PPI) and open field behavior of adult C57BL/6J mice. PB (10 mg kg(-1) day(-1) for 7 days) or saline was administered subcutaneously using osmotic Alzet minipumps implanted under the skin on the back of the mice. At the same time, the mice were exposed to 7 days of intermittent shaker stress. They were tested for ASR (100 dB and 120 dB stimuli) and PPI (70 dB + 100 dB and 70 dB + 120 dB) in the acoustic startle monitor system. The mice were assessed during the shaker stress on days 2 and 7 and 7, 14, 21 and 28 days after discontinuation of treatment. Separate groups of mice were tested in the open field in 15 min sessions on days 1, 3 and 6 during shaker stress and PB treatment. Exposure of mice to PB resulted in an exaggerated ASR, reduced PPI and non-significant decrease in locomotor activity. These behavioral changes were apparent only during exposure to PB. Repeated shaker stress did not have any effect on sensorimotor functions or open field behavior of mice. There was no prolonged or delayed effect of PB and/or stress on individual behavioral variables. The study found C57BL/6J mice to be behaviorally sensitive to PB treatment. (c) 2007 John Wiley & Sons, Ltd.

Review of first trial responses in balance control: influence of vestibular loss and Parkinson's disease.

PubMed

Allum, J H J; Tang, K-S; Carpenter, M G; Oude Nijhuis, L B; Bloem, B R

2011-04-01

The reaction to an unexpected balance disturbance is unpracticed, often startling and frequently associated with falls. This everyday situation can be reproduced in an experimental setting by exposing standing humans to sudden, unexpected and controlled movements of a support surface. In this review, we focus on the responses to the very first balance perturbation, the so-called first trial reactions (FTRs). Detailed analysis of FTRs may have important implications, both for clinical practice (providing new insights into the pathophysiological mechanisms underlying accidental falls in real life) and for understanding human physiology (what triggers and mediates these FTRs, and what is the relation to startle responses?). Several aspects of the FTRs have become clear. FTRs are characterized by an exaggerated postural reaction, with large EMG responses and co-contracting muscles in multiple body segments. This balance reaction is associated with marked postural instability (greater body sway to the perturbation). When the same perturbation is repeated, the size of the postural response habituates and the instability disappears. Other issues about FTRs remain largely unresolved, and these are addressed here. First, the functional role of FTRs is discussed. It appears that FTRs produce primarily increased trunk flexion during the multi-segmental response to postural perturbations, thus producing instability. Second, we consider which sensory signals trigger and modulate FTRs, placing specific emphasis on the role of vestibular signals. Surprisingly, vestibular signals appear to have no triggering role, but vestibular loss leads to excessive upper body FTRs due to loss of the normal modulatory influence. Third, we address the question whether startle-like responses are contributing to FTRs triggered by proprioceptive signals. We explain why this issue is still unresolved, mainly because of methodological difficulties involved in separating FTRs from 'pure' startle responses. Fourth, we review new work about the influence of perturbation direction on FTRs. Recent work from our group shows that the largest FTRs are obtained for toe-up support surface rotations which perturb the COM in the posterior direction. This direction corresponds to the directional preponderance for falls seen both in the balance laboratory and in daily life. Finally, we briefly touch upon clinical diagnostic issues, addressing whether FTRs (as opposed to habituated responses) could provide a more ecologically valid perspective of postural instability in patients compared to healthy subjects. We conclude that FTRs are an important source of information about human balance performance, both in health and disease. Future studies should no longer discard FTRs, but routinely include these in their analyses. Particular emphasis should be placed on the link between FTRs and everyday balance performance (including falls), and on the possible role played by startle reactions in triggering or modulating FTRs. Copyright © 2011 Elsevier B.V. All rights reserved.

Reactivity to uncertain threat as a familial vulnerability factor for alcohol use disorder.

PubMed

Gorka, S M; Hee, D; Lieberman, L; Mittal, V A; Phan, K L; Shankman, S A

2016-12-01

When sober, problematic drinkers display exaggerated reactivity to threats that are uncertain (U-threat). Since this aversive affective state can be alleviated via acute alcohol intoxication, it has been posited that individuals who exhibit heightened reactivity to U-threat at baseline are motivated to use alcohol as a means of avoidance-based coping, setting the stage for excessive drinking. To date, however, no study has attempted to characterize the dispositional nature of exaggerated reactivity to U-threat and test whether it is a vulnerability factor or exclusively a disease marker of problematic alcohol use. The current investigation utilized a family study design to address these gaps by examining whether (1) reactivity to U-threat is associated with risk for problematic alcohol use, defined by family history of alcohol use disorder (AUD) and (2) reactivity to U-threat is correlated amongst adult biological siblings. A total of 157 families, and 458 individuals, participated in the study and two biological siblings completed a threat-of-shock task designed to probe reactivity to U-threat and predictable threat (P-threat). Startle potentiation was collected as an index of aversive responding. Within biological siblings, startle potentiation to U-threat [intraclass correlation (ICC) = 0.35] and P-threat (ICC = 0.63) was significantly correlated. In addition, independent of an individuals' own AUD status, startle potentiation to U-threat, but not P-threat, was positively associated with risk for AUD (i.e. AUD family history). This suggests that heightened reactivity to U-threat may be a familial vulnerability factor for problematic drinking and a novel prevention target for AUD.

From normal fear to pathological anxiety.

PubMed

Rosen, J B; Schulkin, J

1998-04-01

In this article the authors address how pathological anxiety may develop from adaptive fear states. Fear responses (e.g., freezing, startle, heart rate and blood pressure changes, and increased vigilance) are functionally adaptive behavioral and perceptual responses elicited during danger to facilitate appropriate defensive responses that can reduce danger or injury (e.g., escape and avoidance). Fear is a central motive state of action tendencies subserved by fear circuits, with the amygdala playing a central role. Pathological anxiety is conceptualized as an exaggerated fear state in which hyperexcitability of fear circuits that include the amygdala and extended amygdala (i.e., bed nucleus of the stria terminalis) is expressed as hypervigilance and increased behavioral responsivity to fearful stimuli. Reduced thresholds for activation and hyperexcitability in fear circuits develop through sensitization- or kindling-like processes that involve neuropeptides, hormones, and other proteins. Hyperexcitability in fear circuits is expressed as pathological anxiety that is manifested in the various anxiety disorders.

Preimmunization with a heat-killed preparation of Mycobacterium vaccae enhances fear extinction in the fear-potentiated startle paradigm.

PubMed

Fox, James H; Hassell, James E; Siebler, Philip H; Arnold, Mathew R; Lamb, Andrew K; Smith, David G; Day, Heidi E W; Smith, Tessa M; Simmerman, Emma M; Outzen, Alexander A; Holmes, Kaley S; Brazell, Christopher J; Lowry, Christopher A

2017-11-01

The hygiene hypothesis or "Old Friends" hypothesis proposes that inflammatory diseases are increasing in modern urban societies, due in part to reduced exposure to microorganisms that drive immunoregulatory circuits, and a failure to terminate inappropriate inflammatory responses. Inappropriate inflammation is also emerging as a risk factor for trauma-related, anxiety, and affective disorders, including posttraumatic stress disorder (PTSD), which is characterized as persistent re-experiencing of the trauma after a traumatic experience. Traumatic experiences can lead to long-lasting fear memories and exaggerated fear potentiation of the acoustic startle reflex. The acoustic startle reflex is an ethologically relevant reflex and can be potentiated in both humans and rats through Pavlovian conditioning. Mycobacterium vaccae NCTC 11659 is a soil-derived bacterium with immunoregulatory and anti-inflammatory properties that has been demonstrated to confer stress resilience in mice. Here we immunized adult male Sprague Dawley rats 3×, once per week, with a heat-killed preparation of M. vaccae NCTC 11659 (0.1mg, s.c., in 100µl borate-buffered saline) or vehicle, and, then, 3weeks following the final immunization, tested them in the fear-potentiated startle paradigm; controls were maintained under home cage control conditions throughout the experiment (n=11-12 per group). Rats were tested on days 1 and 2 for baseline acoustic startle, received fear conditioning on days 3 and 4, and underwent fear extinction training on days 5-10. Rats were euthanized on day 11 and brain tissue was sectioned for analysis of mRNA expression for genes important in control of brain serotonergic signaling, including tph2, htr1a, slc6a4, and slc22a3, throughout the brainstem dorsal and median raphe nuclei. Immunization with M. vaccae had no effect on baseline acoustic startle or fear expression on day 5. However, M. vaccae-immunized rats showed enhanced between-session and within-session extinction on day 6, relative to vehicle-immunized controls. Immunization with M. vaccae and fear-potentiated startle altered serotonergic gene expression in a gene- and subregion-specific manner. These data are consistent with the hypothesis that immunoregulatory strategies, such as preimmunization with M. vaccae, have potential for prevention of stress- and trauma-related psychiatric disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

The effects of varenicline on sensory gating and exploratory behavior with pretreatment with nicotinic or 5-HT3A receptor antagonists.

PubMed

Kucinski, Aaron; Wersinger, Scott; Stachowiak, Ewa K; Becker, Chani; Lippiello, Pat; Bencherif, Merouane; Stachowiak, Michal K

2015-02-01

Individuals with schizophrenia smoke at high frequency relative to the general population. Despite the harmful effects of cigarette smoking, smoking among schizophrenic patients improves cognitive impairments not addressed or worsened by common neuroleptics. Varenicline, a nonselective neuronal nicotinic receptor (NNR) agonist and full agonist of 5-HT3A receptors, helps reduce smoking among schizophrenic patients. To determine whether varenicline also improves a cognitive symptom of schizophrenia, namely, impaired sensory gating, a transgenic mouse with schizophrenia, th-fgfr1(tk-), was used. Varenicline dose-dependently increased prepulse inhibition (PPI) of the startle response, a measure of sensory gating, in th-fgfr1(tk-) mice and normalized PPI deficits relative to nontransgenic controls. With the highest dose (10 mg/kg), however, there was a robust elevation of PPI and startle response, as well as reduced exploratory behavior in the open field and elevated plus maze. Pretreatment with the nonspecific NNR antagonist mecamylamine attenuated the exaggerated PPI response and, similar to the 5-HT3A receptor antagonist ondansetron, it prevented the reduction in exploratory behavior. Collectively, these results indicate that varenicline at low-to-moderate doses may be beneficial against impaired sensory gating in schizophrenia; however, higher doses may induce anxiogenic effects, which can be prevented with antagonists of NNRs or 5-HT3A receptors.

Effects of oxytocin on background anxiety in rats with high or low baseline startle

PubMed Central

Ayers, Luke; Agostini, Andrew; Schulkin, Jay; Rosen, Jeffrey B.

2016-01-01

Rationale Oxytocin has antianxiety properties in humans and rodents. However, the antianxiety effects have been variable. Objectives To reduce variability and strengthen to the antianxiety effect of oxytocin in fear-potentiated startle, two experiments were performed. First, different amounts of light-shock pairings were given to determine the optimal levels of cue-specific fear conditioning and non-predictable startle (background anxiety). Second, the antianxiety effects of oxytocin were examined in rats with high and low pre-fear conditioning baseline startle to determine if oxytocin differentially affects high and low trait anxiety rats. Methods Baseline pre-fear conditioning startle responses were first measured. Rats then received 1, 5 or 10 light-shock pairings. Fear-potentiated startle was then tested with two trial types: light-cued startle and non-cued startle trials. In the second experiment, rats fear conditioned with 10 light-shock pairings were administered either saline or oxytocin before a fear-potentiated startle test. Rats were categorized as low or high startlers by their pre-fear conditioning startle amplitude. Results Ten shock-pairings produced the largest non-cued startle responses (background anxiety), without increasing cue-specific fear-potentiated startle compared to 1 and 5 light-shock pairings. Cue-specific fear-potentiated startle was unaffected by oxytocin. Oxytocin reduced background anxiety only in rats with low pre-fear startle responses. Conclusions Oxytocin has population selective antianxiety effects on non-cued unpredictable threat, but only in rats with low pre-fear baseline startle responses. The low startle responses are reminiscent of humans with low startle responses and high trait anxiety. PMID:27004789

Somatic and neuroendocrine responses to standard and biologically salient acoustic startle stimuli in monkeys

PubMed Central

Parker, Karen J.; Hyde, Shellie A.; Buckmaster, Christine L.; Tanaka, Serena M.; Brewster, Katharine K.; Schatzberg, Alan F.; Lyons, David M.; Woodward, Steven H.

2010-01-01

SUMMARY The startle response, a simple defensive response to a sudden stimulus signaling proximal threat, has been well studied in rodents and humans, but has been rarely examined in monkeys. The first goal of the present studies was to develop a minimally immobilizing startle measurement paradigm and validate its usefulness by testing two core features of the startle response (habituation and graded responsivity) in squirrel monkey subjects. Two different types of startle stimuli were used: standard broad-band noise bursts, and species-specific alarm vocalizations (“yaps”) which are elicited in response to threat in both wild and captive animals. The second goal of the present studies was to test whether yaps produce enhanced startle responsivity due to their increased biological salience compared to simple, non-biologically relevant noise bursts. The third goal of the present studies was to evaluate the hypothalamic pituitary-adrenal (HPA) axis response to startle stimuli, as little is known about the stress-activating role of startle stimuli in any species. These experiments determined that the whole-body startle response in relatively unrestrained squirrel monkeys habituates across repeated stimulus presentations and is proportional to stimulus intensity. In addition, differential habituation was observed across biologically salient vs. standard acoustic startle stimuli. Responses to “yaps” were larger initially but attenuated more rapidly over trials. Responses to “yaps” were also larger in the early subepochs of the response window but then achieved a lower level than responses to noise bursts in the later subepochs. Finally, adrenocorticotropic hormone and cortisol concentrations were significantly elevated above baseline after startle stimuli presentation, though monkeys did not exhibit differential HPA axis responses to the two types of startle stimuli. The development of monkey startle methodology may further enhance the utility of this paradigm in translational studies of human stress-related psychiatric disorders. PMID:20869176

A Novel Dominant Hyperekplexia Mutation Y705C Alters Trafficking and Biochemical Properties of the Presynaptic Glycine Transporter GlyT2*

PubMed Central

Giménez, Cecilio; Pérez-Siles, Gonzalo; Martínez-Villarreal, Jaime; Arribas-González, Esther; Jiménez, Esperanza; Núñez, Enrique; de Juan-Sanz, Jaime; Fernández-Sánchez, Enrique; García-Tardón, Noemí; Ibáñez, Ignacio; Romanelli, Valeria; Nevado, Julián; James, Victoria M.; Topf, Maya; Chung, Seo-Kyung; Thomas, Rhys H.; Desviat, Lourdes R.; Aragón, Carmen; Zafra, Francisco; Rees, Mark I.; Lapunzina, Pablo; Harvey, Robert J.; López-Corcuera, Beatriz

2012-01-01

Hyperekplexia or startle disease is characterized by an exaggerated startle response, evoked by tactile or auditory stimuli, producing hypertonia and apnea episodes. Although rare, this orphan disorder can have serious consequences, including sudden infant death. Dominant and recessive mutations in the human glycine receptor (GlyR) α1 gene (GLRA1) are the major cause of this disorder. However, recessive mutations in the presynaptic Na+/Cl−-dependent glycine transporter GlyT2 gene (SLC6A5) are rapidly emerging as a second major cause of startle disease. In this study, systematic DNA sequencing of SLC6A5 revealed a new dominant GlyT2 mutation: pY705C (c.2114A→G) in transmembrane domain 11, in eight individuals from Spain and the United Kingdom. Curiously, individuals harboring this mutation show significant variation in clinical presentation. In addition to classical hyperekplexia symptoms, some individuals had abnormal respiration, facial dysmorphism, delayed motor development, or intellectual disability. We functionally characterized this mutation using molecular modeling, electrophysiology, [3H]glycine transport, cell surface expression, and cysteine labeling assays. We found that the introduced cysteine interacts with the cysteine pair Cys-311–Cys-320 in the second external loop of GlyT2. This interaction impairs transporter maturation through the secretory pathway, reduces surface expression, and inhibits transport function. Additionally, Y705C presents altered H+ and Zn2+ dependence of glycine transport that may affect the function of glycinergic neurotransmission in vivo. PMID:22753417

Prenatal immune challenge in rats: effects of polyinosinic-polycytidylic acid on spatial learning, prepulse inhibition, conditioned fear, and responses to MK-801 and amphetamine.

PubMed

Vorhees, Charles V; Graham, Devon L; Braun, Amanda A; Schaefer, Tori L; Skelton, Matthew R; Richtand, Neil M; Williams, Michael T

2015-01-01

Prenatal maternal immune activation increases risk for schizophrenia and/or autism. Previous data suggest that maternal weight change in response to the immune activator polyinosinic-polycytidylic (Poly IC) in rats influences the severity of effect in the offspring as does the exposure period. We treated gravid Sprague-Dawley rats from E14 to 18 with 8mg/kg/day Poly IC or saline. The Poly IC group was divided into those that gained the least weight or lost (Poly IC (L)) and those that gained the most (Poly IC (H)) weight. There were no effects of Poly IC on anxiety (elevated zero-maze, open-field, object burying), or Morris water maze cued learning or working memory or Cincinnati water maze egocentric learning. The Poly IC (H) group males had decreased acoustic startle whereas Poly IC (L) females had reduced startle and increased PPI. Poly IC offspring showed exaggerated hyperactivity in response to amphetamine (primarily in the Poly IC (H) group) and attenuated hyperactivity in response to MK-801 challenge (primarily in the Poly IC (L) group). Poly IC (L) males showed reduced cued conditioned freezing; both sexes showed less time in the dark in a light-dark test, and the Poly IC groups showed impaired Morris water maze hidden platform acquisition and probe performance. The data demonstrate that offspring from the most affected dams were more affected than those from less reactive dams indicating that degree of maternal immune activation predicts severity of effects on offspring behavior. Copyright © 2014 Elsevier Inc. All rights reserved.

Dissecting genetic architecture of startle response in Drosophila melanogaster using multi-omics information.

PubMed

Xue, Angli; Wang, Hongcheng; Zhu, Jun

2017-09-28

Startle behavior is important for survival, and abnormal startle responses are related to several neurological diseases. Drosophila melanogaster provides a powerful system to investigate the genetic underpinnings of variation in startle behavior. Since mechanically induced, startle responses and environmental conditions can be readily quantified and precisely controlled. The 156 wild-derived fully sequenced lines of the Drosophila Genetic Reference Panel (DGRP) were used to identify SNPs and transcripts associated with variation in startle behavior. The results validated highly significant effects of 33 quantitative trait SNPs (QTSs) and 81 quantitative trait transcripts (QTTs) directly associated with phenotypic variation of startle response. We also detected QTT variation controlled by 20 QTSs (tQTSs) and 73 transcripts (tQTTs). Association mapping based on genomic and transcriptomic data enabled us to construct a complex genetic network that underlies variation in startle behavior. Based on principles of evolutionary conservation, human orthologous genes could be superimposed on this network. This study provided both genetic and biological insights into the variation of startle response behavior of Drosophila melanogaster, and highlighted the importance of genetic network to understand the genetic architecture of complex traits.

Startle reveals an absence of advance motor programming in a Go/No-go task.

PubMed

Carlsen, Anthony N; Chua, Romeo; Dakin, Chris J; Sanderson, David J; Inglis, J Timothy; Franks, Ian M

2008-03-21

Presenting a startling stimulus in a simple reaction time (RT) task, can involuntarily trigger the pre-programmed response. However, this effect is not seen when the response is programmed following the imperative stimulus (IS) providing evidence that a startle can only trigger pre-programmed responses. In a "Go/No-go" (GNG) RT task the response may be programmed in advance of the IS because there exists only a single predetermined response. The purpose of the current investigation was to examine if startle could elicit a response in a GNG task. Participants completed a wrist extension task in response to a visual stimulus. A startling acoustic stimulus (124dB) was presented in both Go and No-go trials with Go probability manipulated between groups. The inclusion of a startle did not significantly speed RT and led to more response errors. This result is similar to that observed in a startled choice RT task, indicating that in a GNG task participants waited until the IS complete motor programming.

Whiplash evokes descending muscle recruitment and sympathetic responses characteristic of startle

PubMed Central

Mang, Daniel WH; Siegmund, Gunter P; Blouin, Jean-Sébastien

2014-01-01

Whiplash injuries are the most common injuries following rear-end collisions. During a rear-end collision, the human muscle response consists of both a postural and a startle response that may exacerbate injury. However, most previous studies only assessed the presence of startle using data collected from the neck muscles and head/neck kinematics. The startle response also evokes a descending pattern of muscle recruitment and changes in autonomic activity. Here we examined the recruitment of axial and appendicular muscles along with autonomic responses to confirm whether these other features of a startle response were present during the first exposure to a whiplash perturbation. Ten subjects experienced a single whiplash perturbation while recording electromyography, electrocardiogram, and electrodermal responses. All subjects exhibited a descending pattern of muscle recruitment, and increasing heart rate and electrodermal responses following the collision. Our results provide further support that the startle response is a component of the response to whiplash collisions. PMID:24932015

Heritability and molecular genetic basis of acoustic startle eye blink and affectively modulated startle response: A genome-wide association study

PubMed Central

VAIDYANATHAN, UMA; MALONE, STEPHEN M.; MILLER, MICHAEL B.; McGUE, MATT; IACONO, WILLIAM G.

2014-01-01

Acoustic startle responses have been studied extensively in relation to individual differences and psychopathology. We examined three indices of the blink response in a picture-viewing paradigm—overall startle magnitude across all picture types, and aversive and pleasant modulation scores—in 3,323 twins and parents. Biometric models and molecular genetic analyses showed that half the variance in overall startle was due to additive genetic effects. No single nucleotide polymorphism was genome-wide significant, but GRIK3 did produce a significant effect when examined as part of a candidate gene set. In contrast, emotion modulation scores showed little evidence of heritability in either biometric or molecular genetic analyses. However, in a genome-wide scan, PARP14 did produce a significant effect for aversive modulation. We conclude that, although overall startle retains potential as an endophenotype, emotion-modulated startle does not. PMID:25387708

Effect of combined opioid receptor and α2-adrenoceptor blockade on anxiety and electrically evoked startle responses.

PubMed

Vo, Lechi; Drummond, Peter D

2017-06-01

The R3 component of the electrically evoked blink reflex may form part of a startle reaction. Acoustic startle responses are augmented by yohimbine, an α 2 -adrenoceptor antagonist that blocks α 2 -autoreceptors, and are potentiated by opioid receptor blockade. To investigate these influences on electrically evoked startle responses, 16 mg yohimbine, with (16 participants) or without 50 mg naltrexone (23 participants), was administered in separate double-blind placebo-controlled cross-over experiments. In each experiment, R3 (a probable component of the startle response) was examined before and after high-frequency electrical stimulation of the forearm, a procedure that initiates inhibitory pain controls. Anxiety and somatic symptoms were greater after yohimbine than placebo, and were potentiated by naltrexone. Pain ratings for the electrically evoked startle stimuli decreased after high-frequency electrical stimulation in the placebo session but remained stable after drug administration. Yohimbine with naltrexone, but not yohimbine alone, also blocked an inhibitory effect of high-frequency electrical stimulation on electrically evoked sharp sensations and R3. Together, the findings suggest that adding naltrexone to yohimbine potentiated anxiety and blocked inhibitory influences of high-frequency electrical stimulation on electrically evoked sensations and startle responses. Thus, opioid peptides could reduce activity in nociceptive and startle-reflex pathways, or inhibit crosstalk between these pathways. Failure of this inhibitory opioid influence might be important in chronically painful conditions that are aggravated by startle stimuli.

Recovery of motor performance following startle.

DOT National Transportation Integrated Search

1969-10-01

Sudden, high-intensity sounds, such as those produced by sonic booms, can be quite startling. Although many studies have investigated physiological response to startle, much less is known concerning the effects of startle on performance. The present ...

Genetic and radiation hybrid mapping of the hyperekplexia region on chromosome 5q.

PubMed Central

Ryan, S G; Dixon, M J; Nigro, M A; Kelts, K A; Markand, O N; Terry, J C; Shiang, R; Wasmuth, J J; O'Connell, P

1992-01-01

Hyperekplexia, or startle disease (STHE), is an autosomal dominant neurologic disorder characterized by muscular rigidity of central nervous system origin, particularly in the neonatal period, and by an exaggerated startle response to sudden, unexpected acoustic or tactile stimuli. STHE responds dramatically to the benzodiazepine drug clonazepam, which acts at gamma-aminobutyric acid type A (GABA-A) receptors. The STHE locus (STHE) was recently assigned to chromosome 5q, on the basis of tight linkage to the colony-stimulating factor 1-receptor (CSF1-R) locus in a single large family. We performed linkage analysis in the original and three additional STHE pedigrees with eight chromosome 5q microsatellite markers and placed several of the most closely linked markers on an existing radiation hybrid (RH) map of the region. The results provide strong evidence for genetic locus homogeneity and assign STHE to a 5.9-cM interval defined by CSF1-R and D5S379, which are separated by an RH map distance of 74 centirays (roughly 2.2-3.7 Mb). Two polymorphic markers (D5S119 and D5S209) lie within this region, but they could not be ordered with respect to STHE. RH mapping eliminated the candidate genes GABRA1 and GABRG2, which encode GABA-A receptor components, by showing that they are telomeric to the target region. PMID:1334371

Modeling startle eyeblink electromyogram to assess fear learning.

PubMed

Khemka, Saurabh; Tzovara, Athina; Gerster, Samuel; Quednow, Boris B; Bach, Dominik R

2017-02-01

Pavlovian fear conditioning is widely used as a laboratory model of associative learning in human and nonhuman species. In this model, an organism is trained to predict an aversive unconditioned stimulus from initially neutral events (conditioned stimuli, CS). In humans, fear memory is typically measured via conditioned autonomic responses or fear-potentiated startle. For the latter, various analysis approaches have been developed, but a systematic comparison of competing methodologies is lacking. Here, we investigate the suitability of a model-based approach to startle eyeblink analysis for assessment of fear memory, and compare this to extant analysis strategies. First, we build a psychophysiological model (PsPM) on a generic startle response. Then, we optimize and validate this PsPM on three independent fear-conditioning data sets. We demonstrate that our model can robustly distinguish aversive (CS+) from nonaversive stimuli (CS-, i.e., has high predictive validity). Importantly, our model-based approach captures fear-potentiated startle during fear retention as well as fear acquisition. Our results establish a PsPM-based approach to assessment of fear-potentiated startle, and qualify previous peak-scoring methods. Our proposed model represents a generic startle response and can potentially be used beyond fear conditioning, for example, to quantify affective startle modulation or prepulse inhibition of the acoustic startle response. © 2016 The Authors. Psychophysiology published by Wiley Periodicals, Inc. on behalf of Society for Psychophysiological Research.

Influence of Omega-3 Fatty Acid Status on the Way Rats Adapt to Chronic Restraint Stress

PubMed Central

Hennebelle, Marie; Balasse, Laure; Latour, Alizée; Champeil-Potokar, Gaelle; Denis, Stéphanie; Lavialle, Monique; Gisquet-Verrier, Pascale; Denis, Isabelle; Vancassel, Sylvie

2012-01-01

Omega-3 fatty acids are important for several neuronal and cognitive functions. Altered omega-3 fatty acid status has been implicated in reduced resistance to stress and mood disorders. We therefore evaluated the effects of repeated restraint stress (6 h/day for 21 days) on adult rats fed omega-3 deficient, control or omega-3 enriched diets from conception. We measured body weight, plasma corticosterone and hippocampus glucocorticoid receptors and correlated these data with emotional and depression-like behaviour assessed by their open-field (OF) activity, anxiety in the elevated-plus maze (EPM), the sucrose preference test and the startle response. We also determined their plasma and brain membrane lipid profiles by gas chromatography. Repeated restraint stress caused rats fed a control diet to lose weight. Their plasma corticosterone increased and they showed moderate behavioural changes, with increases only in grooming (OF test) and entries into the open arms (EPM). Rats fed the omega-3 enriched diet had a lower stress-induced weight loss and plasma corticosterone peak, and reduced grooming. Rats chronically lacking omega-3 fatty acid exhibited an increased startle response, a stress-induced decrease in locomotor activity and exaggerated grooming. The brain omega-3 fatty acids increased as the dietary omega-3 fatty acids increased; diets containing preformed long-chain omega-3 fatty acid were better than diets containing the precursor alpha-linolenic acid. However, the restraint stress reduced the amounts of omega-3 incorporated. These data showed that the response to chronic restraint stress was modulated by the omega-3 fatty acid supply, a dietary deficiency was deleterious while enrichment protecting against stress. PMID:22860066

Enhanced startle responsivity 24 hours after acute stress exposure.

PubMed

Herten, Nadja; Otto, Tobias; Adolph, Dirk; Pause, Bettina M; Kumsta, Robert; Wolf, Oliver T

2016-10-01

Cortisol release in a stressful situation can be beneficial for memory encoding and memory consolidation. Stimuli, such as odors, related to the stressful episode may successfully cue memory contents of the stress experience. The current investigation aimed at testing the potency of stress to influence startle responsivity 24 hr later and to implicitly reactivate emotional memory traces triggered by an odor involved. Participants were assigned to either a stress (Trier Social Stress Test [TSST]) or control (friendly TSST [f-TSST]) condition featuring an ambient odor. On the next day, participants underwent an auditory startle paradigm while their eyeblink reflex was recorded by an electrooculogram. Three different olfactory stimuli were delivered, one being the target odor presented the day before. Additionally, negative, positive, and pictures of the committee members were included for comparing general startle responsivity and fear-potentiated startle. Participants of the stress group demonstrated an enhanced startle response across all stimuli compared to participants of the control group. There were no specific effects with regard to the target odor. The typical fear-potentiated startle response occurred. Stressed participants tended to rate the target odor more aversive than control participants. Odor recognition memory did not differ between the groups, suggesting an implicit effect on odor valence. Our results show that acute stress exposure enhances startle responsivity 24 hr later. This effect might be caused by a shift of amygdala function causing heightened sensitivity, but lower levels of specificity. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Performance recovery following startle : a laboratory approach to the study of behavioral response to sudden aircraft emergencies.

DOT National Transportation Integrated Search

1988-08-01

This paper deals with the use of response/recovery rate to auditory startle as a laboratory technique for simulating some of the principal aspects of the initial shock phase of sudden emergency situations. It is submitted that auditory startle, with ...

Empirically based comparisons of the reliability and validity of common quantification approaches for eyeblink startle potentiation in humans

PubMed Central

Bradford, Daniel E.; Starr, Mark J.; Shackman, Alexander J.

2015-01-01

Abstract Startle potentiation is a well‐validated translational measure of negative affect. Startle potentiation is widely used in clinical and affective science, and there are multiple approaches for its quantification. The three most commonly used approaches quantify startle potentiation as the increase in startle response from a neutral to threat condition based on (1) raw potentiation, (2) standardized potentiation, or (3) percent‐change potentiation. These three quantification approaches may yield qualitatively different conclusions about effects of independent variables (IVs) on affect when within‐ or between‐group differences exist for startle response in the neutral condition. Accordingly, we directly compared these quantification approaches in a shock‐threat task using four IVs known to influence startle response in the no‐threat condition: probe intensity, time (i.e., habituation), alcohol administration, and individual differences in general startle reactivity measured at baseline. We confirmed the expected effects of time, alcohol, and general startle reactivity on affect using self‐reported fear/anxiety as a criterion. The percent‐change approach displayed apparent artifact across all four IVs, which raises substantial concerns about its validity. Both raw and standardized potentiation approaches were stable across probe intensity and time, which supports their validity. However, only raw potentiation displayed effects that were consistent with a priori specifications and/or the self‐report criterion for the effects of alcohol and general startle reactivity. Supplemental analyses of reliability and validity for each approach provided additional evidence in support of raw potentiation. PMID:26372120

Investigation of the effects of head irradiation with gamma rays and protons on startle and pre-pulse inhibition behavior in mice.

PubMed

Haerich, Paul; Eggers, Cara; Pecaut, Michael J

2012-05-01

With the increased international emphasis on manned space exploration, there is a growing need to understand the impact of the spaceflight environment on health and behavior. One particularly important aspect of this environment is low-dose radiation. In the present studies, we first characterized the γ- and proton-irradiation dose effect on acoustic startle and pre-pulse inhibition behaviors in mice exposed to 0-5 Gy brain-localized irradiation, and assessed these effects 2 days later. Subsequently, we used 2 Gy to assess the time course of γ- and proton-radiation effects on startle reactivity 0-8 days after exposure. Exposures targeted the brain to minimize the impact of peripheral inflammation-induced sickness behavior. The effects of radiation on startle were subtle and acute. Radiation reduced the startle response at 2 and 5 Gy. Following a 2-Gy exposure, the response reached a minimum at the 2-day point. Proton and γ-ray exposures did not differ in their impact on startle. We found there were no effects of radiation on pre-pulse inhibition of the startle response.

Is boldness a resource-holding potential trait? Fighting prowess and changes in startle response in the sea anemone, Actinia equina.

PubMed

Rudin, Fabian S; Briffa, Mark

2012-05-22

Contest theory predicts the evolution of a stable mixture of different strategies for fighting. Here, we investigate the possibility that stable between-individual differences in startle-response durations influence fighting ability or 'resource-holding potential' (RHP) in the beadlet sea anemone, Actinia equina. Both winners and losers showed significant repeatability of pre-fight startle-response durations but mean pre-fight startle-response durations were greater for eventual losers than for eventual winners, indicating that RHP varies with boldness. In particular, individuals with short startle responses inflicted more attacks on their opponent. Both repeatability and mean-level responses were changed by the experience of fighting, and these changes varied with outcome. In losers, repeatability was disrupted to a greater extent and the mean startle-response durations were subject to a greater increase than in winners. Thus, following a fight, this behavioural correlate of RHP behaves in a way similar to post-fight changes in physiological status, which can also vary between winners and losers. Understanding the links between aggression and boldness therefore has the potential to enhance our understanding of both the evolution of animal personality and the 'winner and loser effects' of post-fight changes in RHP.

Depressed mood enhances anxiety to unpredictable threat

PubMed Central

Robinson, OJ; Overstreet, C; Letkiewicz, A; Grillon, C

2011-01-01

Background Depression and anxiety disorders (AD) are highly comorbid, but the reason for this comorbidity is unclear. One possibility is that they predispose one another. An informative way to examine interactions between disorders without the confounds present in patient populations is to manipulate the psychological processes thought to underlie the pathological states in healthy individuals. In this paper we therefore asked whether a model of the sad mood in depression can enhance psychophysiological responses (startle) to a model of the anxiety in AD. We predicted that sad mood would increase anxious anxiety-potentiated startle responses. Methods In a between-subjects design, participants (N=36) completed either a sad mood induction procedure (N=18) or neutral mood induction procedure (N=18). Startle responses were assessed during short duration predictable electric shock conditions (fear-potentiated startle) or long-duration unpredictable threat of shock conditions (anxiety-potentiated startle). Results Induced sadness enhanced anxiety-, but not fear- potentiated startle. Conclusions This study provides support for the hypothesis that sadness can increase anxious responding measured by the affective startle response. This, taken together with prior evidence that AD can contribute to depression, provides initial experimental support for the proposition that AD and depression are frequently comorbid because they may be mutually reinforcing. PMID:22088577

Voluntary emotion regulation in anorexia nervosa: A preliminary emotion-modulated startle investigation.

PubMed

Racine, Sarah E; Forbush, Kelsie T; Wildes, Jennifer E; Hagan, Kelsey E; Pollack, Lauren O; May, Casey

2016-06-01

Emotion regulation difficulties are implicated in the development and maintenance of anorexia nervosa (AN). However, research has been limited by an almost exclusive reliance on self-report. This study is the first to use the emotion-modulated startle paradigm (EMSP) to investigate emotional reactivity and voluntary emotion regulation in individuals with AN. Twenty women with AN viewed negative, positive, neutral, and food images and were asked to enhance, suppress, or maintain their emotional responses mid-way through picture presentation. Startle eyeblink magnitudes in response to startle probes administered prior, and subsequent, to regulation instructions indexed emotional reactivity and regulation, respectively. On emotional reactivity trials, startle magnitudes were greater for negative, positive, and food images, compared to neutral images. Participants had difficulty suppressing startle responses to negative and food images, as indicated by non-significant suppress-maintain comparisons. In contrast, startle responses to enhance and suppress cues during presentation of pleasant images were comparable and significantly lower than maintain cues. Findings converge with self-report data to suggest that patients with AN have difficulties with voluntary emotion regulation. The EMSP may be a promising trans-diagnostic method for examining emotion regulation difficulties that underlie risk for eating disorders and other psychiatric conditions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cardiopulmonary baroreceptors affect reflexive startle eye blink.

PubMed

Richter, S; Schulz, A; Port, J; Blumenthal, T D; Schächinger, H

2009-12-07

Baroafferent signals originating from the 'high pressure' arterial vascular system are known to impact reflexive startle eye blink responding. However, it is not known whether baroafferent feedback of the 'low pressure' cardiopulmonary system loading status exerts a similar effect. Lower Body Negative Pressure (LBNP) at gradients of 0, -10, -20, and -30mm Hg was applied to unload cardiopulmonary baroreceptors. Acoustic startle noise bursts were delivered 230 and 530ms after spontaneous R-waves, when arterial baroreceptors are either loaded or unloaded. Eye blink responses were measured by EMG, and psychomotor reaction time by button pushes to startle stimuli. The new finding of this study was that unloading of cardiopulmonary baroreceptors increases startle eye blink responsiveness. Furthermore, we replicated the effect of relative loading/unloading of arterial baroreceptors on startle eye blink responsiveness. Effects of either arterial or cardiopulmonary baroreceptor manipulations were not present for psychomotor reaction times. These results demonstrate that the loading status of cardiopulmonary baroreceptors has an impact on brainstem-based CNS processes.

Psychometric properties of startle and corrugator response in NPU, Affective Picture Viewing, and Resting State tasks

PubMed Central

Kaye, Jesse T.; Bradford, Daniel E.; Curtin, John J.

2016-01-01

The current study provides a comprehensive evaluation of critical psychometric properties of commonly used psychophysiology laboratory tasks/measures within the NIMH RDoC. Participants (N = 128) completed the No Shock, Predictable Shock, Unpredictable Shock (NPU) task, Affective Picture Viewing task, and Resting State task at two study visits separated by one week. We examined potentiation/modulation scores in NPU (predictable or unpredictable shock vs. no shock) and Affective Picture Viewing tasks (pleasant or unpleasant vs. neutral pictures) for startle and corrugator responses with two commonly used quantification methods. We quantified startle potentiation/modulation scores with raw and standardized responses. We quantified corrugator potentiation/modulation in the time and frequency domains. We quantified general startle reactivity in the Resting State Task as the mean raw startle response during the task. For these three tasks, two measures, and two quantification methods we evaluated effect size robustness and stability, internal consistency (i.e., split-half reliability), and one-week temporal stability. The psychometric properties of startle potentiation in the NPU task were good but concerns were noted for corrugator potentiation in this task. Some concerns also were noted for the psychometric properties of both startle and corrugator modulation in the Affective Picture Viewing task, in particular for pleasant picture modulation. Psychometric properties of general startle reactivity in the Resting State task were good. Some salient differences in the psychometric properties of the NPU and Affective Picture Viewing tasks were observed within and across quantification methods. PMID:27167717

Effect of stress and attention on startle response and prepulse inhibition.

PubMed

De la Casa, Luis Gonzalo; Mena, Auxiliadora; Ruiz-Salas, Juan Carlos

2016-10-15

The startle reflex magnitude can be modulated when a weak stimulus is presented before the onset of the startle stimulus, a phenomenon termed prepulse inhibition (PPI). Previous research has demonstrated that emotional processes can modulate PPI and startle intensity, but the available evidence is inconclusive. In order to obtain additional evidence in this domain, we conducted two experiments intended to analyze the effect of induced stress and attentional load on PPI and startle magnitude. Specifically, in Experiment 1 we used a between subject strategy to evaluate the effect on startle response and PPI magnitude of performing a difficult task intended to induce stress in the participants, as compared to a group exposed to a control task. In Experiment 2 we evaluated the effect of diverting attention from the acoustic stimulus on startle and PPI intensity. The results seem to indicate that induced stress can reduce PPI, and that startle reflex intensity is reduced when attention is directed away from the auditory stimulus that induces the reflex. Copyright © 2016 Elsevier Inc. All rights reserved.

Meditation and the Startle Response: A Case Study

PubMed Central

Levenson, Robert W.; Ekman, Paul; Ricard, Matthieu

2013-01-01

The effects of two kinds of meditation (open presence and focused) on the facial and physiological aspects of the defensive response to an aversive startle stimulus were studied in a Buddhist monk with approximately 40 years of meditation experience. The participant was exposed to a 115 db, 100 ms acoustic startle stimulus under the two meditation conditions, a distraction condition (to control for cognitive and attentional load) and an unanticipated condition (startle presented without warning or instruction). A completely counterbalanced 24-trial single-subject design was used, with each condition repeated six times. Most aspects of the participant’s responses in the unanticipated condition did not differ from those of a comparison group of 12 age-matched male controls. Both kinds of meditation produced physiological and facial responses to the startle that were smaller than in the distraction condition. Within meditation conditions, open presence meditation produced smaller physiological and facial responses than focused meditation. These results from a single highly expert meditator indicate that these two kinds of meditation can differentially alter the magnitude of a primitive defensive response. PMID:22506498

Molecular Basis of the Dominant Negative Effect of a Glycine Transporter 2 Mutation Associated with Hyperekplexia*

PubMed Central

Arribas-González, Esther; de Juan-Sanz, Jaime; Aragón, Carmen; López-Corcuera, Beatriz

2015-01-01

Hyperekplexia or startle disease is a rare clinical syndrome characterized by an exaggerated startle in response to trivial tactile or acoustic stimuli. This neurological disorder can have serious consequences in neonates, provoking brain damage and/or sudden death due to apnea episodes and cardiorespiratory failure. Hyperekplexia is caused by defective inhibitory glycinergic neurotransmission. Mutations in the human SLC6A5 gene encoding the neuronal GlyT2 glycine transporter are responsible for the presynaptic form of the disease. GlyT2 mediates synaptic glycine recycling, which constitutes the main source of releasable transmitter at glycinergic synapses. Although the majority of GlyT2 mutations detected so far are recessive, a dominant negative mutant that affects GlyT2 trafficking does exist. In this study, we explore the properties and structural alterations of the S512R mutation in GlyT2. We analyze its dominant negative effect that retains wild-type GlyT2 in the endoplasmic reticulum (ER), preventing surface expression. We show that the presence of an arginine rather than serine 512 provoked transporter misfolding, enhanced association to the ER-chaperone calnexin, altered association with the coat-protein complex II component Sec24D, and thereby impeded ER exit. The S512R mutant formed oligomers with wild-type GlyT2 causing its retention in the ER. Overexpression of calnexin rescued wild-type GlyT2 from the dominant negative effect of the mutant, increasing the amount of transporter that reached the plasma membrane and dampening the interaction between the wild-type and mutant GlyT2. The ability of chemical chaperones to overcome the dominant negative effect of the disease mutation on the wild-type transporter was demonstrated in heterologous cells and primary neurons. PMID:25480793

THE ANXIETY SPECTRUM AND THE REFLEX PHYSIOLOGY OF DEFENSE: FROM CIRCUMSCRIBED FEAR TO BROAD DISTRESS

PubMed Central

McTeague, Lisa M.; Lang, Peter J.

2013-01-01

Guided by the diagnostic nosology, anxiety patients are expected to show defensive hyperarousal during affective challenge, irrespective of the principal phenotype. In the current study, patients representing the whole spectrum of anxiety disorders (i.e., specific phobia, social phobia, panic disorder with or without agoraphobia, obsessive-compulsive disorder, generalized anxiety disorder (GAD), posttraumatic stress disorder(PTSD)), and healthy community control participants, completed an imagery-based fear elicitation paradigm paralleling conventional intervention techniques. Participants imagined threatening and neutral narratives as physiological responses were recorded. Clear evidence emerged for exaggerated reactivity to clinically relevant imagery—most pronounced in startle reflex responding. However, defensive propensity varied across principal anxiety disorders. Disorders characterized by focal fear and impairment (e.g., specific phobia) showed robust fear potentiation. Conversely, for disorders of long-enduring, pervasive apprehension and avoidance with broad anxiety and depression comorbidity (e.g., PTSD secondary to cumulative trauma, GAD), startle responses were paradoxically diminished to all aversive contents. Patients whose expressed symptom profiles were intermediate between focal fearfulness and broad anxious-misery in both severity and chronicity exhibited a still heightened but more generalized physiological propensity to respond defensively. Importantly, this defensive physiological gradient—the inverse of self-reported distress—was evident not only between but also within disorders. These results highlight that fear circuitry could be dysregulated in chronic, pervasive anxiety, and preliminary functional neuroimaging findings suggest that deficient amygdala recruitment could underlie attenuated reflex responding. In summary, adaptive defensive engagement during imagery may be compromised by long-term dysphoria and stress—a phenomenon with implications for prognosis and treatment planning. Depression and Anxiety 29:264–281, 2012. PMID:22511362

Effects of VX on Acoustic Startle Response and Acquisition of Operant Behavior in Rats

DTIC Science & Technology

2008-02-01

spontaneous motor activity , fore- and hind-limb grip strength, thermal sensitivity (paw-lick latency), rectal temperature, acoustic startle response, and...whereas spontaneous motor activity and avoidance responding were affected at doses at or above 123 µg/kg, and acoustic startle response was affected...The 60- and 70-dB stimuli were stimulus control conditions presented to ensure that there was not significant activity within the recording chamber

Appetitive startle modulation in the human laboratory predicts Cannabis craving in the natural environment.

PubMed

Mereish, Ethan H; Padovano, Hayley Treloar; Wemm, Stephanie; Miranda, Robert

2018-07-01

Drug-related cues evoke craving and stimulate motivational systems in the brain. The acoustic startle reflex captures activation of these motivational processes and affords a unique measure of reactivity to drug cues. This study examined the effects of cannabis-related cues on subjective and eye blink startle reactivity in the human laboratory and tested whether these effects predicted youth's cue-elicited cannabis craving in the natural environment. Participants were 55 frequent cannabis users, ages 16 to 24 years (M = 19.9, SD = 1.9; 55% male; 56% met criteria for cannabis dependence), who were recruited from a clinical trial to reduce cannabis use. Eye blink electromyographic activity was recorded in response to acoustic probes that elicited startle reactivity while participants viewed pleasant, unpleasant, neutral, and cannabis picture cues. Following the startle assessment, participants completed an ecological momentary assessment protocol that involved repeated assessments of cue-elicited craving in real time in their real-world environments. Multilevel models included the presence or absence of visible cannabis cues in the natural environment, startle magnitude, and the cross-level interaction of cues by startle to test whether cue-modulated startle reactivity in the laboratory was associated with cue-elicited craving in the natural environment. Analyses showed that cannabis-related stimuli evoked an appetitive startle response pattern in the laboratory, and this effect was associated with increased cue-elicited craving in the natural environment, b = - 0.15, p = .022, 95% CI [- 0.28, - 0.02]. Pleasant stimuli also evoked an appetitive response pattern, but in this case, blunted response was associated with increased cue-elicited craving in the natural environment, b = 0.27, p < .001, 95% CI [0.12, 0.43]. Our findings support cue-modulated startle reactivity as an index of the phenotypic expression of cue-elicited cannabis craving.

Startling Differences: Using the Acoustic Startle Response to Study Sex Differences and Neurosteroids in Affective Disorders.

PubMed

Hantsoo, Liisa; Golden, Carla E M; Kornfield, Sara; Grillon, Christian; Epperson, C Neill

2018-05-18

Neuroactive steroid hormones, such as estradiol and progesterone, likely play a role in the pathophysiology of female-specific psychiatric disorders such as premenstrual dysphoric disorder (PMDD) and postpartum depression and may contribute to the marked sex differences observed in the incidence and presentation of affective disorders. However, few tools are available to study the precise contributions of these neuroactive steroids (NSs). In this review, we propose that the acoustic startle response (ASR), an objective measure of an organism's response to an emotional context or stressor, is sensitive to NSs. As such, the ASR represents a unique translational tool that may help to elucidate the contribution of NSs to sex differences in psychiatric disorders. Findings suggest that anxiety-potentiated startle (APS) and prepulse inhibition of startle (PPI) are the most robust ASR paradigms for assessing contribution of NSs to affective disorders, while affective startle response modulation (ASRM) appears less diagnostic of sex or menstrual cycle (MC) effects. However, few studies have appropriately used ASR to test a priori hypotheses about sex or MC differences. We recommend that ASR studies account for sex as a biological variable (SABV) and hormonal status to further knowledge of NS contribution to affective disorders.

Changes in the magnitude of the eyeblink startle response during habituation of sexual arousal.

PubMed

Koukounas, E; Over, R

2000-06-01

Modulation of the startle response was used to examine emotional processing of sexual stimulation across trials within a session. Eyeblink startle was elicited by a probe (burst of intense white noise) presented intermittently while men were viewing an erotic film segment. Repeated display of the film segment resulted in a progressive decrease in sexual arousal. Habituation of sexual arousal was accompanied by a reduction over trials in the extent the men felt absorbed when viewing the erotic stimulus and by an increase over trials in the magnitude of the eyeblink startle response. Replacing the familiar stimulus by a novel erotic stimulus increased in sexual arousal and absorption and reduced startle (novelty effect), while dishabituation was evident for all three response measures when the familiar stimulus was reintroduced. This pattern of results indicates that with repeated presentation an erotic stimulus is experienced not only as less sexually arousing but also as less appetitive and absorbing. The question of whether habituation of sexual arousal is mediated by changes in attentional and affective processing over trials is discussed, as are clinical contexts in which eyeblink startle can be used in studying aspects of sexual functioning.

Peritraumatic startle response predicts the vulnerability to develop PTSD-like behaviors in rats: a model for peritraumatic dissociation

PubMed Central

Dong, Xinwen; Li, Yonghui

2014-01-01

Peritraumatic dissociation, a state characterized by alteration in perception and reduced awareness of surroundings, is considered to be a risk factor for the development of post-traumatic stress disorder (PTSD). However, the predictive ability of peritraumatic dissociation is questioned for the inconsistent results in different time points of assessment. The startle reflex is an objective behavioral measurement of defensive response to abrupt and intense sensory stimulus of surroundings, with potential to be used as an assessment on the dissociative status in both humans and rodents. The present study examined the predictive effect of acoustic startle response (ASR) in different time points around the traumatic event in an animal model of PTSD. The PTSD-like symptoms, including hyperarousal, avoidance, and contextual fear, were assessed 2–3 weeks post-trauma. The results showed that (1) the startle amplitude attenuated immediate after intense footshock in almost half of the stress animals, and (2) the attenuated startle responses at 1 h but not 24 h after stress predicted the development of severe PTSD-like symptoms. These data indicate that the startle alteration at the immediate period after trauma, including 1 h, is more important in PTSD prediction than 24 h after trauma. Our study also suggests that the startle attenuation immediate after intense stress may serve as an objective measurement of peritraumatic dissociation in rats. PMID:24478660

Does intolerance of uncertainty predict anticipatory startle responses to uncertain threat?

PubMed

Nelson, Brady D; Shankman, Stewart A

2011-08-01

Intolerance of uncertainty (IU) has been proposed to be an important maintaining factor in several anxiety disorders, including generalized anxiety disorder, obsessive-compulsive disorder, and social phobia. While IU has been shown to predict subjective ratings and decision-making during uncertain/ambiguous situations, few studies have examined whether IU also predicts emotional responding to uncertain threat. The present study examined whether IU predicted aversive responding (startle and subjective ratings) during the anticipation of temporally uncertain shocks. Sixty-nine participants completed three experimental conditions during which they received: no shocks, temporally certain/predictable shocks, and temporally uncertain shocks. Results indicated that IU was negatively associated with startle during the uncertain threat condition in that those with higher IU had a smaller startle response. IU was also only related to startle during the uncertain (and not the certain/predictable) threat condition, suggesting that it was not predictive of general aversive responding, but specific to responses to uncertain aversiveness. Perceived control over anxiety-related events mediated the relation between IU and startle to uncertain threat, such that high IU led to lowered perceived control, which in turn led to a smaller startle response. We discuss several potential explanations for these findings, including the inhibitory qualities of IU. Overall, our results suggest that IU is associated with attenuated aversive responding to uncertain threat. Copyright © 2011 Elsevier B.V. All rights reserved.

In the face of fear: Anxiety sensitizes defensive responses to fearful faces

PubMed Central

Grillon, Christian; Charney, Danielle R.

2011-01-01

Fearful faces readily activate the amygdala. Yet, whether fearful faces evoke fear is unclear. Startle studies show no potentiation of startle by fearful faces, suggesting that such stimuli do not activate defense mechanisms. However, the response to biologically relevant stimuli may be sensitized by anxiety. The present study tested the hypothesis that startle would not be potentiated by fearful faces in a safe context, but that startle would be larger during fearful faces compared to neutral faces in a threat-of-shock context. Subjects viewed fearful and neutral faces in alternating periods of safety and threat of shock. Acoustic startle stimuli were presented in the presence and absence of the faces. Startle was transiently potentiated by fearful faces compared to neutral faces in the threat periods. This suggests that although fearful faces do not prompt behavioral mobilization in an innocuous context, they can do so in an anxiogenic one. PMID:21824155

Thermal Imaging of the Periorbital Regions during the Presentation of an Auditory Startle Stimulus

PubMed Central

Gane, Luke; Power, Sarah; Kushki, Azadeh; Chau, Tom

2011-01-01

Infrared thermal imaging of the inner canthi of the periorbital regions of the face can potentially serve as an input signal modality for an alternative access system for individuals with conditions that preclude speech or voluntary movement, such as total locked-in syndrome. However, it is unknown if the temperature of these regions is affected by the human startle response, as changes in the facial temperature of the periorbital regions manifested during the startle response could generate false positives in a thermography-based access system. This study presents an examination of the temperature characteristics of the periorbital regions of 11 able-bodied adult participants before and after a 102 dB auditory startle stimulus. The results indicate that the startle response has no substantial effect on the mean temperature of the periorbital regions. This indicates that thermography-based access solutions would be insensitive to startle reactions in their user, an important advantage over other modalities being considered in the context of access solutions for individuals with a severe motor disability. PMID:22073302

Supertaster, super reactive: oral sensitivity for bitter taste modulates emotional approach and avoidance behavior in the affective startle paradigm.

PubMed

Herbert, Cornelia; Platte, Petra; Wiemer, Julian; Macht, Michael; Blumenthal, Terry D

2014-08-01

People differ in both their sensitivity for bitter taste and their tendency to respond to emotional stimuli with approach or avoidance. The present study investigated the relationship between these sensitivities in an affective picture paradigm with startle responding. Emotion-induced changes in arousal and attention (pupil modulation), priming of approach and avoidance behavior (startle reflex modulation), and subjective evaluations (ratings) were examined. Sensitivity for bitter taste was assessed with the 6-n-propylthiouracil (PROP)-sensitivity test, which discriminated individuals who were highly sensitive to PROP compared to NaCl (PROP-tasters) and those who were less sensitive or insensitive to the bitter taste of PROP. Neither pupil responses nor picture ratings differed between the two taster groups. The startle eye blink response, however, significantly differentiated PROP-tasters from PROP-insensitive subjects. Facilitated response priming to emotional stimuli emerged in PROP-tasters but not in PROP-insensitive subjects at shorter startle lead intervals (200-300ms between picture onset and startle stimulus onset). At longer lead intervals (3-4.5s between picture onset and startle stimulus onset) affective startle modulation did not differ between the two taster groups. This implies that in PROP-sensitive individuals action tendencies of approach or avoidance are primed immediately after emotional stimulus exposure. These results suggest a link between PROP taste perception and biologically relevant patterns of emotional responding. Direct perception-action links have been proposed to underlie motivational priming effects of the startle reflex, and the present results extend these to the sensory dimension of taste. Copyright © 2014 Elsevier Inc. All rights reserved.

The startle paradigm in a forensic psychiatric setting: elucidating psychopathy.

PubMed

Loomans, Max M; Tulen, Joke H M; van Marle, Hjalmar J C

2015-02-01

Most people who meet the diagnostic criteria for anti-social personality disorder (ASPD) do not meet the criteria for psychopathy. A differentiating feature is affective-interpersonal style. Eye blink startle reflex paradigms have been used to study affect. The aim of this study is to explore an eye blink startle paradigm as a means of distinguishing between men with both ASPD and psychopathy, and men with ASPD alone. One hundred and thirty-six men were recruited as follows: 31 patients with ASPD and a Psychopathy Checklist-Revised (PCL-R) score of 26 or more, 22 patients with ASPD and a PCL-R score of 25 or less, 50 forensic hospital employees and 33 general population men, none in the latter two groups having abnormal personality traits. Each was presented with 16 pleasant, 16 unpleasant and 16 neutral pictures. Acoustic probes were presented during each category at 300, 800, 1300 and 3800 milliseconds (ms) after picture onset. Eye blink response was measured by electromyography. Overall, both patient groups showed significantly smaller eye blink responses to the startle stimuli compared with the community controls. Both the latter and the ASPD group showed the expected increase in eye blink response at longer startle latencies to unpleasant pictures than pleasant pictures, but this was not present either in the group with psychopathy or in the forensic hospital employees. With increasing startle latency onset, eye blink amplitude increased significantly in both the healthy comparison groups and the ASPD group, but not in the group with psychopathy. We replicated eye blink startle modulation deficiencies among men with psychopathy. We confirmed that the psychopathy and ASPD groups could be distinguished by startle stimulus onset asynchrony, but this pattern was also seen in one healthy group - the forensic hospital employees. This suggests a case for more research with more diverse comparison groups and more differentiation of personality traits before drawing definitive conclusions about distinctive startle response patterns among men with psychopathy. Copyright © 2014 John Wiley & Sons, Ltd.

Reduced Prepulse Inhibition as a Biomarker of Schizophrenia.

PubMed

Mena, Auxiliadora; Ruiz-Salas, Juan C; Puentes, Andrea; Dorado, Inmaculada; Ruiz-Veguilla, Miguel; De la Casa, Luis G

2016-01-01

The startle response is composed by a set of reflex behaviors intended to prepare the organism to face a potentially relevant stimulus. This response can be modulated by several factors as, for example, repeated presentations of the stimulus (startle habituation), or by previous presentation of a weak stimulus (Prepulse Inhibition [PPI]). Both phenomena appear disrupted in schizophrenia that is thought to reflect an alteration in dopaminergic and glutamatergic neurotransmission. In this paper we analyze whether the reported deficits are indicating a transient effect restricted to the acute phase of the disease, or if it reflects a more general biomarker or endophenotype of the disorder. To this end, we measured startle responses in the same set of thirteen schizophrenia patients with a cross-sectional design at two periods: 5 days after hospital admission and 3 months after discharge. The results showed that both startle habituation and PPI were impaired in the schizophrenia patients at the acute stage as compared to a control group composed by 13 healthy participants, and that PPI but not startle habituation remained disrupted when registered 3 months after the discharge. These data point to the consideration of PPI, but not startle habituation, as a schizophrenia biomarker.

Reduced Prepulse Inhibition as a Biomarker of Schizophrenia

PubMed Central

Mena, Auxiliadora; Ruiz-Salas, Juan C.; Puentes, Andrea; Dorado, Inmaculada; Ruiz-Veguilla, Miguel; De la Casa, Luis G.

2016-01-01

The startle response is composed by a set of reflex behaviors intended to prepare the organism to face a potentially relevant stimulus. This response can be modulated by several factors as, for example, repeated presentations of the stimulus (startle habituation), or by previous presentation of a weak stimulus (Prepulse Inhibition [PPI]). Both phenomena appear disrupted in schizophrenia that is thought to reflect an alteration in dopaminergic and glutamatergic neurotransmission. In this paper we analyze whether the reported deficits are indicating a transient effect restricted to the acute phase of the disease, or if it reflects a more general biomarker or endophenotype of the disorder. To this end, we measured startle responses in the same set of thirteen schizophrenia patients with a cross-sectional design at two periods: 5 days after hospital admission and 3 months after discharge. The results showed that both startle habituation and PPI were impaired in the schizophrenia patients at the acute stage as compared to a control group composed by 13 healthy participants, and that PPI but not startle habituation remained disrupted when registered 3 months after the discharge. These data point to the consideration of PPI, but not startle habituation, as a schizophrenia biomarker. PMID:27803654

The startle response and toxicology: Methods, use and interpretation.

EPA Science Inventory

The startle response (SR) is a sensory-evoked motor reflex that has been used successfully in toxicology for decades. Advantages of this procedure include: rapidly objective measurement of a defined neural circuit, measurement of habituation of the response, and a high potential ...

Dexamethasone facilitates fear extinction and safety discrimination in PTSD: A placebo-controlled, double-blind study.

PubMed

Michopoulos, Vasiliki; Norrholm, Seth D; Stevens, Jennifer S; Glover, Ebony M; Rothbaum, Barbara O; Gillespie, Charles F; Schwartz, Ann C; Ressler, Kerry J; Jovanovic, Tanja

2017-09-01

Psychophysiological hallmarks of posttraumatic stress disorder (PTSD) include exaggerated fear responses, impaired inhibition and extinction of conditioned fear, and decreased discrimination between safety and fear cues. This increased fear load associated with PTSD can be a barrier to effective therapy thus indicating the need for new treatments to reduce fear expression in people with PTSD. One potential biological target for reducing fear expression in PTSD is the hypothalamic-pituitary-adrenal (HPA) axis, which is dysregulated in PTSD. Recent translational rodent studies and cross-sectional clinical studies have shown that dexamethasone administration and the resulting suppression of cortisol in individuals with PTSD leads to a decrease in the fear responses characteristic of PTSD. These data, taken together, suggest that dexamethasone may serve as a novel pharmacologic intervention for heightened fear responses in PTSD. We conducted a double-blind, placebo-controlled trial to test our hypothesis that dexamethasone administration and the concomitant suppression of HPA axis hyperactivity would attenuate fear expression and enhance fear extinction in individuals with PTSD. Study participants (n=62) were recruited from Grady Memorial Hospital in Atlanta, GA. Participants were randomized to receive dexamethasone or placebo prior to fear conditioning and extinction, in a counterbalanced design (treatments separated by a week). Both PTSD- (n=37) and PTSD+ (n=25) participants showed significant startle increases in the presence of the danger signal during placebo and dexamethasone treatments (all p<0.05). However, only PTSD- control participants showed decreases in fear-potentiated startle across extinction blocks during both conditions (p's≤0.001), with PTSD+ participants showing deficits in fear extinction and safety discrimination in the placebo condition. Notably, extinction and discrimination deficits in PTSD+ subjects were markedly reversed with dexamethasone (p<0.001). These data suggest that dexamethasone may serve as a pharmacological agent with which to facilitate fear extinction and discrimination in individuals with PTSD. Copyright © 2017 Elsevier Ltd. All rights reserved.

ONTOGENY OF THE ACOUSTIC STARTLE RESPONSE AND SENSITIZATION TO BACKGROUND NOISE IN THE RAT (JOURNAL VERSION)

EPA Science Inventory

The purpose of the study was to characterize the ontogeny of the acoustic startle response (ASR), and response sensitization to background noise, in preweanling rats. With constant low-level (45 dB) background noise, response latency decreased steadily with age, whereas, both res...

Fear-potentiated startle processing in humans: Parallel fMRI and orbicularis EMG assessment during cue conditioning and extinction.

PubMed

Lindner, Katja; Neubert, Jörg; Pfannmöller, Jörg; Lotze, Martin; Hamm, Alfons O; Wendt, Julia

2015-12-01

Studying neural networks and behavioral indices such as potentiated startle responses during fear conditioning has a long tradition in both animal and human research. However, most of the studies in humans do not link startle potentiation and neural activity during fear acquisition and extinction. Therefore, we examined startle blink responses measured with electromyography (EMG) and brain activity measured with functional MRI simultaneously during differential conditioning. Furthermore, we combined these behavioral fear indices with brain network activity by analyzing the brain activity evoked by the startle probe stimulus presented during conditioned visual threat and safety cues as well as in the absence of visual stimulation. In line with previous research, we found a fear-induced potentiation of the startle blink responses when elicited during a conditioned threat stimulus and a rapid decline of amygdala activity after an initial differentiation of threat and safety cues in early acquisition trials. Increased activation during processing of threat cues was also found in the anterior insula, the anterior cingulate cortex (ACC), and the periaqueductal gray (PAG). More importantly, our results depict an increase of brain activity to probes presented during threatening in comparison to safety cues indicating an involvement of the anterior insula, the ACC, the thalamus, and the PAG in fear-potentiated startle processing during early extinction trials. Our study underlines that parallel assessment of fear-potentiated startle in fMRI paradigms can provide a helpful method to investigate common and distinct processing pathways in humans and animals and, thus, contributes to translational research. Copyright © 2015 Elsevier B.V. All rights reserved.

Asians demonstrate reduced sensitivity to unpredictable threat: a preliminary startle investigation using genetic ancestry in a multiethnic sample.

PubMed

Nelson, Brady D; Bishop, Jeffrey R; Sarapas, Casey; Kittles, Rick A; Shankman, Stewart A

2014-06-01

Research has indicated that individuals of Asian descent, relative to other racial groups, demonstrate reduced emotional responding and lower prevalence rates of several anxiety disorders. It is unclear though whether these group differences extend to biomarkers of anxiety disorders and whether genetic differences play a role. This study compared self-identified Caucasian, Latino, and Asian persons (total N = 174) on startle response during a baseline period and while anticipating unpredictable threat-a putative biomarker for certain anxiety disorders--as well as predictable threat. In addition, the association between genetic ancestry and startle response was examined within each racial group to determine potential genetic influences on responding. For the baseline period, Asian participants exhibited a smaller startle response relative to Caucasian and Latino participants, who did not differ. Within each racial group, genetic ancestry was associated with baseline startle. Furthermore, genetic ancestry mediated racial group differences in baseline startle. For the threat conditions, a Race × Condition interaction indicated that Asian participants exhibited reduced startle potentiation to unpredictable, but not predicable, threat relative to Caucasian and Latino participants, who did not differ. However, genetic ancestry was not associated with threat-potentiated startle in any racial group. This study adds to the growing literature on racial differences in emotional responding and provides preliminary evidence suggesting that genetic ancestry may play an important role. Moreover, reduced sensitivity to unpredictable threat may reflect a mechanism for why individuals of Asian descent are at less risk for particular anxiety disorders relative to other racial groups.

Asians Demonstrate Reduced Sensitivity to Unpredictable Threat: A Preliminary Startle Investigation using Genetic Ancestry in a Multi-Ethnic Sample

PubMed Central

Nelson, Brady D.; Bishop, Jeffrey R.; Sarapas, Casey; Kittles, Rick A.; Shankman, Stewart A.

2014-01-01

Research has indicated that individuals of Asian descent, relative to other racial groups, demonstrate reduced emotional responding and lower prevalence rates of several anxiety disorders. It is unclear though whether these group differences extend to biomarkers of anxiety disorders and whether genetic differences play a role. The present study compared self-identified Caucasians, Latinos, and Asians (total N = 174) on startle response during a baseline period and while anticipating unpredictable threat–a putative biomarker for certain anxiety disorders–as well as predictable threat. In addition, the association between genetic ancestry and startle response was examined within each racial group to determine potential genetic influences on responding. For the baseline period, Asian participants exhibited a smaller startle response relative to Caucasian and Latino participants, who did not differ. Within each racial group, genetic ancestry was associated with baseline startle. Furthermore, genetic ancestry mediated racial group differences in baseline startle. For the threat conditions, a Race × Condition interaction indicated that Asian participants exhibited reduced startle potentiation to unpredictable, but not predicable, threat relative to Caucasian and Latino participants, who did not differ. However, genetic ancestry was not associated with threat-potentiated startle in any racial group. The present study adds to the growing literature on racial differences in emotional responding and provides preliminary evidence suggesting that genetic ancestry may play an important role. Moreover, reduced sensitivity to unpredictable threat may reflect a mechanism for why individuals of Asian descent are at less risk for particular anxiety disorders relative to other racial groups. PMID:24708496

Startling sweet temptations: hedonic chocolate deprivation modulates experience, eating behavior, and eyeblink startle.

PubMed

Blechert, Jens; Naumann, Eva; Schmitz, Julian; Herbert, Beate M; Tuschen-Caffier, Brunna

2014-01-01

Many individuals restrict their food intake to prevent weight gain. This restriction has both homeostatic and hedonic effects but their relative contribution is currently unclear. To isolate hedonic effects of food restriction, we exposed regular chocolate eaters to one week of chocolate deprivation but otherwise regular eating. Before and after this hedonic deprivation, participants viewed images of chocolate and images of high-calorie but non-chocolate containing foods, while experiential, behavioral and eyeblink startle responses were measured. Compared to satiety, hedonic deprivation triggered increased chocolate wanting, liking, and chocolate consumption but also feelings of frustration and startle potentiation during the intertrial intervals. Deprivation was further characterized by startle inhibition during both chocolate and food images relative to the intertrial intervals. Individuals who responded with frustration to the manipulation and those who scored high on a questionnaire of impulsivity showed more relative startle inhibition. The results reveal the profound effects of hedonic deprivation on experiential, behavioral and attentional/appetitive response systems and underscore the role of individual differences and state variables for startle modulation. Implications for dieting research and practice as well as for eating and weight disorders are discussed.

Startling Sweet Temptations: Hedonic Chocolate Deprivation Modulates Experience, Eating Behavior, and Eyeblink Startle

PubMed Central

Blechert, Jens; Naumann, Eva; Schmitz, Julian; Herbert, Beate M.; Tuschen-Caffier, Brunna

2014-01-01

Many individuals restrict their food intake to prevent weight gain. This restriction has both homeostatic and hedonic effects but their relative contribution is currently unclear. To isolate hedonic effects of food restriction, we exposed regular chocolate eaters to one week of chocolate deprivation but otherwise regular eating. Before and after this hedonic deprivation, participants viewed images of chocolate and images of high-calorie but non-chocolate containing foods, while experiential, behavioral and eyeblink startle responses were measured. Compared to satiety, hedonic deprivation triggered increased chocolate wanting, liking, and chocolate consumption but also feelings of frustration and startle potentiation during the intertrial intervals. Deprivation was further characterized by startle inhibition during both chocolate and food images relative to the intertrial intervals. Individuals who responded with frustration to the manipulation and those who scored high on a questionnaire of impulsivity showed more relative startle inhibition. The results reveal the profound effects of hedonic deprivation on experiential, behavioral and attentional/appetitive response systems and underscore the role of individual differences and state variables for startle modulation. Implications for dieting research and practice as well as for eating and weight disorders are discussed. PMID:24416437

Between Site Reliability of Startle Prepulse Inhibition Across Two Early Psychosis Consortia

PubMed Central

Addington, Jean; Cannon, Tyrone D.; Cornblatt, Barbara A.; de la Fuente-Sandoval, Camilo; Mathalon, Dan H.; Perkins, Diana O.; Seidman, Larry J.; Tsuang, Ming; Walker, Elaine F.; Woods, Scott W.; Bachman, Peter; Belger, Ayse; Carrión, Ricardo E.; Donkers, Franc C.L.; Duncan, Erica; Johannesen, Jason; León-Ortiz, Pablo; Light, Gregory; Mondragón, Alejandra; Niznikiewicz, Margaret; Nunag, Jason; Roach, Brian J.; Solís-Vivanco, Rodolfo

2014-01-01

Prepulse inhibition (PPI) and reactivity of the acoustic startle response are widely used biobehavioral markers in psychopathology research. Previous studies have demonstrated that PPI and startle reactivity exhibit substantial within-site stability; between-site stability, however, has not been established. In two separate consortia investigating biomarkers of early psychosis, traveling subjects studies were performed as part of quality assurance procedures in order to assess the fidelity of data across sites. In the North American Prodromal Longitudinal Studies (NAPLS) Consortium, 8 normal subjects traveled to each of the 8 NAPLS sites and were tested twice at each site on the startle PPI paradigm. In preparation for a binational study, 10 healthy subjects were assessed twice in both San Diego and Mexico City. Intraclass correlations between and within sites were significant for PPI and startle response parameters, confirming the reliability of startle measures across sites in both consortia. There were between site differences in startle magnitude in the NAPLS study that did not appear to be related to methods or equipment. In planning multi-site studies, it is essential to institute quality assurance procedures early and establish between site reliability to assure comparable data across sites. PMID:23799460

Affective reactivity during smoking cessation of never-quitters as compared with that of abstainers, relapsers, and continuing smokers.

PubMed

Lam, Cho Y; Robinson, Jason D; Versace, Francesco; Minnix, Jennifer A; Cui, Yong; Carter, Brian L; Wetter, David W; Cinciripini, Paul M

2012-04-01

Much effort has been devoted to examining the differences in postcessation affective experience between smoking abstainers and relapsers. However, little attention has been given to the affective changes of smokers who, despite their motivation to quit, fail to achieve even a brief period of abstinence. Using affect-modulated startle response and self-report questionnaires, we measured the postcessation affective changes of 115 smokers (60 men, 55 women) who participated in a laboratory investigation of affective reactivity during smoking cessation. Among our participants, 34 were abstainers (16 men, 18 women), 16 were never-quitters (8 men, 8 women), 19 were relapsers (8 men, 11 women), and 46 were controls (28 men, 18 women). We found a significant Stimulus Valence × Session × Group interaction effect on startle responses, which suggested that while abstainers, relapsers, and control exhibited the prototypical affect-modulated startle response across postcessation sessions, never-quitters displayed an atypical response pattern in which emotional pictures no longer modulated the startle response. Never-quitters also reported increasingly higher negative and lower positive affect across postcessation sessions. Using affect-modulated startle response and self-report questionnaires, this study found a significant difference in the affective reactivity between smokers who could and smokers who could not establish an initial abstinence of 24 hours.

Negative, but not positive emotional images modulate the startle response independent of conscious awareness.

PubMed

Reagh, Zachariah M; Knight, David C

2013-08-01

The emotional response to a threat is influenced by the valence of other stimuli in the environment. This emotional modulation of the threat-elicited response occurs even when negative valence stimuli are not consciously perceived. Relatively little prior research has investigated whether nonconsciously perceived positive valence stimuli modify the response to a threat, and the work that has been completed is in need of additional rigorous testing of stimulus and valence perception. The current study presented images of negative, neutral, and positive valence (1,000 ms and 17 ms durations), followed by a mask. A startle probe (100 dB whitenoise) was presented during 33% of each trial type while eyeblink electromyography (EMG) and skin conductance response (SCR) were measured. During the study, participants rated the emotional content of each image to assess valence perception. Participants accurately classified the valence of 1,000 ms images, but not 17 ms images. Further, participants performed at chance levels on an independent postexperimental forced-choice perception task using 17 ms masked images, indicating they were unable to perceive the valence and content of these images. Greater EMG and SCR were elicited by the startle probe during perceived and unperceived negative images compared to perceived and unperceived positive and neutral images. In addition, perceived, but not unperceived positive images diminished startle responses. The current findings suggest that images of negative valence potentiate the startle response in the absence of conscious stimulus perception. However, the attenuation of the startle response by positive images appears to require perception of the emotional valence of an image. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Alternative forms of axial startle behaviors in fishes.

PubMed

Liu, Yen-Chyi; Hale, Melina E

2014-02-01

For most aquatic vertebrates, axial movements play key roles in the performance of startle responses. In fishes, these axis-based startle behaviors fall into three distinct categories - the C-start, withdrawal, and S-start - defined by patterns of body bending and underlying motor control. Startle behaviors have been widely studied due to their importance for predator evasion. In addition, the neural circuits that control startles are relatively accessible, compared to other vertebrate circuits, and have provided opportunities to understand basic nervous system function. The C-start neural circuit has long been a model in systems neuroscience and considerable work on neural control of withdrawal response has been conducted in the larval lamprey. The S-start response has only recently been explored from a physiological perspective and we focus here on reviewing S-start motor control and movement in the context of the other two responses. Axial elongation has previously been associated with startle behavior in comparisons of C-starts and withdrawal, with extremely elongate animals performing withdrawals. We suggest that the S-start tends to occur with moderate body elongation, complementing the C-start in animals with this body form. As many larval fishes are moderately elongate, we suggest that the S-start may be common in larvae but may be secondarily lost with body shape change through development. Copyright © 2013 Elsevier GmbH. All rights reserved.

Effect of Suppression, Reappraisal, and Acceptance of Emotional Pictures on Acoustic Eye-Blink Startle Magnitude

PubMed Central

Asnaani, Anu; Sawyer, Alice T.; Aderka, Idan M.; Hofmann, Stefan G.

2012-01-01

To examine the effects of different emotion regulation strategies on acoustic eye-blink startle, 65 participants viewed positive, neutral, and negative pictures and were instructed to suppress, reappraise, or accept their emotional responses to these pictures using a within-group experimental design with separate blocks of pictures for each strategy. Instructions to suppress the emotional response led to an attenuation of the eye-blink startle magnitude, in comparison with instructions to reappraise or accept. Reappraisal and acceptance instructions did not differ from one another in their effect on startle. These results are discussed within the context of the existing empirical literature on emotion regulation. PMID:24551448

Fast and singular muscle responses initiate the startle response of Pantodon buchholzi (Osteoglossomorpha).

PubMed

Starosciak, A K; Kalola, R P; Perkins, K P; Riley, J A; Saidel, W M

2008-01-01

The startle response of Pantodon buchholzi, the African butterfly fish, is a complete or incomplete ballistic jump resulting from abduction of the pectoral fins. This study analyzed the neuromuscular basis for such a jump by recording in vivo electromyograms (emgs) from the muscles of abduction, the muscularis abductor superficialis (MAS) and the muscularis abductor profundus (MAP). The motor neurons innervating the MAS muscle were localized by retrograde transport of biocytin. The latency between stimulus and the evoked emg in the MAS was less than 5 ms; the latency of the MAP was about 6.5 ms. A single emg was recorded per jump. High speed video demonstrated that onset of a startle movement began within 10 ms of the onset of fin abduction. The emg associated with this movement is short (<2 ms) and followed by a variably-shaped, slower and smaller potential of 10-30 ms duration. The brief period between stimulus and startle response of Pantodon suggests a Mauthner neuron-related response, only with the behavior occurring in the vertical plane. The MAS may act only in a startle response, whereas the MAP might have a role in other behaviors. Elicited jumping habituates after a single trial. Electrophysiological evidence is presented indicating that the innervating motor neurons are suppressed for seconds following a stimulus. The neurons innervating the MAS are located at the medullary-spinal cord junction and possess an average radius of approximately 17.9 mum. These fish have been historically described as 'fresh water' flying fish. As a single emg occurs per startle response, repetitive pectoral activity generating flying cannot be supported. Pantodon 'flight' is ballistic. Copyright 2007 S. Karger AG, Basel.

The relation between symptoms of bulimia nervosa and obsessive-compulsive disorder: a startle investigation.

PubMed

Altman, Sarah E; Campbell, Miranda L; Nelson, Brady D; Faust, Julianne P; Shankman, Stewart A

2013-11-01

Bulimia nervosa (BN) and obsessive-compulsive disorder (OCD) co-occur at greater rates than chance and may have shared mechanisms of dysfunction. One of these proposed mechanisms is a hyper-responsive aversive system as indicated by heightened startle response to aversive stimuli. The present study examined this hypothesis using 2 types of aversive stimuli: disorder specific (e.g., high-caloric food pictures for BN, contamination pictures for OCD) and nondisorder specific (e.g., knife). Temporal parameters of aversive responding were also examined by assessing startle response in anticipation of and following picture presentation. The sample consisted of 114 undergraduate women selected to have a broad range of BN and/or OCD symptomatology. OCD symptoms were associated with increased startle potentiation during the anticipation and presentation of contamination pictures, and BN symptoms were associated with increased startle potentiation during disorder-related contamination pictures (e.g., sink, toilet). BN symptoms were also associated with increased startle potentiation during and following the presentation of food pictures (though the former effect was only a trend). Additionally, the interaction of BN and OCD symptoms was associated with elevated startle responding during the presentation of contamination and threat stimuli. Overall, the present study provides evidence that BN and OCD symptoms are associated with heightened aversive responding to disorder-specific stimuli, and comorbid BN and OCD symptoms are associated with heightened aversive responding across disorder-specific and nonspecific aversive stimuli. Clinical and theoretical implications are discussed. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Contextual startle responses moderate the relation between behavioral inhibition and anxiety in middle childhood.

PubMed

Barker, Tyson V; Reeb-Sutherland, Bethany; Degnan, Kathryn A; Walker, Olga L; Chronis-Tuscano, Andrea; Henderson, Heather A; Pine, Daniel S; Fox, Nathan A

2015-11-01

Behavioral inhibition (BI), a temperament characterized in early childhood by wariness and avoidance of novelty, is a risk factor for anxiety disorders. An enhanced startle response has been observed in adolescents characterized with BI in childhood, particularly when they also manifest concurrent symptoms of anxiety. However, no prior study has examined relations among BI, startle responsivity, and anxiety in a prospective manner. Data for the present study were from a longitudinal study of infant temperament. Maternal reports and observations of BI were assessed at ages 2 and 3. At age 7, participants completed a startle procedure, while electromyography was collected, where participants viewed different colors on a screen that were associated with either the delivery of an aversive stimulus (i.e., puff of air to the larynx; threat cue) or the absence of the aversive stimulus (i.e., safety cue). Parental reports of child anxiety were collected when children were 7 and 9 years of age. Results revealed that startle responses at age 7 moderated the relation between early BI and 9-year anxiety. These findings provide insight into one potential mechanism that may place behaviorally inhibited children at risk for anxiety. © 2015 Society for Psychophysiological Research.

Anticipation of public speaking in virtual reality reveals a relationship between trait social anxiety and startle reactivity.

PubMed

Cornwell, Brian R; Johnson, Linda; Berardi, Luciano; Grillon, Christian

2006-04-01

Startle reflex modification has become valuable to the study of fear and anxiety, but few studies have explored startle reactivity in socially threatening situations. Healthy participants ranging in trait social anxiety entered virtual reality (VR) that simulates standing center-stage in front of an audience to anticipate giving a speech and count backward. We measured startle and autonomic reactivity during anticipation of both tasks inside VR after a single baseline recording outside VR. Trait social anxiety, but not general trait anxiety, was positively correlated with startle before entering VR and most clearly during speech anticipation inside VR. Speech anticipation inside VR also elicited stronger physiologic responses relative to anticipation of counting. Under social-evaluative threat, startle reactivity showed robust relationships with fear of negative evaluation, a central aspect of social anxiety and clinical social phobia. Context-specific startle modification may be an endophenotype for subtypes of pathological anxiety.

Relationship between Physiological and Parent-Observed Auditory Over-Responsiveness in Children with Typical Development and Those with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Takahashi, Hidetoshi; Nakahachi, Takayuki; Stickley, Andrew; Ishitobi, Makoto; Kamio, Yoko

2018-01-01

The objective of this study was to investigate relationships between caregiver-reported sensory processing abnormalities, and the physiological index of auditory over-responsiveness evaluated using acoustic startle response measures, in children with autism spectrum disorders and typical development. Mean acoustic startle response magnitudes in…

Sex-Specific Brain Deficits in Auditory Processing in an Animal Model of Cocaine-Related Schizophrenic Disorders

PubMed Central

Broderick, Patricia A.; Rosenbaum, Taylor

2013-01-01

Cocaine is a psychostimulant in the pharmacological class of drugs called Local Anesthetics. Interestingly, cocaine is the only drug in this class that has a chemical formula comprised of a tropane ring and is, moreover, addictive. The correlation between tropane and addiction is well-studied. Another well-studied correlation is that between psychosis induced by cocaine and that psychosis endogenously present in the schizophrenic patient. Indeed, both of these psychoses exhibit much the same behavioral as well as neurochemical properties across species. Therefore, in order to study the link between schizophrenia and cocaine addiction, we used a behavioral paradigm called Acoustic Startle. We used this acoustic startle paradigm in female versus male Sprague-Dawley animals to discriminate possible sex differences in responses to startle. The startle method operates through auditory pathways in brain via a network of sensorimotor gating processes within auditory cortex, cochlear nuclei, inferior and superior colliculi, pontine reticular nuclei, in addition to mesocorticolimbic brain reward and nigrostriatal motor circuitries. This paper is the first to report sex differences to acoustic stimuli in Sprague-Dawley animals (Rattus norvegicus) although such gender responses to acoustic startle have been reported in humans (Swerdlow et al. 1997 [1]). The startle method monitors pre-pulse inhibition (PPI) as a measure of the loss of sensorimotor gating in the brain's neuronal auditory network; auditory deficiencies can lead to sensory overload and subsequently cognitive dysfunction. Cocaine addicts and schizophrenic patients as well as cocaine treated animals are reported to exhibit symptoms of defective PPI (Geyer et al., 2001 [2]). Key findings are: (a) Cocaine significantly reduced PPI in both sexes. (b) Females were significantly more sensitive than males; reduced PPI was greater in females than in males. (c) Physiological saline had no effect on startle in either sex. Thus, the data elucidate gender-specificity to the startle response in animals. Finally, preliminary studies show the effect of cocaine on acoustic startle in tandem with effects on estrous cycle. The data further suggest that hormones may play a role in these sex differences to acoustic startle reported herein. PMID:24961412

Measuring anxious responses to predictable and unpredictable threat in children and adolescents

PubMed Central

Schmitz, Anja; Merikangas, Kathleen; Swendsen, Haruka; Cui, Lihong; Heaton, Leanne; Grillon, Christian

2011-01-01

Research has highlighted the need for new methods to assess emotions in children on multiple levels in order to gain better insight into the complex processes of emotional development. The startle reflex is a unique translational tool that has been utilized to study physiological processes during fear and anxiety in rodents and in human subjects. However, it has been challenging to implement developmentally-appropriate startle experiments in children. This paper describes a procedure that uses predictable and unpredictable aversive events to distinguish between phasic fear and sustained anxiety in children and adolescents. We investigated anxious responses, as measured with the startle reflex, in youth (N = 36, mean age[range] = 12.63 [7–17]) across three conditions: no aversive events (N), predictable aversive events (P), and unpredictable aversive events (U). Short-duration cues were presented several times in each condition. Aversive events were signaled by the cues in P, but were presented randomly in U. Participants showed fear-potentiated startle to the threat cue in P. Startle responses were also elevated between cues in U compared to N, suggesting that unpredictable aversive events can evoke a sustained state of anxiety in youth. This latter effect was influenced by sex, being greater in girls compared to boys. These findings indicate the feasibility of this experimental induction of the startle reflex in response to predictable and unpredictable events in children and adolescents, enabling future research on inter-individual differences in fear and anxiety and their development in youth. PMID:21440905

Startling similarity: Effects of facial self-resemblance and familiarity on the processing of emotional faces

PubMed Central

Larra, Mauro F.; Merz, Martina U.; Schächinger, Hartmut

2017-01-01

Facial self-resemblance has been associated with positive emotional evaluations, but this effect may be biased by self-face familiarity. Here we report two experiments utilizing startle modulation to investigate how the processing of facial expressions of emotion is affected by subtle resemblance to the self as well as to familiar faces. Participants of the first experiment (I) (N = 39) were presented with morphed faces showing happy, neutral, and fearful expressions which were manipulated to resemble either their own or unknown faces. At SOAs of either 300 ms or 3500–4500 ms after picture onset, startle responses were elicited by binaural bursts of white noise (50 ms, 105 dB), and recorded at the orbicularis oculi via EMG. Manual reaction time was measured in a simple emotion discrimination paradigm. Pictures preceding noise bursts by short SOA inhibited startle (prepulse inhibition, PPI). Both affective modulation and PPI of startle in response to emotional faces was altered by physical similarity to the self. As indexed both by relative facilitation of startle and faster manual responses, self-resemblance apparently induced deeper processing of facial affect, particularly in happy faces. Experiment II (N = 54) produced similar findings using morphs of famous faces, yet showed no impact of mere familiarity on PPI effects (or response time, either). The results are discussed with respect to differential (presumably pre-attentive) effects of self-specific vs. familiar information in face processing. PMID:29216226

Corticosteroid dependent and independent effects of a cannabinoid agonist on core temperature, motor activity, and prepulse inhibition of the acoustic startle reflex in Wistar rats.

PubMed

Avdesh, Avdesh; Cornelisse, Vincent; Martin-Iverson, Mathew Thomas

2012-03-01

There are inconsistent reports on the effects of cannabinoid agonists on prepulse inhibition of the startle reflex (PPI) with increases, decreases, and no effects. It has been hypothesized that the conflicting observations may be as a result of modulation of the effects of cannabinoid agonists by the regulation of corticosteroid release. The purpose of the present study was to determine the effects of CP55940, a cannabinoid agonist, and metyrapone, a corticosteroid synthesis inhibitor on core temperature, motor activity, the startle reflex, and PPI. Startle responses were measured in 64 male Wistar rats while varying startling stimulus intensities, analogous to dose-response curves. A stimulus potency measure (ES(50)) and a response measure, the maximal achievable response (R (MAX)) were derived from the stimulus-response curves. CP55940 reduced core temperature and motor activity; these effects were potentiated by metyrapone. CP55940 increased R (MAX) of startle in the absence of a prepulse by a corticosteroid-dependent mechanism but decreased it when metyrapone was administered before CP55940, a corticosteroid-independent mechanism. The inverse of stimulus potency (ES(50)) was not affected by either drug alone but was increased by the combined drugs. CP55940 increased the prepulse motor gating effects and decreased the prepulse sensory gating effects of the same prepulses but only when given after metyrapone. The most parsimonious interpretation of these effects is that CP55940 has some effects through corticosteroid-dependent actions and opposite effects by corticosteroid-independent actions. These two putative sites of actions affect stimulus gating opposite to their effects on response gating.

In Your Face: Startle to Emotional Facial Expressions Depends on Face Direction.

PubMed

Åsli, Ole; Michalsen, Henriette; Øvervoll, Morten

2017-01-01

Although faces are often included in the broad category of emotional visual stimuli, the affective impact of different facial expressions is not well documented. The present experiment investigated startle electromyographic responses to pictures of neutral, happy, angry, and fearful facial expressions, with a frontal face direction (directed) and at a 45° angle to the left (averted). Results showed that emotional facial expressions interact with face direction to produce startle potentiation: Greater responses were found for angry expressions, compared with fear and neutrality, with directed faces. When faces were averted, fear and neutrality produced larger responses compared with anger and happiness. These results are in line with the notion that startle is potentiated to stimuli signaling threat. That is, a forward directed angry face may signal a threat toward the observer, and a fearful face directed to the side may signal a possible threat in the environment.

The time course of face processing: startle eyeblink response modulation by face gender and expression.

PubMed

Duval, Elizabeth R; Lovelace, Christopher T; Aarant, Justin; Filion, Diane L

2013-12-01

The purpose of this study was to investigate the effects of both facial expression and face gender on startle eyeblink response patterns at varying lead intervals (300, 800, and 3500ms) indicative of attentional and emotional processes. We aimed to determine whether responses to affective faces map onto the Defense Cascade Model (Lang et al., 1997) to better understand the stages of processing during affective face viewing. At 300ms, there was an interaction between face expression and face gender with female happy and neutral faces and male angry faces producing inhibited startle. At 3500ms, there was a trend for facilitated startle during angry compared to neutral faces. These findings suggest that affective expressions are perceived differently in male and female faces, especially at short lead intervals. Future studies investigating face processing should take both face gender and expression into account. © 2013.

Do infants find snakes aversive? Infants' physiological responses to "fear-relevant" stimuli.

PubMed

Thrasher, Cat; LoBue, Vanessa

2016-02-01

In the current research, we sought to measure infants' physiological responses to snakes-one of the world's most widely feared stimuli-to examine whether they find snakes aversive or merely attention grabbing. Using a similar method to DeLoache and LoBue (Developmental Science, 2009, Vol. 12, pp. 201-207), 6- to 9-month-olds watched a series of multimodal (both auditory and visual) stimuli: a video of a snake (fear-relevant) or an elephant (non-fear-relevant) paired with either a fearful or happy auditory track. We measured physiological responses to the pairs of stimuli, including startle magnitude, latency to startle, and heart rate. Results suggest that snakes capture infants' attention; infants showed the fastest startle responses and lowest average heart rate to the snakes, especially when paired with a fearful voice. Unexpectedly, they also showed significantly reduced startle magnitude during this same snake video plus fearful voice combination. The results are discussed with respect to theoretical perspectives on fear acquisition. Copyright © 2015 Elsevier Inc. All rights reserved.

Enhanced startle reflexivity during presentation of visual nurture cues in young adults who experienced parental divorce in early childhood.

PubMed

Hengesch, Xenia; Larra, Mauro F; Finke, Johannes B; Blumenthal, Terry D; Schächinger, Hartmut

2017-10-01

Adverse childhood experiences (ACE) may influence stress and affective processing in adulthood. Animal and human studies show enhanced startle reflexivity in adult participants with ACE. This study examined the impact of one of the most common ACE, parental divorce, on startle reflexivity in adulthood. Affective modulation of acoustically-elicited startle eye blink was assessed in a group of 23 young adults with self-reported history of parental divorce, compared to an age- and sex-matched control group (n=18). Foreground pictures were either aversive (e.g. mutilation and injury), standard appetitive (e.g. erotic, recreational sport), or nurture pictures (e.g. related to early life, parental care), intermixed with neutral pictures (e.g. household objects), and organized in three valence blocks delivered in a balanced, pseudo-randomized sequence. During picture viewing startle eye blinks were elicited by binaural white noise bursts (50ms, 105 dB) via headphones and recorded at the left orbicularis oculi muscle via EMG. A significant interaction of group×picture valence (p=0.01) was observed. Contrast with controls revealed blunted startle responsiveness of the ACE group during presentation of aversive pictures, but enhanced startle during presentation of nurture-related pictures. No group differences were found during presentation of standard appetitive pictures. ACE participants rated nurture pictures as more arousing (p=0.02) than did control participants. Results suggest that divorce in childhood led to altered affective context information processing in early adulthood. When exposed to unpleasant (vs. neutral) pictures participants with ACE showed less startle potentiation than controls. Nurture context, however, potentiated startle in ACE participants, suggesting visual cuing to activate protective behavioral responses. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of brain-derived and glial cell line-derived neurotrophic factors on startle response and disrupted prepulse inhibition in mice of DBA/2J inbred strain.

PubMed

Naumenko, Vladimir S; Bazovkina, Daria V; Morozova, Maryana V; Popova, Nina K

2013-08-29

Prepulse inhibition (PPI), the reduction in acoustic startle reflex when it is preceded by weak prepulse stimuli, is a measure of critical to normal brain functioning sensorimotor gating. PPI deficit was shown in a variety of psychiatric disorders including schizophrenia, and in DBA/2J mouse strain. In the current study, we examined the effects of brain-derived (BDNF) and glial cell line-derived (GDNF) neurotrophic factors on acoustic startle response and PPI in DBA/2J mice. It was found that BDNF (300 ng, i.c.v.) significantly increased amplitude of startle response and restored disrupted PPI in 7 days after acute administration. GDNF (800 ng, i.c.v.) did not produce significant alteration neither in amplitude of startle response nor in PPI in DBA/2J mice. The reversal effect of BDNF on PPI deficit was unusually long-lasting: significant increase in PPI was found 1.5 months after single acute BDNF administration. Long-term ameliorative effect BDNF on disrupted PPI suggested the implication of epigenetic mechanism in BDNF action on neurogenesis. BDNF rather than GDNF could be a perspective drug for the treatment of sensorimotor gating impairments. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

ACUTE EFFECTS OF AMITRAZ ON THE ACOUSTIC STARTLE RESPONSE AND MOTOR ACTIVITY

EPA Science Inventory

To characterize further the behavioral toxicity of amitraz, comparisons were made between the effects of amitraz on motor activity, the acoustic startle response, body temperature, and body weight in male Long-Evans rats. cute dosage-effect and time-course determinations of motor...

Moral identity and emotion in athletes.

PubMed

Kavussanu, Maria; Willoughby, Adrian; Ring, Christopher

2012-12-01

The purpose of this study was to investigate the effects of moral identity on physiological responses to affective pictures, namely, the startle blink reflex and pain-related evoked potential. Male (n = 48) and female (n = 46) athletes participating in contact team sports were randomly assigned to either a moral identity group or a non-moral identity group and viewed a series of unpleasant, neutral, and pleasant sport-specific pictures. During picture viewing, a noxious electrocutaneous stimulus was delivered as the startle probe and the startle blink and pain-related evoked potential were measured. Upon completion of physiological measures, participants reviewed the pictures and rated them for valence and arousal. ANOVAs revealed that participants in the moral identity group displayed larger startle blinks and smaller pain-related potentials than did those in the non-moral identity group across all picture valence categories. However, the difference in the magnitude of startle blinks between the moral and non-moral identity groups was larger in response to unpleasant than pleasant and neutral pictures. Our findings suggest that moral identity affects physiological responses to sport-specific affective pictures, thereby providing objective evidence for the link between moral identity and emotion in athletes.

Meta-analytic review of the effects of a single dose of intranasal oxytocin on threat processing in humans.

PubMed

Leppanen, Jenni; Ng, Kah Wee; Kim, Youl-Ri; Tchanturia, Kate; Treasure, Janet

2018-01-01

Heightened threat sensitivity is a transdiagnostic feature in several psychiatric disorders. The neuropeptide oxytocin has been shown to reduce fear related behaviours and facilitated fear extinction in animals. These findings have led to increasing interest to explore the effects of intranasal oxytocin on threat processing in humans. The review included 26 studies (N = 1173), nine of which included clinical populations (N = 234). The clinical groups included were people with borderline personality disorder (BPD), anorexia nervosa, bulimia nervosa, depression, anxiety, and alcohol dependence disorder. We examined the effects of a single dose of intranasal oxytocin on startle response, attentional responses, and behavioural responses to threat. A single dose of intranasal oxytocin significantly increased the physiological startle response to threat in healthy people with a small effect size. However, oxytocin did not have significant effects on attentional bias towards social or disorder-specific threat, fixation towards threatening stimuli among healthy or clinical populations, or on threat related behavioural approach or avoidance responses. No studies investigated the effects of oxytocin on the startle response to threat among clinical populations. Additionally, only one of the reviewed studies had sufficient power to detect at least a moderate effect of oxytocin according to our criterion. The synthesis of literature suggest that oxytocin may influence the salience of threatening stimuli among healthy individuals, increasing the startle response to threat. It would be of interest to investigate the effects of oxytocin on the startle response to threat among clinical populations. Copyright © 2017 Elsevier B.V. All rights reserved.

The Influence of Stuttering Severity on Acoustic Startle Responses

ERIC Educational Resources Information Center

Ellis, John B.; Finan, Donald S.; Ramig, Peter R.

2008-01-01

Purpose: This study examined the potential impact of stuttering severity, as measured by the Perceptions of Stuttering Inventory (Woolf, 1967) on acoustic startle responses. Method: Three groups, consisting of 10 nonstuttering adults, 9 mild stutterering adults, and 11 moderate/severe stutterering adults, were presented with identical 95-dB…

EFFECTS OF TWO PYRETHROID INSECTICIDES ON MOTOR ACTIVITY AND THE ACOUSTIC STARTLE RESPONSE IN THE RAT

EPA Science Inventory

To better characterize the behavioral toxicity of pyrethroid insecticides, comparisons were made of the effects of cismethrin and deltamethrin exposure on motor activity and the acoustic startle response in male Long-Evans rats. Acute dose-effect, acute time course, and 30-day re...

Effects of smoking on the acoustic startle response and prepulse inhibition in smokers with and without posttraumatic stress disorder.

PubMed

Vrana, Scott R; Calhoun, Patrick S; McClernon, F Joseph; Dennis, Michelle F; Lee, Sherman T; Beckham, Jean C

2013-12-01

Cigarette smokers smoke in part because nicotine helps regulate attention. Prepulse inhibition (PPI) of the startle reflex is a measure of early attentional gating that is reduced in abstinent smokers and in groups with attention regulation difficulties. Attention difficulties are found in people with posttraumatic stress disorder (PTSD). The aim of this study is to assess whether smoking and abstinence differentially affect the startle response and PPI in smokers with and without PTSD. Startle response and PPI (prepulses at 60, 120, or 240 ms) were measured in smokers with (N = 39) and without (N = 61) PTSD, while smoking and again while abstinent. Participants with PTSD produced both larger magnitude and faster latency startle responses than controls. Across groups, PPI was greater when smoking than when abstinent. The PTSD and control group exhibited different patterns of PPI across prepulse intervals when smoking and when abstinent. Older age was associated with reduced PPI, but only when abstinent from smoking. The effects of PTSD on startle magnitude and of smoking on PPI replicate earlier studies. The different pattern of PPI exhibited in PTSD and control groups across prepulse intervals, while smoking and abstinent suggests that previous research on smoking and PPI has been limited by not including longer prepulse intervals, and that nicotine may affect the time course as well as increasing the level of PPI. The reduced PPI among older participants during abstinence suggests that nicotine may play a role in maintaining attention in older smokers, which may motivate continued smoking in older individuals.

Acute Tryptophan Depletion Increases Translational Indices of Anxiety but not Fear: Serotonergic Modulation of the Bed Nucleus of the Stria Terminalis?

PubMed Central

Robinson, Oliver J; Overstreet, Cassie; Allen, Phillip S; Pine, Daniel S; Grillon, Christian

2012-01-01

Serotonin is strongly implicated in the mammalian stress response, but surprisingly little is known about its mode of action. Recent data suggest that serotonin can inhibit aversive responding in humans, but this remains underspecified. In particular, data in rodents suggest that global serotonin depletion may specifically increase long-duration bed nucleus of the stria terminalis (BNST)-mediated aversive responses (ie, anxiety), but not short-duration BNST-independent responses (ie, fear). Here, we extend these findings to humans. In a balanced, placebo-controlled crossover design, healthy volunteers (n=20) received a controlled diet with and without the serotonin precursor tryptophan (acute tryptophan depletion; ATD). Aversive states were indexed by translational acoustic startle measures. Fear and anxiety were operationally defined as the increase in startle reactivity during short- and long-duration threat periods evoked by predictable shock (fear-potentiated startle) and by the context in which the shocks were administered (anxiety-potentiated startle), respectively. ATD significantly increased long-duration anxiety-potentiated startle but had no effect on short-duration fear-potentiated startle. These results suggest that serotonin depletion in humans selectively increases anxiety but not fear. Current translational frameworks support the proposition that ATD thus disinhibits dorsal raphé-originating serotonergic control of corticotropin-releasing hormone-mediated excitation of the BNST. This generates a candidate neuropharmacological mechanism by which depleted serotonin may increase response to sustained threats, alongside clear implications for our understanding of the manifestation and treatment of mood and anxiety disorders. PMID:22491355

Emotion modulation of the startle reflex in essential tremor: Blunted reactivity to unpleasant and pleasant pictures.

PubMed

Lafo, Jacob A; Mikos, Ania; Mangal, Paul C; Scott, Bonnie M; Trifilio, Erin; Okun, Michael S; Bowers, Dawn

2017-01-01

Essential tremor is a highly prevalent movement disorder characterized by kinetic tremor and mild cognitive-executive changes. These features are commonly attributed to abnormal cerebellar changes, resulting in disruption of cerebellar-thalamo-cortical networks. Less attention has been paid to alterations in basic emotion processing in essential tremor, despite known cerebellar-limbic interconnectivity. In the current study, we tested the hypothesis that a psychophysiologic index of emotional reactivity, the emotion modulated startle reflex, would be muted in individuals with essential tremor relative to controls. Participants included 19 essential tremor patients and 18 controls, who viewed standard sets of unpleasant, pleasant, and neutral pictures for six seconds each. During picture viewing, white noise bursts were binaurally presented to elicit startle eyeblinks measured over the orbicularis oculi. Consistent with past literature, controls' startle eyeblink responses were modulated according to picture valence (unpleasant > neutral > pleasant). In essential tremor participants, startle eyeblinks were not modulated by emotion. This modulation failure was not due to medication effects, nor was it due to abnormal appraisal of emotional picture content. Neuroanatomically, it remains unclear whether diminished startle modulation in essential tremor is secondary to aberrant cerebellar input to the amygdala, which is involved in priming the startle response in emotional contexts, or due to more direct disruption between the cerebellum and brainstem startle circuitry. If the former is correct, these findings may be the first to reveal dysregulation of emotional networks in essential tremor. Copyright © 2016 Elsevier Ltd. All rights reserved.

Startle reduces recall of a recently learned internal model.

PubMed

Wright, Zachary; Patton, James L; Ravichandran, Venn

2011-01-01

Recent work has shown that preplanned motor programs are released early from subcortical areas by the using a startling acoustic stimulus (SAS). Our question is whether this response might also contain a recently learned internal model, which draws on experience to predict and compensate for expected perturbations in a feedforward manner. Studies of adaptation to robotic forces have shown some evidence of this, but were potentially confounded by cocontraction caused by startle. We performed a new adaptation experiment using a visually distorted field that could not be confounded by cocontraction. We found that in all subjects that exhibited startle, the startle stimulus (1) reduced performance of the recently learned task (2) reduced after-effect magnitudes. Because startle reduced but did not eliminate the recall of learned control, we suggest that multiple neural centers (cortical and subcortical) are involved in such learning and adaptation, which can impact training areas such as piloting, teleoperation, sports, and rehabilitation. © 2011 IEEE

Stuttering in adults: the acoustic startle response, temperamental traits, and biological factors.

PubMed

Alm, Per A; Risberg, Jarl

2007-01-01

The purpose of this study was to investigate the relation between stuttering and a range of variables of possible relevance, with the main focus on neuromuscular reactivity, and anxiety. The explorative analysis also included temperament, biochemical variables, heredity, preonset lesions, and altered auditory feedback (AAF). An increased level of neuromuscular reactivity in stuttering adults has previously been reported by [Guitar, B. (2003). Acoustic startle responses and temperament in individuals who stutter. Journal of Speech Language and Hearing Research, 46, 233-240], also indicating a link to anxiety and temperament. The present study included a large number of variables in order to enable analysis of subgroups and relations between variables. Totally 32 stuttering adults were compared with nonstuttering controls. The acoustic startle eyeblink response was used as a measure of neuromuscular reactivity. No significant group difference was found regarding startle, and startle was not significantly correlated with trait anxiety, stuttering severity, or AAF. Startle was mainly related to calcium and prolactin. The stuttering group had significantly higher scores for anxiety and childhood ADHD. Two subgroups of stuttering were found, with high versus low traits of childhood ADHD, characterized by indications of preonset lesions versus heredity for stuttering. The study does not support the view that excessive reactivity is a typical characteristic of stuttering. The increased anxiety is suggested to mainly be an effect of experiences of stuttering. As a result of reading this article, the reader will be able to: (a) critically discuss the literature regarding stuttering in relation to acoustic startle, anxiety, and temperament; (b) describe the effect of calcium on neuromuscular reactivity; (c) discuss findings supporting the importance of early neurological incidents in some cases of stuttering, and the relation between such incidents and traits of ADHD or ADD; and (d) discuss the role of genetics in stuttering.

Deficient prepulse inhibition of acoustic startle in Hooded-Wistar rats compared with Sprague-Dawley rats.

PubMed

van den Buuse, Maarten

2003-04-01

1. Prepulse inhibition of acoustic startle has been suggested as a model of sensorimotor gating and central sensory information processing. Prepulse inhibition is impaired in patients with schizophrenia and responses can be restored by antipsychotic drug treatment. In the present study, startle and prepulse inhibition of startle were compared in different rat strains. 2. Sprague-Dawley rats showed robust inhibition of startle responses by increasing intensities of prepulse delivered just before the startle stimulus. In contrast, at both 4 and 10 weeks of age, rats of the Hooded-Wistar line had markedly reduced prepulse inhibition, although startle responses were not different. 3. Treatment with the dopamine receptor agonist apomorphine (0.1 mg/kg) or the N-methyl-d-aspartate (NMDA) receptor antagonist MK-801 (0.1 mg/kg) caused disruption of prepulse inhibition in Sprague-Dawley rats. In Hooded-Wistar rats, apomorphine further reduced the already low level of prepulse inhibition, but MK-801 treatment had no significant effect. This suggests that the impaired prepulse inhibition in Hooded-Wistar rats could be caused by changes in glutamatergic activity and/or NMDA receptors in these rats. 4. In photocell cages, spontaneous exploratory activity and inner zone activity were significantly lower in Hooded-Wistar rats than in Sprague-Dawley rats. Similarly, on the elevated plus-maze, Hooded-Wistar rats showed a lower propensity to visit the open arms. In contrast, amphetamine (0.5 mg/kg)-induced locomotor hyperactivity, an animal model of psychosis, was enhanced in Hooded-Wistar rats. 5. These data suggest that the Hooded-Wistar line could be a useful genetic animal model to study the interaction of glutamatergic and dopaminergic mechanisms in anxiety and schizophrenia.

The Gap-Startle Paradigm for Tinnitus Screening in Animal Models: Limitations and Optimization

PubMed Central

Lobarinas, Edward; Hayes, Sarah H.; Allman, Brian L.

2012-01-01

In 2006, Turner and colleagues (Behav Neurosci, 120:188–195) introduced the gap-startle paradigm as a high-throughput method for tinnitus screening in rats. Under this paradigm, gap detection ability was assessed by determining the level of inhibition of the acoustic startle reflex produced by a short silent gap inserted in an otherwise continuous background sound prior to a loud startling stimulus. Animals with tinnitus were expected to show impaired gap detection ability (i.e., lack of inhibition of the acoustic startle reflex) if the background sound containing the gap was qualitatively similar to the tinnitus pitch. Thus, for the gap-startle paradigm to be a valid tool to screen for tinnitus, a robust startle response from which to inhibit must be present. Because recent studies have demonstrated that the acoustic startle reflex could be dramatically reduced following noise exposure, we endeavored to 1) modify the gap-startle paradigm to be more resilient in the presence of hearing loss, and 2) evaluate whether a reduction in startle reactivity could confound the interpretation of gap prepulse inhibition and lead to errors in screening for tinnitus. In the first experiment, the traditional broadband noise (BBN) startle stimulus was replaced by a bandpass noise in which the sound energy was concentrated in the lower frequencies (5–10 kHz) in order to maintain audibility of the startle stimulus after unilateral high frequency noise exposure (16 kHz). However, rats still showed a 57% reduction in startle amplitude to the bandpass noise post-noise exposure. A follow-up experiment on a separate group of rats with transiently-induced conductive hearing loss revealed that startle reactivity was better preserved when the BBN startle stimulus was replaced by a rapid airpuff to the back of the rats neck. Furthermore, it was found that transient unilateral conductive hearing loss, which was not likely to induce tinnitus, caused an impairment in gap prepulse inhibition as assessed with the traditional BBN gap-startle paradigm, resulting in a false-positive screening for tinnitus. Thus, the present study identifies significant caveats of the traditional gap-startle paradigm, and describes experimental parameters using an airpuff startle stimulus which may help to limit the negative consequences of reduced startle reactivity following noise exposure, thereby allowing researchers to better screen for tinnitus in animals with hearing loss. PMID:22728305

Baseline and Modulated Acoustic Startle Responses in Adolescent Girls with Posttraumatic Stress Disorder

ERIC Educational Resources Information Center

Lipschitz, Deborah S.; Mayes, Linda M.; Rasmusson, Ann M.; Anyan, Walter; Billingslea, Eileen; Gueorguieva, Ralitza; Southwick, Steven M.

2005-01-01

Objective: To assess baseline and modulated acoustic startle responses in adolescent girls with posttraumatic stress disorder (PTSD). Method: Twenty-eight adolescent girls with PTSD and 23 healthy control girls were recruited for participation in the study. Acoustic stimuli were bursts of white noise of 104 dB presented biaurally through…

"Glass fairies" and "bone children": adolescents and young adults with anorexia nervosa show positive reactions towards extremely emaciated body pictures measured by the startle reflex paradigm.

PubMed

Reichel, Valeska A; Schneider, Nora; Grünewald, Barbara; Kienast, Thorsten; Pfeiffer, Ernst; Lehmkuhl, Ulrike; Korte, Alexander

2014-02-01

In this study, we investigated the emotional processing of extremely emaciated body cues in adolescents and young adults with (n  =  36) and without (n =  36) anorexia nervosa (AN), introducing a new picture type, which was taken from websites that promote extreme thinness and is targeted specifically at adolescents interested in extreme thinness. A startle reflex paradigm was used for implicit reactions, while a self-assessment instrument was used for subjective responses. We found a significant group difference with a startle inhibition (appetitive response) among the patients and a startle potentiation (aversive response) among the controls, whereas no such difference for subjective measures was found. The results are in contrast to previous studies, which proposed a general failure to activate the appetitive motivational system in AN, but in keeping with findings from other addictions, where the same response pattern has been found. Implications for prevention and therapy are discussed. Copyright © 2013 Society for Psychophysiological Research.

An acoustic startle alters knee joint stiffness and neuromuscular control.

PubMed

DeAngelis, A I; Needle, A R; Kaminski, T W; Royer, T R; Knight, C A; Swanik, C B

2015-08-01

Growing evidence suggests that the nervous system contributes to non-contact knee ligament injury, but limited evidence has measured the effect of extrinsic events on joint stability. Following unanticipated events, the startle reflex leads to universal stiffening of the limbs, but no studies have investigated how an acoustic startle influences knee stiffness and muscle activation during a dynamic knee perturbation. Thirty-six individuals were tested for knee stiffness and muscle activation of the quadriceps and hamstrings. Subjects were seated and instructed to resist a 40-degree knee flexion perturbation from a relaxed state. During some trials, an acoustic startle (50 ms, 1000 Hz, 100 dB) was applied 100 ms prior to the perturbation. Knee stiffness, muscle amplitude, and timing were quantified across time, muscle, and startle conditions. The acoustic startle increased short-range (no startle: 0.044 ± 0.011 N·m/deg/kg; average startle: 0.047 ± 0.01 N·m/deg/kg) and total knee stiffness (no startle: 0.036 ± 0.01 N·m/deg/kg; first startle 0.027 ± 0.02 N·m/deg/kg). Additionally, the startle contributed to decreased [vastus medialis (VM): 13.76 ± 33.6%; vastus lateralis (VL): 6.72 ± 37.4%] but earlier (VM: 0.133 ± 0.17 s; VL: 0.124 ± 0.17 s) activation of the quadriceps muscles. The results of this study indicate that the startle response can significantly disrupt knee stiffness regulation required to maintain joint stability. Further studies should explore the role of unanticipated events on unintentional injury. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Modification of caffeine effects on the affect-modulated startle by neuropeptide S receptor gene variation.

PubMed

Domschke, Katharina; Klauke, Benedikt; Winter, Bernward; Gajewska, Agnes; Herrmann, Martin J; Warrings, Bodo; Mühlberger, Andreas; Wosnitza, Katherina; Dlugos, Andrea; Naunin, Swantje; Nienhaus, Kathrin; Fobker, Manfred; Jacob, Christian; Arolt, Volker; Pauli, Paul; Reif, Andreas; Zwanzger, Peter; Deckert, Jürgen

2012-08-01

Both the neuropeptide S (NPS) system and antagonism at the adenosine A2A receptor (e.g., by caffeine) were found to play a crucial role in the mediation of arousal and anxiety/panic in animal and human studies. Furthermore, a complex interaction of the neuropeptide S and the adenosinergic system has been suggested with administration of the adenosine A2A receptor antagonist caffeine downregulating NPS levels (Lage et al., 2006) and attenuating the stimulatory effects of NPS in rodents (Boeck et al., 2010). Thus, in the present study, the impact of the functional neuropeptide S receptor (NPSR) A/T (Asn(107)Ile; rs324981) variant on affect-modulated (neutral, unpleasant, and pleasant IAPS pictures) startle response depending on the administration of 300 mg caffeine citrate was investigated in a sample of 124 (m = 58, f = 66) healthy probands using a double-blind, placebo-controlled design. ANOVA revealed a significant interaction between NPSR genotype, challenge condition, and picture valence. Comparing startle magnitudes upon stimulation with neutral or emotional pictures between the placebo and caffeine condition, in AA/AT non-risk genotype carriers no significant difference was discerned, while TT risk genotype carriers showed a significantly increased startle magnitude in response to neutral stimuli (p = .02) and a significantly decreased startle magnitude in response to unpleasant stimuli (p = .02) in the caffeine condition as compared to the placebo condition. In summary, the present findings - extending previous evidence from rodent studies - for the first time provide support for a complex, non-linear interaction of the neuropeptide S and adenosinergic systems affecting the affect-modulated startle response as an intermediate phenotype of anxiety in humans.

Auditory sensitivity of larval zebrafish (Danio rerio) measured using a behavioral prepulse inhibition assay

PubMed Central

Bhandiwad, Ashwin A.; Zeddies, David G.; Raible, David W.; Rubel, Edwin W.; Sisneros, Joseph A.

2013-01-01

SUMMARY Zebrafish (Danio rerio) have become a valuable model for investigating the molecular genetics and development of the inner ear in vertebrates. In this study, we employed a prepulse inhibition (PPI) paradigm to assess hearing in larval wild-type (AB) zebrafish during early development at 5–6 days post-fertilization (d.p.f.). We measured the PPI of the acoustic startle response in zebrafish using a 1-dimensional shaker that simulated the particle motion component of sound along the fish's dorsoventral axis. The thresholds to startle-inducing stimuli were determined in 5–6 d.p.f. zebrafish, and their hearing sensitivity was then characterized using the thresholds of prepulse tone stimuli (90–1200 Hz) that inhibited the acoustic startle response to a reliable startle stimulus (820 Hz at 20 dB re. 1 m s−2). Hearing thresholds were defined as the minimum prepulse tone level required to significantly reduce the startle response probability compared with the baseline (no-prepulse) condition. Larval zebrafish showed greatest auditory sensitivity from 90 to 310 Hz with corresponding mean thresholds of −19 to −10 dB re. 1 m s−2, respectively. Hearing thresholds of prepulse tones were considerably lower than previously predicted by startle response assays. The PPI assay was also used to investigate the relative contribution of the lateral line to the detection of acoustic stimuli. After aminoglycoside-induced neuromast hair-cell ablation, we found no difference in PPI thresholds between treated and control fish. We propose that this PPI assay can be used to screen for novel zebrafish hearing mutants and to investigate the ontogeny of hearing in zebrafish and other fishes. PMID:23966590

Effects of anxiety sensitivity and expectations on the modulation of the startle eyeblink response during a caffeine challenge.

PubMed

Benke, Christoph; Blumenthal, Terry D; Modeß, Christiane; Hamm, Alfons O; Pané-Farré, Christiane A

2015-09-01

The way in which the tendency to fear somatic arousal sensations (anxiety sensitivity), in interaction with the created expectations regarding arousal induction, might affect defensive responding to a symptom provocation challenge is not yet understood. The present study investigated the effect of anxiety sensitivity on autonomic arousal, startle eyeblink responses, and reported arousal and alertness to expected vs. unexpected caffeine consumption. To create a match/mismatch of expected and experienced arousal, high and low anxiety sensitive participants received caffeine vs. no drug either mixed in coffee (expectation of arousal induction) or in bitter lemon soda (no expectation of arousal induction) on four separate occasions. Autonomic arousal (heart rate, skin conductance level), respiration (end-tidal CO2, minute ventilation), defensive reflex responses (startle eyeblink), and reported arousal and alertness were recorded prior to, immediately and 30 min after beverage ingestion. Caffeine increased ventilation, autonomic arousal, and startle response magnitudes. Both groups showed comparable levels of autonomic and respiratory responses. The startle eyeblink responses were decreased when caffeine-induced arousal occurred unexpectedly, e.g., after administering caffeine in bitter lemon. This effect was more accentuated in high anxiety sensitive persons. Moreover, in high anxiety sensitive persons, the expectation of arousal (coffee consumption) led to higher subjective alertness when administering caffeine and increased arousal even if no drug was consumed. Unexpected symptom provocation leads to increased attention allocation toward feared arousal sensations in high anxiety sensitive persons. This finding broadens our understanding of modulatory mechanisms in defensive responding to bodily symptoms.

Emotion dysregulation in alexithymia: Startle reactivity to fearful affective imagery and its relation to heart rate variability.

PubMed

Panayiotou, Georgia; Constantinou, Elena

2017-09-01

Alexithymia is associated with deficiencies in recognizing and expressing emotions and impaired emotion regulation, though few studies have verified the latter assertion using objective measures. This study examined startle reflex modulation by fearful imagery and its associations with heart rate variability in alexithymia. Fifty-four adults (27 alexithymic) imagined previously normed fear scripts. Startle responses were assessed during baseline, first exposure, and reexposure. During first exposure, participants, in separate trials, engaged in either shallow or deep emotion processing, giving emphasis on descriptive or affective aspects of imagery, respectively. Resting heart rate variability was assessed during 2 min of rest prior to the experiment, with high alexithymic participants demonstrating significantly higher LF/HF (low frequency/high frequency) ratio than controls. Deep processing was associated with nonsignificantly larger and faster startle responses at first exposure for alexithymic participants. Lower LF/HF ratio, reflecting higher parasympathetic cardiac activity, predicted greater startle amplitude habituation for alexithymia but lower habituation for controls. Results suggest that, when exposed to prolonged threat, alexithymics may adjust poorly, showing a smaller initial defensive response but slower habituation. This pattern seems related to their low emotion regulation ability as indexed by heart rate variability. © 2017 Society for Psychophysiological Research.

PYRETHROID INSECTICIDES AND THE GAMMA-AMINOBUTYRIC ACID (ALPHA) RECEPTOR COMPLEX: MOTOR ACTIVITY AND THE ACOUSTIC STARTLE RESPONSE IN THE RAT (JOURNAL VERSION)

EPA Science Inventory

Two behavioral tests, locomotor activity and the acoustic startle response (ASR), were utilized to test for dose-addition of cismethrin, a Type I, or deltamethrin, a Type II pyrethroid, with compounds active to the gamma-aminobutryic acid (GABA) receptor complex (picrotoxin, musc...

Sexual orientation-related differences in prepulse inhibition of the human startle response.

PubMed

Rahman, Qazi; Kumari, Veena; Wilson, Glenn D

2003-10-01

Prepulse inhibition (PPI) refers to a reduction in the startle response to a strong sensory stimulus when this stimulus is preceded by a weaker stimulus--the prepulse. PPI reflects a nonlearned sensorimotor gating mechanism and also shows a robust gender difference, with women exhibiting lower PPI than men. The present study examined the eyeblink startle responses to acoustic stimuli of 59 healthy heterosexual and homosexual men and women. Homosexual women showed significantly masculinized PPI compared with heterosexual women, whereas no difference was observed in PPI between homosexual and heterosexual men. These data provide the first evidence for within-gender differences in basic sensorimotor gating mechanisms and implicate the known neural substrates of PPI in human sexual orientation. (c) 2003 APA, all rights reserved

Effects of Nicotine and Nicotinic Antagonists on the Acoustic Startle Response and on Pre-Pulse Inhibition in Rats

DTIC Science & Technology

1996-06-07

the auditory nerve, the ventral cochlear nucleus , nuclei of the lateral lemniscus, nucleus reticularis pontis caudalis, spinal neuron, and lower... nucleus , nuclei of the lateral lemniscus, nucleus reticularis pontis caudalis, hippocampus, and striatum (Davis, et al., 1982; Swerdlow, et aI, 1992...Davis, M. (1985) Cocaine effects on acoustic startle and startle elicited electrically from cochlear nucleus . P§ychQpharmacology, 87, 396-399 James

Effect of facial self-resemblance on the startle response and subjective ratings of erotic stimuli in heterosexual men.

PubMed

Lass-Hennemann, Johanna; Deuter, Christian E; Kuehl, Linn K; Schulz, Andre; Blumenthal, Terry D; Schachinger, Hartmut

2011-10-01

Cues of kinship are predicted to increase prosocial behavior due to the benefits of inclusive fitness, but to decrease approach motivation due to the potential costs of inbreeding. Previous studies have shown that facial resemblance, a putative cue of kinship, increases prosocial behavior. However, the effects of facial resemblance on mating preferences are equivocal, with some studies finding that facial resemblance decreases sexual attractiveness ratings, while other studies show that individuals choose mates partly on the basis of similarity. To further investigate this issue, a psychophysiological measure of affective processing, the startle response, was used in this study, assuming that differences in approach motivation to erotic pictures will modulate startle. Male volunteers (n = 30) viewed 30 pictures of erotic female nudes while startle eyeblink responses were elicited by acoustic noise probes. The female nude pictures were digitally altered so that the face either resembled the male participant or another participant, or were not altered. Non-nude neutral pictures were also included. Importantly, the digital alteration was undetected by the participants. Erotic pictures were rated as being pleasant and clearly reduced startle eyeblink magnitude as compared to neutral pictures. Participants showed greater startle inhibition to self-resembling than to other-resembling or non-manipulated female nude pictures, but subjective pleasure and arousal ratings did not differ among the three erotic picture categories. Our data suggest that visual facial resemblance of opposite-sex nudes increases approach motivation in men, and that this effect was not due to their conscious evaluation of the erotic stimuli.

Pontine hyperperfusion in sporadic hyperekplexia

PubMed Central

Vetrugno, Roberto; Mascalchi, Mario; Vella, Alessandra; Nave, Riccardo Della; Guerrini, Laura; Vattimo, Angelo; del Giudice, Emanuele Miraglia; Plazzi, Giuseppe; D'Angelo, Roberto; Greco, Giovanni; Montagna, Pasquale

2007-01-01

Objective To explore with neuroimaging techniques the anatomical and functional correlates of sporadic hyperekplexia. Methods Two elderly women with sporadic hyperekplexia underwent neurophysiological assessment, MRI of the brain and proton magnetic resonance spectroscopy (1H‐MRS) of the brainstem and frontal lobes. Regional cerebral blood flow was investigated with single photon emission tomography (SPECT) during evoked startles and at rest. Results Both patients showed excessively large and non‐habituating startle responses. In both patients, MRI showed impingement of the brainstem by the vertebrobasilar artery, lack of frontal or brainstem abnormalities on 1H‐MRS and hyperperfusion in the dorsal pons and cingulate cortex, and superior frontal gyrus at SPECT during evoked startles. Conclusions In our patients with hyperekplexia, the vertebrobasilar arteries were found to impinge on the brainstem. Neurophysiological findings and neurofunctional imaging of evoked startles indicated a pontine origin of the movement disorder modulated by activation in cortical, especially frontal, areas. The neurofunctional correlates of evoked startles in human sporadic hyperekplexia are similar to those observed for the startle circuit in animals. PMID:17702784

Pontine hyperperfusion in sporadic hyperekplexia.

PubMed

Vetrugno, Roberto; Mascalchi, Mario; Vella, Alessandra; Della Nave, Riccardo; Guerrini, Laura; Vattimo, Angelo; del Giudice, Emanuele Miraglia; Plazzi, Giuseppe; D'Angelo, Roberto; Greco, Giovanni; Montagna, Pasquale

2007-09-01

To explore with neuroimaging techniques the anatomical and functional correlates of sporadic hyperekplexia. Two elderly women with sporadic hyperekplexia underwent neurophysiological assessment, MRI of the brain and proton magnetic resonance spectroscopy (1H-MRS) of the brainstem and frontal lobes. Regional cerebral blood flow was investigated with single photon emission tomography (SPECT) during evoked startles and at rest. Both patients showed excessively large and non-habituating startle responses. In both patients, MRI showed impingement of the brainstem by the vertebrobasilar artery, lack of frontal or brainstem abnormalities on 1H-MRS and hyperperfusion in the dorsal pons and cingulate cortex, and superior frontal gyrus at SPECT during evoked startles. In our patients with hyperekplexia, the vertebrobasilar arteries were found to impinge on the brainstem. Neurophysiological findings and neurofunctional imaging of evoked startles indicated a pontine origin of the movement disorder modulated by activation in cortical, especially frontal, areas. The neurofunctional correlates of evoked startles in human sporadic hyperekplexia are similar to those observed for the startle circuit in animals.

Does anxiety sensitivity correlate with startle habituation? An examination in two independent samples.

PubMed

Campbell, Miranda L; Gorka, Stephanie M; McGowan, Sarah K; Nelson, Brady D; Sarapas, Casey; Katz, Andrea C; Robison-Andrew, E Jenna; Shankman, Stewart A

2014-01-01

Individuals with anxiety disorders have previously demonstrated abnormal habituation to aversiveness over time. As anxiety sensitivity (AS), or an individuals' propensity to fear of anxiety-related sensations, has been shown to be a risk factor for anxiety disorders (particularly panic disorder), the present study examined whether AS was also associated with abnormal habituation. This association was examined in two independent samples of undergraduates (Ntotal=178). Habituation was operationalised as the reduction in startle response to multiple startle probes presented over 2.5 minutes and three definitions of this reduction were employed. Results indicated that individuals with higher levels of AS evidenced deficits in startle habituation, but the strength of this relationship was somewhat dependent on the definition of startle habituation, with the most robust definition being an analysis of participants' individual slopes across all nine blinks. The present findings suggest that startle habituation is a key mechanism underlying AS, and may help elucidate the role this risk factor plays in the pathogenesis of anxiety disorders.

Degraded expression of learned feedforward control in movements released by startle.

PubMed

Wright, Zachary A; Carlsen, Anthony N; MacKinnon, Colum D; Patton, James L

2015-08-01

Recent work has shown that preplanned motor programs can be rapidly released via fast conducting pathways using a startling acoustic stimulus. Our question was whether the startle-elicited response might also release a recently learned internal model, which draws on experience to predict and compensate for expected perturbations in a feedforward manner. Our initial investigation using adaptation to robotically produced forces showed some evidence of this, but the results were potentially confounded by co-contraction caused by startle. In this study, we eliminated this confound by asking subjects to make reaching movements in the presence of a visual distortion. Results show that a startle stimulus (1) decreased performance of the recently learned task and (2) reduced after-effect magnitude. Since the recall of learned control was reduced, but not eliminated during startle trials, we suggest that multiple neural centers (cortical and subcortical) are involved in such learning and adaptation. These findings have implications for motor training in areas such as piloting, teleoperation, sports, and rehabilitation.

Startle habituation, sensory, and sensorimotor gating in trauma-affected refugees with posttraumatic stress disorder.

PubMed

Meteran, Hanieh; Vindbjerg, Erik; Uldall, Sigurd Wiingaard; Glenthøj, Birte; Carlsson, Jessica; Oranje, Bob

2018-05-17

Impairments in mechanisms underlying early information processing have been reported in posttraumatic stress disorder (PTSD); however, findings in the existing literature are inconsistent. This current study capitalizes on technological advancements of research on electroencephalographic event-related potential and applies it to a novel PTSD population consisting of trauma-affected refugees. A total of 25 trauma-affected refugees with PTSD and 20 healthy refugee controls matched on age, gender, and country of origin completed the study. In two distinct auditory paradigms sensory gating, indexed as P50 suppression, and sensorimotor gating, indexed as prepulse inhibition (PPI), startle reactivity, and habituation of the eye-blink startle response were examined. Within the P50 paradigm, N100 and P200 amplitudes were also assessed. In addition, correlations between psychophysiological and clinical measures were investigated. PTSD patients demonstrated significantly elevated stimuli responses across the two paradigms, reflected in both increased amplitude of the eye-blink startle response, and increased N100 and P200 amplitudes relative to healthy refugee controls. We found a trend toward reduced habituation in the patients, while the groups did not differ in PPI and P50 suppression. Among correlations, we found that eye-blink startle responses were associated with higher overall illness severity and lower levels of functioning. Fundamental gating mechanisms appeared intact, while the pattern of deficits in trauma-affected refugees with PTSD point toward a different form of sensory overload, an overall neural hypersensitivity and disrupted the ability to down-regulate stimuli responses. This study represents an initial step toward elucidating sensory processing deficits in a PTSD subgroup.

Forebrain-specific CRF overproduction during development is sufficient to induce enduring anxiety and startle abnormalities in adult mice.

PubMed

Toth, Mate; Gresack, Jodi E; Bangasser, Debra A; Plona, Zach; Valentino, Rita J; Flandreau, Elizabeth I; Mansuy, Isabelle M; Merlo-Pich, Emilio; Geyer, Mark A; Risbrough, Victoria B

2014-05-01

Corticotropin releasing factor (CRF) regulates physiological and behavioral responses to stress. Trauma in early life or adulthood is associated with increased CRF in the cerebrospinal fluid and heightened anxiety. Genetic variance in CRF receptors is linked to altered risk for stress disorders. Thus, both heritable differences and environmentally induced changes in CRF neurotransmission across the lifespan may modulate anxiety traits. To test the hypothesis that CRF hypersignaling is sufficient to modify anxiety-related phenotypes (avoidance, startle, and conditioned fear), we induced transient forebrain-specific overexpression of CRF (CRFOE) in mice (1) during development to model early-life stress, (2) in adulthood to model adult-onset stress, or (3) across the entire postnatal lifespan to model heritable increases in CRF signaling. The consequences of these manipulations on CRF peptide levels and behavioral responses were examined in adulthood. We found that transient CRFOE during development decreased startle habituation and prepulse inhibition, and increased avoidance (particularly in females) recapitulating the behavioral effects of lifetime CRFOE despite lower CRF peptide levels at testing. In contrast, CRFOE limited to adulthood reduced contextual fear learning in females and increased startle reactivity in males but did not change avoidance or startle plasticity. These findings suggest that forebrain CRFOE limited to development is sufficient to induce enduring alterations in startle plasticity and anxiety, while forebrain CRFOE during adulthood results in a different phenotype profile. These findings suggest that startle circuits are particularly sensitive to forebrain CRFOE, and that the impact of CRFOE may be dependent on the time of exposure.

Startle response memory and hippocampal changes in adult zebrafish pharmacologically-induced to exhibit anxiety/depression-like behaviors.

PubMed

Pittman, Julian T; Lott, Chad S

2014-01-17

Zebrafish (Danio rerio) are rapidly becoming a popular animal model for neurobehavioral and psychopharmacological research. While startle testing is a well-established assay to investigate anxiety-like behaviors in different species, screening of the startle response and its habituation in zebrafish is a new direction of translational biomedical research. This study focuses on a novel behavioral protocol to assess a tapping-induced startle response and its habituation in adult zebrafish that have been pharmacologically-induced to exhibit anxiety/depression-like behaviors. We demonstrated that zebrafish exhibit robust learning performance in a task adapted from the mammalian literature, a modified plus maze, and showed that ethanol and fluoxetine impair memory performance in this maze when administered after training at a dose that does not impair motor function, however, leads to significant upregulation of hippocampal serotoninergic neurons. These results suggest that the maze associative learning paradigm has face and construct validity and that zebrafish may become a translationally relevant study species for the analysis of the mechanisms of learning and memory changes associated with psychopharmacological treatment of anxiety/depression. © 2013.

A cost minimisation and Bayesian inference model predicts startle reflex modulation across species.

PubMed

Bach, Dominik R

2015-04-07

In many species, rapid defensive reflexes are paramount to escaping acute danger. These reflexes are modulated by the state of the environment. This is exemplified in fear-potentiated startle, a more vigorous startle response during conditioned anticipation of an unrelated threatening event. Extant explanations of this phenomenon build on descriptive models of underlying psychological states, or neural processes. Yet, they fail to predict invigorated startle during reward anticipation and instructed attention, and do not explain why startle reflex modulation evolved. Here, we fill this lacuna by developing a normative cost minimisation model based on Bayesian optimality principles. This model predicts the observed pattern of startle modification by rewards, punishments, instructed attention, and several other states. Moreover, the mathematical formalism furnishes predictions that can be tested experimentally. Comparing the model with existing data suggests a specific neural implementation of the underlying computations which yields close approximations to the optimal solution under most circumstances. This analysis puts startle modification into the framework of Bayesian decision theory and predictive coding, and illustrates the importance of an adaptive perspective to interpret defensive behaviour across species. Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.

Effects of Olanzapine, Risperidone and Haloperidol on Prepulse Inhibition in Schizophrenia Patients: A Double-Blind, Randomized Controlled Trial

PubMed Central

Wynn, Jonathan K.; Green, Michael F.; Sprock, Joyce; Light, Gregory A.; Widmark, Clifford; Reist, Christopher; Erhart, Stephen; Marder, Stephen R.; Mintz, Jim; Braff, David L.

2009-01-01

Prepulse inhibition (PPI), whereby the startle eyeblink response is inhibited by a relatively weak non-startling stimulus preceding the powerful startle eliciting stimulus, is a measure of sensorimotor gating and has been shown to be deficient in schizophrenia patients. There is considerable interest in whether conventional and/or atypical antipsychotic medications can “normalize” PPI deficits in schizophrenia patients. 51 schizophrenia patients participated in a randomized, double-blind controlled trial on the effects of three commonly-prescribed antipsychotic medications (risperidone, olanzapine, or haloperidol) on PPI, startle habituation, and startle reactivity. Patients were tested at baseline, Week 4 and Week 8. Mixed model regression analyses revealed that olanzapine significantly improved PPI from Week 4 to Week 8, and that at Week 8 patients receiving olanzapine produced significantly greater PPI than those receiving risperidone, but not haloperidol. There were no effects of medication on startle habituation or startle reactivity. These results support the conclusion that olanzapine effectively increased PPI in schizophrenia patients, but that risperidone and haloperidol had no such effects. The results are discussed in terms of animal models, neural substrates, and treatment implications. PMID:17662577

Psychophysiological assessment of emotional processing in patients with borderline personality disorder with and without comorbid substance use.

PubMed

Baschnagel, Joseph S; Coffey, Scott F; Hawk, Larry W; Schumacher, Julie A; Holloman, Garland

2013-07-01

This study assessed physiological measures for the study of emotional dysregulation associated with borderline personality disorder (BPD). Two patient groups, the first comprised of individuals with BPD only (n = 16) and the second, individuals with BPD and co-occurring substance-use disorder (SUD; n = 35), and a group of healthy controls (n = 45) were shown standardized pictures of varying valance and arousal levels. Affective modification of startle eye-blink responses, heart rate, facial electromyography (EMG, including corrugator and zygomatic activity), and skin-conductance responses were collected during picture presentation and during a brief recovery period. Startle data during picture presentation indicated a trend toward the expected increase in startle response magnitude to negative stimuli, to be moderated by group status, with patients with BPD-SUD showing a lack of affective modification and the BPD-only group showing similar affective modification to that of controls. Heart-rate data suggested lower reactivity to negative pictures for both patient groups. Differences in facial EMG responses did not provide a clear pattern, and skin-conductance responses were not significantly different between groups. The data did not suggest differences between groups in recovery from exposure to the emotional stimuli. The startle and heart-rate data suggest a possible hyporeactivity to emotional stimuli in BPD.

Development of a New Technique to Assess Susceptibility to Predation Resulting from Sublethal Stresses (Indirect Mortality)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cada, G.F.

2003-08-25

Fish that pass through a hydroelectric turbine may not be killed directly, but may nonetheless experience sublethal stresses that will increase their susceptibility to predators (indirect mortality). There is a need to develop reliable tests for indirect mortality so that the full consequences of passage through turbines (and other routes around a hydroelectric dam) can be assessed. We evaluated a new technique for assessing indirect mortality, based on a behavioral response to a startling stimulus (akin to perceiving an approaching predator). We compare this technique to the standard predator preference test. The behavioral response is a rapid movement commonly referredmore » to as a startle response, escape response, or C-shape, based on the characteristic body position assumed by the fish. When viewed from above, a startled fish bends into a C-shape, then springs back and swims away in a direction different from its original orientation. This predator avoidance (escape) behavior can be compromised by sublethal stresses that temporarily stun or disorient the fish. We subjected striped shiners and fathead minnows to varying intensities of either turbulence (10-, 20- or 30-min) or 2-min exposures to a fish anesthetic (100 or 200 mg/L of tricaine methanesulfonate), and evaluated their subsequent behavior. Individual fish were given a startle stimulus and filmed with a high-speed video camera. Each fish was startled and filmed twice before being stressed, and then at 1-, 5-, 15-, and 30-min post-exposure. The resulting image files were analyzed for a variety of behavioral measures including: presence of a response, time to first reaction, duration of reaction, time to formation of maximum C-shape, time to completion of C-shape, and completeness of C-shape. The most immediate measure of potential changes in fish behavior was whether stressed fish exhibited a startle response. For striped shiners, the number of fish not responding to the stimulus was significantly different from controls at 1-min post-exposure and for fathead minnows at 1- and 5-min post-exposure. The greatest effects occurred with exposure to the fish anesthetic; in fathead minnows all of the recorded measures were significantly different from controls at 1-min and 5-min post-exposure at the 100 mg/L dose. For striped shiners all recorded behavioral measures were significantly different from controls at 1-min at the 200 and 100 mg/L doses and for selected behavioral measures at 5-min. Turbulence also had significant effects on striped shiner startle responses following 20- and 30-min exposures for all behavioral measures at 1-min. The patterns suggest that any effects on startle response due to turbulence or low doses of anesthetic are short-lived, but can be evaluated using the escape behavior technique. The most useful indication of changes in escape behavior in these tests was the simple reaction/no reaction to the startle stimulus. The startle response occurred reliably among unstressed fish, and was frequently reduced or eliminated in fish exposed to turbulence or anesthesia. The other behavioral parameters observed were often altered by the sublethal stresses as well. A standard predator preference test was also conducted with largemouth bass as the predators and fathead minnows as prey. In this test design, groups of 10 unstressed fish (controls) and 10 stressed fish were put in a tank with a predator. The stressed fathead minnows were exposed to turbulence or fish anesthetic. The predator was allowed to eat half of the prey, and the data were evaluated to determine whether predators consumed greater proportions of stressed minnows than control minnows. The predation test indicated that exposure to MS-222 resulted in significant predation in fathead minnows, but exposure to turbulence did not. This pattern was the same as seen in fathead minnows using the startle response (escape behavior) test. For the sublethal stresses we applied, evaluation of changes in fish escape behavior yielded results comparable to traditional predator preference tests. Because this fish behavior test is simpler and quicker to conduct than predator preference tests, it shows promise as a useful technique for assessing indirect mortality resulting from sublethal stresses.« less

Exaggerated blood pressure response to exercise in athletes: dysmetabolism or altered autonomic nervous system modulation?

PubMed

Turmel, Julie; Bougault, Valérie; Boulet, Louis-Philippe; Poirier, Paul

2012-10-01

The importance of exercise-induced exaggerated blood pressure (BP) response in endurance athletes is not known. To assess the hemodynamic parameters and metabolic profile in athletes with an exaggerated BP response to exercise. Forty-four endurance athletes underwent a maximal exercise test, a 24-h ambulatory blood pressure monitoring, a 24-h Holter assessment, and sampling of blood on two occasions: (a) during intense training and (b) following 3 weeks without training. During the training period, 11 athletes showed an exaggerated BP response to exercise, whereas seven of these 11 athletes also showed an exaggerated BP response during the resting period. Elevation in systolic BP was greater in athletes with an exaggerated BP response than athletes with a normal BP response to exercise (resting: 84 ± 22 vs. 60 ± 18 mmHg, P = 0.02; training: 100 ± 21 vs. 70 ± 18 mmHg, P = 0.004). During the training period, athletes with an exaggerated BP response to exercise showed higher systolic BP values on 24-h ambulatory blood pressure monitoring (136 ± 15 vs. 118 ± 8 mmHg, P = 0.02). During the resting period, athletes with an exaggerated BP response to exercise had lower apolipoprotein-A1 (1.3 ± 0.1 vs. 1.5 ± 0.2 g/l, P = 0.009), and higher SDNN (259 ± 47 vs. 209 ± 52 ms, P = 0.03) and pNN50 (0.4 ± 0.1 vs. 0.3 ± 0.1%, P = 0.05). These observations may represent the first sign of a slight metabolic disturbance associated with vascular wall abnormalities, although the parameters remain within normal values.

Gap prepulse inhibition and auditory brainstem-evoked potentials as objective measures for tinnitus in guinea pigs

PubMed Central

Dehmel, Susanne; Eisinger, Daniel; Shore, Susan E.

2012-01-01

Tinnitus or ringing of the ears is a subjective phantom sensation necessitating behavioral models that objectively demonstrate the existence and quality of the tinnitus sensation. The gap detection test uses the acoustic startle response elicited by loud noise pulses and its gating or suppression by preceding sub-startling prepulses. Gaps in noise bands serve as prepulses, assuming that ongoing tinnitus masks the gap and results in impaired gap detection. This test has shown its reliability in rats, mice, and gerbils. No data exists for the guinea pig so far, although gap detection is similar across mammals and the acoustic startle response is a well-established tool in guinea pig studies of psychiatric disorders and in pharmacological studies. Here we investigated the startle behavior and prepulse inhibition (PPI) of the guinea pig and showed that guinea pigs have a reliable startle response that can be suppressed by 15 ms gaps embedded in narrow noise bands preceding the startle noise pulse. After recovery of auditory brainstem response (ABR) thresholds from a unilateral noise over-exposure centered at 7 kHz, guinea pigs showed diminished gap-induced reduction of the startle response in frequency bands between 8 and 18 kHz. This suggests the development of tinnitus in frequency regions that showed a temporary threshold shift (TTS) after noise over-exposure. Changes in discharge rate and synchrony, two neuronal correlates of tinnitus, should be reflected in altered ABR waveforms, which would be useful to objectively detect tinnitus and its localization to auditory brainstem structures. Therefore, we analyzed latencies and amplitudes of the first five ABR waves at suprathreshold sound intensities and correlated ABR abnormalities with the results of the behavioral tinnitus testing. Early ABR wave amplitudes up to N3 were increased for animals with tinnitus possibly stemming from hyperactivity and hypersynchrony underlying the tinnitus percept. Animals that did not develop tinnitus after noise exposure showed the opposite effect, a decrease in wave amplitudes for the later waves P4–P5. Changes in latencies were only observed in tinnitus animals, which showed increased latencies. Thus, tinnitus-induced changes in the discharge activity of the auditory nerve and central auditory nuclei are represented in the ABR. PMID:22666193

Evolution of behavior and neural control of the fast-start escape response.

PubMed

Hale, Melina E; Long, John H; McHenry, Matthew J; Westneat, Mark W

2002-05-01

The fast-start startle behavior is the primary mechanism of rapid escape in fishes and is a model system for examining neural circuit design and musculoskeletal function. To develop a dataset for evolutionary analysis of the startle response, the kinematics and muscle activity patterns of the fast-start were analyzed for four fish species at key branches in the phylogeny of vertebrates. Three of these species (Polypterus palmas, Lepisosteus osseus, and Amia calva) represent the base of the actinopterygian radiation. A fourth species (Oncorhynchus mykiss) provided data for a species in the central region of the teleost phylogeny. Using these data, we explored the evolution of this behavior within the phylogeny of vertebrates. To test the hypothesis that startle features are evolutionarily conservative, the variability of motor patterns and kinematics in fast-starts was described. Results show that the evolution of the startle behavior in fishes, and more broadly among vertebrates, is not conservative. The fast-start has undergone substantial change in suites of kinematics and electromyogram features, including the presence of either a one- or a two-stage kinematic response and change in the extent of bilateral muscle activity. Comparative methods were used to test the evolutionary hypothesis that changes in motor control are correlated with key differences in the kinematics and behavior of the fast-start. Significant evolutionary correlations were found between several motor pattern and behavioral characters. These results suggest that the startle neural circuit itself is not conservative. By tracing the evolution of motor pattern and kinematics on a phylogeny, it is shown that major changes in the neural circuit of the startle behavior occur at several levels in the phylogeny of vertebrates.

Atypical antipsychotic clozapine reversed deficit on prepulse inhibition of the acoustic startle reflex produced by microinjection of DOI into the inferior colliculus in rats.

PubMed

de Oliveira, Rodolpho Pereira; Nagaishi, Karen Yuriko; Barbosa Silva, Regina Cláudia

2017-05-15

Dysfunctions of the serotonergic system have been suggested to be important in the neurobiology of schizophrenia. Patients with schizophrenia exhibit deficits in an operational measure of sensorimotor gating: prepulse inhibition (PPI) of startle. PPI is the normal reduction in the startle response caused by a low intensity non-startling stimulus (prepulse) which is presented shortly before the startle stimulus (pulse). The hallucinogen 2,5-dimethoxy-4-iodoamphetamine (DOI), a 5-hydroxytryptamine(HT) 2 receptor agonist disrupted PPI in rats. The inferior colliculus (IC) is a critical nucleus of the auditory pathway mediating acoustic PPI. The activation of the IC by the acoustic prepulse reduces startle magnitude. The present study investigated the role of serotonergic transmission in the IC on the expression of acoustic PPI. For that we investigated whether 5-HT2A receptor activation or blockade would affect this response. Unilateral microinjection of DOI (10μg/0.3μl) into the IC disrupted PPI, while microinjection of the 5-HT2A receptor antagonist ritanserin (4μg/0.3μl), into this structure did not alter PPI. We also examined the ability of the atypical antipsychotic clozapine (5.0mg/kg; I.P.) to reverse the disruption of PPI produced by unilateral microinjections of DOI into the IC of rats. Pretreatment with clozapine blocked DOI-induced disruption of PPI. Altogether, these results suggest that serotonin-mediated mechanisms of the IC are involved in the expression of PPI in rodents and that this response is sensitive to atypical antipsychotic clozapine. Copyright © 2017 Elsevier B.V. All rights reserved.

Atypical antipsychotic olanzapine reversed deficit on prepulse inhibition of the acoustic startle reflex produced by microinjection of dizocilpine (MK-801) into the inferior colliculus in rats.

PubMed

Zangrando, Julia; Carvalheira, Renata; Labbate, Giovanna; Medeiros, Priscila; Longo, Beatriz Monteiro; Melo-Thomas, Liana; Silva, Regina Claudia Barbosa

2013-11-15

Patients with schizophrenia exhibit deficits in an operational measure of sensorimotor gating: prepulse inhibition (PPI) of startle. PPI is the normal reduction in the startle response caused by a low intensity non-startling stimulus (prepulse) which is presented shortly before the startle stimulus (pulse). MK-801 is an NMDA receptor-antagonist known to produce hyperactivity, deficits in prepulse inhibition and social withdrawal, behaviors which correlate well with some of the positive, cognitive and negative symptoms of schizophrenia. The inferior colliculus (IC) is a critical part of the auditory pathway mediating acoustic PPI. The activation of the IC by the acoustic prepulse reduces startle magnitude. Thus, the purpose of the present study was to elucidate the role of glutamatergic transmission in the IC on the expression of acoustic PPI. For that we investigated whether NMDA receptor stimulation or blockade would affect this response. Unilateral microinjections of NMDA (30 nmol/0.5 μL) into the IC did not alter PPI while microinjections of MK-801 (30 nmol/0.5 μL) into this structure disrupted PPI. We also examined the ability of the atypical antipsychotic olanzapine (5.0mg/kg; i.p.) to reverse the disruption of pre-pulse inhibition produced by unilateral microinjections of MK-801 into the IC of rats. Pretreatment with olanzapine blocked MK-801-induced disruption of PPI. Altogether, these results suggest that glutamate-mediated mechanisms of the IC are involved in the expression of PPI in rodents and that this response is sensitive to atypical antipsychotic olanzapine. Copyright © 2013 Elsevier B.V. All rights reserved.

Probabilistic information transmission in a network of coupled oscillators reveals speed-accuracy trade-off in responding to threats

PubMed Central

Chicoli, Amanda; Paley, Derek A.

2016-01-01

Individuals in a group may obtain information from other group members about the environment, including the location of a food source or the presence of a predator. Here, we model how information spreads in a group using a susceptible-infected-removed epidemic model. We apply this model to a simulated shoal of fish using the motion dynamics of a coupled oscillator model, in order to test the biological hypothesis that polarized or aligned shoaling leads to faster and more accurate escape responses. The contributions of this study are the (i) application of a probabilistic model of epidemics to the study of collective animal behavior; (ii) testing the biological hypothesis that group cohesion improves predator escape; (iii) quantification of the effect of social cues on startle propagation; and (iv) investigation of the variation in response based on network connectivity. We find that when perfectly aligned individuals in a group are startled, there is a rapid escape by individuals that directly detect the threat, as well as by individuals responding to their neighbors. However, individuals that are not startled do not head away from the threat. In startled groups that are randomly oriented, there is a rapid, accurate response by individuals that directly detect the threat, followed by less accurate responses by individuals responding to neighbor cues. Over the simulation duration, however, even unstartled individuals head away from the threat. This study illustrates a potential speed-accuracy trade-off in the startle response of animal groups, in agreement with several previous experimental studies. Additionally, the model can be applied to a variety of group decision-making processes, including those involving higher-dimensional motion. PMID:27907996

Probabilistic information transmission in a network of coupled oscillators reveals speed-accuracy trade-off in responding to threats

NASA Astrophysics Data System (ADS)

Chicoli, Amanda; Paley, Derek A.

2016-11-01

Individuals in a group may obtain information from other group members about the environment, including the location of a food source or the presence of a predator. Here, we model how information spreads in a group using a susceptible-infected-removed epidemic model. We apply this model to a simulated shoal of fish using the motion dynamics of a coupled oscillator model, in order to test the biological hypothesis that polarized or aligned shoaling leads to faster and more accurate escape responses. The contributions of this study are the (i) application of a probabilistic model of epidemics to the study of collective animal behavior; (ii) testing the biological hypothesis that group cohesion improves predator escape; (iii) quantification of the effect of social cues on startle propagation; and (iv) investigation of the variation in response based on network connectivity. We find that when perfectly aligned individuals in a group are startled, there is a rapid escape by individuals that directly detect the threat, as well as by individuals responding to their neighbors. However, individuals that are not startled do not head away from the threat. In startled groups that are randomly oriented, there is a rapid, accurate response by individuals that directly detect the threat, followed by less accurate responses by individuals responding to neighbor cues. Over the simulation duration, however, even unstartled individuals head away from the threat. This study illustrates a potential speed-accuracy trade-off in the startle response of animal groups, in agreement with several previous experimental studies. Additionally, the model can be applied to a variety of group decision-making processes, including those involving higher-dimensional motion.

Probabilistic information transmission in a network of coupled oscillators reveals speed-accuracy trade-off in responding to threats.

PubMed

Chicoli, Amanda; Paley, Derek A

2016-11-01

Individuals in a group may obtain information from other group members about the environment, including the location of a food source or the presence of a predator. Here, we model how information spreads in a group using a susceptible-infected-removed epidemic model. We apply this model to a simulated shoal of fish using the motion dynamics of a coupled oscillator model, in order to test the biological hypothesis that polarized or aligned shoaling leads to faster and more accurate escape responses. The contributions of this study are the (i) application of a probabilistic model of epidemics to the study of collective animal behavior; (ii) testing the biological hypothesis that group cohesion improves predator escape; (iii) quantification of the effect of social cues on startle propagation; and (iv) investigation of the variation in response based on network connectivity. We find that when perfectly aligned individuals in a group are startled, there is a rapid escape by individuals that directly detect the threat, as well as by individuals responding to their neighbors. However, individuals that are not startled do not head away from the threat. In startled groups that are randomly oriented, there is a rapid, accurate response by individuals that directly detect the threat, followed by less accurate responses by individuals responding to neighbor cues. Over the simulation duration, however, even unstartled individuals head away from the threat. This study illustrates a potential speed-accuracy trade-off in the startle response of animal groups, in agreement with several previous experimental studies. Additionally, the model can be applied to a variety of group decision-making processes, including those involving higher-dimensional motion.

Emotional effects of startling background music during reading news reports: The moderating influence of dispositional BIS and BAS sensitivities.

PubMed

Ravaja, Niklas; Kallinen, Kari

2004-07-01

We examined the moderating influence of dispositional behavioral inhibition system (BIS) and behavioral activation system (BAS) sensitivities on the relationship of startling background music with emotion-related subjective and physiological responses elicited during reading news reports, and with memory performance among 26 adult men and women. Physiological parameters measured were respiratory sinus arrhythmia (RSA), electrodermal activity (EDA), and facial electromyography (EMG). The results showed that, among high BAS individuals, news stories with startling background music were rated as more interesting and elicited higher zygomatic EMG activity and RSA than news stories with non-startling music. Among low BAS individuals, news stories with startling background music were rated as less pleasant and more arousing and prompted higher EDA. No BIS-related effects or effects on memory were found. Startling background music may have adverse (e.g., negative arousal) or beneficial effects (e.g., a positive emotional state and stronger positive engagement) depending on dispositional BAS sensitivity of an individual. Actual or potential applications of this research include the personalization of media presentations when using modern media and communications technologies.

Processing emotions: Effects of menstrual cycle phase and premenstrual symptoms on the startle reflex, facial EMG and heart rate.

PubMed

Armbruster, Diana; Grage, Tobias; Kirschbaum, Clemens; Strobel, Alexander

2018-10-01

Emotional reactivity varies across the menstrual cycle although physiological findings are not entirely consistent. We assessed facial EMG and heart rate (HR) changes in healthy free cycling women (N = 45) with an emotional startle paradigm both during the early follicular and the late luteal phase, verified by repeated salivary 17β-estradiol, progesterone and testosterone assessments. Cycle phase impacted startle responses with larger magnitudes during the luteal phase. Notably, this effect was only present when premenstrual symptoms and sequence of lab sessions were included as co-variates. At rest, participants showed a tendency towards higher HR and reduced high frequency (HF) power during the luteal phase indicating reduced parasympathetic tone. HF power was also negatively associated with startle magnitudes. HR changes in response to emotional images differed between the two cycle phases. Initial HR deceleration was more marked during the follicular phase particularly when viewing negative pictures. However, cycle phase did not significantly impact corrugator and zygomaticus activity in response to emotional pictures. Among the three gonadal steroids, correlation patterns were most consistent for testosterone. During the follicular phase, testosterone was associated with zygomaticus activity while viewing neutral or positive pictures and with less pronounced HR deceleration in response to negative images. During the luteal phase, testosterone was negatively associated with fear potentiated startle. The findings underscore the importance of considering menstrual cycle phase when investigating physiological indicators of emotion. However, the modulating effect of premenstrual symptoms also emphasizes potential inter-individual differences. Copyright © 2018 Elsevier B.V. All rights reserved.

Involvement of noradrenergic and corticoid receptors in the consolidation of the lasting anxiogenic effects of predator stress.

PubMed

Adamec, R; Muir, C; Grimes, M; Pearcey, K

2007-05-16

The roles of beta-NER (beta-noradrenergic receptor), GR (glucocorticoid) and mineral corticoid receptors (MR) in the consolidation of anxiogenic effects of predator stress were studied. One minute after predator stress, different groups of rats were injected (ip) with vehicle, propranolol (beta-NER blocker, 5 and 10 mg/kg), mifepristone (RU486, GR blocker, 20 mg/kg), spironolactone (MR blocker, 50 mg/kg), propranolol (5 mg/kg) plus RU486 (20 mg/kg) or the anxiolytic, chloradiazepoxide (CPZ, 10 mg/kg). One week later, rodent anxiety was assessed in elevated plus maze, hole board, light/dark box, social interaction and acoustic startle. Considering all tests except startle, propranolol dose dependently blocked consolidation of lasting anxiogenic effects of predator stress in all tests. GR receptor block alone was ineffective. However, GR block in combination with an ineffective dose of propranolol did blocked consolidation of predator stress effects in all tests, suggesting a synergism between beta-NER and GR. Surprisingly, MR block prevented consolidation of anxiogenic effects in all tests except the light/dark box. CPZ post stress was ineffective against the anxiogenic impact of predator stress. Study of startle was complicated by the fact that anxiogenic effects of stress on startle amplitude manifested as both an increase and a decrease in startle amplitude. Suppression of startle occurred in stressed plus vehicle injected groups handled three times prior to predator stress. In contrast, stressed plus vehicle rats handled five times prior to predator stress showed increases in startle, as did all predator stressed only groups. Mechanisms of consolidation of the different startle responses appear to differ. CPZ post stress blocked startle suppression but not enhancement of startle. Propranolol post stress had no effect on either suppression or enhancement of startle. GR block alone post stress prevented suppression of startle, but not enhancement. In contrast blocking GR and beta-NER together prevented startle enhancement. MR block also prevented startle enhancement. Effects of MR block on startle suppression were not tested. Delay of habituation to startle was found in all stressed rats. Consolidation of delay of habituation was blocked or attenuated by post stress MR block, GR plus beta-NER block and CPZ but not by post stress GR or beta-NER block alone. Taken together, present findings suggest consolidation of lasting anxiogenic effects of predator stress may share some of the same neurochemical mechanisms implicated in some forms of fear memory consolidation. Implications of these findings for the study of stress-induced changes in affect including posttraumatic stress disorder (PTSD) are discussed.

TRIMETHYLTIN DISRUPTS ACOUSTIC STARTLE RESPONDING IN ADULT RATS

EPA Science Inventory

Trimethyltin (TMT) is a limbic-system toxicant which also produces sensory dysfunction in adult animals. In the present experiment, the authors examined the effects of TMT on the acoustic startle response. Adult male, Long-Evans rats (N=12/dose) received a single i.p. injection o...

Methadone patients exhibit increased startle and cortisol response after intravenous yohimbine.

PubMed

Stine, S M; Grillon, C G; Morgan, C A; Kosten, T R; Charney, D S; Krystal, J H

2001-03-01

Brain noradrenergic systems have been shown to be altered in opioid dependence and to mediate aspects of opioid withdrawal. Pre-clinical and clinical studies by others have shown that yohimbine, which increases noradrenergic activity, also increases both baseline and fear enhancement of the magnitude of the acoustic startle response (ASR). In a separate report from this experiment, it was shown that yohimbine produced opioid withdrawal-like symptoms, including anxiety, in clinically stable methadone-maintained patients and also produced elevations in the norepinepherine (NE) metabolite, 3-methoxy-4 hydroxyphenethyleneglycol (MHPG), and cortisol serum levels. The current study reports the effects of intravenous yohimbine hydrochloride, 0.4 mg/kg versus saline (double-blind), on ASR magnitude, plasma MHPG, and cortisol levels in eight methadone-maintained patients and 13 healthy subjects in a double-blind fashion. Yohimbine increased startle magnitude in both groups. There was no basal (placebo day) difference between the startle response of the two groups, but methadone patients had a larger startle magnitude increase in response to yohimbine than healthy controls. Methadone-maintained patients had lower baseline plasma levels of MHPG and similar baseline plasma cortisol levels compared with normal subjects. Yohimbine caused significant elevation in cortisol and MHPG in both groups. Methadone-maintained subjects had higher elevations in cortisol levels and MHPG (methadone main effect) levels in response to yohimbine. However, when MHPG levels were corrected for baseline differences by analysis of covariance (ANCOVA), the yohimbine effect, but not the methadone effect remained statistically significant. These results are consistent with the previous report and support the hypothesis that abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis and of noradrenergic mechanisms of stress response persist in opioid-agonist maintenance. The ASR effect extends the previous report and provides an additional objective measure for perturbation of noradrenergic and stress responses in these patients.

GABAergic Neural Activity Involved in Salicylate-Induced Auditory Cortex Gain Enhancement

PubMed Central

Lu, Jianzhong; Lobarinas, Edward; Deng, Anchun; Goodey, Ronald; Stolzberg, Daniel; Salvi, Richard J.; Sun, Wei

2011-01-01

Although high doses of sodium salicylate impair cochlear function, it paradoxically enhances sound-evoked activity in the auditory cortex (AC) and augments acoustic startle reflex responses, neural and behavioral metrics associated with hyperexcitability and hyperacusis. To explore the neural mechanisms underlying salicylate-induced hyperexcitability and “increased central gain”, we examined the effects of γ-aminobutyric acid (GABA) receptor agonists and antagonists on salicylate-induced hyperexcitability in the AC and startle reflex responses. Consistent with our previous findings, local or systemic application of salicylate significantly increased the amplitude of sound-evoked AC neural activity, but generally reduced spontaneous activity in the AC. Systemic injection of salicylate also significantly increased the acoustic startle reflex. S-baclofen or R-baclofen, GABA-B agonists, which suppressed sound-evoked AC neural firing rate and local field potentials, also suppressed the salicylate-induced enhancement of the AC field potential and the acoustic startle reflex. Local application of vigabatrin, which enhances GABA concentration in the brain, suppressed the salicylate-induced enhancement of AC firing rate. Systemic injection of vigabatrin also reduced the salicylate-induced enhancement of acoustic startle reflex. Collectively, these results suggest that the sound-evoked behavioral and neural hyperactivity induced by salicylate may arise from a salicylate-induced suppression GABAergic inhibition in the AC. PMID:21664433

Assessing the Comprehensive Soldier Fitness Program: Measuring Startle Response and Prepulse Inhibition

DTIC Science & Technology

2011-04-01

increase PPI, but dopamine agonists can have the opposite effect by reducing PPI. Fortunately, caffeine appears to have no significant effect on PPI...violent behavior, and sexual risk behavior. Landis, C., & Hunt, W.A. (1939). The Startle Pattern. New York: Farrar. An example of early research on

POSSIBLE ROLE OF THE BRAINSTEM IN THE MEDIATION OF PREPULSE INHIBITION IN THE RAT (JOURNAL VERSION)

EPA Science Inventory

Bilateral stimulation of electrodes aimed at the cuneiform nucleus produced significant inhibition of the startle response produced by presentation of an 8 KHz, 110 dB tone. Stimulation of electrodes aimed at the deep mesencephalic nucleus also reduced the magnitude of the startl...

Effect of D-amphetamine on emotion-potentiated startle in healthy humans: implications for psychopathy and antisocial behaviour.

PubMed

Corr, Philip J; Kumari, Veena

2013-01-01

An emerging literature associates increased dopaminergic neurotransmission with altered brain response to aversive stimuli in humans. The direction of the effect of dopamine on aversive motivation, however, remains unclear, with some studies reporting increased and others decreased amygdala activation to aversive stimuli following the administration of dopamine agonists. Potentiation of the startle response by aversive foreground stimuli provides an objective and directional measure of emotional reactivity and is considered useful as an index of the emotional effects of different drugs. We investigated the effects of two doses of D-amphetamine (5 and 10 mg), compared to placebo, for the first time to our knowledge, using the affect-startle paradigm. The study employed a between-subjects, double-blind design, with three conditions: 0 mg (placebo), and 5 and 10 mg D-amphetamine (initially n = 20/group; final sample: n = 18, placebo; n = 18, 5 mg; n = 16, 10 mg). After drug/placebo administration, startle responses (eyeblinks) to intermittent noise probes were measured during viewing of pleasant, neutral and unpleasant images. Participants' general and specific impulsivity and fear-related personality traits were also assessed. The three groups were comparable on personality traits. Only the placebo group showed significant startle potentiation by unpleasant, relative to neutral, images; this effect was absent in both 5- and 10-mg D-amphetamine groups (i.e. the same effect of D-amphetamine observed at different doses in different people). Our findings demonstrate a reduced aversive emotional response under D-amphetamine and may help to account for the known link between the use of psychostimulant drugs and antisocial behaviour.

Mourning dove ( Zenaida macroura) wing-whistles may contain threat-related information for con- and hetero-specifics

NASA Astrophysics Data System (ADS)

Coleman, Seth W.

2008-10-01

Distinct acoustic whistles are associated with the wing-beats of many doves, and are especially noticeable when doves ascend from the ground when startled. I thus hypothesized that these sounds may be used by flock-mates as cues of potential danger. To test this hypothesis, I compared the responses of mourning doves ( Zenaida macroura), northern cardinals ( Cardinalis cardinalis), and house sparrows ( Passer domesticus) to audio playbacks of dove ‘startle wing-whistles’, cardinal alarm calls, dove ‘nonstartle wing-whistles’, and sparrow ‘social chatter’. Following playbacks of startle wing-whistles and alarm calls, conspecifics and heterospecifics startled and increased vigilance more than after playbacks of other sounds. Also, the latency to return to feeding was greater following playbacks of startle wing-whistles and alarm calls than following playbacks of other sounds. These results suggest that both conspecifics and heterospecifics may attend to dove wing-whistles in decisions related to antipredator behaviors. Whether the sounds of dove wing-whistles are intentionally produced signals warrants further testing.

Resting heart rate variability and the startle reflex to briefly presented affective pictures.

PubMed

Ruiz-Padial, Elisabeth; Thayer, Julian F

2014-12-01

We have previously shown that persons with low HRV showed potentiated startle responses to neutral stimuli. In the present study we replicated our prior findings and extended them to examine the effects of HRV on the startle magnitude to pictures that were presented outside of conscious awareness. A total of 85 male and female students were stratified via median split on their resting HRV. They were presented pictures for 6 s or for 30 ms. Results indicated that the high HRV group showed the context appropriate startle magnitude increase to unpleasant foreground. The low HRV group showed startle magnitude increase from pleasant to neutral pictures but no difference between the neutral and unpleasant pictures. This pattern of results was similar for the 30 ms and the 6 s conditions. These results suggest that having high HRV may allow persons to more efficiently process emotional stimuli and to better recognize threat and safety signals. Copyright © 2014 Elsevier B.V. All rights reserved.

Repeated low-dose exposures to sarin, soman, or VX affect acoustic startle in guinea pigs.

PubMed

Smith, C D; Lee, R B; Moran, A V; Sipos, M L

2016-01-01

Chemical warfare nerve agents (CWNAs) are known to cause behavioral abnormalities in cases of human exposures and in animal models. The behavioral consequences of single exposures to CWNAs that cause observable toxic signs are particularly well characterized in animals; however, less is known regarding repeated smaller exposures that may or may not cause observable toxic signs. In the current study, guinea pigs were exposed to fractions (0.1, 0.2, or 0.4) of a medial lethal dose (LD50) of sarin, soman, or VX for two weeks. On each exposure day, and for a post-exposure period, acoustic startle response (ASR) was measured in each animal. Although relatively few studies use guinea pigs to measure behavior, this species is ideal for CWNA-related experiments because their levels of carboxylesterases closely mimic those of humans, unlike rats or mice. Results showed that the 0.4 LD50 doses of soman and VX transiently increased peak startle amplitude by the second week of injections, with amplitude returning to baseline by the second week post-exposure. Sarin also increased peak startle amplitude independent of week. Latencies to peak startle and PPI were affected by agent exposure but not consistently among the three agents. Most of the changes in startle responses returned to baseline following the cessation of exposures. These data suggest that doses of CWNAs not known to produce observable toxic signs in guinea pigs can affect behavior in the ASR paradigm. Further, these deficits are transient and usually return to baseline shortly after the end of a two-week exposure period. Published by Elsevier Inc.

The effect of choice on the physiology of emotion: An affective startle modulation study

PubMed Central

Genevsky, Alexander; Gard, David E.

2014-01-01

The affective startle modulation task has been an important measure in understanding physiological aspects of emotion and motivational responses. Research utilizing this method has relied primarily on a ‘passive’ viewing paradigm, which stands in contrast to everyday life where much of emotion and motivation involves some active choice or agency. The present study investigated the role of choice on the physiology of emotion. Eighty-four participants were randomized into ‘choice’ (n=44) or ‘no-choice’ (n=40) groups distinguished by the ability to choose between stimuli. EMG eye blink responses were recorded in both anticipation and stimulus viewing. Results indicated a significant attenuation of the startle magnitude in choice condition trials (relative to no-choice) across all picture categories and probe times. We interpret these findings as an indication that the act of choice may decrease one’s defensive response, or conversely, lacking choice may heighten the defensive response. Implications for future research are discussed. PMID:22285891

The effect of choice on the physiology of emotion: an affective startle modulation study.

PubMed

Genevsky, Alexander; Gard, David E

2012-04-01

The affective startle modulation task has been an important measure in understanding physiological aspects of emotion and motivational responses. Research utilizing this method has relied primarily on a 'passive' viewing paradigm, which stands in contrast to everyday life where much of emotion and motivation involves some active choice or agency. The present study investigated the role of choice on the physiology of emotion. Eighty-four participants were randomized into 'choice' (n=44) or 'no-choice' (n=40) groups distinguished by the ability to choose between stimuli. EMG eye blink responses were recorded in both anticipation and stimulus viewing. Results indicated a significant attenuation of the startle magnitude in choice condition trials (relative to no-choice) across all picture categories and probe times. We interpret these findings as an indication that the act of choice may decrease one's defensive response, or conversely, lacking choice may heighten the defensive response. Implications for future research are discussed. Copyright © 2012 Elsevier B.V. All rights reserved.

Distinct Contributions of Median Raphe Nucleus to Contextual Fear Conditioning and Fear-Potentiated Startle

PubMed Central

Silva, R. C. B.; Cruz, A. P. M.; Avanzi, V.; Landeira-Fernandez, J.; Brandão, M. L.

2002-01-01

Ascending 5-HT projections from the median raphe nucleus (MRN), probably to the hippocampus, are implicated in the acquisition of contextual fear (background stimuli), as assessed by freezing behavior. Foreground cues like light, used as a conditioned stimulus (CS) in classical fear conditioning, also cause freezing through thalamic transmission to the amygdala. As the MRN projects to the hippocampus and amygdala, the role of this raphe nucleus in fear conditioning to explicit cues remains to be explained. Here we analyzed the behavior of rats with MRN electrolytic lesions in a contextual conditioning situation and in a fear-potentiated startle procedure. The animals received MRN electrolytic lesions either before or on the day after two consecutive training sessions in which they were submitted to 10 conditioning trials, each in an experimental chamber (same context) where they. received foot-shocks (0.6 mA, 1 sec) paired to a 4-sec light CS. Seven to ten days later, the animals were submitted to testing sessions for assessing conditioned fear when they were placed for five shocks, and the duration of contextual freezing was recorded. The animals were then submitted to a fear-potentiated startle in response to a 4-sec light-CS, followed by white noise (100 dB, 50 ms). Control rats (sham) tested in the same context showed more freezing than did rats with pre- or post-training MRN lesions. Startle was clearly potentiated in the presence of light CS in the sham-lesioned animals. Whereas pretraining lesions reduced both freezing and fear-potentiated startle, the post-training lesions reduced only freezing to context, without changing the fear-potentiated startle. In a second experiment, neurotoxic lesions of the MRN with local injections of N-methyl-D-aspartate or the activation of 5-HT1A somatodendritic auto-receptors of the MRN by microinjections of the 5-HT1A receptor agonist 8-hydroxy- 2-(di-n-propylamino)tetralin (8-OH-DPAT) before the training sessions also reduced the amount of freezing and the fear-potentiated startle. Freezing is a prominent response of contextual fear conditioning, but does not seem to be crucial for the enhancement of the startle reflex by explicit aversive cues. As fear-potentiated startle may be produced in posttraining lesioned rats that are unable to freeze to fear contextual stimuli, dissociable systems seem to be recruited in each condition. Thus, contextual fear and fear-potentiated startle are conveyed by distinct 5-HT-mediated circuits of the MRN. PMID:12959153

Major Depression Is Not Associated with Blunting of Aversive Responses; Evidence for Enhanced Anxious Anticipation

PubMed Central

Grillon, Christian; Franco-Chaves, Jose A.; Mateus, Camilo F.; Ionescu, Dawn F.; Zarate, Carlos A.

2013-01-01

According to the emotion-context insensitivity (ECI) hypothesis, major depressive disorder (MDD) is associated with a diminished ability to react emotionally to positive stimuli and with blunting of defensive responses to threat. That defensive responses are blunted in MDD seems inconsistent with the conceptualization and diagnostic nosology of MDD. The present study tested the ECI hypothesis in MDD using a threat of shock paradigm. Twenty-eight patients with MDD (35.5±10.4 years) were compared with 28 controls (35.1±7.4 years). Participants were exposed to three conditions: no shock, predictable shock, and unpredictable shock. Startle magnitude was used to assess defensive responses. Inconsistent with the ECI hypothesis, startle potentiation to predictable and unpredictable shock was not reduced in the MDD group. Rather, MDD patients showed elevated startle throughout testing as well as increased contextual anxiety during the placement of the shock electrodes and in the predictable condition. A regression analysis indicated that illness duration and Beck depression inventory scores explained 37% (p<.005) of the variance in patients’ startle reactivity. MDD is not associated with emotional blunting but rather enhanced defensive reactivity during anticipation of harm. These results do not support a strong version of the ECI hypothesis. Understanding the nature of stimuli or situations that lead to blunted or enhanced defensive reactivity will provide better insight into dysfunctional emotional experience in MDD. PMID:23951057

Viewing loved faces inhibits defense reactions: a health-promotion mechanism?

PubMed

Guerra, Pedro; Sánchez-Adam, Alicia; Anllo-Vento, Lourdes; Ramírez, Isabel; Vila, Jaime

2012-01-01

We have known for decades that social support is associated with positive health outcomes. And yet, the neurophysiological mechanisms underlying this association remain poorly understood. The link between social support and positive health outcomes is likely to depend on the neurophysiological regulatory mechanisms underlying reward and defensive reactions. The present study examines the hypothesis that emotional social support (love) provides safety cues that activate the appetitive reward system and simultaneously inhibit defense reactions. Using the startle probe paradigm, 54 undergraduate students (24 men) viewed black and white photographs of loved (romantic partner, father, mother, and best friend), neutral (unknown), and unpleasant (mutilated) faces. Eye-blink startle, zygomatic major activity, heart rate, and skin conductance responses to the faces, together with subjective ratings of valence, arousal, and dominance, were obtained. Viewing loved faces induced a marked inhibition of the eye-blink startle response accompanied by a pattern of zygomatic, heart rate, skin conductance, and subjective changes indicative of an intense positive emotional response. Effects were similar for men and women, but the startle inhibition and the zygomatic response were larger in female participants. A comparison between the faces of the romantic partner and the parent who shares the partner's gender further suggests that this effect is not attributable to familiarity or arousal. We conclude that this inhibitory capacity may contribute to the health benefits associated with social support.

Sleep duration, depression, and oxytocinergic genotype influence prepulse inhibition of the startle reflex in postpartum women.

PubMed

Comasco, Erika; Gulinello, Maria; Hellgren, Charlotte; Skalkidou, Alkistis; Sylven, Sara; Sundström-Poromaa, Inger

2016-04-01

The postpartum period is characterized by a post-withdrawal hormonal status, sleep deprivation, and susceptibility to affective disorders. Postpartum mothering involves automatic and attentional processes to screen out new external as well as internal stimuli. The present study investigated sensorimotor gating in relation to sleep duration, depression, as well as catecholaminergic and oxytocinergic genotypes in postpartum women. Prepulse inhibition (PPI) of the startle reflex and startle reactivity were assessed two months postpartum in 141 healthy and 29 depressed women. The catechol-O-methyltransferase (COMT) Val158Met, and oxytocin receptor (OXTR) rs237885 and rs53576 polymorphisms were genotyped, and data on sleep duration were collected. Short sleep duration (less than four hours in the preceding night) and postpartum depression were independently associated with lower PPI. Also, women with postpartum depression had higher startle reactivity in comparison with controls. The OXTR rs237885 genotype was related to PPI in an allele dose-dependent mode, with T/T healthy postpartum women carriers displaying the lowest PPI. Reduced sensorimotor gating was associated with sleep deprivation and depressive symptoms during the postpartum period. Individual neurophysiological vulnerability might be mediated by oxytocinergic genotype which relates to bonding and stress response. These findings implicate the putative relevance of lower PPI of the startle response as an objective physiological correlate of liability to postpartum depression. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Increased sensorimotor gating in recreational and dependent cocaine users is modulated by craving and attention-deficit/hyperactivity disorder symptoms.

PubMed

Preller, Katrin H; Ingold, Nina; Hulka, Lea M; Vonmoos, Matthias; Jenni, Daniela; Baumgartner, Markus R; Vollenweider, Franz X; Quednow, Boris B

2013-02-01

Cocaine dependence has been associated with blunted dopamine and norepinephrine signaling, but it is unknown if recreational cocaine use is also associated with alterations of catecholamine systems. Prepulse inhibition (PPI) of the acoustic startle response-a measure of sensorimotor gating-is highly sensitive for manipulations of the catecholamine system. Therefore, we investigated whether relatively pure recreational users (RCU) and dependent cocaine users (DCU) display alterations of PPI, startle reactivity, and habituation. Moreover, the influences of methylenedioxymethamphetamine and cannabis co-use, craving, and attention-deficit/hyperactivity disorder (ADHD) symptoms on startle measures were examined. In 64 RCU, 29 DCU, and 66 stimulant-naïve control subjects, PPI of acoustic startle response, startle reactivity, habituation, ADHD symptoms, and cocaine craving were assessed. Drug use of all participants was controlled by hair and urine toxicologies. Both RCU and DCU showed increased PPI in comparison with control participants (Cohen's d=.38 and d=.67, respectively), while RCU and DCU did not differ in PPI measures (d=.12). No significant group differences were found in startle reactivity or habituation measures. In cocaine users, PPI was positively correlated with cumulative cocaine dose used, craving for cocaine, and ADHD symptoms. Users with a diagnosis of ADHD and strong craving symptoms displayed the highest PPI levels compared with control subjects (d=.78). The augmented PPI in RCU and DCU suggests that recreational use of cocaine is associated with altered catecholamine signaling, in particular if ADHD or craving symptoms are present. Finally, ADHD might be a critical risk factor for cocaine-induced changes of the catecholamine system. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Exercise Blood Pressure Guidelines: Time to Re-evaluate What is Normal and Exaggerated?

PubMed

Currie, Katharine D; Floras, John S; La Gerche, Andre; Goodman, Jack M

2018-03-24

Blood pressure responses to graded exercise testing can provide important diagnostic and prognostic information. While published guidelines outline what constitutes a "normal" and "abnormal" (i.e., exaggerated) blood pressure response to exercise testing, the widespread use of exaggerated blood pressure responses as a clinical tool is limited due to sparse and inconsistent data. A review of the original sources from these guidelines reveals an overall lack of empirical evidence to support both the normal blood pressure responses and their upper limits. In this current opinion, we critically evaluate the current exercise blood pressure guidelines including (1) the normal blood pressure responses to graded exercise testing; (2) the upper limits of this normal response; (3) the blood pressure criteria for test termination; and (4) the thresholds for exaggerated blood pressure responses. We provide evidence that exercise blood pressure responses vary according to subject characteristics, and subsequently a re-evaluation of what constitutes normal and abnormal responses is necessary to strengthen the clinical utility of this assessment.

Does trait anxiety influence effects of oxytocin on eye-blink startle reactivity? A randomized, double-blind, placebo-controlled crossover study.

PubMed

Schumacher, Sonja; Oe, Misari; Wilhelm, Frank H; Rufer, Michael; Heinrichs, Markus; Weidt, Steffi; Moergeli, Hanspeter; Martin-Soelch, Chantal

2018-01-01

Previous research has demonstrated that the neuropeptide oxytocin modulates social behaviors and reduces anxiety. However, effects of oxytocin on startle reactivity, a well-validated measure of defense system activation related to fear and anxiety, have been inconsistent. Here we investigated the influence of oxytocin on startle reactivity with particular focus on the role of trait anxiety. Forty-four healthy male participants attended two experimental sessions. They received intranasal oxytocin (24 IU) in one session and placebo in the other. Startle probes were presented in combination with pictures of social and non-social content. Eye-blink startle magnitude was measured by electromyography over the musculus orbicularis oculi in response to 95 dB noise bursts. Participants were assigned to groups of high vs. low trait anxiety based on their scores on the trait form of the Spielberger State-Trait Anxiety Inventory (STAI). A significant interaction effect of oxytocin with STAI confirmed that trait anxiety moderated the effect of oxytocin on startle reactivity. Post-hoc tests indicated that for participants with elevated trait anxiety, oxytocin increased startle magnitude, particularly when watching non-social pictures, while this was not the case for participants with low trait anxiety. Results indicate that effects of oxytocin on defense system activation depend on individual differences in trait anxiety. Trait anxiety may be an important moderator variable that should be considered in human studies on oxytocin effects.

Glycine inhibits startle-mediating neurons in the caudal pontine reticular formation but is not involved in synaptic depression underlying short-term habituation of startle.

PubMed

Geis, Hans-Ruediger; Schmid, Susanne

2011-10-01

The mammalian startle response is controlled by glycine inhibition in the spinal cord. Evidence for additional glycine inhibition on the level of the brainstem, namely in the caudal pontine reticular nucleus (PnC), is controversial. Startle mediating PnC neurons receive fast input from sensory pathways and project to cranial and spinal motoneurons. Synaptic depression in the sensory synapses in the PnC has been indicated as underlying mechanism of short-term habituation of startle. We here performed patch-clamp recordings of PnC giant neurons in rat brain slices to test the hypothesis that the activation of glycine receptors inhibits PnC neurons and that this inhibition is involved in synaptic depression in the PnC. Glycine strongly inhibited PnC neuron activity and synaptic signalling, indicating that functional glycine receptors mediate a powerful inhibition of PnC neurons over a wide range of glycine concentrations. Strychnine reversed all glycine effects, but had no effect on PnC neurons itself. Thus, we found no evidence for a tonic glycine inhibition or for glycine activation within the primary startle pathway indicating that baseline startle reactions are unlikely to be controlled by glycine in the PnC. Most importantly, synaptic depression underlying short-term habituation was not affected by glycine or strychnine. Copyright © 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Differential neuroendocrine responses to chronic variable stress in adult Long Evans rats exposed to handling-maternal separation as neonates.

PubMed

Ladd, Charlotte O; Thrivikraman, K V; Huot, Rebecca L; Plotsky, Paul M

2005-07-01

Burgeoning evidence supports a preeminent role for early- and late-life stressors in the development of physio- and psychopathology. Handling-maternal separation (HMS) in neonatal Long Evans hooded rats leads to stable phenotypes ranging from resilient to vulnerable to later stressor exposure. Handling with 180 min of maternal separation yields a phenotype of stress hyper-responsiveness associated with facilitation of regional CRF neurocircuits and glucocorticoid resistance. This study assessed whether or not prolonged HMS (180 min/day, HMS180) on post-natal days 2-14 sensitizes the adult limbic hypothalamo-pituitary-adrenal (LHPA) axis to chronic variable stress (CS) compared to brief HMS (15 min/day, HMS15). We examined regional mRNA densities of corticotropin-releasing factor (CRF), its receptor CRF1, glucocorticoid receptor (GR), and mineralocorticoid receptor (MR); regional CRF1 and CRF2alpha binding, and pituitary-adrenal responses to an acute air-puff startle (APS) stressor in four groups: HMS15, nonstressed; HMS15, stressed; HMS180, nonstressed; HMS180, stressed. As expected we observed exaggerated pituitary-adrenal responses to APS, increased regional CRF mRNA density, decreased regional CRF1 binding, and decreased cortical GR mRNA density in nonstressed HMS180 vs. HMS15 animals. However, in contrast to our hypothesis, CS decreased pituitary-adrenal reactivity and central amygdala CRF mRNA density in HMS180 rats, while increasing cortical GR mRNA density and CRF1 binding. CS had no effect on the pituitary-adrenal response to APS in HMS15 rats, despite tripling hypothalamic paraventricular CRF mRNA density. The data suggest that many effects of prolonged HMS are reversible in adulthood by CS, while the neuroendocrine adaptations imbued by brief HMS are sufficiently stable to restrain pituitary-adrenal stress responses even following CS.

Intolerance of uncertainty and startle potentiation in relation to different threat reinforcement rates.

PubMed

Chin, Brian; Nelson, Brady D; Jackson, Felicia; Hajcak, Greg

2016-01-01

Fear conditioning research on threat predictability has primarily examined the impact of temporal (i.e., timing) predictability on the startle reflex. However, there are other key features of threat that can vary in predictability. For example, the reinforcement rate (i.e., frequency) of threat is a crucial factor underlying fear learning. The present study examined the impact of threat reinforcement rate on the startle reflex and self-reported anxiety during a fear conditioning paradigm. Forty-five participants completed a fear learning task in which the conditioned stimulus was reinforced with an electric shock to the forearm on 50% of trials in one block and 75% of trials in a second block, in counter-balanced order. The present study also examined whether intolerance of uncertainty (IU), the tendency to perceive or experience uncertainty as stressful or unpleasant, was associated with the startle reflex during conditions of low (50%) vs. high (75%) reinforcement. Results indicated that, across all participants, startle was greater during the 75% relative to the 50% reinforcement condition. IU was positively correlated with startle potentiation (i.e., increased startle response to the CS+ relative to the CS-) during the 50%, but not the 75%, reinforcement condition. Thus, despite receiving fewer electric shocks during the 50% reinforcement condition, individuals with high IU uniquely demonstrated greater defense system activation when impending threat was more uncertain. The association between IU and startle was independent of state anxiety. The present study adds to a growing literature on threat predictability and aversive responding, and suggests IU is associated with abnormal responding in the context of uncertain threat. Copyright © 2015 Elsevier B.V. All rights reserved.

Corticotropin-releasing factor (CRF) and α 2 adrenergic receptors mediate heroin withdrawal-potentiated startle in rats.

PubMed

Park, Paula E; Vendruscolo, Leandro F; Schlosburg, Joel E; Edwards, Scott; Schulteis, Gery; Koob, George F

2013-09-01

Anxiety is one of the early symptoms of opioid withdrawal and contributes to continued drug use and relapse. The acoustic startle response (ASR) is a component of anxiety that has been shown to increase during opioid withdrawal in both humans and animals. We investigated the role of corticotropin-releasing factor (CRF) and norepinephrine (NE), two key mediators of the brain stress system, on acute heroin withdrawal-potentiated ASR. Rats injected with heroin (2 mg/kg s.c.) displayed an increased ASR when tested 4 h after heroin treatment. A similar increase in ASR was found in rats 10-20 h into withdrawal from extended access (12 h) to i.v. heroin self-administration, a model that captures several aspects of heroin addiction in humans. Both the α 2 adrenergic receptor agonist clonidine (10 μg/kg s.c.) and CRF1 receptor antagonist N,N-bis(2-methoxyethyl)-3-(4-methoxy-2-methylphenyl)-2,5-dimethyl-pyrazolo[1,5-a] pyrimidin-7-amine (MPZP; 20 mg/kg s.c.) blocked heroin withdrawal-potentiated startle. To investigate the relationship between CRF1 and α 2 adrenergic receptors in the potentiation of the ASR, we tested the effect of MPZP on yohimbine (1.25 mg/kg s.c.)-potentiated startle and clonidine on CRF (2 μg i.c.v.)-potentiated startle. Clonidine blocked CRF-potentiated startle, whereas MPZP partially attenuated but did not reverse yohimbine-potentiated startle, suggesting that CRF may drive NE release to potentiate startle. These results suggest that CRF1 and α 2 receptors play an important role in the heightened anxiety-like behaviour observed during acute withdrawal from heroin, possibly via CRF inducing the release of NE in stress-related brain regions.

Hypnotizability, Hypnosis and Prepulse Inhibition of the Startle Reflex in Healthy Women: An ERP Analysis

PubMed Central

De Pascalis, Vilfredo; Russo, Emanuela

2013-01-01

A working model of the neurophysiology of hypnosis suggests that highly hypnotizable individuals (HHs) have more effective frontal attentional systems implementing control, monitoring performance, and inhibiting unwanted stimuli from conscious awareness, than low hypnotizable individuals (LHs). Recent studies, using prepulse inhibition (PPI) of the auditory startle reflex (ASR), suggest that HHs, in the waking condition, may show reduced sensory gating although they may selectively attend and disattend different stimuli. Using a within subject design and a strict subject selection procedure, in waking and hypnosis conditions we tested whether HHs compared to LHs showed a significantly lower inhibition of the ASR and startle-related brain activity in both time and intracerebral source localization domains. HHs, as compared to LH participants, exhibited (a) longer latency of the eyeblink startle reflex, (b) reduced N100 responses to startle stimuli, and (c) higher PPI of eyeblink startle and of the P200 and P300 waves. Hypnosis yielded smaller N100 waves to startle stimuli and greater PPI of this component than in the waking condition. sLORETA analysis revealed that, for the N100 (107 msec) elicited during startle trials, HHs had a smaller activation in the left parietal lobe (BA2/40) than LHs. Auditory pulses of pulse-with prepulse trials in HHs yielded less activity of the P300 (280 msec) wave than LHs, in the cingulate and posterior cingulate gyrus (BA23/31). The present results, on the whole, are in the opposite direction to PPI findings on hypnotizability previously reported in the literature. These results provide support to the neuropsychophysiological model that HHs have more effective sensory integration and gating (or filtering) of irrelevant stimuli than LHs. PMID:24278150

Hypnotizability, hypnosis and prepulse inhibition of the startle reflex in healthy women: an ERP analysis.

PubMed

De Pascalis, Vilfredo; Russo, Emanuela

2013-01-01

A working model of the neurophysiology of hypnosis suggests that highly hypnotizable individuals (HHs) have more effective frontal attentional systems implementing control, monitoring performance, and inhibiting unwanted stimuli from conscious awareness, than low hypnotizable individuals (LHs). Recent studies, using prepulse inhibition (PPI) of the auditory startle reflex (ASR), suggest that HHs, in the waking condition, may show reduced sensory gating although they may selectively attend and disattend different stimuli. Using a within subject design and a strict subject selection procedure, in waking and hypnosis conditions we tested whether HHs compared to LHs showed a significantly lower inhibition of the ASR and startle-related brain activity in both time and intracerebral source localization domains. HHs, as compared to LH participants, exhibited (a) longer latency of the eyeblink startle reflex, (b) reduced N100 responses to startle stimuli, and (c) higher PPI of eyeblink startle and of the P200 and P300 waves. Hypnosis yielded smaller N100 waves to startle stimuli and greater PPI of this component than in the waking condition. sLORETA analysis revealed that, for the N100 (107 msec) elicited during startle trials, HHs had a smaller activation in the left parietal lobe (BA2/40) than LHs. Auditory pulses of pulse-with prepulse trials in HHs yielded less activity of the P300 (280 msec) wave than LHs, in the cingulate and posterior cingulate gyrus (BA23/31). The present results, on the whole, are in the opposite direction to PPI findings on hypnotizability previously reported in the literature. These results provide support to the neuropsychophysiological model that HHs have more effective sensory integration and gating (or filtering) of irrelevant stimuli than LHs.

Increased startle potentiation to unpredictable stressors in alcohol dependence: Possible stress neuroadaptation in humans

PubMed Central

Moberg, Christine A.; Bradford, Daniel E.; Kaye, Jesse T.; Curtin, John J.

2017-01-01

Stress plays a key role in addiction etiology and relapse. Rodent models posit that following repeated periods of alcohol and other drug intoxication, compensatory allostatic changes occur in the central nervous system (CNS) circuits involved in behavioral and emotional response to stressors. We examine a predicted manifestation of this neuroadaptation in recently abstinent alcohol dependent humans. Participants completed a translational laboratory task that uses startle potentiation to unpredictable (vs. predictable) stressors implicated in the putative CNS mechanisms that mediate this neuroadaptation. Alcohol dependent participants displayed significantly greater startle potentiation to unpredictable than predictable stressors relative to non-alcoholic controls. The size of this effect covaried with alcohol-related problems and degree of withdrawal syndrome. This supports the rodent model thesis of a sensitized stress response in abstinent alcoholics. However, this effect could also represent pre-morbid risk or mark more severe and/or comorbid psychopathology. Regardless, pharmacotherapy and psychological interventions may target unpredictable stressor response to reduce stress-induced relapse. PMID:28394145

Anticipation of interoceptive threat in highly anxiety sensitive persons.

PubMed

Melzig, Christiane A; Michalowski, Jaroslaw M; Holtz, Katharina; Hamm, Alfons O

2008-10-01

Anticipatory anxiety plays a major role in the etiology of panic disorder. Although anticipatory anxiety elicited by expectation of interoceptive cues is specifically relevant for panic patients, it has rarely been studied. Using a population analogue in high fear of such interoceptive arousal sensations (highly anxiety sensitive persons) we evaluated a new experimental paradigm to assess anticipatory anxiety during anticipation of interoceptive (somatic sensations evoked by hyperventilation) and exteroceptive (electric shock) threat. Symptom reports, autonomic arousal, and defensive response mobilization (startle eyeblink response) were monitored during threat and matched safe conditions in 26 highly anxiety sensitive persons and 22 controls. The anticipation of exteroceptive threat led to a defensive and autonomic mobilization as indexed by a potentiation of the startle response and an increase in skin conductance level in both experimental groups. During interoceptive threat, however, only highly anxiety sensitive persons but not the controls exhibited a startle response potentiation as well as autonomic activation. The anticipation of a hyperventilation procedure thus seems a valid paradigm to investigate anticipatory anxiety elicited by interoceptive cues in the clinical context.

Emotion regulation during threat: Parsing the time course and consequences of safety signal processing

PubMed Central

HEFNER, KATHRYN R.; VERONA, EDELYN; CURTIN, JOHN. J.

2017-01-01

Improved understanding of fear inhibition processes can inform the etiology and treatment of anxiety disorders. Safety signals can reduce fear to threat, but precise mechanisms remain unclear. Safety signals may acquire attentional salience and affective properties (e.g., relief) independent of the threat; alternatively, safety signals may only hold affective value in the presence of simultaneous threat. To clarify such mechanisms, an experimental paradigm assessed independent processing of threat and safety cues. Participants viewed a series of red and green words from two semantic categories. Shocks were administered following red words (cue+). No shocks followed green words (cue−). Words from one category were defined as safety signals (SS); no shocks were administered on cue+ trials. Words from the other (control) category did not provide information regarding shock administration. Threat (cue+ vs. cue−) and safety (SS+ vs. SS−) were fully crossed. Startle response and ERPs were recorded. Startle response was increased during cue+ versus cue−. Safety signals reduced startle response during cue+, but had no effect on startle response during cue−. ERP analyses (PD130 and P3) suggested that participants parsed threat and safety signal information in parallel. Motivated attention was not associated with safety signals in the absence of threat. Overall, these results confirm that fear can be reduced by safety signals. Furthermore, safety signals do not appear to hold inherent hedonic salience independent of their effect during threat. Instead, safety signals appear to enable participants to engage in effective top-down emotion regulatory processes. PMID:27088643

Modality of fear cues affects acoustic startle potentiation but not heart-rate response in patients with dental phobia

PubMed Central

Wannemüller, André; Sartory, Gudrun; Elsesser, Karin; Lohrmann, Thomas; Jöhren, Hans P.

2015-01-01

The acoustic startle response (SR) has consistently been shown to be enhanced by fear-arousing cross-modal background stimuli in phobics. Intra-modal fear-potentiation of acoustic SR was rarely investigated and generated inconsistent results. The present study compared the acoustic SR to phobia-related sounds with that to phobia-related pictures in 104 dental phobic patients and 22 controls. Acoustic background stimuli were dental treatment noises and birdsong and visual stimuli were dental treatment and neutral control pictures. Background stimuli were presented for 4 s, randomly followed by the administration of the startle stimulus. In addition to SR, heart-rate (HR) was recorded throughout the trials. Irrespective of their content, background pictures elicited greater SR than noises in both groups with a trend for phobic participants to show startle potentiation to phobia-related pictures but not noises. Unlike controls, phobics showed HR acceleration to both dental pictures and noises. HR acceleration of the phobia group was significantly positively correlated with SR in the noise condition only. The acoustic SR to phobia-related noises is likely to be inhibited by prolonged sensorimotor gating. PMID:25774142

The Influence of Agreeableness and Ego Depletion on Emotional Responding.

PubMed

Finley, Anna J; Crowell, Adrienne L; Harmon-Jones, Eddie; Schmeichel, Brandon J

2017-10-01

Agreeable individuals report more intense withdrawal-oriented negative emotions across aversive situations. Two studies tested the hypothesis that self-regulatory depletion (i.e., ego depletion) moderates the relationship between trait Agreeableness and negative emotional responding. Ego depletion was manipulated using a writing task. Emotional responding was measured with startle eye-blink responses (Study 1, N = 71) and self-reported valence, arousal, and empathic concern (Study 2, N = 256) during emotional picture viewing. Trait Agreeableness was measured using a questionnaire. In Study 1, Agreeableness predicted especially large startle responses during aversive images and especially small startles during appetitive images. After exercising self-control, the relationship between startle magnitudes and Agreeableness decreased. In Study 2, Agreeableness predicted more empathic concern for aversive images, which in turn predicted heightened self-reported negative emotions. After exercising self-control, the relationship between Agreeableness and empathic concern decreased. Agreeable individuals exhibit heightened negative emotional responding. Ego depletion reduced the link between Agreeableness and negative emotional responding in Study 1 and moderated the indirect effect of Agreeableness on negative emotional responding via empathic concern in Study 2. Empathic concern appears to be a resource-intensive process underlying heightened responding to aversive stimuli among agreeable persons. © 2016 Wiley Periodicals, Inc.

Histamine-dependent behavioral response to methamphetamine in 12-month-old male mice

PubMed Central

Acevedo, Summer F.; Raber, Jacob

2011-01-01

Methamphetamine (MA) use is a growing problem across the United States. Effects of MA include hyperactivity and increased anxiety. Using a mouse model system, we examined behavioral performance in the open field and elevated zero maze and shock-startle response of 12-month-old wild-type mice injected with MA once (1mg/kg) 30 min prior to behavioral testing. MA treatment resulted in behavioral sensitization in the open field, consistent with studies in younger mice. There was an increased activity in the elevated zero maze and an increased shock-startle response 30 and 60 min post-injection. Since histamine mediates some effects of MA in the brain, we assessed whether 12-month-old mice lacking histidine decarboxylase (Hdc−/−), the enzyme required to synthesize histamine, respond differently to MA than wild-type (Hdc+/+) mice. Compared to saline treatment, acute and repeated MA administration increased activity in the open field and measures of anxiety, though more so in Hdc−/− than Hdc+/+ mice. In the elevated zero maze, opposite effects of MA on activity and measures of anxiety were seen in Hdc+/+ mice. In contrast, MA similarly increased the shock-startle response in Hdc−/− and Hdc+/+ mice, compared to saline-treated genotype-matched mice. These results are similar to those in younger mice suggesting that the effects are not age-dependent. Overall, single or repeated MA treatment causes histamine-dependent changes in 12-month-old mice in the open field and elevated zero-maze, but not in the shock-startle response. PMID:21466792

Becoming the center of attention in social anxiety disorder: Startle reactivity to a virtual audience during speech anticipation

PubMed Central

Cornwell, Brian R.; Heller, Randi; Biggs, Arter; Pine, Daniel S.; Grillon, Christian

2012-01-01

Objective A detailed understanding of how individuals diagnosed with social anxiety disorder (SAD) respond physiologically under social-evaluative threat is lacking. We aimed to isolate the specific components of public speaking that trigger fear in vulnerable individuals and best discriminate among SAD and healthy individuals. Method Sixteen individuals diagnosed with SAD and 16 healthy individuals were asked to prepare and deliver a short speech in a virtual reality (VR) environment. The VR environment simulated standing center stage before a live audience and allowed us to gradually introduce social cues during speech anticipation. Startle eye-blink responses were elicited periodically by white noise bursts presented during anticipation, speech delivery, and recovery in VR, as well as outside VR during an initial habituation phase. Results SAD individuals reported greater distress and state anxiety than healthy individuals across the entire procedure (ps < .005). Analyses of startle reactivity revealed a robust group difference during speech anticipation in VR, specifically as audience members directed their eye gaze and turned their attention toward participants (p < .05, Bonferroni corrected). Conclusions The VR environment is sufficiently realistic to provoke fear and anxiety in individuals highly vulnerable to socially threatening situations. SAD individuals showed potentiated startle, indicative of a strong phasic fear response, specifically when they perceived themselves as occupying the focus of others' attention as speech time approached. Potentiated startle under social-evaluative threat indexes SAD-related fear of negative evaluation. PMID:21034683

A network analysis of DSM-5 posttraumatic stress disorder and functional impairment in UK treatment-seeking veterans.

PubMed

Ross, Jana; Murphy, Dominic; Armour, Cherie

2018-05-28

Network analysis is a relatively new methodology for studying psychological disorders. It focuses on the associations between individual symptoms which are hypothesized to mutually interact with each other. The current study represents the first network analysis conducted with treatment-seeking military veterans in UK. The study aimed to examine the network structure of posttraumatic stress disorder (PTSD) symptoms and four domains of functional impairment by identifying the most central (i.e., important) symptoms of PTSD and by identifying those symptoms of PTSD that are related to functional impairment. Participants were 331 military veterans with probable PTSD. In the first step, a network of PTSD symptoms based on the PTSD Checklist for DSM-5 was estimated. In the second step, functional impairment items were added to the network. The most central symptoms of PTSD were recurrent thoughts, nightmares, negative emotional state, detachment and exaggerated startle response. Functional impairment was related to a number of different PTSD symptoms. Impairments in close relationships were associated primarily with the negative alterations in cognitions and mood symptoms and impairments in home management were associated primarily with the reexperiencing symptoms. The results are discussed in relation to previous PTSD network studies and include implications for clinical practice. Copyright © 2018 Elsevier Ltd. All rights reserved.

The emotional brain and sleep: an intimate relationship.

PubMed

Vandekerckhove, Marie; Cluydts, Raymond

2010-08-01

Research findings confirm our own experiences in life where daytime events and especially emotionally stressful events have an impact on sleep quality and well-being. Obviously, daytime emotional stress may have a differentiated effect on sleep by influencing sleep physiology and dream patterns, dream content and the emotion within a dream, although its exact role is still unclear. Other effects that have been found are the exaggerated startle response, decreased dream recall and elevated awakening thresholds from rapid eye movement (REM)-sleep, increased or decreased latency to REM-sleep, increased REM-density, REM-sleep duration and the occurrence of arousals in sleep as a marker of sleep disruption. However, not only do daytime events affect sleep, also the quality and amount of sleep influences the way we react to these events and may be an important determinant in general well-being. Sleep seems restorative in daily functioning, whereas deprivation of sleep makes us more sensitive to emotional and stressful stimuli and events in particular. The way sleep impacts next day mood/emotion is thought to be affected particularly via REM-sleep, where we observe a hyperlimbic and hypoactive dorsolateral prefrontal functioning in combination with a normal functioning of the medial prefrontal cortex, probably adaptive in coping with the continuous stream of emotional events we experience. (c) 2010 Elsevier Ltd. All rights reserved.

Gangliosidoses.

PubMed

Patterson, Marc C

2013-01-01

The gangliosidoses comprise a family of lysosomal storage diseases characterized by the accumulation of complex glycosphingolipids in the nervous system and other tissues, secondary to the deficient activity of lysosomal hydrolases or their associated activator proteins. GM1 and GM2 gangliosidosis are associated with deficiency of β-galactosidase and β-hexosaminidase respectively. All gangliosidoses are characterized by progressive neurodegeneration, the severity of which is proportional to the residual enzyme activity. The GM1 gangliosidoses are characterized by dysostosis, organomegaly and coarsening in their most severe forms, whereas children with classic infantile GM2 gangliosidosis (Tay-Sachs disease) are usually spared systemic involvement, except in the case of the Sandhoff variant, in which organomegaly may occur. Cherry-red macular spots occur in the early onset forms of the gangliosidoses, but are less frequently seen in the less severe, later onset phenotypes. Macrocephaly, an exaggerated startle response, cognitive decline, seizures, ataxia, and progressive muscular atrophy may occur in different forms of gangliosidosis. The diagnosis is made by assay of enzyme activity, and can be confirmed by mutation analysis. Carrier screening for Tay-Sachs disease has been remarkably successful in reducing the incidence of this disease in the at-risk Ashkenazi population. There are no proven disease-modifying therapies for the gangliosidoses. Copyright © 2013 Elsevier B.V. All rights reserved.

Axonal conduction block as a novel mechanism of prepulse inhibition

PubMed Central

Lee, A. H.; Megalou, E. V.; Wang, J.; Frost, W.N.

2012-01-01

In prepulse inhibition (PPI), the startle response to a strong, unexpected stimulus is diminished if shortly preceded by the onset of a different stimulus. Because deficits in this inhibitory gating process are a hallmark feature of schizophrenia and certain other psychiatric disorders, the mechanisms underlying PPI are of significant interest. We previously used the invertebrate model system Tritonia diomedea to identify the first cellular mechanism for PPI–presynaptic inhibition of transmitter release from the afferent neurons (S-cells) mediating the startle response. Here we report the involvement of a second, more powerful PPI mechanism in Tritonia: prepulse-elicited conduction block of action potentials traveling in the startle pathway caused by identified inhibitory interneurons activated by the prepulse. This example of axo-axonic conduction block–neurons in one pathway inhibiting the propagation of action potentials in another–represents a novel and potent mechanism of sensory gating in prepulse inhibition. PMID:23115164

Subjective and physiological reactivity to chocolate images in high and low chocolate cravers.

PubMed

Rodríguez, Sonia; Fernández, María Carmen; Cepeda-Benito, Antonio; Vila, Jaime

2005-09-01

Cue-reactivity to chocolate images was assessed using self-report and physiological measures. From a pre-screening sample of 454, young women were selected and assigned to high and low chocolate craving groups (N = 36/group). The experimental procedure consisted in the elicitation and measurement of the cardiac defense and startle reflexes while viewing chocolate and standard affective images selected from the International Affective Picture System. In response to chocolate images, high cravers reported more pleasure and arousal but less control than low cravers. In high cravers, viewing chocolate images inhibited the cardiac defense but potentiated the startle reflex, as compared to low cravers. The results confirmed at the physiological level that the motivational state that underlies the experience of chocolate craving include both appetitive (inhibition of the defense reflex) and aversive (potentiation of the startle response) components. The findings supported a motivational conflict theory of chocolate craving.

Increased levels of conditioned fear and avoidance behavior coincide with changes in phosphorylation of the protein kinase B (AKT) within the amygdala in a mouse model of extremes in trait anxiety.

PubMed

Yen, Yi-Chun; Mauch, Christoph P; Dahlhoff, Maik; Micale, Vincenzo; Bunck, Mirjam; Sartori, Simone B; Singewald, Nicolas; Landgraf, Rainer; Wotjak, Carsten T

2012-07-01

Patients diagnosed for anxiety disorders often display faster acquisition and slower extinction of learned fear. To gain further insights into the mechanisms underlying these phenomenona, we studied conditioned fear in mice originating form a bi-directional selective breeding approach, which is based on elevated plus-maze behavior and results in CD1-derived high (HAB), normal (NAB), and low (LAB) anxiety-related behavior mice. HAB mice displayed pronounced cued-conditioned fear compared to NAB/CD1 and LAB mice that coincided with increased phosphorylation of the protein kinase B (AKT) in the basolateral amygdala 45 min after conditioning. No similar changes were observed after non-associative immediate shock presentations. Fear extinction of recent but not older fear memories was preserved. However, HAB mice were more prone to relapse of conditioned fear with the passage of time. HAB mice also displayed higher levels of contextual fear compared to NAB and LAB mice and exaggerated avoidance following step-down avoidance training. Interestingly, HAB mice showed lower and LAB mice higher levels of acoustic startle responses compared to NAB controls. The increase in arousal observed in LAB mice coincided with the general absence of conditioned freezing. Taken together, our results suggest that the genetic predisposition to high anxiety-related behavior may increase the risk of forming traumatic memories, phobic-like fear and avoidance behavior following aversive encounters, with a clear bias towards passive coping styles. In contrast, genetic predisposition to low anxiety-related and high risk-taking behavior seems to be associated with an increase in active coping styles. Our data imply changes in AKT phosphorylation as a therapeutic target for the prevention of exaggerated fear memories. Copyright © 2012 Elsevier Inc. All rights reserved.

Light exaggerates apical hook curvature through phytochrome actions in tomato seedlings.

PubMed

Shichijo, Chizuko; Ohuchi, Hisako; Iwata, Naoko; Nagatoshi, Yukari; Takahashi, Miki; Nakatani, Eri; Inoue, Kentaroh; Tsurumi, Seiji; Tanaka, Osamu; Hashimoto, Tohru

2010-02-01

Contrary to the established notion that the apical hook of dark-grown dicotyledonous seedlings opens in response to light, we found in tomato (Solanum lycopersicum L.) that the apical hook curvature is exaggerated by light. Experiments with several tomato cultivars and phytochrome mutants, irradiated with red and far-red light either as a brief pulse (Rp, FRp) or continuously (Rc, FRc), revealed: the hook-exaggeration response is maximal at the emergence of the hypocotyl from the seed; the effect of Rp is FRp-reversible; fluence-response curves to a single Rp or FRp show an involvement of low and very low fluence responses (LFR, VLFR); the effect of Rc is fluence-rate dependent, but that of FRc is not; the phyA mutant (phyA hp-1) failed to respond to an Rp of less than 10(-2) micromol m(-2) and to an FRp of all fluences tested as well as to FRc, thus indicating that the hook-exaggeration response involves phyA-mediated VLFR. The Rp fluence-response curve with the same mutant also confirmed the presence of an LFR mediated by phytochrome(s) other than phyA, although the phyB1 mutant (phyB1 hp-1) still showed full response probably due to other redundant phytochrome species (e.g., phyB2). Simulation experiments led to the possible significance of hook exaggeration in the field that the photoresponse may facilitate the release of seed coat when seeds germinate at some range of depth in soil. It was also observed that seed coat and/or endosperm are essential to the hook exaggeration.

The Functional Networks of Prepulse Inhibition: Neuronal Connectivity Analysis Based on FDG-PET in Awake and Unrestrained Rats.

PubMed

Rohleder, Cathrin; Wiedermann, Dirk; Neumaier, Bernd; Drzezga, Alexander; Timmermann, Lars; Graf, Rudolf; Leweke, F Markus; Endepols, Heike

2016-01-01

Prepulse inhibition (PPI) is a neuropsychological process during which a weak sensory stimulus ("prepulse") attenuates the motor response ("startle reaction") to a subsequent strong startling stimulus. It is measured as a surrogate marker of sensorimotor gating in patients suffering from neuropsychological diseases such as schizophrenia, as well as in corresponding animal models. A variety of studies has shown that PPI of the acoustical startle reaction comprises three brain circuitries for: (i) startle mediation, (ii) PPI mediation, and (iii) modulation of PPI mediation. While anatomical connections and information flow in the startle and PPI mediation pathways are well known, spatial and temporal interactions of the numerous regions involved in PPI modulation are incompletely understood. We therefore combined [(18)F]fluoro-2-deoxyglucose positron-emission-tomography (FDG-PET) with PPI and resting state control paradigms in awake rats. A battery of subtractive, correlative as well as seed-based functional connectivity analyses revealed a default mode-like network (DMN) active during resting state only. Furthermore, two functional networks were observed during PPI: Metabolic activity in the lateral circuitry was positively correlated with PPI effectiveness and involved the auditory system and emotional regions. The medial network was negatively correlated with PPI effectiveness, i.e., associated with startle, and recruited a spatial/cognitive network. Our study provides evidence for two distinct neuronal networks, whose continuous interplay determines PPI effectiveness in rats, probably by either protecting the prepulse or facilitating startle processing. Discovering similar networks affected in neuropsychological disorders may help to better understand mechanisms of sensorimotor gating deficits and provide new perspectives for therapeutic strategies.

Reactivity to unpredictable threat as a treatment target for fear-based anxiety disorders.

PubMed

Gorka, S M; Lieberman, L; Klumpp, H; Kinney, K L; Kennedy, A E; Ajilore, O; Francis, J; Duffecy, J; Craske, M G; Nathan, J; Langenecker, S; Shankman, S A; Phan, K L

2017-10-01

Heightened reactivity to unpredictable threat (U-threat) is a core individual difference factor underlying fear-based psychopathology. Little is known, however, about whether reactivity to U-threat is a stable marker of fear-based psychopathology or if it is malleable to treatment. The aim of the current study was to address this question by examining differences in reactivity to U-threat within patients before and after 12-weeks of selective serotonin reuptake inhibitors (SSRIs) or cognitive-behavioral therapy (CBT). Participants included patients with principal fear (n = 22) and distress/misery disorders (n = 29), and a group of healthy controls (n = 21) assessed 12-weeks apart. A well-validated threat-of-shock task was used to probe reactivity to predictable (P-) and U-threat and startle eyeblink magnitude was recorded as an index of defensive responding. Across both assessments, individuals with fear-based disorders displayed greater startle magnitude to U-threat relative to healthy controls and distress/misery patients (who did not differ). From pre- to post-treatment, startle magnitude during U-threat decreased only within the fear patients who received CBT. Moreover, within fear patients, the magnitude of decline in startle to U-threat correlated with the magnitude of decline in fear symptoms. For the healthy controls, startle to U-threat across the two time points was highly reliable and stable. Together, these results indicate that startle to U-threat characterizes fear disorder patients and is malleable to treatment with CBT but not SSRIs within fear patients. Startle to U-threat may therefore reflect an objective, psychophysiological indicator of fear disorder status and CBT treatment response.

Homocysteine, visceral adiposity-related novel cardiometabolic risk factors, and exaggerated blood pressure response to the exercise treadmill test.

PubMed

Türker Duyuler, Pinar; Duyuler, Serkan; Demir, Mevlüt; Uçar Elalmiş, Özgül; Güray, Ümit; İleri, Mehmet

2017-12-01

Exaggerated blood pressure response to exercise is a risk factor for the development of future hypertension. In this study, we aimed to investigate the association between homocysteine, epicardial fat thickness, nonalcoholic hepatic steatosis, and exaggerated blood pressure response to exercise. We included 44 normotensive and 40 patients with exaggerated blood pressure response to exercise who have normal resting blood pressure and without a previous diagnosis of hypertension. All patients underwent treadmill exercise test and clinical, ultrasonographic, and echocardiographic evaluation. Exaggerated blood pressure response to exercise is defined as peak exercise systolic blood pressure of at least 210 mmHg in men and at least 190 mmHg in women. Homocysteine and other biochemical parameters were determined with standardized automated laboratory tests. Mean age of all participants is 47.9±8.5 years, and 36 of 84 participants were female. The frequency of diabetes mellitus in both groups was similar (P=0.250). Homeostasis model assessment index-insulin resistance had a statistically insignificant trend to be higher in a patient with exercise hypertension (P=0.058). The nonalcoholic fatty liver was more frequent in patients with exercise hypertension (13.6 vs. 47.5%, P=0.002). Epicardial fat thickness was increased in patients with exercise hypertension (5.5±1.5 vs. 7.3±1.1 mm; P=0.001). However, homocysteine levels did not significantly differ between normotensive and exercise hypertensive patients [12.3 μmol/l (5.7-16.9 μmol/l) vs. 13 μmol/l (5.9-28.3 μmol/l); P=0.883]. In our study, homocysteine levels were not associated with exaggerated blood pressure response to exercise; however, fatty liver and epicardial fat thickness as visceral adiposity-related cardiometabolic risk factors were significantly related with exaggerated blood pressure response to exercise in patients without a previous diagnosis of hypertension.

Ethylene Is Not Responsible for Phytochrome-Mediated Apical Hook Exaggeration in Tomato

PubMed Central

Takahashi-Asami, Miki; Shichijo, Chizuko; Tsurumi, Seiji; Hashimoto, Tohru

2016-01-01

The apical hook of tomato seedlings is exaggerated by phytochrome actions, while in other species such as bean, pea and Arabidopsis, the hook is exaggerated by ethylene and opens by phytochrome actions. The present study was aimed to clarify mainly whether ethylene is responsible for the phytochrome-mediated hook exaggeration of tomato seedlings. Dark-grown 5-day-old seedlings were subjected to various ways of ethylene application in the dark as well as under the actions of red (R) or far-red light (FR). The ethylene emitted by seedlings was also quantified relative to hook exaggeration. The results show: Ambient ethylene, up-to about 1.0 μL L-1, suppressed (opened) the hooks formed in the dark as well as the ones exaggerated by R or FR, while at 3.0–10 μL L-1 it enhanced (closed) the hook only slightly as compared with the most-suppressed level at about 1.0 μL L-1. Treatment with 1-aminocyclopropane-1-carboxylic acid (ACC), the immediate precursor of ethylene biosynthesis, did not enhance the hook, only mimicking the suppressive effects of ambient ethylene. The biosynthesis inhibitor, CoCl2 or aminoethoxyvinylglycine, enhanced hook curvature, and the enhancement was canceled by supplement of ethylene below 1.0 μL L-1. Auxin transport inhibitor, N-1-naphthylphthalamic acid, by contrast, suppressed curvature markedly without altering ethylene emission. The effects of the above-stated treatments did not differentiate qualitatively among the R-, FR-irradiated seedlings and dark control so as to explain phytochrome-mediated hook exaggeration. In addition, ethylene emission by seedlings was affected neither by R nor FR at such fluences as to cause hook exaggeration. In conclusion, (1) ethylene suppresses not only the light-exaggerated hook, but also the dark-formed one; (2) ethylene emission is not affected by R or FR, and also not correlated with the hook exaggerations; thus ethylene is not responsible for the hook exaggeration in tomato; and (3) auxin is essential for the maintenance and development of the hook in tomato as is the case in other species lacking phytochrome-mediated hook exaggeration. A possible mechanism of phytochrome action for hook exaggeration is discussed. PMID:27933077

Acute blood glucose, cardiovascular and exaggerated responses to HIIT and moderate-intensity continuous training in men with type 2 diabetes mellitus.

PubMed

Wormgoor, Shohn G; Dalleck, Lance C; Zinn, Caryn; Harris, Nigel K

2018-01-01

Optimizing exercise-induced physiological responses without increasing the risk of negative exaggerated responses is an important aspect of exercise prescription for people with type 2 diabetes mellitus (T2DM). However, knowledge of acute responses, including exaggerated responses, of different training modalities is limited. The aim of the study was to compare acute physiological responses of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) in T2DM. Baseline data were used to randomly assign male participants into supervised training groups for a 12-week intervention. During week 7, participants trialed either a fully progressed MICT (N.=11) or HIIT (N.=11) (combined with resistance training) session. The MICT included 26 minutes at 55% estimated maximum workload (eWLmax) while the HIIT included twelve 1-minute bouts at 95% eWLmax interspersed with 1-minute bouts at 40% eWLmax. While energy expenditure and peak systolic and diastolic blood pressure responses were similar between groups (P=0.47, P=0.71, P=0.56, respectively), peak heart rate, workload and perceived exertion were higher in the HIIT group (P=0.04, P<0.001, and P<0.001, respectively). Acute exaggerated responses were similar (P=0.39) for MICT (64%) and HIIT (36%) participants. While structured MICT and HIIT sessions resulted in comparable acute physiological responses, the individual variations and exaggerated responses, even after preparatory training, necessitated precautionary respite in T2DM men.

Impact of Hypoxia on Startle Response (C-start) of Fish in a Tropical Urban Estuary

NASA Astrophysics Data System (ADS)

Sánchez-García, M.; Zottoli, S. J.; Roberson, L.

2016-02-01

Hypoxic zones have become more prevalent in marine ecosystems as a result of physical changes to the coastal zone, pollution and eutrophication, and are expected to increase in prevalence with climate change. While some studies have examined the behavioral effects of hypoxia on coastal fishes in temperate and sub-tropical zones, none have focused on tropical coastal zones. Behavioral changes may affect fish survival, predator-prey interactions and ultimately ecosystem structure. Through behavioral endpoints we evaluated the effects of non-lethal levels of hypoxia on estuarine fish collected from the tropical Condado Lagoon, San Juan P.R, in a laboratory setting. Two groups of 10 fishes were placed individually in a sound test chamber and oxygen concentrations were modulated from a pre-treatment at 100% oxygen to increasing levels of hypoxia (80, 70, & 60%), followed by a reversal treatment (100%) to test for recovery of pretreatment behavior. An abrupt sound stimulus was used to elicit a startle response, a quantifiable biological endpoint, while recording with a high speed camera. This approach can lend valuable insight into changes in the central nervous system and effects of anthropogenic inputs on tropical ecosystems at the individual- and population-level. We found that hypoxic conditions significantly decrease fish responsiveness; fish startled only half the time at 80% O2 and dropped as much as 61% at 60% O2. Additionally, responsiveness in reversal tests were significantly lower than under pre-treatment conditions. These results indicate that hypoxia may have long-term or possibly permanent effects, even under relatively mild hypoxia conditions common to tropical estuaries. Future work will aim to understand if the startle response can be regained after a hypoxic event.

Untangling the effects of tinnitus and hypersensitivity to sound (hyperacusis) in the gap detection test.

PubMed

Salloum, R H; Sandridge, S; Patton, D J; Stillitano, G; Dawson, G; Niforatos, J; Santiago, L; Kaltenbach, J A

2016-01-01

In recent years, there has been increasing use of the gap detection reflex test to demonstrate induction of tinnitus in animals. Animals with tinnitus show weakened gap detection ability for background noise that matches the pitch of the tinnitus. The usual explanation is that the tinnitus 'fills in the gap'. It has recently been shown, however, that tinnitus is commonly associated with hyperacusis-like enhancements of the acoustic startle response, a change which might potentially alter responses in the gap detection test. We hypothesized that such enhancements could lead to an apparent reduction of gap suppression, resembling that caused by tinnitus, by altering responses to the startle stimulus or the background noise. To test this hypothesis, we compared gap detection abilities in 3 subsets of noise-exposed animals with those in unexposed controls. The results showed that exposed animals demonstrated altered gap detection abilities, but these alterations were sometimes explained as consequences of hyper-responsiveness to either the startle stimulus or to the background noise. Two of the three subsets of animals studied, however, displayed weakened gap detection abilities that could not be explained by enhanced responses to these stimuli or by reduced sound sensitivity or a reduction of temporal processing speed, consistent with the induction of tinnitus. These results demonstrate that not only hearing loss but also changes in sensitivity to background noise or to startle stimuli are potential confounds that, when present, can underlie changes in gap detection irrespective of tinnitus. We discuss how such confounds can be recognized and how they can be avoided. Copyright © 2015 Elsevier B.V. All rights reserved.

Planning of Ballistic Movement following Stroke: Insights from the Startle Reflex

PubMed Central

Honeycutt, Claire Fletcher; Perreault, Eric Jon

2012-01-01

Following stroke, reaching movements are slow, segmented, and variable. It is unclear if these deficits result from a poorly constructed movement plan or an inability to voluntarily execute an appropriate plan. The acoustic startle reflex provides a means to initiate a motor plan involuntarily. In the presence of a movement plan, startling acoustic stimulus triggers non-voluntary early execution of planned movement, a phenomenon known as the startReact response. In unimpaired individuals, the startReact response is identical to a voluntarily initiated movement, except that it is elicited 30–40 ms. As the startReact response is thought to be mediated by brainstem pathways, we hypothesized that the startReact response is intact in stroke subjects. If startReact is intact, it may be possible to elicit more task-appropriate patterns of muscle activation than can be elicited voluntarily. We found that startReact responses were intact following stroke. Responses were initiated as rapidly as those in unimpaired subjects, and with muscle coordination patterns resembling those seen during unimpaired volitional movements. Results were striking for elbow flexion movements, which demonstrated no significant differences between the startReact responses elicited in our stroke and unimpaired subject groups. The results during planned extension movements were less straightforward for stroke subjects, since the startReact response exhibited task inappropriate activity in the flexors. This inappropriate activity diminished over time. This adaptation suggests that the inappropriate activity was transient in nature and not related to the underlying movement plan. We hypothesize that the task-inappropriate flexor activity during extension results from an inability to suppress the classic startle reflex, which primarily influences flexor muscles and adapts rapidly with successive stimuli. These results indicate that stroke subjects are capable of planning ballistic elbow movements, and that when these planned movements are involuntarily executed they can be as rapid and appropriate as those in unimpaired individuals. PMID:22952634

Gender differences in emotional responses: a psychophysiological study.

PubMed

Bianchin, Marta; Angrilli, Alessandro

2012-02-28

Gender differences in emotional responses have been investigated in two groups of students, 22 males and 21 females. Participants watched a set of sixty emotional standardized slides divided into pleasant, neutral and unpleasant, while Startle reflex, Evoked Potentials, Heart Rate, facial EMG and Skin Conductance were recorded. Startle reflex amplitude, an index modulated by amygdala and orbitofrontal cortex and sensitive to aversive emotional stimuli, was overall larger in women. In addition, startle emotion modulation was greater in women with respect to men. Slow Evoked Potentials (400-800 ms), a measure representing the cognitive component of the emotional response, revealed gender differences in the left prefrontal site, with women showing greater positivity to unpleasant compared with pleasant slides while men had greater positivity to pleasant vs. neutral slides. Women, compared with men, perceived all slides as less pleasant and reported greater arousal to unpleasant condition. Results are in line with known functional brain differences, at level of limbic and paralimbic structures, between men and women, and point to biologically grounded greater sensitivity and vulnerability of women to adverse/stressful events. Copyright © 2011 Elsevier Inc. All rights reserved.

Becoming the center of attention in social anxiety disorder: startle reactivity to a virtual audience during speech anticipation.

PubMed

Cornwell, Brian R; Heller, Randi; Biggs, Arter; Pine, Daniel S; Grillon, Christian

2011-07-01

A detailed understanding of how individuals diagnosed with social anxiety disorder (SAD) respond physiologically under social-evaluative threat is lacking. Our aim was to isolate the specific components of public speaking that trigger fear in vulnerable individuals and best discriminate between SAD and healthy individuals. Sixteen individuals diagnosed with SAD (DSM-IV-TR criteria) and 16 healthy individuals were enrolled in the study from December 2005 to March 2008. Subjects were asked to prepare and deliver a short speech in a virtual reality (VR) environment. The VR environment simulated standing center stage before a live audience and allowed us to gradually introduce social cues during speech anticipation. Startle eye-blink responses were elicited periodically by white noise bursts presented during anticipation, speech delivery, and recovery in VR, as well as outside VR during an initial habituation phase, and startle reactivity was measured by electromyography. Subjects rated their distress at 4 timepoints in VR using a 0-10 scale, with anchors being "not distressed" to "highly distressed." State anxiety was measured before and after VR with the Spielberger State-Trait Anxiety Inventory. Individuals with SAD reported greater distress and state anxiety than healthy individuals across the entire procedure (P values < .005). Analyses of startle reactivity revealed a robust group difference during speech anticipation in VR, specifically as audience members directed their eye gaze and turned their attention toward participants (P < .05, Bonferroni-corrected). The VR environment is sufficiently realistic to provoke fear and anxiety in individuals highly vulnerable to socially threatening situations. Individuals with SAD showed potentiated startle, indicative of a strong phasic fear response, specifically when they perceived themselves as occupying the focus of others' attention as speech time approached. Potentiated startle under social-evaluative threat indexes SAD-related fear of negative evaluation. © Copyright 2011 Physicians Postgraduate Press, Inc.

More meditation, less habituation? The effect of mindfulness practice on the acoustic startle reflex.

PubMed

Antonova, Elena; Chadwick, Paul; Kumari, Veena

2015-01-01

Mindfulness as a mode of sustained and receptive attention promotes openness to each incoming stimulus, even if repetitive and/or aversive. Mindful attention has been shown to attenuate sensory habituation in expert meditators; however, others were not able to replicate this effect. The present study used acoustic startle reflex to investigate the effect of mindfulness practice intensity on sensory habituation. Auditory Startle Response (ASR) to 36 startling probes (12 trials x 3 block with 40 ms inter-block intervals), was measured using electromyography (EMG) in three groups of participants (N = 12/group): meditation-naïve, moderate practice, and intensive practice. Intensive practice group showed attenuated startle habituation as evidenced by significantly less habituation over the entire experiment relative to the meditation-naïve and moderate practice groups. Furthermore, there was a significant linear effect showing between-block habituation in meditation-naïve and moderate practice groups, but not in the intensive practice group. However, the Block x Group interaction between the intensive practice and the meditation-naive groups was not significant. Moderate practice group was not significantly different from the meditation-naïve in the overall measure of habituation, but showed significantly stronger habituation than both meditation-naïve and intensive practice groups in Block 1. Greater practice intensity was significantly correlated with slower overall habituation and habituation rate in Blocks 2 and 3 in the intensive, but not in the moderate, practice group. The study provides tentative evidence that intensive mindfulness practice attenuates acoustic startle habituation as measured by EMG, but the effect is modest.Moderate practice, on the other hand, appears to enhance habituation, suggesting the effect of mindfulness practice on startle habituation might be non-linear [corrected] . Better understanding of the effect of mindful attention on startle habituation may shed new light on sensory information processing capacity of the human brain and its potential for de-automatisation of hard-wired processes.

A Cyfip2-Dependent Excitatory Interneuron Pathway Establishes the Innate Startle Threshold.

PubMed

Marsden, Kurt C; Jain, Roshan A; Wolman, Marc A; Echeverry, Fabio A; Nelson, Jessica C; Hayer, Katharina E; Miltenberg, Ben; Pereda, Alberto E; Granato, Michael

2018-04-17

Sensory experiences dynamically modify whether animals respond to a given stimulus, but it is unclear how innate behavioral thresholds are established. Here, we identify molecular and circuit-level mechanisms underlying the innate threshold of the zebrafish startle response. From a forward genetic screen, we isolated five mutant lines with reduced innate startle thresholds. Using whole-genome sequencing, we identify the causative mutation for one line to be in the fragile X mental retardation protein (FMRP)-interacting protein cyfip2. We show that cyfip2 acts independently of FMRP and that reactivation of cyfip2 restores the baseline threshold after phenotype onset. Finally, we show that cyfip2 regulates the innate startle threshold by reducing neural activity in a small group of excitatory hindbrain interneurons. Thus, we identify a selective set of genes critical to establishing an innate behavioral threshold and uncover a circuit-level role for cyfip2 in this process. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Prospective relations between intrusive parenting and child behavior problems: Differential moderation by parasympathetic nervous system regulation and child sex.

PubMed

Rudd, Kristen L; Alkon, Abbey; Yates, Tuppett M

2017-10-15

This study examined children's parasympathetic nervous system (PNS) regulation, which was indexed by respiratory sinus arrhythmia (RSA) during rest, reactivity, and recovery episodes, and sex as moderators of predicted relations between observed intrusive parenting and later observer-rated child behavior problems. Child-caregiver dyads (N=250; 50% girls; 46% Latino/a) completed a series of laboratory assessments yielding independent measures of intrusive parenting at age 4, PNS regulation at age 6, and child behavior problems at age 8. Results indicated that intrusive parenting was related to more internalizing problems among boys who showed low RSA reactivity (i.e., PNS withdrawal from pre-startle to startle challenge), but RSA reactivity did not moderate this relation among girls. Interestingly, RSA recovery (i.e., PNS activation from startle challenge to post-startle) moderated these relations differently for boys and girls. For girls with relatively low RSA post-startle (i.e., less recovery), intrusive parenting was positively related to both internalizing and externalizing problems. However, the reverse was true for boys, such that there was a significant positive relation between intrusive parenting and later externalizing problems among boys who evidenced relatively high RSA post-startle (i.e., more recovery). Findings provide evidence for the moderation of intrusive caregiving effects by children's PNS regulation while highlighting the differential patterning of these relations across distinct phases of the regulatory response and as a function of child sex. Copyright © 2017 Elsevier Inc. All rights reserved.

Dealing With Unexpected Events on the Flight Deck: A Conceptual Model of Startle and Surprise.

PubMed

Landman, Annemarie; Groen, Eric L; van Paassen, M M René; Bronkhorst, Adelbert W; Mulder, Max

2017-12-01

A conceptual model is proposed in order to explain pilot performance in surprising and startling situations. Today's debate around loss of control following in-flight events and the implementation of upset prevention and recovery training has highlighted the importance of pilots' ability to deal with unexpected events. Unexpected events, such as technical malfunctions or automation surprises, potentially induce a "startle factor" that may significantly impair performance. Literature on surprise, startle, resilience, and decision making is reviewed, and findings are combined into a conceptual model. A number of recent flight incident and accident cases are then used to illustrate elements of the model. Pilot perception and actions are conceptualized as being guided by "frames," or mental knowledge structures that were previously learned. Performance issues in unexpected situations can often be traced back to insufficient adaptation of one's frame to the situation. It is argued that such sensemaking or reframing processes are especially vulnerable to issues caused by startle or acute stress. Interventions should focus on (a) increasing the supply and quality of pilot frames (e.g., though practicing a variety of situations), (b) increasing pilot reframing skills (e.g., through the use of unpredictability in training scenarios), and (c) improving pilot metacognitive skills, so that inappropriate automatic responses to startle and surprise can be avoided. The model can be used to explain pilot behavior in accident cases, to design experiments and training simulations, to teach pilots metacognitive skills, and to identify intervention methods.

Emotion-modulated startle in psychopathy: Clarifying familiar effects

PubMed Central

Baskin-Sommers, Arielle R.; Curtin, John J.; Newman, Joseph P.

2012-01-01

The behavior of psychopathic individuals is thought to reflect a core fear deficit that prevents these individuals from appreciating the consequences of their choices and actions. However, growing evidence suggests that psychopathy-related emotion deficits are moderated by attention and, thus, may not reflect a reduced capacity for emotion responding. The present study attempts to reconcile this attention perspective with one of the most cited findings in psychopathy, which reports emotion-modulated startle deficits among psychopathic individuals during picture viewing. In this study, we evaluate the potential effects of a putative attention bottleneck on the emotion processing of psychopathic offenders during picture viewing by manipulating picture familiarity and examining emotion-modulated startle and late positive potential (LPP). As predicted, psychopathic individuals displayed the classic deficit in emotion-modulated startle during novel pictures, but they showed no deficit in emotion-modulated startle during familiar pictures. Conversely, results for LPP responses revealed psychopathy-related differences during familiar pictures and no psychopathy-related differences during novel pictures. Important differences related to the two Factors of psychopathy are also discussed. Overall, the results of this study not only highlight the differential importance of perceptual load on emotion processing in psychopathy, but also raise interesting questions about the varied effects of attention on psychopathy-related emotion deficits. PMID:23356218

Maturation of the human fetal startle response: evidence for sex-specific maturation of the human fetus.

PubMed

Buss, Claudia; Davis, Elysia Poggi; Class, Quetzal A; Gierczak, Matt; Pattillo, Carol; Glynn, Laura M; Sandman, Curt A

2009-10-01

Despite the evidence for early fetal experience exerting programming influences on later neurological development and health risk, very few prospective studies of human fetal behavior have been reported. In a prospective longitudinal study, fetal nervous system maturation was serially assessed by monitoring fetal heart rate (FHR) responses to vibroacoustic stimulation (VAS) in 191 maternal/fetal dyads. Responses were not detected at 26 weeks gestational age (GA). Sex-specific, age-characteristic changes in the FHR response to VAS were observed by 31 weeks' GA. Males showed larger responses and continued to exhibit maturational changes until 37 weeks' GA, females however, presented with a mature FHR startle response by 31 weeks' GA. The results indicate that there are different rates of maturation in the male and female fetuses that may have implications for sex-specific programming influences.

Pain increases during sympathetic arousal in patients with complex regional pain syndrome.

PubMed

Drummond, P D; Finch, P M; Skipworth, S; Blockey, P

2001-10-09

To investigate the effect of sympathetic arousal on pain and vasomotor responses in healthy control subjects and patients with complex regional pain syndrome (CRPS), and to determine whether pain increases in patients with particular symptoms. In experiments 1 and 2, capsaicin was applied to the forearm of 24 healthy subjects to induce thermal hyperalgesia. Vascular responses were monitored and subjects rated thermal hyperalgesia before and after being startled (experiment 1), and before, during, and after mental arithmetic, breath holding, forehead cooling, the Valsalva maneuver, and a cold pressor test in experiment 2. In a third experiment, sensitivity to heat, cold, and mechanical stimulation was investigated in 61 patients with CRPS. Pain ratings and vascular and electrodermal responses were recorded after patients were startled and during forehead cooling. In experiment 1, thermal hyperalgesia decreased in healthy control subjects after they were startled, and digital blood vessels constricted symmetrically. In experiment 2, thermal hyperalgesia decreased during and after other forms of sympathetic arousal. However, in experiment 3, ratings of clinical pain increased during forehead cooling or after being startled in over 70% of patients with CRPS. Pain increased most consistently during forehead cooling in patients with cold allodynia or punctate allodynia. Digital blood vessels constricted more intensely on the symptomatic than the nonsymptomatic side in patients with CRPS during sympathetic arousal. Normal inhibitory influences on pain during sympathetic arousal are compromised in the majority of patients with CRPS. The augmented vasoconstrictor response in the symptomatic limb during sympathetic arousal is consistent with adrenergic supersensitivity. An adrenergic sensitivity in nociceptive afferents might contribute to pain and hyperalgesia during sympathetic arousal in certain patients with CRPS.

Child maltreatment, callous-unemotional traits, and defensive responding in high-risk children: An investigation of emotion-modulated startle response.

PubMed

Dackis, Melissa N; Rogosch, Fred A; Cicchetti, Dante

2015-11-01

Child maltreatment is associated with disruptions in physiological arousal, emotion regulation, and defensive responses to cues of threat and distress, as well as increased risk for callous unemotional (CU) traits and externalizing behavior. Developmental models of CU traits have focused on biological and genetic risk factors that contribute to hypoarousal and antisocial behavior, but have focused less on environmental influences (Blair, 2004; Daversa, 2010; Hare, Frazell, & Cox, 1978; Krueger, 2000; Shirtcliff et al., 2009; Viding, Fontaine, & McCrory, 2012). The aim of the present investigation was to measure the independent and combined effects of child maltreatment and high CU traits on emotion-modulated startle response in children. Participants consisted of 132 low-income maltreated (n = 60) and nonmaltreated (n = 72) children between 8 and 12 years old who attended a summer camp program. Acoustic startle response (ASR) was elicited in response to a 110-dB 50-ms probe while children viewed a slideshow of pleasant, neutral, and unpleasant IAPS images. Maltreatment status was assessed through examination of Department of Human Services records. CU traits were measured using counselor reports from the Inventory of Callous and Unemotional Traits (Frick, 2004), and conduct problems were measured using counselor and child self-report. We found no significant differences in emotion-modulated startle in the overall sample. However, significant differences in ASR by maltreatment status, maltreatment subtype, and level of CU traits were apparent. Results indicated differential physiological responses for maltreated and nonmaltreated children based on CU traits, including a pathway of hypoarousal for nonmaltreated/high CU children that differed markedly from a more normative physiological trajectory for maltreated/high CU children. Further, we found heightened ASR for emotionally and physically neglected children with high CU and elevated antisocial behavior in these children. Results provide further support for differential trajectories by which experience and biology may influence the development of antisocial behavior in youth and highlight potential avenues for intervention.

Child Maltreatment, Callous-Unemotional Traits, and Defensive Responding In High-Risk Children: An Investigation of Emotion-Modulated Startle Response

PubMed Central

Dackis, Melissa N.; Rogosch, Fred A.; Cicchetti, Dante

2015-01-01

Child maltreatment is associated with disruptions in physiological arousal, emotion regulation, and defensive responses to cues of threat and distress, as well as increased risk for callous unemotional (CU) traits and externalizing behavior. Developmental models of callous unemotional (CU) traits have focused on biological and genetic risk factors that contribute to hypoarousal and antisocial behavior, but have focused less on environmental influences (Blair, 2004; Daversa, 2010; Hare, Frazell, & Cox, 1978; Krueger, 2000; Shirtcliff et al., 2009; Viding, Fontaine, & McCrory, 2012). The aim of the present investigation was to measure the independent and combined effects of child maltreatment and high CU trait on emotion-modulated startle (EMS) response in children. Participants consisted of 132 low-income maltreated (n = 60) and nonmaltreated (n = 72) children between 8–12 years old who attended a summer camp program. Acoustic startle response (ASR) was elicited in response to a 110-dB 50-ms probe while children viewed a slideshow of pleasant, neutral, and unpleasant IAPS images. Maltreatment status was assessed through examination of Department of Human Services records. CU traits were measured using counselor reports from the Inventory of Callous and Unemotional Traits (ICU; Frick, 2004), and conduct problems were measured using counselor and child self-report. We found no significant differences in emotion-modulated startle in the overall sample. However, significant differences in ASR by maltreatment status, maltreatment subtype, and level of CU traits were apparent. Results indicated differential physiological responses for maltreated and nonmaltreated children based on CU traits, including a pathway of hypoarousal for nonmaltreated/high CU children that differed markedly from a more normative physiological trajectory for maltreated/high CU children. Further, we found heightened ASR for emotionally and physically neglected children with high CU and elevated antisocial behavior in these children. Results provide further support for differential trajectories by which experience and biology may influence the development of antisocial behavior in youth and highlight potential avenues for intervention. PMID:26535942

Myoclonus

MedlinePlus

... injury, stroke, brain tumors, kidney or liver failure, lipid storage disease, chemical or drug poisoning, or other ... example, is in the brain stem close to structures that are responsible for the startle response, an ...

Somatostatin-28 modulates prepulse inhibition of the acoustic startle response, reward processes and spontaneous locomotor activity in rats

PubMed Central

Semenova, Svetlana; Hoyer, Daniel; Geyer, Mark A.; Markou, Athina

2011-01-01

Somatostatins have been shown to be involved in the pathophysiology of motor and affective disorders, as well as psychiatry disorders, including schizophrenia. We hypothesized that in addition to motor function, somatostatin may be involved in somatosensory gating and reward processes that have been shown to be dysregulated in schizophrenia. Accordingly, we evaluated the effects of intracerebroventricular administration of somatostatin-28 on spontaneous locomotor and exploratory behavior measured in a behavioral pattern monitor, sensorimotor gating, prepulse inhibition (PPI) of the acoustic startle reflex, and brain reward function (measured in a discrete trial intracranial self-stimulation procedure) in rats. Somatostatin-28 decreased spontaneous locomotor activity during the first 10 min of a 60 min testing session with no apparent changes in the exploratory activity of rats. The highest somatostatin-28 dose (10 μg/5 μl/side) induced PPI deficits with no effect on the acoustic startle response or startle response habituation. The somatostatin-induced PPI deficit was partially reversed by administration of SRA-880, a selective somatostatin 1 (sst1) receptor antagonist. Somatostatin-28 also induced elevations in brain reward thresholds, reflecting an anhedonic-like state. SRA-880 had no effect on brain reward function under baseline conditions. Altogether these findings suggest that somatostatin-28 modulates PPI and brain reward function but does not have a robust effect on spontaneous exploratory activity. Thus, increases in somatostatin transmission may represent one of the neurochemical mechanisms underlying anhedonia, one of the negative symptoms of schizophrenia, and sensorimotor gating deficits associated with cognitive impairments in schizophrenia patients. PMID:20537385

Neurobehavioral Impairments Caused by Developmental Imidacloprid Exposure in Zebrafish

PubMed Central

Crosby, Emily B.; Bailey, Jordan M.; Oliveri, Anthony N.; Levin, Edward D.

2015-01-01

BACKGROUND Neonicotinoid insecticides are becoming more widely applied as organophosphate (OP) insecticides are decreasing in use. Because of their relative specificity to insect nicotinic receptors, they are thought to have reduced risk of neurotoxicity in vertebrates. However, there is scant published literature concerning the neurobehavioral effects of developmental exposure of vertebrates to neonicotinoids. METHODS Using zebrafish, we investigated the neurobehavioral effects of developmental exposure to imidacloprid, a prototypic neonicotinoid pesticide. Nicotine was also administered for comparison. Zebrafish were exposed via immersion in aqueous solutions containing 45 μM or 60 μM of imidacloprid or nicotine (or vehicle control) from 4 h to 5 d post fertilization. The functional effects of developmental exposure to both imidacloprid and nicotine were assessed in larvae using an activity assay and during adolescence and adulthood using a battery of neurobehavioral assays, including assessment of sensorimotor response and habituation in a tactile startle test, novel tank swimming, and shoaling behavior. RESULTS In larvae, developmental imidacloprid exposure at both doses significantly decreased swimming activity. The 5D strain of zebrafish were more sensitive to both nicotine and imidacloprid than the AB* strain. In adolescent and adult fish, developmental exposure to imidacloprid significantly decreased novel tank exploration and increased sensorimotor response to startle stimuli. While nicotine did not affect novel tank swimming, it increased sensorimotor response to startle stimuli at the low dose. No effects of either compound were found on shoaling behavior or habituation to a startling stimulus. DISCUSSION Early developmental exposure to imidacloprid has both early-life and persisting effects on neurobehavioral function in zebrafish. Its developmental neurotoxicity should be further investigated. PMID:25944383

Startle Reflex Potentiation During Aversive Picture Viewing as an Indicator of Trait Fear

PubMed Central

Vaidyanathan, Uma; Patrick, Christopher J.; Bernat, Edward M.

2009-01-01

Measures of fearfulness and measures of psychopathy show positive and negative associations, respectively, with startle reflex potentiation during unpleasant picture viewing. We tested the hypothesis that a common bipolar trait dimension underlies these differing associations. Blink responses to noise probes were recorded during pleasant, neutral, and unpleasant pictures in 88 undergraduates assessed with a battery of self-report scales indexing fear and psychopathy/fearlessness. A significant positive association was found between an omnibus index of fear, consisting of scores on the first component from a PCA of these various scales, and startle potentiation during aversive picture viewing. This association was most robust, across participants overall and within gender subgroups, for scenes that were most directly threatening. Implications for psychophysiological research on individual differences and psychopathology are discussed. PMID:19055499

Dealing With Unexpected Events on the Flight Deck: A Conceptual Model of Startle and Surprise

PubMed Central

Landman, Annemarie; Groen, Eric L.; van Paassen, M. M. (René); Bronkhorst, Adelbert W.; Mulder, Max

2017-01-01

Objective: A conceptual model is proposed in order to explain pilot performance in surprising and startling situations. Background: Today’s debate around loss of control following in-flight events and the implementation of upset prevention and recovery training has highlighted the importance of pilots’ ability to deal with unexpected events. Unexpected events, such as technical malfunctions or automation surprises, potentially induce a “startle factor” that may significantly impair performance. Method: Literature on surprise, startle, resilience, and decision making is reviewed, and findings are combined into a conceptual model. A number of recent flight incident and accident cases are then used to illustrate elements of the model. Results: Pilot perception and actions are conceptualized as being guided by “frames,” or mental knowledge structures that were previously learned. Performance issues in unexpected situations can often be traced back to insufficient adaptation of one’s frame to the situation. It is argued that such sensemaking or reframing processes are especially vulnerable to issues caused by startle or acute stress. Conclusion: Interventions should focus on (a) increasing the supply and quality of pilot frames (e.g., though practicing a variety of situations), (b) increasing pilot reframing skills (e.g., through the use of unpredictability in training scenarios), and (c) improving pilot metacognitive skills, so that inappropriate automatic responses to startle and surprise can be avoided. Application: The model can be used to explain pilot behavior in accident cases, to design experiments and training simulations, to teach pilots metacognitive skills, and to identify intervention methods. PMID:28777917

Sex differences in affective responses to homoerotic stimuli: evidence for an unconscious bias among heterosexual men, but not heterosexual women.

PubMed

Mahaffey, Amanda L; Bryan, Angela; Hutchison, Kent E

2005-10-01

Antigay bias is a well-documented social problem among heterosexual men, though heterosexual women display a lesser tendency toward this bias. Startle eye blink has been established as a valid measure of the affective component of antigay bias in heterosexual men. In the current study, a sample of 91 heterosexual women and 87 heterosexual men were exposed to a variety of sexual photographic stimuli accompanied by startle probes. Heterosexual men who expressed more bias against gay men using a social distance measure (i.e., discomfort with being in close quarters with a gay man) displayed a startle response consistent with greater negative affect (e.g., fear and disgust) toward gay male stimuli, while those with less self-reported antigay bias did not display a physiological bias against gay men, and none of these men showed a relationship between bias against lesbians and physiological responses while viewing lesbian images. There were no such physiological manifestations of antigay bias in heterosexual women while viewing lesbian or gay male images, even among those who self-reported such bias. It appears that heterosexual women do not tend to have the same affective response toward homosexuals that some heterosexual men experience.

Blood Pressure Response to Exercise and Cardiovascular Disease.

PubMed

Schultz, Martin G; La Gerche, Andre; Sharman, James E

2017-10-18

This review aimed to provide a clinical update on exercise blood pressure (BP) and its relationship to cardiovascular disease (CVD), outlining key determinants of abnormal exercise BP responses. We also highlight current evidence gaps that need addressing in order to optimise the relevance of exercise BP as clinical CVD risk factor. Abnormal exercise BP manifests as either exercise hypotension (low BP response) or as exaggerated exercise BP (high BP response). Exercise hypotension is an established sign of existing and likely severe CVD, but exaggerated exercise BP also carries elevated CVD risk due to its association with sub-clinical hypertension. Although exaggerated exercise BP is related to heightened CVD risk at any exercise intensity, recent data suggest that the BP response to submaximal intensity exercise holds greater prognostic and clinical significance than BP achieved at peak/maximal intensity exercise. Cardiorespiratory fitness is a strong modifier of the exercise BP response, and should be taken into consideration when assessing the association with CVD. Both exercise hypotension and exaggerated exercise BP serve as markers that should prompt evaluation for potential underlying CVD. However, the clinical utility of these markers is currently inhibited by the lack of consensus informing the definitions and thresholds for abnormalities in exercise BP.

Symptoms of posttraumatic stress disorder in a clinical sample of refugees: a network analysis

PubMed Central

Spiller, Tobias R.; Schick, Matthis; Schnyder, Ulrich; Bryant, Richard A.; Nickerson, Angela; Morina, Naser

2017-01-01

ABSTRACT Background: Network analysis is an emerging methodology for investigating psychopathological symptoms. Given the unprecedented number of refugees and the increased prevalence of mental disorders such as posttraumatic stress disorder (PTSD) in this population, new methodologies that help us better to understand psychopathology in refugees are crucial. Objective: The objective of this study was to explore the network structure and centrality indices of DSM-5 PTSD symptoms in a cross-sectional clinical sample of 151 severely traumatized refugees with and without a formal PTSD diagnosis. Method: The R-packages qgraph and bootnet were used to estimate the structure of a PTSD symptom network and its centrality indices. In addition, robustness and significance analyses for the edges weights and the order of centrality were performed. Results: Three pairs of symptoms showed significantly stronger connections than at least half of the other connections: hypervigilance and exaggerated startle response, intrusion and difficulties falling asleep, and irritability or outbursts of anger and self-destructive or reckless behaviour. Emotional cue reactivity had the highest centrality and trauma-related amnesia the lowest. Conclusion: Although only 51.0% of participants fulfilled criteria for a probable PTSD diagnosis, emotional cue reactivity showed the highest centrality, emphasizing the importance of emotional trauma reminders in severely traumatized refugees attending an outpatient clinic. However, due to the small sample size, the results should be interpreted with care. PMID:29038688

Homeostatic response to sleep/rest deprivation by constant water flow in larval zebrafish in both dark and light conditions.

PubMed

Aho, Vilma; Vainikka, Maija; Puttonen, Henri A J; Ikonen, Heidi M K; Salminen, Tiia; Panula, Pertti; Porkka-Heiskanen, Tarja; Wigren, Henna-Kaisa

2017-06-01

Sleep-or sleep-like states-have been reported in adult and larval zebrafish using behavioural criteria. These reversible quiescent periods, displaying circadian rhythmicity, have been used in pharmacological, genetic and neuroanatomical studies of sleep-wake regulation. However, one of the important criteria for sleep, namely sleep homeostasis, has not been demonstrated unequivocally. To study rest homeostasis in zebrafish larvae, we rest-deprived 1-week-old larvae with a novel, ecologically relevant method: flow of water. Stereotyped startle responses to sensory stimuli were recorded after the rest deprivation to study arousal threshold using a high-speed camera, providing an appropriate time resolution to detect species-specific behavioural responses occurring in a millisecond time-scale. Rest-deprived larvae exhibited fewer startle responses than control larvae during the remaining dark phase and the beginning of the light phase, which can be interpreted as a sign of rest homeostasis-often used as equivalent of sleep homeostasis. To address sleep homeostasis further, we probed the adenosinergic system, which in mammals regulates sleep homeostasis. The adenosine A1 receptor agonist, cyclohexyladenosine, administered during the light period, decreased startle responses and increased immobility bouts, while the adenosine antagonist, caffeine, administered during the dark period, decreased immobility bouts. These results suggest that the regulation of sleep homeostasis in zebrafish larvae consists of the same elements as that of other species. © 2017 European Sleep Research Society.

Rasd2 Modulates Prefronto-Striatal Phenotypes in Humans and ‘Schizophrenia-Like Behaviors' in Mice

PubMed Central

Vitucci, Daniela; Di Giorgio, Annabella; Napolitano, Francesco; Pelosi, Barbara; Blasi, Giuseppe; Errico, Francesco; Attrotto, Maria Teresa; Gelao, Barbara; Fazio, Leonardo; Taurisano, Paolo; Di Maio, Anna; Marsili, Valentina; Pasqualetti, Massimo; Bertolino, Alessandro; Usiello, Alessandro

2016-01-01

Rasd2 is a thyroid hormone target gene, which encodes for a GTP-binding protein enriched in the striatum where, among other functions, it modulates dopaminergic neurotransmission. Here we report that human RASD2 mRNA is abundant in putamen, but it also occurs in the cerebral cortex, with a distinctive expression pattern that differs from that present in rodents. Consistent with its localization, we found that a genetic variation in RASD2 (rs6518956) affects postmortem prefrontal mRNA expression in healthy humans and is associated with phenotypes of relevance to schizophrenia, including prefrontal and striatal grey matter volume and physiology during working memory, as measured with magnetic resonance imaging. Interestingly, quantitative real-time PCR analysis indicated that RASD2 mRNA is slightly reduced in postmortem prefrontal cortex of patients with schizophrenia. In the attempt to uncover the neurobiological substrates associated with Rasd2 activity, we used knockout mice to analyze the in vivo influence of this G-protein on the prepulse inhibition of the startle response and psychotomimetic drug-related behavioral response. Data showed that Rasd2 mutants display deficits in basal prepulse inhibition that, in turn, exacerbate gating disruption under psychotomimetic drug challenge. Furthermore, we documented that lack of Rasd2 strikingly enhances the behavioral sensitivity to motor stimulation elicited by amphetamine and phencyclidine. Based on animal model data, along with the finding that RASD2 influences prefronto-striatal phenotypes in healthy humans, we suggest that genetic mutation or reduced levels of this G-protein might have a role in cerebral circuitry dysfunction underpinning exaggerated psychotomimetic drugs responses and development of specific biological phenotypes linked to schizophrenia. PMID:26228524

Rasd2 Modulates Prefronto-Striatal Phenotypes in Humans and 'Schizophrenia-Like Behaviors' in Mice.

PubMed

Vitucci, Daniela; Di Giorgio, Annabella; Napolitano, Francesco; Pelosi, Barbara; Blasi, Giuseppe; Errico, Francesco; Attrotto, Maria Teresa; Gelao, Barbara; Fazio, Leonardo; Taurisano, Paolo; Di Maio, Anna; Marsili, Valentina; Pasqualetti, Massimo; Bertolino, Alessandro; Usiello, Alessandro

2016-02-01

Rasd2 is a thyroid hormone target gene, which encodes for a GTP-binding protein enriched in the striatum where, among other functions, it modulates dopaminergic neurotransmission. Here we report that human RASD2 mRNA is abundant in putamen, but it also occurs in the cerebral cortex, with a distinctive expression pattern that differs from that present in rodents. Consistent with its localization, we found that a genetic variation in RASD2 (rs6518956) affects postmortem prefrontal mRNA expression in healthy humans and is associated with phenotypes of relevance to schizophrenia, including prefrontal and striatal grey matter volume and physiology during working memory, as measured with magnetic resonance imaging. Interestingly, quantitative real-time PCR analysis indicated that RASD2 mRNA is slightly reduced in postmortem prefrontal cortex of patients with schizophrenia. In the attempt to uncover the neurobiological substrates associated with Rasd2 activity, we used knockout mice to analyze the in vivo influence of this G-protein on the prepulse inhibition of the startle response and psychotomimetic drug-related behavioral response. Data showed that Rasd2 mutants display deficits in basal prepulse inhibition that, in turn, exacerbate gating disruption under psychotomimetic drug challenge. Furthermore, we documented that lack of Rasd2 strikingly enhances the behavioral sensitivity to motor stimulation elicited by amphetamine and phencyclidine. Based on animal model data, along with the finding that RASD2 influences prefronto-striatal phenotypes in healthy humans, we suggest that genetic mutation or reduced levels of this G-protein might have a role in cerebral circuitry dysfunction underpinning exaggerated psychotomimetic drugs responses and development of specific biological phenotypes linked to schizophrenia.

Hypnotizability and Placebo Analgesia in Waking and Hypnosis as Modulators of Auditory Startle Responses in Healthy Women: An ERP Study.

PubMed

De Pascalis, Vilfredo; Scacchia, Paolo

2016-01-01

We evaluated the influence of hypnotizability, pain expectation, placebo analgesia in waking and hypnosis on tonic pain relief. We also investigated how placebo analgesia affects somatic responses (eye blink) and N100 and P200 waves of event-related potentials (ERPs) elicited by auditory startle probes. Although expectation plays an important role in placebo and hypnotic analgesia, the neural mechanisms underlying these treatments are still poorly understood. We used the cold cup test (CCT) to induce tonic pain in 53 healthy women. Placebo analgesia was initially produced by manipulation, in which the intensity of pain induced by the CCT was surreptitiously reduced after the administration of a sham analgesic cream. Participants were then tested in waking and hypnosis under three treatments: (1) resting (Baseline); (2) CCT-alone (Pain); and (3) CCT plus placebo cream for pain relief (Placebo). For each painful treatment, we assessed pain and distress ratings, eye blink responses, N100 and P200 amplitudes. We used LORETA analysis of N100 and P200 waves, as elicited by auditory startle, to identify cortical regions sensitive to pain reduction through placebo and hypnotic analgesia. Higher pain expectation was associated with higher pain reductions. In highly hypnotizable participants placebo treatment produced significant reductions of pain and distress perception in both waking and hypnosis condition. P200 wave, during placebo analgesia, was larger in the frontal left hemisphere while placebo analgesia, during hypnosis, involved the activity of the left hemisphere including the occipital region. These findings demonstrate that hypnosis and placebo analgesia are different processes of top-down regulation. Pain reduction was associated with larger EMG startle amplitudes, N100 and P200 responses, and enhanced activity within the frontal, parietal, and anterior and posterior cingulate gyres. LORETA results showed that placebo analgesia modulated pain-responsive areas known to reflect the ongoing pain experience.

Hypnotizability and Placebo Analgesia in Waking and Hypnosis as Modulators of Auditory Startle Responses in Healthy Women: An ERP Study

PubMed Central

De Pascalis, Vilfredo; Scacchia, Paolo

2016-01-01

We evaluated the influence of hypnotizability, pain expectation, placebo analgesia in waking and hypnosis on tonic pain relief. We also investigated how placebo analgesia affects somatic responses (eye blink) and N100 and P200 waves of event-related potentials (ERPs) elicited by auditory startle probes. Although expectation plays an important role in placebo and hypnotic analgesia, the neural mechanisms underlying these treatments are still poorly understood. We used the cold cup test (CCT) to induce tonic pain in 53 healthy women. Placebo analgesia was initially produced by manipulation, in which the intensity of pain induced by the CCT was surreptitiously reduced after the administration of a sham analgesic cream. Participants were then tested in waking and hypnosis under three treatments: (1) resting (Baseline); (2) CCT-alone (Pain); and (3) CCT plus placebo cream for pain relief (Placebo). For each painful treatment, we assessed pain and distress ratings, eye blink responses, N100 and P200 amplitudes. We used LORETA analysis of N100 and P200 waves, as elicited by auditory startle, to identify cortical regions sensitive to pain reduction through placebo and hypnotic analgesia. Higher pain expectation was associated with higher pain reductions. In highly hypnotizable participants placebo treatment produced significant reductions of pain and distress perception in both waking and hypnosis condition. P200 wave, during placebo analgesia, was larger in the frontal left hemisphere while placebo analgesia, during hypnosis, involved the activity of the left hemisphere including the occipital region. These findings demonstrate that hypnosis and placebo analgesia are different processes of top-down regulation. Pain reduction was associated with larger EMG startle amplitudes, N100 and P200 responses, and enhanced activity within the frontal, parietal, and anterior and posterior cingulate gyres. LORETA results showed that placebo analgesia modulated pain-responsive areas known to reflect the ongoing pain experience. PMID:27486748

Round window closure affects cochlear responses to suprathreshold stimuli.

PubMed

Cai, Qunfeng; Whitcomb, Carolyn; Eggleston, Jessica; Sun, Wei; Salvi, Richard; Hu, Bo Hua

2013-12-01

The round window acts as a vent for releasing inner ear pressure and facilitating basilar membrane vibration. Loss of this venting function affects cochlear function, which leads to hearing impairment. In an effort to identify functional changes that might be used in clinical diagnosis of round window atresia, the current investigation was designed to examine how the cochlea responds to suprathreshold stimuli following round window closure. Prospective, controlled, animal study. A rat model of round window occlusion (RWO) was established. With this model, the thresholds of auditory brainstem responses (ABR) and the input/output (IO) functions of distortion product otoacoustic emissions (DPOAEs) and acoustic startle responses were examined. Round window closure caused a mild shift in the thresholds of the auditory brainstem response (13.5 ± 9.1 dB). It also reduced the amplitudes of the distortion product otoacoustic emissions and the slope of the input/output functions. This peripheral change was accompanied by a significant reduction in the amplitude, but not the threshold, of the acoustic startle reflex, a motor response to suprathreshold sounds. In addition to causing mild increase in the threshold of the auditory brainstem response, round window occlusion reduced the slopes of both distortion product otoacoustic emissions and startle reflex input/output functions. These changes differ from those observed for typical conductive or sensory hearing loss, and could be present in patients with round window atresia. However, future clinical observations in patients are needed to confirm these findings. Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

Emotions in Go/NoGo conflicts.

PubMed

Schacht, Annekathrin; Nigbur, Roland; Sommer, Werner

2009-11-01

On the basis of current emotion theories and functional and neurophysiological ties between the processing of conflicts and errors on the one hand and errors and emotions on the other hand we predicted that conflicts between prepotent Go responses and occasional NoGo trials in the Go/NoGo task would induce emotions. Skin conductance responses (SCRs), corrugator muscle activity, and startle blink responses were measured in three experiments requiring speeded Go responses intermixed with NoGo trials of different relative probability and in a choice reaction experiment serving as a control. NoGo trials affected several of these emotion-sensitive indicators as SCRs and startle blinks were reduced whereas corrugator activity was prolonged as compared to Go trials. From the pattern of findings we suggest that NoGo conflicts are not aversive. Instead, they appear to be appraised as obstructive for the response goal and as less action relevant than Go trials.

MitoPark mice, an animal model of Parkinson's disease, show enhanced prepulse inhibition of acoustic startle and no loss of gating in response to the adenosine A(2A) antagonist SCH 412348.

PubMed

Grauer, Steven M; Hodgson, Robert; Hyde, Lynn A

2014-04-01

Psychoses are debilitating side effects associated with current dopaminergic treatments for Parkinson's disease (PD). Prepulse inhibition (PPI), in which a non-startling stimulus reduces startle response to a subsequent startle-eliciting stimulus, is important in filtering out extraneous sensory stimuli. PPI deficits induced by dopamine agonists can model symptoms of psychosis. Adenosine A(2A) receptor antagonists, being developed as novel PD treatments, indirectly modulate dopamine signaling in the basal ganglia and may have an improved psychosis profile which could be detected using the PPI model. The aims of this study is to characterize PPI in MitoPark mice, which exhibit progressive loss of dopamine signaling and develop a Parkinson-like motor phenotype, and assess standard and novel PD treatment effects on PPI in MitoPark mice, which more closely mimic the basal ganglia dopamine status of PD patients. MitoPark mice displayed enhanced PPI as dopamine tone decreased with age, consistent with studies in intact mice that show enhanced PPI in response to dopamine antagonists. Paradoxically, older MitoParks were more sensitive to PPI disruption when challenged with dopamine agonists such as apomorphine or pramipexole. Alternatively, SCH 412348, an adenosine A(2A) antagonist, did not disrupt PPI in MitoPark mice at doses that normalized hypoactivity. Use of MitoPark mice in the PPI assay to assess the potential for PD treatment to produce psychoses likely represents a more disease-relevant model. SCH 412348 does not differentially disrupt PPI as do dopamine agonists, perhaps indicative of an improved psychosis profile of adenosine A(2A) antagonists, even in PD patients with decreased dopamine tone in the basal ganglia.

Neurobehavioral impairments caused by developmental imidacloprid exposure in zebrafish.

PubMed

Crosby, Emily B; Bailey, Jordan M; Oliveri, Anthony N; Levin, Edward D

2015-01-01

Neonicotinoid insecticides are becoming more widely applied as organophosphate (OP) insecticides are decreasing in use. Because of their relative specificity to insect nicotinic receptors, they are thought to have reduced risk of neurotoxicity in vertebrates. However, there is scant published literature concerning the neurobehavioral effects of developmental exposure of vertebrates to neonicotinoids. Using zebrafish, we investigated the neurobehavioral effects of developmental exposure to imidacloprid, a prototypic neonicotinoid pesticide. Nicotine was also administered for comparison. Zebrafish were exposed via immersion in aqueous solutions containing 45 μM or 60 μM of imidacloprid or nicotine (or vehicle control) from 4h to 5d post fertilization. The functional effects of developmental exposure to both imidacloprid and nicotine were assessed in larvae using an activity assay and during adolescence and adulthood using a battery of neurobehavioral assays, including assessment of sensorimotor response and habituation in a tactile startle test, novel tank swimming, and shoaling behavior. In larvae, developmental imidacloprid exposure at both doses significantly decreased swimming activity. The 5D strains of zebrafish were more sensitive to both nicotine and imidacloprid than the AB* strain. In adolescent and adult fish, developmental exposure to imidacloprid significantly decreased novel tank exploration and increased sensorimotor response to startle stimuli. While nicotine did not affect novel tank swimming, it increased sensorimotor response to startle stimuli at the low dose. No effects of either compound were found on shoaling behavior or habituation to a startling stimulus. Early developmental exposure to imidacloprid has both early-life and persisting effects on neurobehavioral function in zebrafish. Its developmental neurotoxicity should be further investigated. Copyright © 2015 Elsevier Inc. All rights reserved.

Acoustic startle response in rats predicts inter-individual variation in fear extinction.

PubMed

Russo, Amanda S; Parsons, Ryan G

2017-03-01

Although a large portion of the population is exposed to a traumatic event at some point, only a small percentage of the population develops post-traumatic stress disorder (PTSD), suggesting the presence of predisposing factors. Abnormal acoustic startle response (ASR) has been shown to be associated with PTSD, implicating it as a potential predictor of the development of PTSD-like behavior. Since poor extinction and retention of extinction learning are characteristic of PTSD patients, it is of interest to determine if abnormal ASR is predictive of development of such deficits. To determine whether baseline ASR has utility in predicting the development of PTSD-like behavior, the relationship between baseline ASR and freezing behavior following Pavlovian fear conditioning was examined in a group of adult, male Sprague-Dawley rats. Baseline acoustic startle response (ASR) was assessed preceding exposure to a Pavlovian fear conditioning paradigm where freezing behavior was measured during fear conditioning, extinction training, and extinction testing. Although there was no relationship between baseline ASR and fear memory following conditioning, rats with low baseline ASR had significantly lower magnitude of retention of the extinction memory than rats with high baseline ASR. The results suggest that baseline ASR has value as a predictive index of the development of a PTSD-like phenotype. Copyright © 2017 Elsevier Inc. All rights reserved.

The not-so-bitter pill: Effects of combined oral contraceptives on peripheral physiological indicators of emotional reactivity.

PubMed

Armbruster, Diana; Kirschbaum, Clemens; Strobel, Alexander

2017-08-01

Combined oral contraceptives (COC) are used by millions of women worldwide. Although findings are not entirely consistent, COC have been found to impact on brain function and, thus, to modulate affective processes. Here, we investigated electro-physiological responses to emotional stimuli in free cycling women in both the early follicular and late luteal phase as well as in COC users. Skin conductance response (SCR), startle reflex, corrugator and zygomaticus activity were assessed. COC users showed reduced overall startle magnitude and SCR amplitude, but heightened overall zygomaticus activity, although effect sizes were small. Thus, COC users displayed reduced physiological reactions indicating negative affect and enhanced physiological responses signifying positive affect. In free cycling women, endogenous 17β-estradiol levels were associated with fear potentiated startle in both cycle phases as well as with SCR and zygomaticus activity during the follicular phase. Testosterone was associated with corrugator and zygomaticus activity during the luteal phase, while progesterone levels correlated with corrugator activity in the follicular phase. To the contrary, in COC users, endogenous hormones were not associated with electro-physiological measures. The results further underscore the importance of considering COC use in psychophysiological studies on emotional processing. Copyright © 2017 Elsevier Inc. All rights reserved.

Immobility and hyperthermia in the tail suspension test: association with the Porsolt test and the reflex startle reaction in 11 inbred mouse strains and the effects of genetic knockout of MAO A.

PubMed

Popova, N K; Tibeikina, M A

2010-06-01

Immobility and hyperthermia induced by unavoidable stress imposed by the tail suspension test (TST) and the acoustic startle reaction were assessed in mice of 11 inbred strains and in Tg8 mice, which have genetic knockout of MAO A. Sharp genotypic differences in immobility were seen, while there was no correlation with the hyperthermic response to the TST. A correlation was found between the extent of immobility in the TST and the startle reaction. Studies of 11 strains of mice revealed a positive correlation between the duration of immobility in the TST and the Porsolt "despair test." Genetic knockout of MAO A, one of the key enzymes in catecholamine and serotonin metabolism in the brain, weakened the startle reaction and TST-induced hyperthermia but had no significant effect on the immobility of Tg8 mice, which provides evidence of differences in the neurochemical regulation of these reactions. These data provide grounds for using the TST as a "dry" Porsolt test and identify TST-induced hyperthermia as a model for reactions to unavoidable stress.

Startle Auditory Stimuli Enhance the Performance of Fast Dynamic Contractions

PubMed Central

Fernandez-Del-Olmo, Miguel; Río-Rodríguez, Dan; Iglesias-Soler, Eliseo; Acero, Rafael M.

2014-01-01

Fast reaction times and the ability to develop a high rate of force development (RFD) are crucial for sports performance. However, little is known regarding the relationship between these parameters. The aim of this study was to investigate the effects of auditory stimuli of different intensities on the performance of a concentric bench-press exercise. Concentric bench-presses were performed by thirteen trained subjects in response to three different conditions: a visual stimulus (VS); a visual stimulus accompanied by a non-startle auditory stimulus (AS); and a visual stimulus accompanied by a startle auditory stimulus (SS). Peak RFD, peak velocity, onset movement, movement duration and electromyography from pectoralis and tricep muscles were recorded. The SS condition induced an increase in the RFD and peak velocity and a reduction in the movement onset and duration, in comparison with the VS and AS condition. The onset activation of the pectoralis and tricep muscles was shorter for the SS than for the VS and AS conditions. These findings point out to specific enhancement effects of loud auditory stimulation on the rate of force development. This is of relevance since startle stimuli could be used to explore neural adaptations to resistance training. PMID:24489967

Motivational priming and processing interrupt: startle reflex modulation during shallow and deep processing of emotional words.

PubMed

Herbert, Cornelia; Kissler, Johanna

2010-05-01

Valence-driven modulation of the startle reflex, that is larger eyeblinks during viewing of unpleasant pictures and inhibited blinks while viewing pleasant pictures, is well documented. The current study investigated, whether this motivational priming pattern also occurs during processing of unpleasant and pleasant words, and to what extent it is influenced by shallow vs. deep encoding of verbal stimuli. Emotional and neutral adjectives were presented for 5s, and the acoustically elicited startle eyeblink response was measured while subjects memorized the words by means of shallow or deep processing strategies. Results showed blink potentiation to unpleasant and blink inhibition to pleasant adjectives in subjects using shallow encoding strategies. In subjects using deep-encoding strategies, blinks were larger for pleasant than unpleasant or neutral adjectives. In line with this, free recall of pleasant words was also better in subjects who engaged in deep processing. The results suggest that motivational priming holds as long as processing is perceptual. However, during deep processing the startle reflex appears to represent a measure of "processing interrupt", facilitating blinks to those stimuli that are more deeply encoded. Copyright 2010 Elsevier B.V. All rights reserved.

Contribution of autonomic dysfunction to abnormal exercise blood pressure in type 2 diabetes mellitus.

PubMed

Weston, Kassia S; Sacre, Julian W; Jellis, Christine L; Coombes, Jeff S

2013-01-01

The purpose of this study was to compare the presence and severity of autonomic dysfunction in type 2 diabetes mellitus patients, with and without exaggerated blood pressure responses to exercise. We performed a cross-sectional analysis of 98 patients with type 2 diabetes mellitus (aged 59±9). Both time (standard deviation of RR intervals, root-mean-square of successive RR interval differences) and frequency (total spectral power, high frequency, low frequency, very low frequency) domains of heart rate variability were analysed in a 5 min recording at rest and 20 min after a maximal treadmill test. An exaggerated blood pressure response to exercise was identified by peak blood pressure ≥190/105 mmHg (women) or ≥210/105 mmHg (men). Each group of either exaggerated exercise blood pressure response or normal blood pressure response consisted of 49 patients. At rest there were no significant differences between groups for all time and frequency domain parameters of heart rate variability. Post-exercise, there was a significant (p<0.05) reduction in the SDNN, RMSSD and TP in the exaggerated exercise blood pressure group. Independent correlates (p<0.01) of exercise systolic blood pressure included post-exercise TP, resting systolic blood pressure, cardiac autonomic neuropathy and beta-blockers (beta=-0.28, adj. R² = 0.32, p<0.001). Reduced post-exercise heart rate variability in patients with type 2 diabetes mellitus, with an exaggerated exercise blood pressure response suggests preclinical autonomic dysfunction characterized by impaired vagal modulation. Copyright © 2012 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Sensorimotor Gating in Neurotensin-1 Receptor Null Mice

PubMed Central

Feifel, D.; Pang, Z.; Shilling, P.D.; Melendez, G.; Schreiber, R.; Button, D.

2009-01-01

BACKGROUND Converging evidence has implicated endogenous neurotensin (NT) in the pathophysiology of brain processes relevant to schizophrenia. Prepulse inhibition of the startle reflex (PPI) is a measure of sensorimotor gating and considered to be of strong relevance to neuropsychiatric disorders associated with psychosis and cognitive dysfunction. Mice genetically engineered to not express NT display deficits in PPI that model the PPI deficits seen in schizophrenia patients. NT1 receptors have been most strongly implicated in mediating the psychosis relevant effects of NT such as attenuating PPI deficits. To investigate the role of NT1 receptors in the regulation of PPI, we measured baseline PPI in wildtype (WT) and NT1 knockout (KO) mice. We also tested the effects of amphetamine and dizocilpine, a dopamine agonist and NMDA antagonist, respectively, that reduce PPI as well as the NT1 selective receptor agonist, PD149163, known to increase PPI in rats. METHODS Baseline PPI and acoustic startle response were measured in WT and NT1 knockout KO mice. After baseline testing, mice were tested again after receiving intraperatoneal (IP) saline or one of three doses of amphetamine (1.0, 3.0 and 10.0 mg/kg), dizocilpine (0.3, 1.0 and 3.0 mg/kg) and PD149163 (0.5, 2.0 and 6.0 mg/kg) on separate test days. RESULTS Baseline PPI and acoustic startle response in NT1 KO mice were not significantly different from NT1 WT mice. WT and KO mice exhibited similar responses to the PPI-disrupting effects of dizocilpine and amphetamine. PD149163 significantly facilitated PPI (P < 0.004) and decreased the acoustic startle response (P < 0.001) in WT but not NT1 KO mice. CONCLUSIONS The data does not support the regulation of baseline PPI or the PPI disruptive effects of amphetamine or dizocilpine by endogenous NT acting at the NT1 receptor, although they support the antipsychotic potential of pharmacological activation of NT1 receptors by NT1 agonists. PMID:19596359

Ultrasonic vocalizations, predictability and sensorimotor gating in the rat

PubMed Central

Webber, Emily S.; Mankin, David E.; McGraw, Justin J.; Beckwith, Travis J.; Cromwell, Howard C.

2013-01-01

Prepulse inhibition (PPI) is a measure of sensorimotor gating in diverse groups of animals including humans. Emotional states can influence PPI in humans both in typical subjects and in individuals with mental illness. Little is known about emotional regulation during PPI in rodents. We used ultrasonic vocalization recording to monitor emotional states in rats during PPI testing. We altered the predictability of the PPI trials to examine any alterations in gating and emotional regulation. We also examined PPI in animals selectively bred for high or low levels of 50 kHz USV emission. Rats emitted high levels of 22 kHz calls consistently throughout the PPI session. USVs were sensitive to prepulses during the PPI session similar to startle. USV rate was sensitive to predictability among the different levels tested and across repeated experiences. Startle and inhibition of startle were not affected by predictability in a similar manner. No significant differences for PPI or startle were found related the different levels of predictability; however, there was a reduction in USV signals and an enhancement of PPI after repeated exposure. Animals selectively bred to emit high levels of USVs emitted significantly higher levels of USVs during the PPI session and a reduced ASR compared to the low and random selective lines. Overall, the results support the idea that PPI tests in rodents induce high levels of negative affect and that manipulating emotional styles of the animals alters the negative impact of the gating session as well as the intensity of the startle response. PMID:23850353

Inhibition of amygdaloid dopamine D2 receptors impairs emotional learning measured with fear-potentiated startle.

PubMed

Greba, Q; Gifkins, A; Kokkinidis, L

2001-04-27

Considerable advances have been made in understanding the neurocircuitry underlying the acquisition and expression of Pavlovian conditioned fear responses. Within the complex cellular and molecular processes mediating fearfulness, amygdaloid dopamine (DA), originating from cells in the ventral tegmental area (VTA) of the midbrain, is thought to contribute to fear-motivated responding. Considering that blockade of DA D(2) receptors is a common mechanism of action for antipsychotic agents, we hypothesized that inhibition of D(2) receptors in the amygdala may be involved in the antiparanoid effects of these drugs. To assess the role of amygdaloid DA D(2) receptors in aversive emotionality, the D(2) receptor antagonist raclopride was infused into the amygdala prior to Pavlovian fear conditioning. Potentiated startle was used as a behavioral indicator of fear and anxiety. Classical fear conditioning and acoustic startle testing were conducted in a single session allowing for the concomitant assessment of shock reactivity with startle enhancement. Depending on dose, the results found conditioned fear acquisition and retention to be impaired following administration of raclopride into the amygdala. Additionally, the learning deficit was dissociated from shock detection and from fear expression assessed with the shock sensitization of acoustic startle. These findings further refine the known neural mechanisms of amygdala-based emotional learning and memory and were interpreted to suggest that, along with D(1) receptors, D(2) receptors in the amygdala may mediate the formation and the retention of newly-acquired fear associations.

Control of ethanol withdrawal symptoms in mice by phenytoin.

PubMed

Sprague, G L; Craigmill, A L

1976-12-01

Mice were made physically dependent upon ethanol using either of two methods which involved ethanol vapor inhalation. Following the cessation of exposure to ethanol, the severity of handling-induced convulsions and changes in the response to an electric foot shock (startle reflex) were recorded. Animals given isotonic saline or propylene glycol:ethanol vehicle during withdrawal exhibited handling-induced convulsions, and ethanol (2.0-4.0 g/kg) or phenytoin (5-20 mg/kg) administration during withdrawal resulted in a reduction in the severity of these convulsions. A reduced startle reflex threshold was also evident during withdrawal in mice given isotonic saline or propylene glycol:ethanol vehicle. Ethanol (0.5-4.0 g/kg) or phenytoin (10-20 mg/kg) administration during withdrawal resulted in a significant elevation of the startle reflex threshold compared to control animals. The results are discussed as they relate to others obtained in experimental and clinical studies.

Dependence of the Startle Response on Temporal and Spectral Characteristics of Acoustic Modulatory Influences in Rats and Gerbils

PubMed Central

Steube, Natalie; Nowotny, Manuela; Pilz, Peter K. D.; Gaese, Bernhard H.

2016-01-01

The acoustic startle response (ASR) and its modulation by non-startling prepulses, presented shortly before the startle-eliciting stimulus, is a broadly applied test paradigm to determine changes in neural processing related to auditory or psychiatric disorders. Modulation by a gap in background noise as a prepulse is especially used for tinnitus assessment. However, the timing and frequency-related aspects of prepulses are not fully understood. The present study aims to investigate temporal and spectral characteristics of acoustic stimuli that modulate the ASR in rats and gerbils. For noise-burst prepulses, inhibition was frequency-independent in gerbils in the test range between 4 and 18 kHz. Prepulse inhibition (PPI) by noise-bursts in rats was constant in a comparable range (8–22 kHz), but lower outside this range. Purely temporal aspects of prepulse–startle-interactions were investigated for gap-prepulses focusing mainly on gap duration. While very short gaps had no (rats) or slightly facilitatory (gerbils) influence on the ASR, longer gaps always had a strong inhibitory effect. Inhibition increased with durations up to 75 ms and remained at a high level of inhibition for durations up to 1000 ms for both, rats and gerbils. Determining spectral influences on gap-prepulse inhibition (gap-PPI) revealed that gerbils were unaffected in the limited frequency range tested (4–18 kHz). The more detailed analysis in rats revealed a variety of frequency-dependent effects. Gaps in pure-tone background elicited constant and high inhibition (around 75%) over a broad frequency range (4–32 kHz). For gaps in noise-bands, on the other hand, a clear frequency-dependency was found: inhibition was around 50% at lower frequencies (6–14 kHz) and around 70% at high frequencies (16–20 kHz). This pattern of frequency-dependency in rats was specifically resulting from the inhibitory effect by the gaps, as revealed by detailed analysis of the underlying startle amplitudes. An interaction of temporal and spectral influences, finally, resulted in higher inhibition for 500 ms gaps than for 75 ms gaps at all frequencies tested. Improved prepulse paradigms based on these results are well suited to quantify the consequences of central processing disorders. PMID:27445728

Gender Differences in Posttraumatic Stress Symptoms after a Terrorist Attack: A Network Approach.

PubMed

Birkeland, Marianne S; Blix, Ines; Solberg, Øivind; Heir, Trond

2017-01-01

Background: Posttraumatic stress symptoms are more prevalent in women than in men. To improve our understanding of gender differences in PTSD, detailed knowledge about the underlying symptom networks and gender specific symptom profiles is needed. Objective: We aimed to describe the gender differences in levels of individual posttraumatic stress symptoms after a terrorist attack, as well as identify possible gender differences in associations between posttraumatic stress symptoms. Method: This study used survey data from ministerial employees directly ( n = 190) and indirectly ( n = 1,615) exposed to the 2011 Oslo bombing. Data was collected approximately 10 months after the event. In order to investigate gender differences in levels of symptoms, we used bootstrapped means and standard deviations. Network analyses were conducted to identify gender differences in the associations between posttraumatic stress symptoms. Results: Women reported higher levels of all symptoms, and the strongest effect sizes were found for symptoms of re-experiencing, and anxious and dysphoric arousal. Among individuals with considerable levels of posttraumatic stress symptoms, women reported higher levels of physiological cue activity and exaggerated startle response. No significant gender differences in the networks of posttraumatic stress were found. Conclusions: The present results find no indication that the gender difference in prevalence of PTSD can be explained by differences in associations between symptoms. In order to determine if this finding can be applied to other participants and circumstances, future studies should seek to replicate this study in both community and clinical samples.

Gender Differences in Posttraumatic Stress Symptoms after a Terrorist Attack: A Network Approach

PubMed Central

Birkeland, Marianne S.; Blix, Ines; Solberg, Øivind; Heir, Trond

2017-01-01

Background: Posttraumatic stress symptoms are more prevalent in women than in men. To improve our understanding of gender differences in PTSD, detailed knowledge about the underlying symptom networks and gender specific symptom profiles is needed. Objective: We aimed to describe the gender differences in levels of individual posttraumatic stress symptoms after a terrorist attack, as well as identify possible gender differences in associations between posttraumatic stress symptoms. Method: This study used survey data from ministerial employees directly (n = 190) and indirectly (n = 1,615) exposed to the 2011 Oslo bombing. Data was collected approximately 10 months after the event. In order to investigate gender differences in levels of symptoms, we used bootstrapped means and standard deviations. Network analyses were conducted to identify gender differences in the associations between posttraumatic stress symptoms. Results: Women reported higher levels of all symptoms, and the strongest effect sizes were found for symptoms of re-experiencing, and anxious and dysphoric arousal. Among individuals with considerable levels of posttraumatic stress symptoms, women reported higher levels of physiological cue activity and exaggerated startle response. No significant gender differences in the networks of posttraumatic stress were found. Conclusions: The present results find no indication that the gender difference in prevalence of PTSD can be explained by differences in associations between symptoms. In order to determine if this finding can be applied to other participants and circumstances, future studies should seek to replicate this study in both community and clinical samples. PMID:29250014

Validation of an auditory startle response system using chemicals or parametric modulation as positive controls.

PubMed

Marable, Brian R; Maurissen, Jacques P J

2004-01-01

Neurotoxicity regulatory guidelines mandate that automated test systems be validated using chemicals. However, in some cases, chemicals may not necessarily be needed to prove test system validity. To examine this issue, two independent experiments were conducted to validate an automated auditory startle response (ASR) system. In Experiment 1, we used adult (PND 63) and weanling (PND 22) Sprague-Dawley rats (10/sex/dose) to determine the effect of either d-amphetamine (4.0 or 8.0 mg/kg) or clonidine (0.4 or 0.8 mg/kg) on the ASR peak amplitude (ASR PA). The startle response of each rat to a short burst of white noise (120 dB SPL) was recorded over 50 consecutive trials. The ASR PA was significantly decreased (by clonidine) and increased (by d-amphetamine) compared to controls in PND 63 rats. In PND 22 rats, the response to clonidine was similar to adults, but d-amphetamine effects were not significant. Neither drug affected the rate of the decrease in ASR PA over time (habituation). In Experiment 2, PND 31 Sprague-Dawley rats (8/sex) were presented with 150 trials consisting of either white noise bursts of variable intensity (70-120 dB SPL in 10 dB increments, presented in random order) or null (0 dB SPL) trials. Statistically significant sex- and intensity-dependent differences were detected in the ASR PA. These results suggest that in some cases, parametric modulation may be an alternative to using chemicals for test system validation.

Relationship between Toxoplasma gondii seropositivity and acoustic startle response in an inner-city population.

PubMed

Massa, Nick M; Duncan, Erica; Jovanovic, Tanja; Kerley, Kimberly; Weng, Lei; Gensler, Lauren; Lee, Samuel S; Norrholm, Seth; Powers, Abigail; Almli, Lynn M; Gillespie, Charles F; Ressler, Kerry; Pearce, Bradley D

2017-03-01

Toxoplasma gondii (TOXO) is a neuroinvasive protozoan parasite that induces the formation of persistent cysts in mammalian brains. It infects approximately 1.1million people in the United States annually. Latent TOXO infection is implicated in the etiology of psychiatric disorders, especially schizophrenia (SCZ), and has been correlated with modestly impaired cognition. The acoustic startle response (ASR) is a reflex seen in all mammals. It is mediated by a simple subcortical circuit, and provides an indicator of neural function. We previously reported the association of TOXO with slowed acoustic startle latency, an index of neural processing speed, in a sample of schizophrenia and healthy control subjects. The alterations in neurobiology with TOXO latent infection may not be specific to schizophrenia. Therefore we examined TOXO in relation to acoustic startle in an urban, predominately African American, population with mixed psychiatric diagnoses, and healthy controls. Physiological and diagnostic data along with blood samples were collected from 364 outpatients treated at an inner-city hospital. TOXO status was determined with an ELISA assay for TOXO-specific IgG. A discrete titer was calculated based on standard cut-points as an indicator of seropositivity, and the TOXO-specific IgG concentration served as serointensity. A series of linear regression models were used to assess the association of TOXO seropositivity and serointensity with ASR magnitude and latency in models adjusting for demographics and psychiatric diagnoses (PTSD, major depression, schizophrenia, psychosis, substance abuse). ASR magnitude was 11.5% higher in TOXO seropositive subjects compared to seronegative individuals (p=0.01). This effect was more pronounced in models with TOXO serointensity that adjusted for sociodemographic covariates (F=7.41, p=0.0068; F=10.05, p=0.0017), and remained significant when psychiatric diagnoses were stepped into the models. TOXO showed no association with startle latency (t=0.49, p=0.63) in an unadjusted model, nor was TOXO associated with latency in models that included demographic factors. After stepping in individual psychiatric disorders, we found a significant association of latency with a diagnosis of PTSD (F=5.15, p=0.024), but no other psychiatric diagnoses, such that subjects with PTSD had longer startle latency. The mechanism by which TOXO infection is associated with high startle magnitude is not known, but possible mechanisms include TOXO cyst burden in the brain, parasite recrudescence, or molecular mimicry of a host epitope by TOXO. Future studies will focus on the neurobiology underlying the effects of latent TOXO infection as a potential inroad to the development of novel treatment targets for psychiatric disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Ultrasonic vocalizations, predictability and sensorimotor gating in the rat.

PubMed

Webber, Emily S; Mankin, David E; McGraw, Justin J; Beckwith, Travis J; Cromwell, Howard C

2013-09-15

Prepulse inhibition (PPI) is a measure of sensorimotor gating in diverse groups of animals including humans. Emotional states can influence PPI in humans both in typical subjects and in individuals with mental illness. Little is known about emotional regulation during PPI in rodents. We used ultrasonic vocalization recording to monitor emotional states in rats during PPI testing. We altered the predictability of the PPI trials to examine any alterations in gating and emotional regulation. We also examined PPI in animals selectively bred for high or low levels of 50kHz USV emission. Rats emitted high levels of 22kHz calls consistently throughout the PPI session. USVs were sensitive to prepulses during the PPI session similar to startle. USV rate was sensitive to predictability among the different levels tested and across repeated experiences. Startle and inhibition of startle were not affected by predictability in a similar manner. No significant differences for PPI or startle were found related to the different levels of predictability; however, there was a reduction in USV signals and an enhancement of PPI after repeated exposure. Animals selectively bred to emit high levels of USVs emitted significantly higher levels of USVs during the PPI session and a reduced ASR compared to the low and random selective lines. Overall, the results support the idea that PPI tests in rodents induce high levels of negative affect and that manipulating emotional styles of the animals alters the negative impact of the gating session as well as the intensity of the startle response. Copyright © 2013 Elsevier B.V. All rights reserved.

Effects of stress on human mating preferences: stressed individuals prefer dissimilar mates

PubMed Central

Lass-Hennemann, Johanna; Deuter, Christian E.; Kuehl, Linn K.; Schulz, André; Blumenthal, Terry D.; Schachinger, Hartmut

2010-01-01

Although humans usually prefer mates that resemble themselves, mating preferences can vary with context. Stress has been shown to alter mating preferences in animals, but the effects of stress on human mating preferences are unknown. Here, we investigated whether stress alters men's preference for self-resembling mates. Participants first underwent a cold-pressor test (stress induction) or a control procedure. Then, participants viewed either neutral pictures or pictures of erotic female nudes whose facial characteristics were computer-modified to resemble either the participant or another participant, or were not modified, while startle eyeblink responses were elicited by noise probes. Erotic pictures were rated as being pleasant, and reduced startle magnitude compared with neutral pictures. In the control group, startle magnitude was smaller during foreground presentation of photographs of self-resembling female nudes compared with other-resembling female nudes and non-manipulated female nudes, indicating a higher approach motivation to self-resembling mates. In the stress group, startle magnitude was larger during foreground presentation of self-resembling female nudes compared with other-resembling female nudes and non-manipulated female nudes, indicating a higher approach motivation to dissimilar mates. Our findings show that stress affects human mating preferences: unstressed individuals showed the expected preference for similar mates, but stressed individuals seem to prefer dissimilar mates. PMID:20219732

Cardiac Modulation of Startle: Effects on Eye Blink and Higher Cognitive Processing

ERIC Educational Resources Information Center

Schulz, Andre; Reichert, Carolin F.; Richter, Steffen; Lass-Hennemann, Johanna; Blumenthal, Terry D.; Schachinger, Hartmut

2009-01-01

Cardiac cycle time has been shown to affect pre-attentive brainstem startle processes, such as the magnitude of acoustically evoked reflexive startle eye blinks. These effects were attributed to baro-afferent feedback mechanisms. However, it remains unclear whether cardiac cycle time plays a role in higher startle-related cognitive processes, as…

Defensive Physiological Reactions to Rejection

PubMed Central

Gyurak, Anett; Ayduk, Özlem

2014-01-01

We examined the hypothesis that rejection automatically elicits defensive physiological reactions in people with low self-esteem (SE) but that attentional control moderates this effect. Undergraduates (N = 67) completed questionnaire measures of SE and attentional control. Their eye-blink responses to startle probes were measured while they viewed paintings related to rejection and acceptance themes. The stimuli also included positive-, negative-, and neutral-valence control paintings unrelated to rejection. As predicted, compared with people high in SE, those low in SE showed stronger startle eye-blink responses to paintings related to rejection, but not to negative paintings. Paintings related to acceptance did not attenuate their physiological reactivity. Furthermore, attentional control moderated their sensitivity to rejection, such that low SE was related to greater eye-blink responses to rejection only among individuals who were low in attentional control. Implications of the role of attentional control as a top-down process regulating emotional reactivity in people with low SE are discussed. PMID:17894606

Anxiety and Depression Symptom Dimensions Demonstrate Unique Relationships with the Startle Reflex in Anticipation of Unpredictable Threat in 8 to 14 Year-Old Girls.

PubMed

Nelson, Brady D; Hajcak, Greg

2017-02-01

There is growing evidence that heightened sensitivity to unpredictability is a core mechanism of anxiety disorders. In adults, multiple anxiety disorders have been associated with a heightened startle reflex in anticipation of unpredictable threat. Child and adolescent anxiety has been linked to an increased startle reflex across baseline, safety, and threat conditions. However, it is unclear whether anxiety in youth is related to the startle reflex as a function of threat predictability. In a sample of 90 8 to 14 year-old girls, the present study examined the association between anxiety symptom dimensions and startle potentiation during a no, predictable, and unpredictable threat task. Depression symptom dimensions were also examined given their high comorbidity with anxiety and mixed relationship with the startle reflex and sensitivity to unpredictability. To assess current symptoms, participants completed the self-report Screen for Child Anxiety Related Emotional Disorders and Children's Depression Inventory. Results indicated that social phobia symptoms were associated with heightened startle potentiation in anticipation of unpredictable threat and attenuated startle potentiation in anticipation of predictable threat. Negative mood and negative self-esteem symptoms were associated with attenuated and heightened startle potentiation in anticipation of unpredictable threat, respectively. All results remained significant after controlling for the other symptom dimensions. The present study provides initial evidence that anxiety and depression symptom dimensions demonstrate unique associations with the startle reflex in anticipation of unpredictable threat in children and adolescents.

Anxiety and Depression Symptom Dimensions Demonstrate Unique Relationships with the Startle Reflex in Anticipation of Unpredictable Threat in 8 to 14 Year-Old Girls

PubMed Central

Nelson, Brady D.; Hajcak, Greg

2016-01-01

There is growing evidence that heightened sensitivity to unpredictability is a core mechanism of anxiety disorders. In adults, multiple anxiety disorders have been associated with a heightened startle reflex in anticipation of unpredictable threat. Child and adolescent anxiety has been linked to an increased startle reflex across baseline, safety, and threat conditions. However, it is unclear whether anxiety in youth is related to the startle reflex as a function of threat predictability. In a sample of 90 8 to 14 year-old girls, the present study examined the association between anxiety symptom dimensions and startle potentiation during a no, predictable, and unpredictable threat task. Depression symptom dimensions were also examined given their high comorbidity with anxiety and mixed relationship with the startle reflex and sensitivity to unpredictability. To assess current symptoms, participants completed the self-report Screen for Child Anxiety Related Emotional Disorders and Children’s Depression Inventory. Results indicated that social phobia symptoms were associated with heightened startle potentiation in anticipation of unpredictable threat and attenuated startle potentiation in anticipation of predictable threat. Negative mood and negative self-esteem symptoms were associated with attenuated and heightened startle potentiation in anticipation of unpredictable threat, respectively. All results remained significant after controlling for the other symptom dimensions. The present study provides initial evidence that anxiety and depression symptom dimensions demonstrate unique associations with the startle reflex in anticipation of unpredictable threat in children and adolescents. PMID:27224989

Cortisol, but not intranasal insulin, affects the central processing of visual food cues.

PubMed

Ferreira de Sá, Diana S; Schulz, André; Streit, Fabian E; Turner, Jonathan D; Oitzl, Melly S; Blumenthal, Terry D; Schächinger, Hartmut

2014-12-01

Stress glucocorticoids and insulin are important endocrine regulators of energy homeostasis, but little is known about their central interaction on the reward-related processing of food cues. According to a balanced group design, healthy food deprived men received either 40IU intranasal insulin (n=13), 30mg oral cortisol (n=12), both (n=15), or placebo (n=14). Acoustic startle responsiveness was assessed during presentation of food and non-food pictures. Cortisol enhanced startle responsiveness during visual presentation of "high glycemic" food pictures, but not during presentation of neutral and pleasant non-food pictures. Insulin had no effect. Based on the "frustrative nonreward" model these results suggest that the reward value of high glycemic food items is specifically increased by cortisol. Copyright © 2014 Elsevier Ltd. All rights reserved.

Pre-pubertal stress exposure affects adult behavioral response in association with changes in circulating corticosterone and brain-derived neurotrophic factor.

PubMed

Bazak, Noam; Kozlovsky, Nitsan; Kaplan, Zeev; Matar, Michael; Golan, Hava; Zohar, Joseph; Richter-Levin, Gal; Cohen, Hagit

2009-07-01

Early-life stress produces a cascade of neurobiological events that cause enduring changes in neural plasticity and synaptic efficacy that appear to play pivotal roles in the pathophysiology of post-traumatic stress disorder (PTSD). Brain-derived neurotrophic factor (BDNF) has been implicated in the neurobiological mechanisms of these changes, in interaction with components of the stress response, such as corticosterone. This study examined the consequences of juvenile stress for behavior during adulthood in association with circulating corticosterone levels and BDNF expression. The experiments examined single exposure to predator scent stress (soiled cat litter for 10 min) as compared to repeated exposure, early in life and later on. Behavioral responses were assessed in the elevated plus maze and the acoustic startle response paradigms at 28, 60 and 90 days of age. Plasma corticosterone was measured and brain areas analyzed for BDNF levels. The results show that juvenile stress exposure increased anxiety-like behavior and startle amplitude and decreased plasma corticosterone. This response was seen immediately after exposure and also long term. Adult stress exposure increased anxiety-like behavior, startle amplitude and plasma corticosterone. Exposure to both early and later life trauma elicited reduced levels of corticosterone following the initial exposure, which were not raised by re-exposure, and elicited significant downregulation of BDNF mRNA and protein levels in the hippocampus CA1 subregion. The consequences of adult stress exposure were more severe in rats were exposed to the same stressor as juveniles, indicated increased vulnerability. The results suggest that juvenile stress has resounding effects in adulthood reflected in behavioral responses. The concomitant changes in BDNF and corticosterone levels may mediate the changes in neural plasticity and synaptic functioning underlying clinical manifestations of PTSD.

Fear inhibition in high trait anxiety.

PubMed

Kindt, Merel; Soeter, Marieke

2014-01-01

Trait anxiety is recognized as an individual risk factor for the development of anxiety disorders but the neurobiological mechanisms remain unknown. Here we test whether trait anxiety is associated with impaired fear inhibition utilizing the AX+/BX- conditional discrimination procedure that allows for the independent evaluation of startle fear potentiation and inhibition of fear. Sixty undergraduate students participated in the study--High Trait Anxious: n = 28 and Low Trait Anxious: n = 32. We replicated earlier findings that a transfer of conditioned inhibition for startle responses requires contingency awareness. However, contrary to the fear inhibition hypothesis, our data suggest that high trait anxious individuals show a normal fear inhibition of conditioned startle responding. Only at the cognitive level the high trait anxious individuals showed evidence for impaired inhibitory learning of the threat cue. Together with other findings where impaired fear inhibition was only observed in those PTSD patients who were either high on hyperarousal symptoms or with current anxiety symptoms, we question whether impaired fear inhibition is a biomarker for the development of anxiety disorders.

Gender specific gene-environment interactions on laboratory-assessed aggression.

PubMed

Verona, Edelyn; Joiner, Thomas E; Johnson, Frank; Bender, Theodore W

2006-01-01

We examined gene-environment interactive effects on aggressive behavior among men and women genotyped (short versus long alleles) for the serotonin transporter gene. Aggressive behavior was indexed via a laboratory paradigm that measured the intensity and duration of shocks delivered to a putative "employee". Half of the participants were exposed to a physical stressor during the procedure (stress) and half were not (no-stress). Participants' physiological responses were gauged via acoustic startle eyeblink reactions (startle reactivity). Results were that men with the homozygous short (s/s) genotype showed increased aggression only under stress, whereas women and men carrying the long allele did not show differences in aggression in stress versus no-stress. However, although stress exposure produced increases in startle reactivity, there were no genotype or gender differences in physiology. These results replicate longitudinal research findings confirming the interactive effects of genes and environment on behavioral reactivity and on the development of externalizing psychopathological syndromes, at least in men.

Physiological correlates of emotional reactivity and regulation in early adolescents.

PubMed

Latham, Melissa D; Cook, Nina; Simmons, Julian G; Byrne, Michelle L; Kettle, Jonathan W L; Schwartz, Orli; Vijayakumar, Nandita; Whittle, Sarah; Allen, Nicholas B

2017-07-01

Few studies have examined physiological correlates of emotional reactivity and regulation in adolescents, despite the occurrence in this group of significant developmental changes in emotional functioning. The current study employed multiple physiological measures (i.e., startle-elicited eyeblink and ERP, skin conductance, facial EMG) to assess the emotional reactivity and regulation of 113 early adolescents in response to valenced images. Reactivity was measured while participants viewed images, and regulation was measured when they were asked to discontinue or maintain their emotional reactions to the images. Adolescent participants did not exhibit fear-potentiated startle blink. However, they did display affect-consistent zygomatic and corrugator activity during reactivity, as well as inhibition of some of these facial patterns during regulation. Skin conductance demonstrated arousal dependent activity during reactivity, and overall decreases during regulation. These findings suggest that early adolescents display reactivity to valenced pictures, but not to startle probes. Psychophysiological patterns during emotion regulation indicate additional effort and/or attention during the regulation process. Copyright © 2017 Elsevier B.V. All rights reserved.

Food deprivation and emotional reactions to food cues: implications for eating disorders.

PubMed

Drobes, D J; Miller, E J; Hillman, C H; Bradley, M M; Cuthbert, B N; Lang, P J

2001-01-01

Two studies examined emotional responding to food cues. In experiment 1, normal college students were assigned to 0-, 6- or 24-h of food deprivation prior to presentations of standard emotional and food-related pictures. Food deprivation had no impact on responses elicited by standard emotional pictures. However, subjective and psychophysiological reactions to food pictures were affected significantly by deprivation. Importantly, food-deprived subjects viewing food pictures showed an enhanced startle reflex and increased heart rate. Experiment 2 replicated the food deprivation effects from experiment 1, and examined participants reporting either a habitual pattern of restrained (anorexia-like) or binge (bulimia-like) eating. Food-deprived and binge eater groups showed startle potentiation to food cues, and rated these stimuli as more pleasant, relative to restrained eaters and control subjects. The results are interpreted from the perspective that startle modulation reflects activation of defensive or appetitive motivation. Implications of the data for understanding eating disorders are considered.

Oxytocin receptor neurotransmission in the dorsolateral bed nucleus of the stria terminalis facilitates the acquisition of cued fear in the fear-potentiated startle paradigm in rats.

PubMed

Moaddab, Mahsa; Dabrowska, Joanna

2017-07-15

Oxytocin (OT) is a hypothalamic neuropeptide that modulates fear and anxiety-like behaviors. Dorsolateral bed nucleus of the stria terminalis (BNST dl ) plays a critical role in the regulation of fear and anxiety, and expresses high levels of OT receptor (OTR). However, the role of OTR neurotransmission within the BNST dl in mediating these behaviors is unknown. Here, we used adult male Sprague-Dawley rats to investigate the role of OTR neurotransmission in the BNST dl in the modulation of the acoustic startle response, as well as in the acquisition and consolidation of conditioned fear using fear potentiated startle (FPS) paradigm. Bilateral intra-BNST dl administration of OT (100 ng) did not affect the acquisition of conditioned fear response. However, intra-BNST dl administration of specific OTR antagonist (OTA), (d(CH 2 ) 5 1 , Tyr(Me) 2 , Thr 4 , Orn 8 , des-Gly-NH 2 9 )-vasotocin, (200 ng), prior to the fear conditioning session, impaired the acquisition of cued fear, without affecting a non-cued fear component of FPS. Neither OTA, nor OT affected baseline startle or shock reactivity during fear conditioning. Therefore, the observed impairment of cued fear after OTA infusion resulted from the specific effect on the formation of cued fear. In contrast to the acquisition, neither OTA nor OT affected the consolidation of FPS, when administered after the completion of fear conditioning session. Taken together, these results reveal the important role of OTR neurotransmission in the BNST dl in the formation of conditioned fear to a discrete cue. This study also highlights the role of the BNST dl in learning to discriminate between threatening and safe stimuli. Copyright © 2017 Elsevier Ltd. All rights reserved.

Predicting impaired extinction of traumatic memory and elevated startle.

PubMed

Nalloor, Rebecca; Bunting, Kristopher; Vazdarjanova, Almira

2011-01-01

Emotionally traumatic experiences can lead to debilitating anxiety disorders, such as phobias and Post-Traumatic Stress Disorder (PTSD). Exposure to such experiences, however, is not sufficient to induce pathology, as only up to one quarter of people exposed to such events develop PTSD. These statistics, combined with findings that smaller hippocampal size prior to the trauma is associated with higher risk of developing PTSD, suggest that there are pre-disposing factors for such pathology. Because prospective studies in humans are limited and costly, investigating such pre-dispositions, and thus advancing understanding of the genesis of such pathologies, requires the use of animal models where predispositions are identified before the emotional trauma. Most existing animal models are retrospective: they classify subjects as those with or without a PTSD-like phenotype long after experiencing a traumatic event. Attempts to create prospective animal models have been largely unsuccessful. Here we report that individual predispositions to a PTSD-like phenotype, consisting of impaired rate and magnitude of extinction of an emotionally traumatic event coupled with long-lasting elevation of acoustic startle responses, can be revealed following exposure to a mild stressor, but before experiencing emotional trauma. We compare, in rats, the utility of several classification criteria and report that a combination of criteria based on acoustic startle responses and behavior in an anxiogenic environment is a reliable predictor of a PTSD-like phenotype. There are individual predispositions to developing impaired extinction and elevated acoustic startle that can be identified after exposure to a mildly stressful event, which by itself does not induce such a behavioral phenotype. The model presented here is a valuable tool for studying the etiology and pathophysiology of anxiety disorders and provides a platform for testing behavioral and pharmacological interventions that can reduce the probability of developing pathologic behaviors associated with such disorders.

Chronic stress exposure may affect the brain's response to high calorie food cues and predispose to obesogenic eating habits

USDA-ARS?s Scientific Manuscript database

Exaggerated reactivity to food cues involving calorically-dense foods may significantly contribute to food consumption beyond caloric need Exaggerated reactivity to food cues involving calorically-dense foods may significantly contribute to food consumption beyond caloric need. Chronic stress, whi...

Different effects of isolation-rearing and neonatal MK-801 treatment on attentional modulations of prepulse inhibition of startle in rats.

PubMed

Wu, Zhe-Meng; Ding, Yu; Jia, Hong-Xiao; Li, Liang

2016-09-01

Prepulse inhibition (PPI) is suppression of the startle reflex by a weaker sensory stimulus (prepulse) preceding the startling stimulus. In people with schizophrenia, impairment of attentional modulation of PPI, but not impairment of baseline PPI, is correlated with symptom severity. In rats, both fear conditioning of prepulse and perceptually spatial separation between the conditioned prepulse and a noise masker enhance PPI (the paradigms of attentional modulation of PPI). As a neurodevelopmental model of schizophrenia, isolation rearing impairs both baseline PPI and attentional modulations of PPI in rats. This study examined in Sprague-Dawley male rats whether neonatally blocking N-methyl-D-aspartate (NMDA) receptors specifically affects attentional modulations of PPI during adulthood. Both socially reared rats with neonatal exposure to the NMDA receptor antagonist MK-801 and isolation-reared rats exhibited augmented startle responses, but only isolation rearing impaired baseline PPI. Fear conditioning of the prepulse enhanced PPI in socially reared rats, but MK-801-treated rats lost the prepulse feature specificity. Perceptually spatial separation between the conditioned prepulse and a noise masker further enhanced PPI only in normally reared rats. Clozapine administration during adulthood generally weakened startle, enhanced baseline PPI in neonatally interrupted rats, and restored the fear conditioning-induced PPI enhancement in isolation-reared rats with a loss of the prepulse feature specificity. Clozapine administration also abolished both the perceptual separation-induced PPI enhancement in normally reared rats and the fear conditioning-induced PPI enhancement in MK-801-treated rats. Isolation rearing impairs both baseline PPI and attentional modulations of PPI, but neonatally disrupting NMDA receptor-mediated transmissions specifically impair attentional modulations of PPI. Clozapine has limited alleviating effects.

Effects of anticipated emotional category and temporal predictability on the startle reflex.

PubMed

Parisi, Elizabeth A; Hajcak, Greg; Aneziris, Eleni; Nelson, Brady D

2017-09-01

Anticipated emotional category and temporal predictability are key characteristics that have both been shown to impact psychophysiological indices of defensive motivation (e.g., the startle reflex). To date, research has primarily examined these features in isolation, and it is unclear whether they have additive or interactive effects on defensive motivation. In the present study, the startle reflex was measured in anticipation of low arousal neutral, moderate arousal pleasant, and high arousal unpleasant pictures that were presented with either predictable or unpredictable timing. Linear mixed-effects modeling was conducted to examine startle magnitude across time, and the intercept at the beginning and end of the task. Across the entire task, the anticipation of temporally unpredictable (relative to predictable) pictures and emotional (relative to neutral) pictures potentiated startle magnitude, but there was no interaction between the two features. However, examination of the intercept at the beginning of the task indicated a Predictability by Emotional Category interaction, such that temporal unpredictability enhanced startle potentiation in anticipation of unpleasant pictures only. Examination of the intercept at the end of the task indicated that the effects of predictability and emotional category on startle magnitude were largely diminished. The present study replicates previous reports demonstrating that emotional category and temporal predictability impact the startle reflex, and provides novel evidence suggesting an interactive effect on defensive motivation at the beginning of the task. This study also highlights the importance of examining the time course of the startle reflex. Copyright © 2017 Elsevier B.V. All rights reserved.

Increased fear-potentiated startle in major depressive disorder patients with lifetime history of suicide attempt.

PubMed

Ballard, Elizabeth D; Ionescu, Dawn F; Vande Voort, Jennifer L; Slonena, Elizabeth E; Franco-Chaves, Jose A; Zarate, Carlos A; Grillon, Christian

2014-06-01

Suicide is a common reason for psychiatric emergency and morbidity, with few effective treatments. Anxiety symptoms have emerged as potential modifiable risk factors in the time before a suicide attempt, but few studies have been conducted using laboratory measures of fear and anxiety. We operationally defined fear and anxiety as increased startle reactivity during anticipation of predictable (fear-potentiated startle) and unpredictable (anxiety-potentiated startle) shock. We hypothesized that a lifetime history of suicide attempt (as compared to history of no suicide attempt) would be associated with increased fear-potentiated startle. A post-hoc analysis of fear- and anxiety-potentiated startle was conducted in 28 medication-free patients with Major Depressive Disorder (MDD) divided according to suicide attempt history. The magnitude of fear-potentiated startle was increased in depressed patients with lifetime suicide attempts compared to those without a lifetime history of suicide attempt (F(1,26)=5.629, p=.025). There was no difference in anxiety-potentiated startle by suicide attempt history. This is a post-hoc analysis of previously analyzed patient data from a study of depressed inpatients. Further replication of the finding with a larger patient sample is indicated. Increased fear-potentiated startle in suicide attempters suggests the role of amygdala in depressed patients with a suicide attempt history. Findings highlight the importance of anxiety symptoms in the treatment of patients at increased suicide risk. Published by Elsevier B.V.

Heart rate, startle response, and intrusive trauma memories

PubMed Central

Chou, Chia-Ying; Marca, Roberto La; Steptoe, Andrew; Brewin, Chris R

2014-01-01

The current study adopted the trauma film paradigm to examine potential moderators affecting heart rate (HR) as an indicator of peritraumatic psychological states and as a predictor of intrusive memories. We replicated previous findings that perifilm HR decreases predicted the development of intrusive images and further showed this effect to be specific to images rather than thoughts, and to detail rather than gist recognition memory. Moreover, a group of individuals showing both an atypical sudden reduction in HR after a startle stimulus and higher trait dissociation was identified. Only among these individuals was lower perifilm HR found to indicate higher state dissociation, fear, and anxiety, along with reduced vividness of intrusions. The current findings emphasize how peritraumatic physiological responses relate to emotional reactions and intrusive memory. The moderating role of individual difference in stress defense style was highlighted. PMID:24397333

Interoceptive threat leads to defensive mobilization in highly anxiety sensitive persons.

PubMed

Melzig, Christiane A; Holtz, Katharina; Michalowski, Jaroslaw M; Hamm, Alfons O

2011-06-01

To study defensive mobilization elicited by the exposure to interoceptive arousal sensations, we exposed highly anxiety sensitive students to a symptom provocation task. Symptom reports, autonomic arousal, and the startle eyeblink response were monitored during guided hyperventilation and a recovery period in 26 highly anxiety sensitive persons and 22 controls. Normoventilation was used as a non-provocative comparison condition. Hyperventilation led to autonomic arousal and a marked increase in somatic symptoms. While high and low anxiety sensitive persons did not differ in their defensive activation during hyperventilation, group differences were detected during early recovery. Highly anxiety sensitive students exhibited a potentiation of startle response magnitudes and increased autonomic arousal after hyper- as compared to after normoventilation, indicating defensive mobilization evoked by the prolonged presence of feared somatic sensations. Copyright © 2010 Society for Psychophysiological Research.

Sex differences in the time course of emotion.

PubMed

Gard, Marja Germans; Kring, Ann M

2007-05-01

Conventional wisdom holds that women are more "emotional" than men. However, research evidence suggests that sex differences in emotion are considerably more complex. The authors tested hypotheses about sex differences in the engagement of the approach and avoidance motivational systems thought to underpin emotional responses. The authors measured reported emotional experience and startle response magnitude both during the presentation and after the offset of emotional stimuli that engage these motivational systems to assess whether men and women differ in their patterns of immediate response to emotional stimuli and in their patterns of recovery from these responses. Our findings indicated that women were more experientially reactive to negative, but not positive, emotional pictures compared to men, and that women scored higher than men on measure of aversive motivational system sensitivity. Although both men and women exhibited potentiation of the startle response during the presentation of negative pictures relative to neutral pictures, only women continued to show this relative potentiation during the recovery period, indicating that women were continuing to engage the aversive motivational system after the offset of negative emotional pictures.

Nucleus accumbens carbachol disrupts olfactory and contextual fear-potentiated startle and attenuates baseline startle reactivity.

PubMed

Cousens, Graham A; Skrobacz, Cheryl G; Blumenthal, Anna

2011-01-20

Although the nucleus accumbens (NAc) typically is not considered a primary component of the circuitry underlying either the acquisition or retrieval of conditioned fear, evidence suggests that this region may play some role in modulating fear-related behaviors. The goal of the present study was to explore a potential role for NAc cholinergic receptors in the expression of fear-potentiated startle (FPS) and baseline startle reactivity. Intra-NAc infusion of the broad-acting cholinergic receptor agonist, carbachol, suppressed FPS elicited by re-exposure to both a discrete odor previously paired with footshock and the conditioning context. Although carbachol elevated spontaneous motor activity, activity bouts did not account for startle suppression in carbachol-treated Ss. In addition, intra-NAc carbachol suppressed baseline startle over a range of acoustic pulse intensities in the absence of explicit fear conditioning. Collectively, these findings suggest that NAc cholinergic receptors play a role in the modulation of baseline startle reactivity, rather than in the retrieval of learned fear, and that this role is independent of overt motor activity. Copyright © 2010 Elsevier B.V. All rights reserved.

Emotion regulation of the affect-modulated startle reflex during different picture categories.

PubMed

Conzelmann, Annette; McGregor, Victoria; Pauli, Paul

2015-09-01

Previous studies on emotion regulation of the startle reflex found an increase in startle amplitude from down-, to non-, to up-regulation for pleasant and unpleasant stimuli. We wanted to clarify whether this regulation effect remains stable for different picture categories within pleasant and unpleasant picture sets. We assessed startle amplitude of 31 participants during down-, non-, or up-regulation of feelings elicited by pleasant erotic and adventure and unpleasant victim and threat pictures. Startle amplitude was smaller during adventure and erotic compared to victim and threat pictures and increased from down-, to non-, to up-regulation independently of the picture category. Results indicate that the motivational priming effect on startle modulation elicited by different picture categories is independent of emotion regulation instructions. In addition, the emotion regulation effect is independent of motivational priming effects. © 2015 Society for Psychophysiological Research.

Social stimuli increase physiological reactivity but not defensive responses.

PubMed

Kosonogov, Vladimir; Sanchez-Navarro, Juan Pedro; Martinez-Selva, Jose Maria; Torrente, Ginesa; Carrillo-Verdejo, Eduvigis

2016-10-01

Emotional reactions are crucial in survival because they provide approach and withdrawal behaviors. However, an unsolved question is whether the social content of the affective stimuli has a specific effect on emotional responses. We studied whether the social content of affective pictures influenced the defensive response and response mobilization. For this purpose, we recorded startle blink reflex (a defensive response) and skin conductance responses (a measure of unspecific physiological reactivity or arousal) in 73 participants while they viewed a series of 81 pictures of varying affective valence and social content. Our results revealed that defense response, as indicated by increases in the magnitude of the startle blink reflex, was mainly dependent on threatening or unpleasant cues, but was unrelated to the social content of the pictures. The social content, however, had an influence on pleasant stimuli, provoking an increase in resource mobilization, as reflected by changes in electrodermal activity. Hence, the social content of the affective stimuli may increase the physiological arousal elicited by pleasant stimuli, and it appears to be unrelated to the defense reactivity provoked by unpleasant stimuli. © 2016 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

Startle modulation and explicit valence evaluations dissociate during backward fear conditioning.

PubMed

Luck, Camilla C; Lipp, Ottmar V

2017-05-01

Blink startle magnitude is linearly modulated by affect such that, relative to neutral stimuli, startle magnitude is inhibited during pleasant stimuli and potentiated during unpleasant stimuli. Andreatta, Mühlberger, Yarali, Gerber, and Pauli (2010), however, report a dissociation between startle modulation and explicit valence evaluations during backward conditioning, a procedure in which the unconditional stimulus precedes the conditional stimulus (CS). Relative to controls, startles elicited during the CS were inhibited, suggesting that the CS had acquired positive valence, but participants still evaluated the CS as unpleasant after the experiment. In Experiment 1, we aimed to replicate this dissociation using a trial-by-trial measure of CS valence to measure startle modulation and CS valence simultaneously during forward and backward differential fear conditioning. In Experiment 2, we examined whether early and late portions of the CS could acquire differential valence by presenting startle probes at early and late probe positions during the CS. In both experiments, the dissociation between startle modulation and explicit valence evaluations in backward conditioning replicated, with CS+ evaluated as less pleasant than CS-, but startles elicited during CS+ inhibited relative to CS-. In Experiment 2, we provide preliminary evidence that this inhibition was present early, but not late, during the CS+. The results replicate the dissociation between implicit and explicit CS valence reported by Andreatta et al. (2010) using a trial-by-trial measure of valence. We also provide preliminary evidence that this dissociation may occur because the implicit and explicit measures are recorded at different times during the CS presentation. © 2017 Society for Psychophysiological Research.

Detecting symptom exaggeration in combat veterans using the MMPI-2 symptom validity scales: a mixed group validation.

PubMed

Tolin, David F; Steenkamp, Maria M; Marx, Brian P; Litz, Brett T

2010-12-01

Although validity scales of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2; J. N. Butcher, W. G. Dahlstrom, J. R. Graham, A. Tellegen, & B. Kaemmer, 1989) have proven useful in the detection of symptom exaggeration in criterion-group validation (CGV) studies, usually comparing instructed feigners with known patient groups, the application of these scales has been problematic when assessing combat veterans undergoing posttraumatic stress disorder (PTSD) examinations. Mixed group validation (MGV) was employed to determine the efficacy of MMPI-2 exaggeration scales in compensation-seeking (CS) and noncompensation-seeking (NCS) veterans. Unlike CGV, MGV allows for a mix of exaggerating and nonexaggerating individuals in each group, does not require that the exaggeration versus nonexaggerating status of any individual be known, and can be adjusted for different base-rate estimates. MMPI-2 responses of 377 male veterans were examined according to CS versus NCS status. MGV was calculated using 4 sets of base-rate estimates drawn from the literature. The validity scales generally performed well (adequate sensitivity, specificity, and efficiency) under most base-rate estimations, and most produced cutoff scores that showed adequate detection of symptom exaggeration, regardless of base-rate assumptions. These results support the use of MMPI-2 validity scales for PTSD evaluations in veteran populations, even under varying base rates of symptom exaggeration.

Emotion processing deficits in alexithymia and response to a depth of processing intervention.

PubMed

Constantinou, Elena; Panayiotou, Georgia; Theodorou, Marios

2014-12-01

Findings on alexithymic emotion difficulties have been inconsistent. We examined potential differences between alexithymic and control participants in general arousal, reactivity, facial and subjective expression, emotion labeling, and covariation between emotion response systems. A depth of processing intervention was introduced. Fifty-four participants (27 alexithymic), selected using the Toronto Alexithymia Scale-20, completed an imagery experiment (imagining joy, fear and neutral scripts), under instructions for shallow or deep emotion processing. Heart rate, skin conductance, facial electromyography and startle reflex were recorded along with subjective ratings. Results indicated hypo-reactivity to emotion among high alexithymic individuals, smaller and slower startle responses, and low covariation between physiology and self-report. No deficits in facial expression, labeling and emotion ratings were identified. Deep processing was associated with increased physiological reactivity and lower perceived dominance and arousal in high alexithymia. Findings suggest a tendency for avoidance of intense, unpleasant emotions and less defensive action preparation in alexithymia. Copyright © 2014 Elsevier B.V. All rights reserved.

A scoring system predicting the clinical course of CLPB defect based on the foetal and neonatal presentation of 31 patients.

PubMed

Pronicka, Ewa; Ropacka-Lesiak, Mariola; Trubicka, Joanna; Pajdowska, Magdalena; Linke, Markus; Ostergaard, Elsebet; Saunders, Carol; Horsch, Sandra; van Karnebeek, Clara; Yaplito-Lee, Joy; Distelmaier, Felix; Õunap, Katrin; Rahman, Shamima; Castelle, Martin; Kelleher, John; Baris, Safa; Iwanicka-Pronicka, Katarzyna; Steward, Colin G; Ciara, Elżbieta; Wortmann, Saskia B

2017-11-01

Recently, CLPB deficiency has been shown to cause a genetic syndrome with cataracts, neutropenia, and 3-methylglutaconic aciduria. Surprisingly, the neurological presentation ranges from completely unaffected to patients with virtual absence of development. Muscular hypo- and hypertonia, movement disorder and progressive brain atrophy are frequently reported. We present the foetal, peri- and neonatal features of 31 patients, of which five are previously unreported, using a newly developed clinical severity scoring system rating the clinical, metabolic, imaging and other findings weighted by the age of onset. Our data are illustrated by foetal and neonatal videos. The patients were classified as having a mild (n = 4), moderate (n = 13) or severe (n = 14) disease phenotype. The most striking feature of the severe subtype was the neonatal absence of voluntary movements in combination with ventilator dependency and hyperexcitability. The foetal and neonatal presentation mirrored the course of disease with respect to survival (current median age 17.5 years in the mild group, median age of death 35 days in the severe group), severity and age of onset of all findings evaluated. CLPB deficiency should be considered in neonates with absence of voluntary movements, respiratory insufficiency and swallowing problems, especially if associated with 3-methylglutaconic aciduria, neutropenia and cataracts. Being an important differential diagnosis of hyperekplexia (exaggerated startle responses), we advise performing urinary organic acid analysis, blood cell counts and ophthalmological examination in these patients. The neonatal presentation of CLPB deficiency predicts the course of disease in later life, which is extremely important for counselling.

Rate of initial recovery and subsequent radar monitoring performance following a simulated emergency involving startle.

DOT National Transportation Integrated Search

1983-09-01

The present study employed auditory startle to simulate the principal components (unexpectedness, fear, and physiological arousal) that are common to many types of sudden emergencies and compared performance recovery following startle with recovery f...

Linking Dimensional Models of Internalizing Psychopathology to Neurobiological Systems: Affect-Modulated Startle as an Indicator of Fear and Distress Disorders and Affiliated Traits

PubMed Central

Vaidyanathan, Uma; Patrick, Christopher J.; Cuthbert, Bruce N.

2009-01-01

Integrative hierarchical models have sought to account for the extensive comorbidity between various internalizing disorders in terms of broad individual difference factors these disorders share. However, such models have been developed largely on the basis of self-report and diagnostic symptom data. Toward the goal of linking such models to neurobiological systems, we review studies that have employed variants of the affect-modulated startle paradigm to investigate emotional processing in internalizing disorders as well as personality constructs known to be associated with these disorders. Specifically, we focus on four parameters of startle reactivity: fear-potentiated startle, inhibition of startle in the context of pleasant stimuli, context-potentiated startle, and general startle reactivity. On the basis of available data, we argue that these varying effects index differing neurobiological processes related to mood and anxiety disorders that are interpretable from the standpoint of dimensional models of the internalizing spectrum. Further, we contend that these empirical findings can feed back into and help reshape conceptualizations of internalizing disorders in ways that make them more amenable to neurobiological analysis. PMID:19883142

Aversive Startle Potentiation and Fear Pathology: Mediating Role of Threat Sensitivity and Moderating Impact of Depression

PubMed Central

Yancey, James R.; Vaidyanathan, Uma; Patrick, Christopher J.

2015-01-01

Enhanced startle during exposure to unpleasant cues (aversive startle potentiation; ASP) appears in the RDoC matrix as a physiological index of acute threat response. Increased ASP has been linked to focal fear disorders and to scale measures of dispositional fearfulness (i.e., threat sensitivity; THT+). However, some studies have reported reduced ASP for fear pathology accompanied by major depressive disorder (MDD) or pervasive distress. The current study evaluated whether (a) THT+ as indexed by reported dispositional fearfulness mediates the relationship between fear disorders (when unaccompanied by depression) and ASP, and (b) depression moderates relations of THT+ and fear disorders with ASP. Fear disorder participants without MDD showed enhanced ASP whereas those with MDD (or other distress conditions) showed evidence of reduced ASP. Continuous THT+ scores also predicted ASP, and this association: (a) was likewise moderated by depression/distress, and (b) accounted for the relationship between ASP and fear pathology without MDD. These findings point to a role for the RDoC construct of acute threat, operationalized dispositionally, in enhanced ASP shown by individuals with fear pathology unaccompanied by distress pathology. PMID:25448265

The GABA(B) receptor positive modulator BHF177 attenuated anxiety, but not conditioned fear, in rats.

PubMed

Li, Xia; Kaczanowska, Katarzyna; Finn, M G; Markou, Athina; Risbrough, Victoria B

2015-10-01

GABAB (γ-aminobutyric acid B) receptors may be a therapeutic target for anxiety disorders. Here we characterized the effects of the GABAB receptor positive allosteric modulator (PAM) BHF177 on conditioned and unconditioned physiological responses to threat in the light-enhanced startle (LES), stress-induced hyperthermia, and fear-potentiated startle (FPS) procedures in rats. The effects of BHF177 on LES were compared with those of the GABAB receptor agonists baclofen and CGP44532, and the positive control buspirone, a 5-HT1A receptor partial agonist with anxiolytic activity in humans. Baclofen (0.4, 0.9 and 1.25 mg/kg) and CGP44532 (0.065, 0.125 and 0.25 mg/kg) administration had significant sedative, but not anxiolytic, activity reflected in overall decrease in the startle response in the LES tests. BHF177 (10, 20 and 40 mg/kg) had no effect on LES, nor did it produce an overall sedative effect. Interesting, however, when rats were grouped by high and low LES responses, BHF177 had anxiolytic-like effects only on LES in high, but not low, LES responding rats. BHF177 also blocked stress-induced hyperthermia, but had no effect on conditioned fear responses in the FPS test. Buspirone (1 and 3 mg/kg) had an anxiolytic-like profile in both LES and FPS tests. These results indicate that BHF177 may specifically attenuate unconditioned anxiety in individuals that exhibit a high anxiety state, and has fewer sedative effects than direct agonists. Thus, BHF177 or other GABAB receptor PAMs may be promising compounds for alleviating increased anxiety seen in various psychiatric disorders with a superior side-effect profile compared to GABAB receptor agonists. Published by Elsevier Ltd.

High doses of salicylate causes prepulse facilitation of onset-gap induced acoustic startle response.

PubMed

Sun, Wei; Doolittle, Lauren; Flowers, Elizabeth; Zhang, Chao; Wang, Qiuju

2014-01-01

Prepulse inhibition of acoustic startle reflex (PPI), a well-established method for evaluating sensorimotor gating function, has been used to detect tinnitus in animal models. Reduced gap induced PPI (gap-PPI) was considered as a sign of tinnitus. The silent gap used in the test contains both onset and offset signals. Tinnitus may affect these cues differently. In this experiment, we studied the effects of a high dose of salicylate (250 mg/kg, i.p.), an inducer of reversible tinnitus and sensorineural hearing loss, on gap-PPI induced by three different gaps: an onset-gap with 0.1 ms onset and 25 ms offset time, an offset-gap with 25 ms onset and 0.1 ms offset time, and an onset-offset-gap with 0.1 ms onset and offset time. We found that the onset-gaps induced smaller inhibitions than the offset-gaps before salicylate treatment. The offset-gap induced PPI was significantly reduced 1-3h after salicylate treatment. However, the onset-gap caused a facilitation of startle response. These results suggest that salicylate induced reduction of gap-PPI was not only caused by the decrease of offset-gap induced PPI, but also by the facilitation induced by the onset-gap. Since the onset-gap induced PPI is caused by neural offset response, our results suggest that salicylate may cause a facilitation of neural response to an offset acoustical signal. Treatment of vigabatrin (60 mg/kg/day, 14 days), which elevates the GABA level in the brain, blocked the offset-gap induced PPI and onset-gap induced facilitation caused by salicylate. These results suggest that enhancing GABAergic activities can alleviate salicylate induced tinnitus. Published by Elsevier B.V.

A convergent and essential interneuron pathway for Mauthner-cell-mediated escapes.

PubMed

Lacoste, Alix M B; Schoppik, David; Robson, Drew N; Haesemeyer, Martin; Portugues, Ruben; Li, Jennifer M; Randlett, Owen; Wee, Caroline L; Engert, Florian; Schier, Alexander F

2015-06-01

The Mauthner cell (M-cell) is a command-like neuron in teleost fish whose firing in response to aversive stimuli is correlated with short-latency escapes [1-3]. M-cells have been proposed as evolutionary ancestors of startle response neurons of the mammalian reticular formation [4], and studies of this circuit have uncovered important principles in neurobiology that generalize to more complex vertebrate models [3]. The main excitatory input was thought to originate from multisensory afferents synapsing directly onto the M-cell dendrites [3]. Here, we describe an additional, convergent pathway that is essential for the M-cell-mediated startle behavior in larval zebrafish. It is composed of excitatory interneurons called spiral fiber neurons, which project to the M-cell axon hillock. By in vivo calcium imaging, we found that spiral fiber neurons are active in response to aversive stimuli capable of eliciting escapes. Like M-cell ablations, bilateral ablations of spiral fiber neurons largely eliminate short-latency escapes. Unilateral spiral fiber neuron ablations shift the directionality of escapes and indicate that spiral fiber neurons excite the M-cell in a lateralized manner. Their optogenetic activation increases the probability of short-latency escapes, supporting the notion that spiral fiber neurons help activate M-cell-mediated startle behavior. These results reveal that spiral fiber neurons are essential for the function of the M-cell in response to sensory cues and suggest that convergent excitatory inputs that differ in their input location and timing ensure reliable activation of the M-cell, a feedforward excitatory motif that may extend to other neural circuits. Copyright © 2015 Elsevier Ltd. All rights reserved.

Possible evidence for re-regulation of HPA axis and brain reward systems over time in treatment in prescription opioid-dependent patients.

PubMed

Bunce, Scott C; Harris, Jonathan D; Bixler, Edward O; Taylor, Megan; Muelly, Emilie; Deneke, Erin; Thompson, Kenneth W; Meyer, Roger E

2015-01-01

There is growing evidence for a neuroadaptive model underlying vulnerability to relapse in opioid dependence. The purpose of this study was to evaluate clinical measures hypothesized to mirror elements of allostatic dysregulation in patients dependent on prescription opioids at 2 time points after withdrawal, compared with healthy control participants. Recently withdrawn (n = 7) prescription opioid-dependent patients were compared with the patients in supervised residential care for 2 to 3 months (extended care; n = 7) and healthy controls (n = 7) using drug cue reactivity, affect-modulated startle response tasks, salivary cortisol, and 8 days of sleep actigraphy. Prefrontal cortex was monitored with functional near-infrared spectroscopy during the cue reactivity task. Startle response results indicated reduced hedonic response to natural rewards among patients recently withdrawn from opioids relative to extended care patients. The recently withdrawn patients showed increased activation to pill stimuli in right dorsolateral prefrontal cortex relative to extended care patients. Cortisol levels were elevated among recently withdrawn patients and intermediate for extended care relative to healthy controls. Actigraphy indicated disturbed sleep between recently withdrawn patients and extended care patients; extended care patients were similar to controls. Dorsolateral prefrontal cortex activation to drug and natural reward cues, startle responses to natural reward cues, day-time cortisol levels, time in bed, and total time spent sleeping were all correlated with the number of days since last drug use (ie, time in supervised residential treatment). These results suggest possible re-regulation of dysregulated hypothalamic-pituitary-adrenal axis and brain reward systems in prescription opioid-dependent patients over the drug-free period in residential treatment.

Attenuation of acoustic and tactile startle responses of vitamin B-6 deficient rats.

PubMed

Schaeffer, M C

1987-01-01

Vitamin B-6 deficient rats exhibit changes in behavior, sensory function, and other nervous system abnormalities such as convulsive seizures and motor disturbances. Sensorimotor reactivity was evaluated quantitatively by measuring auditory and tactile startle responses in 12 week old female Long-Evans rats fed a diet devoid of added vitamin B-6 (DEF) or a control diet, either ad lib (AL-CON) or pair-fed to deficient rats (PF-CON). Deficiency was confirmed with a tryptophan-load test administered to a separate group of rats fed simultaneously according to the same protocol. At week 18, body weight and feed efficiency were different among groups (p less than 0.001), and were lowest in DEF. Amplitude of response to both acoustic and tactile stimuli was depressed in DEF compared to both control groups, which generally did not differ in response. This effect was seen most dramatically in responses to the acoustic stimulus (p = 0.034), and especially to the first presentation (p = 0.017). Latency to maximum response was not affected by diet. Possible mechanisms for this nervous system abnormality, not previously reported in vitamin B-6 deficiency, are discussed.

Oxytocin and Social Support as Synergistic Inhibitors of Aversive Fear Conditioning and Fear-Potentiated Startle in Male Rats

DTIC Science & Technology

2009-09-01

startle amplitude. They then received Pavlovian fear conditioning of five pairings of a 3 s light co-terminating with a 500 ms, 0.6mA footshock. Four...Synergistic Inhibitors of Aversive Fear Conditioning and Fear-Potentiated Startle in Male Rats PRINCIPAL INVESTIGATOR: Jeffrey B. Rosen, Ph.D...NUMBER Oxytocin and Social Support as Synergistic Inhibitors of Aversive Fear Conditioning and Fear-Potentiated Startle in Male Rats 5b. GRANT

Increased auditory startle reflex in children with functional abdominal pain.

PubMed

Bakker, Mirte J; Boer, Frits; Benninga, Marc A; Koelman, Johannes H T M; Tijssen, Marina A J

2010-02-01

To test the hypothesis that children with abdominal pain-related functional gastrointestinal disorders have a general hypersensitivity for sensory stimuli. Auditory startle reflexes were assessed in 20 children classified according to Rome III classifications of abdominal pain-related functional gastrointestinal disorders (13 irritable bowel syndrome [IBS], 7 functional abdominal pain syndrome; mean age, 12.4 years; 15 girls) and 23 control subjects (14 girls; mean age, 12.3 years) using a case-control design. The activity of 6 left-sided muscles and the sympathetic skin response were obtained by an electromyogram. We presented sudden loud noises to the subjects through headphones. Both the combined response of 6 muscles and the blink response proved to be significantly increased in patients with abdominal pain compared with control subjects. A significant increase of the sympathetic skin response was not found. Comorbid anxiety disorders (8 patients with abdominal pain) or Rome III subclassification did not significantly affect these results. This study demonstrates an objective hyperresponsivity to nongastrointestinal stimuli. Children with abdominal pain-related functional gastrointestinal disorders may have a generalized hypersensitivity of the central nervous system. Copyright 2010 Mosby, Inc. All rights reserved.

Effects of context preexposure and delay until anxiety retrieval on generalization of contextual anxiety

PubMed Central

Neueder, Dorothea; Glotzbach-Schoon, Evelyn; Mühlberger, Andreas

2017-01-01

Animal studies suggest that time delay between acquisition and retrieval of contextual anxiety increases generalization. Moreover, such generalization is prevented by preexposure to the context (CTX), presumably due to an improved representation of such context. We investigated whether preexposure and time-passing modulate generalization of contextual anxiety, in humans. On Day 1, 42 participants (preexposure group) explored two virtual offices, while 41 participants (no-preexposure group) explored a virtual stadium. On Day 2 (24 h later), all participants learned to associate one office (CTX+) with unpredictable unconditioned stimuli (USs), and another office (CTX−) with safety. On Day 3, either 24 h (recent test) or 2 wk (remote test) later, participants revisited CTX− and CTX+ without USs, as well as a generalization context (G-CTX). Results revealed successfully conditioned anxiety and anxiety generalization for ratings (G-CTX was as aversive as CTX+ was), while safety generalization was found for startle responses (G-CTX elicited startle attenuation as CTX− did). Time between learning and testing enhanced generalization as reflected by comparable startle responses to all three offices in the remote test. Contextual preexposure facilitated extinction of explicit conditioned anxiety assessed with ratings. These results suggest that memory trace of a context degrades with passage of time in humans like in animals and, consequently, anxiety generalization enhances. After context preexposure, high cognitive processes seem to be crucially involved in facilitating extinction (or safety) learning. PMID:27980075

Direct effects of diazepam on emotional processing in healthy volunteers

PubMed Central

Murphy, S. E.; Downham, C.; Cowen, P. J.

2008-01-01

Rationale Pharmacological agents used in the treatment of anxiety have been reported to decrease threat relevant processing in patients and healthy controls, suggesting a potentially relevant mechanism of action. However, the effects of the anxiolytic diazepam have typically been examined at sedative doses, which do not allow the direct actions on emotional processing to be fully separated from global effects of the drug on cognition and alertness. Objectives The aim of this study was to investigate the effect of a lower, but still clinically effective, dose of diazepam on emotional processing in healthy volunteers. Materials and methods Twenty-four participants were randomised to receive a single dose of diazepam (5 mg) or placebo. Sixty minutes later, participants completed a battery of psychological tests, including measures of non-emotional cognitive performance (reaction time and sustained attention) and emotional processing (affective modulation of the startle reflex, attentional dot probe, facial expression recognition, and emotional memory). Mood and subjective experience were also measured. Results Diazepam significantly modulated attentional vigilance to masked emotional faces and significantly decreased overall startle reactivity. Diazepam did not significantly affect mood, alertness, response times, facial expression recognition, or sustained attention. Conclusions At non-sedating doses, diazepam produces effects on attentional vigilance and startle responsivity that are consistent with its anxiolytic action. This may be an underlying mechanism through which benzodiazepines exert their therapeutic effects in clinical anxiety. PMID:18581100

Psychosocial stress alters the strength of reticulospinal input to the human upper trapezius.

PubMed

Marker, Ryan J; Campeau, Serge; Maluf, Katrina S

2017-01-01

Psychosocial stress has been shown to influence several aspects of human motor control associated with the fight-or-flight response, including augmentation of upper trapezius muscle activity. Given the established role of the reticular formation in arousal, this study investigated the contribution of reticulospinal activation to trapezius muscle activity during exposure to an acute psychosocial stressor. Twenty-five healthy adults were exposed to startling acoustic stimuli (SAS) while performing a motor task during periods of low and high psychosocial stress. Acoustic startle reflexes (ASRs) were recorded in the upper trapezius during low intensity contractions using both surface and intramuscular electromyography. Exposure to the stressor increased subjective and physiological measures of arousal (P < 0.01). The majority of participants demonstrated inhibitory ASRs, whereas a small subgroup with significantly higher trait anxiety (n = 5) demonstrated excitatory ASRs in the low stress condition. Changes in synaptic input for inhibitory ASRs were confirmed by decreases in the discharge rate of single motor units in response to the SAS. ASRs decreased in magnitude for all participants during exposure to the acute psychosocial stressor. These findings suggest that the reticular formation has predominately inhibitory effects on the human upper trapezius during an ongoing motor task and that disinhibition caused by psychosocial stress may contribute to augmentation of trapezius muscle activity. Further research is required to investigate mechanisms underlying the complex ASRs characterized by this study, particularly the phase reversal to excitatory responses observed among more anxious individuals. This study is the first to quantify stress-evoked changes in the acoustic startle reflex in the upper trapezius muscle of humans, and our findings reveal a complex pattern of inhibitory and facilitatory responses consistent with observations in nonhuman primates. We further demonstrate that psychosocial stress consistently reduces the amplitude of these responses. These findings have implications for the control of motor behaviors in response to stress. Copyright © 2017 the American Physiological Society.

Psychosocial stress alters the strength of reticulospinal input to the human upper trapezius

PubMed Central

Marker, Ryan J.; Campeau, Serge

2016-01-01

Psychosocial stress has been shown to influence several aspects of human motor control associated with the fight-or-flight response, including augmentation of upper trapezius muscle activity. Given the established role of the reticular formation in arousal, this study investigated the contribution of reticulospinal activation to trapezius muscle activity during exposure to an acute psychosocial stressor. Twenty-five healthy adults were exposed to startling acoustic stimuli (SAS) while performing a motor task during periods of low and high psychosocial stress. Acoustic startle reflexes (ASRs) were recorded in the upper trapezius during low intensity contractions using both surface and intramuscular electromyography. Exposure to the stressor increased subjective and physiological measures of arousal (P < 0.01). The majority of participants demonstrated inhibitory ASRs, whereas a small subgroup with significantly higher trait anxiety (n = 5) demonstrated excitatory ASRs in the low stress condition. Changes in synaptic input for inhibitory ASRs were confirmed by decreases in the discharge rate of single motor units in response to the SAS. ASRs decreased in magnitude for all participants during exposure to the acute psychosocial stressor. These findings suggest that the reticular formation has predominately inhibitory effects on the human upper trapezius during an ongoing motor task and that disinhibition caused by psychosocial stress may contribute to augmentation of trapezius muscle activity. Further research is required to investigate mechanisms underlying the complex ASRs characterized by this study, particularly the phase reversal to excitatory responses observed among more anxious individuals. NEW & NOTEWORTHY This study is the first to quantify stress-evoked changes in the acoustic startle reflex in the upper trapezius muscle of humans, and our findings reveal a complex pattern of inhibitory and facilitatory responses consistent with observations in nonhuman primates. We further demonstrate that psychosocial stress consistently reduces the amplitude of these responses. These findings have implications for the control of motor behaviors in response to stress. PMID:27832595

Differential startle magnitude in mice selected for high and low swim analgesia is not related to difference in nociception.

PubMed

Blaszczyk, Janusz W; Lapo, Iwona B; Werka, Tomasz; Sadowski, Bogdan

2010-01-01

The acoustic startle response (ASR) elicited by 110 dB 10-ms pulses was studied in relation to pain sensitivity in mouse lines selectively bred for high (HA) and for low (LA) swim analgesia. The magnitudes of ASR, similarly as hot-plate latencies, differed between the lines in the rank order HA is greater than unselected controls (C) greater than LA. The animals' nociception did not change after the ASR session consisting of a sequence of 20 acoustic stimuli. Morphine hydrochloride (5 and 10 mg per kg i.p.) increased hot-plate latencies in the order of HA greater than C greater than LA, and was not effective on ASR magnitude in HA as well as in C mice. In the LA line, 10 mg per kg of morphine slightly attenuated ASR, but caused only a little analgesia. We conclude that (1) the difference in ASR between the selected lines is inversely correlated with the difference in pain sensitivity; (2) the magnitude of ASR is not altered by morphine analgesia; (3) the procedure of ASR using brief acoustic pulses is not stressful enough to elicit a form of stress analgesia. The lack of a direct relationship between the readiness to startle and pain sensation may be beneficial for an animal's survival in dangerous situations. It is beneficial when the startle to a warning signal precedes defensive behaviors and it often must be effectuated in a state of decreased nociception.

Spatial hearing ability of the pigmented Guinea pig (Cavia porcellus): Minimum audible angle and spatial release from masking in azimuth.

PubMed

Greene, Nathaniel T; Anbuhl, Kelsey L; Ferber, Alexander T; DeGuzman, Marisa; Allen, Paul D; Tollin, Daniel J

2018-08-01

Despite the common use of guinea pigs in investigations of the neural mechanisms of binaural and spatial hearing, their behavioral capabilities in spatial hearing tasks have surprisingly not been thoroughly investigated. To begin to fill this void, we tested the spatial hearing of adult male guinea pigs in several experiments using a paradigm based on the prepulse inhibition (PPI) of the acoustic startle response. In the first experiment, we presented continuous broadband noise from one speaker location and switched to a second speaker location (the "prepulse") along the azimuth prior to presenting a brief, ∼110 dB SPL startle-eliciting stimulus. We found that the startle response amplitude was systematically reduced for larger changes in speaker swap angle (i.e., greater PPI), indicating that using the speaker "swap" paradigm is sufficient to assess stimulus detection of spatially separated sounds. In a second set of experiments, we swapped low- and high-pass noise across the midline to estimate their ability to utilize interaural time- and level-difference cues, respectively. The results reveal that guinea pigs can utilize both binaural cues to discriminate azimuthal sound sources. A third set of experiments examined spatial release from masking using a continuous broadband noise masker and a broadband chirp signal, both presented concurrently at various speaker locations. In general, animals displayed an increase in startle amplitude (i.e., lower PPI) when the masker was presented at speaker locations near that of the chirp signal, and reduced startle amplitudes (increased PPI) indicating lower detection thresholds when the noise was presented from more distant speaker locations. In summary, these results indicate that guinea pigs can: 1) discriminate changes in source location within a hemifield as well as across the midline, 2) discriminate sources of low- and high-pass sounds, demonstrating that they can effectively utilize both low-frequency interaural time and high-frequency level difference sound localization cues, and 3) utilize spatial release from masking to discriminate sound sources. This report confirms the guinea pig as a suitable spatial hearing model and reinforces prior estimates of guinea pig hearing ability from acoustical and physiological measurements. Copyright © 2018 Elsevier B.V. All rights reserved.

Pentadecapeptide BPC 157 attenuates chronic amphetamine-induced behavior disturbances.

PubMed

Sikiric, Predrag; Jelovac, Nikola; Jelovac-Gjeldum, Andjelka; Dodig, Goran; Staresinic, Mario; Anic, Tomislav; Zoricic, Ivan; Rak, Davor; Perovic, Darko; Aralica, Gorana; Buljat, Gojko; Prkacin, Ingrid; Lovric-Bencic, Martina; Separovic, Jadranka; Seiwerth, Sven; Rucman, Rudolf; Petek, Marijan; Turkovic, Branko; Ziger, Tihomil; Boban-Blagaic, Alenka; Bedekovic, Vlado; Tonkic, Ante; Babic, Slaven

2002-05-01

To investigate the effect of pentadecapeptide BPC 157 on chronic exposure to amphetamine in rats, particularly the changes commonly referred in chronic amphetamine studies as tolerance (lesser grade of stereotyped behavior, without increased excitability) and reverse tolerance (ie, prominent stereotyped behavior and heightened startle response upon late amphetamine challenges). After initial application (initial single dose-regimen), amphetamine (10 mg/kg,ip) was given once daily till d 5 (continuous administration-regimen), and thereafter on d 8, 16, and 46 (intermittent administration regimen). Fo r stereotyped behavior and heightened startle response the observation period was 120 min after amphetamine application, and each animal was observed for 10 s in 5 min intervals. Pentadecapeptide BPC 157 (10 microg/kg or 10 ng/k g, ip) or saline (5.0 mL/kg, ip) were given only at the beginning of the experiment, simultaneously with the initial dose of amphetamine. In relation to applied initial-single/continuous/intermittent amphetamine applications regimen, the control amphetamine rats throughout the experiment showed the changes in stereotyped behavior and heightened startle response, increment or decrement, commonly explained in chronic amphetamine studies as tolerance and reverse tolerance. After t he initial application of the amphetamine, the higher BPC 157 dosage apparently attenuated the stereotyped behavior, while the lower dosage of BPC 157 did not reach a statistical significance. Considering the forthcoming amphetamine challenges, in the rats initially treated with pentadecapeptide BPC 157, either 10 microg- or 10 ng-dose, at the time of the first application of amphetamine, the stereotyped behavior remains to be attenuated after all additional amphetamine challenges (on d 2-5, 8, 16, and 46). This attenuation was not limited to stereotyped behavior only. After the initial application of the amphetamine the heighten ed startle response was also apparently mitigated in rats receiving the BPC 157 dosage, either higher or lower. Later, confronted with the forthcoming amphetamine challenges, they showed apparently less abnormal excitability at all tested points. In summary, gastric pentadecapeptide BPC 157 (ie, both microg- and ng-BPC 157 regimens) attenuated chronic amphetamine disturbances. This effect was present throughout the observation period at a statistically significant level. Therefore, it seems that this gastric pentadecapeptide BPC 157 has a modulatory effect on dopamine system, and it could be used in chronic amphetamine disturbances.

Intrathecal fentanyl abolishes the exaggerated blood pressure response to cycling in hypertensive men

PubMed Central

Barbosa, Thales C.; Vianna, Lauro C.; Fernandes, Igor A.; Prodel, Eliza; Rocha, Helena N. M.; Garcia, Vinicius P.; Rocha, Natalia G.; Secher, Niels H.

2016-01-01

Key points The increase in blood pressure observed during physical activities is exaggerated in patients with hypertension, exposing them to a higher cardiovascular risk.Neural signals from the skeletal muscles appear to be overactive, resulting in this abnormal response in hypertensive patients.In the present study, we tested whether the attenuation of these neural signals in hypertensive patients could normalize their abnormal increase in blood pressure during physical activity.Attenuation of the neural signals from the leg muscles with intrathecal fentanyl injection reduced the blood pressure of hypertensive men during cycling exercise to a level comparable to that of normotensive men.Skeletal muscle afferent overactivity causes the abnormal cardiovascular response to exercise and was reverted in this experimental model, appearing as potential target for treatment. Abstract Hypertensive patients present an exaggerated increase in blood pressure and an elevated cardiovascular risk during exercise. Although controversial, human studies suggest that group III and IV skeletal muscle afferents might contribute to this abnormal response. In the present study, we investigated whether attenuation of the group III and IV muscle afferent signal of hypertensive men eliminates the exaggerated increase in blood pressure occurring during exercise. Eight hypertensive men performed two sessions of 5 min of cycling exercise at 40 W. Between sessions, the subjects were provided with a lumbar intrathecal injection of fentanyl, a μ‐opioid receptor agonist, aiming to attenuate the central projection of opioid‐sensitive group III and IV muscle afferent nerves. The cardiovascular response to exercise of these subjects was compared with that of six normotensive men. During cycling, the hypertensive group demonstrated an exaggerated increase in blood pressure compared to the normotensive group (mean ± SEM: +17 ± 3 vs. +8 ± 1 mmHg, respectively; P < 0.05), whereas the increase in heart rate, stroke volume, cardiac output and vascular conductance was similar (P > 0.05). Fentanyl inhibited the blood pressure response to exercise in the hypertensive group (+11 ± 2 mmHg) to a level comparable to that of the normotensive group (P > 0.05). Moreover, fentanyl increased the responses of vascular conductance and stroke volume to exercise (P < 0.05), whereas the heart rate response was attenuated (P < 0.05) and the cardiac output response was maintained (P > 0.05). The results of the present study show that attenuation of the exercise pressor reflex normalizes the blood pressure response to cycling exercise in hypertensive individuals. PMID:26659384

A Day of Great Illumination: B. F. Skinner's Discovery of Shaping

ERIC Educational Resources Information Center

Peterson, Gail B.

2004-01-01

Despite the seminal studies of response differentiation by the method of successive approximation detailed in chapter 8 of "The Behavior of Organisms" (1938), B. F. Skinner never actually shaped an operant response by hand until a memorable incident of startling serendipity on the top floor of a flour mill in Minneapolis in 1943. That occasion…

A model for the development of mothers' perceived vulnerability of preterm infants.

PubMed

Horwitz, Sarah McCue; Storfer-Isser, Amy; Kerker, Bonnie D; Lilo, Emily; Leibovitz, Ann; St John, Nick; Shaw, Richard J

2015-06-01

Some mothers of preterm infants continue to view them as vulnerable after their health has improved. These exaggerated perceptions of vulnerability lead to poor parent-child interactions and, subsequently, to adverse child outcomes. However, there is no theoretical model to explain why these exaggerated perceptions develop in only some mother-child dyads. Data for this study come from a randomized trial of an intervention to reduce distress in mothers of preterm infants. A total of 105 mothers older than 18 years of infants aged 25-34 weeks, weighing >600 g and with clinically significant anxiety, depression, or trauma symptoms, were recruited and randomized. Women were assessed at baseline, after intervention, and at 6 months after birth. The outcome for these analyses was perceptions of infant vulnerability as measured by the Vulnerable Baby Scale (VBS) at 6 months after birth. A theoretical model developed from the extant literature was tested using the MacArthur Mediator-Moderator Approach. A dysfunctional coping style, high depression, anxiety, or trauma symptoms in response to the preterm birth, and low social support were related to 6-month VBS scores. Maternal response to trauma was directly related to VBS, and an important precursor of maternal response to trauma was a dysfunctional coping style. This model suggests that maternal responses to trauma are critical in the formation of exaggerated perceptions of vulnerability as are dysfunctional coping styles and low social support. Women with these characteristics should be targeted for intervention to prevent poor parenting practices that result from exaggerated perceptions of vulnerability.

Oxidative stress exaggerates skeletal muscle contraction-evoked reflex sympathoexcitation in rats with hypertension induced by angiotensin II.

PubMed

Koba, Satoshi; Watanabe, Ryosuke; Kano, Naoko; Watanabe, Tatsuo

2013-01-01

Muscle contraction stimulates thin fiber muscle afferents and evokes reflex sympathoexcitation. In hypertension, this reflex is exaggerated. ANG II, which is elevated in hypertension, has been reported to trigger the production of superoxide and other reactive oxygen species. In the present study, we tested the hypothesis that increased ANG II in hypertension exaggerates skeletal muscle contraction-evoked reflex sympathoexcitation by inducing oxidative stress in the muscle. In rats, subcutaneous infusion of ANG II at 450 ng·kg(-1)·min(-1) for 14 days significantly (P < 0.05) elevated blood pressure compared with sham-operated (sham) rats. Electrically induced 30-s hindlimb muscle contraction in decerebrate rats with hypertension evoked larger renal sympathoexcitatory and pressor responses [+1,173 ± 212 arbitrary units (AU) and +35 ± 5 mmHg, n = 10] compared with sham normotensive rats (+419 ± 103 AU and +13 ± 2 mmHg, n = 11). Tempol, a SOD mimetic, injected intra-arterially into the hindlimb circulation significantly reduced responses in hypertensive rats, whereas this compound had no effect on responses in sham rats. Tiron, another SOD mimetic, also significantly reduced reflex renal sympathetic and pressor responses in a subset of hypertensive rats (n = 10). Generation of muscle superoxide, as evaluated by dihydroethidium staining, was increased in hypertensive rats. RT-PCR and immunoblot experiments showed that mRNA and protein for gp91(phox), a NADPH oxidase subunit, in skeletal muscle tissue were upregulated in hypertensive rats. Taken together, hese results suggest that increased ANG II in hypertension induces oxidative stress in skeletal muscle, thereby exaggerating the muscle reflex.

Cardiovascular reactivity patterns and pathways to hypertension: a multivariate cluster analysis.

PubMed

Brindle, R C; Ginty, A T; Jones, A; Phillips, A C; Roseboom, T J; Carroll, D; Painter, R C; de Rooij, S R

2016-12-01

Substantial evidence links exaggerated mental stress induced blood pressure reactivity to future hypertension, but the results for heart rate reactivity are less clear. For this reason multivariate cluster analysis was carried out to examine the relationship between heart rate and blood pressure reactivity patterns and hypertension in a large prospective cohort (age range 55-60 years). Four clusters emerged with statistically different systolic and diastolic blood pressure and heart rate reactivity patterns. Cluster 1 was characterised by a relatively exaggerated blood pressure and heart rate response while the blood pressure and heart rate responses of cluster 2 were relatively modest and in line with the sample mean. Cluster 3 was characterised by blunted cardiovascular stress reactivity across all variables and cluster 4, by an exaggerated blood pressure response and modest heart rate response. Membership to cluster 4 conferred an increased risk of hypertension at 5-year follow-up (hazard ratio=2.98 (95% CI: 1.50-5.90), P<0.01) that survived adjustment for a host of potential confounding variables. These results suggest that the cardiac reactivity plays a potentially important role in the link between blood pressure reactivity and hypertension and support the use of multivariate approaches to stress psychophysiology.

Negative Self-Focused Cognitions Mediate the Effect of Trait Social Anxiety on State Anxiety

PubMed Central

Schulz, Stefan M.; Alpers, Georg W.; Hofmann, Stefan G.

2008-01-01

The cognitive model of social anxiety predicts that negative self-focused cognitions increase anxiety when anticipating social threat. To test this prediction, 36 individuals were asked to anticipate and perform a public speaking task. During anticipation, negative self-focused cognitions or relaxation were experimentally induced while self-reported anxiety, autonomic arousal (heart rate, heart rate variability, skin conductance level), and acoustic eye-blink startle response were assessed. As predicted, negative self-focused cognitions mediated the effects of trait social anxiety on self-reported anxiety and heart rate variability during negative anticipation. Furthermore, trait social anxiety predicted increased startle amplitudes. These findings support a central assumption of the cognitive model of social anxiety. PMID:18321469

Effects of social defeat on sleep and behaviour: importance of the confrontational behaviour.

PubMed

Kinn Rød, Anne Marie; Murison, Robert; Mrdalj, Jelena; Milde, Anne Marita; Jellestad, Finn Konow; Øvernes, Leif Arvid; Grønli, Janne

2014-03-29

We studied the short- and long-term effects of a double social defeat (SD) on sleep parameters, EEG power, behaviour in the open field emergence test, corticosterone responsiveness, and acoustic startle responses. Pre-stress levels of corticosterone were assessed before all rats were surgically implanted with telemetric transmitters for sleep recording, and allowed 3weeks of recovery. Rats in the SD group (n=10) were exposed to 1hour SD on two consecutive days, while control rats (n=10) were left undisturbed. Telemetric sleep recordings were performed before SD (day -1), day 1 post SD, and once weekly for 3weeks thereafter. The open field emergence test was performed on day 9 and weekly for 2weeks thereafter. Blood samples for measures of corticosterone responsiveness were drawn after the last emergence test (day 23). Acoustic startle responses were tested on day 24 post SD. Overall, SD rats as a group were not affected by the social conflict. Effects of SD seemed, however, to vary according to the behaviours that the intruder displayed during the social confrontation with the resident. Compared to those SD rats showing quick submission (SDS, n=5), SD rats fighting the resident during one or both SD confrontations before defeat (SDF, n=5) showed more fragmented slow wave sleep, both in SWS1 and SWS2. They also showed longer latency to leave the start box and spent less time in the open field arena compared to SDS rats. In the startle test, SDF rats failed to show response decrement at the lowest sound level. Our results indicate that how animals behave during a social confrontation is more important than exposure to the SD procedure itself, and that rapid submission during a social confrontation might be more adaptive than fighting back. Copyright © 2014 Elsevier Inc. All rights reserved.

Gap-induced reductions of evoked potentials in the auditory cortex: A possible objective marker for the presence of tinnitus in animals.

PubMed

Berger, Joel I; Owen, William; Wilson, Caroline A; Hockley, Adam; Coomber, Ben; Palmer, Alan R; Wallace, Mark N

2018-01-15

Animal models of tinnitus are essential for determining the underlying mechanisms and testing pharmacotherapies. However, there is doubt over the validity of current behavioural methods for detecting tinnitus. Here, we applied a stimulus paradigm widely used in a behavioural test (gap-induced inhibition of the acoustic startle reflex GPIAS) whilst recording from the auditory cortex, and showed neural response changes that mirror those found in the behavioural tests. We implanted guinea pigs (GPs) with electrocorticographic (ECoG) arrays and recorded baseline auditory cortical responses to a startling stimulus. When a gap was inserted in otherwise continuous background noise prior to the startling stimulus, there was a clear reduction in the subsequent evoked response (termed gap-induced reductions in evoked potentials; GIREP), suggestive of a neural analogue of the GPIAS test. We then unilaterally exposed guinea pigs to narrowband noise (left ear; 8-10 kHz; 1 h) at one of two different sound levels - either 105 dB SPL or 120 dB SPL - and recorded the same responses seven-to-ten weeks following the noise exposure. Significant deficits in GIREP were observed for all areas of the auditory cortex (AC) in the 120 dB-exposed GPs, but not in the 105 dB-exposed GPs. These deficits could not simply be accounted for by changes in response amplitudes. Furthermore, in the contralateral (right) caudal AC we observed a significant increase in evoked potential amplitudes across narrowband background frequencies in both 105 dB and 120 dB-exposed GPs. Taken in the context of the large body of literature that has used the behavioural test as a demonstration of the presence of tinnitus, these results are suggestive of objective neural correlates of the presence of noise-induced tinnitus and hyperacusis. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Role of cyclooxygenase in the vascular responses to extremity cooling in Caucasian and African males.

PubMed

Maley, Matthew J; House, James R; Tipton, Michael J; Eglin, Clare M

2017-07-01

What is the central question of this study? Compared with Caucasians, African individuals are more susceptible to non-freezing cold injury and experience greater cutaneous vasoconstriction and cooler finger skin temperatures upon hand cooling. We investigated whether the enzyme cyclooxygenase is, in part, responsible for the exaggerated response to local cooling. What is the main finding and its importance? During local hand cooling, individuals of African descent experienced significantly lower finger skin blood flow and skin temperature compared with Caucasians irrespective of cyclooxygenase inhibition. These data suggest that in young African males the cyclooxygenase pathway appears not to be the primary reason for the increased susceptibility to non-freezing cold injury. Individuals of African descent (AFD) are more susceptible to non-freezing cold injury (NFCI) and experience an exaggerated cutaneous vasoconstrictor response to hand cooling compared with Caucasians (CAU). Using a placebo-controlled, cross-over design, this study tested the hypothesis that cyclooxygenase (COX) may, in part, be responsible for the exaggerated vasoconstrictor response to local cooling in AFD. Twelve AFD and 12 CAU young healthy men completed foot cooling and hand cooling (separately, in 8°C water for 30 min) with spontaneous rewarming in 30°C air after placebo or aspirin (COX inhibition) treatment. Skin blood flow, expressed as cutaneous vascular conductance (as flux per millimetre of mercury), and skin temperature were measured throughout. Irrespective of COX inhibition, the responses to foot cooling, but not hand cooling, were similar between ethnicities. Specifically, during hand cooling after placebo, AFD experienced a lower minimal skin blood flow [mean (SD): 0.5 (0.1) versus 0.8 (0.2) flux mmHg -1 , P < 0.001] and a lower minimal finger skin temperature [9.5 (1.4) versus 10.7 (1.3)°C, P = 0.039] compared with CAU. During spontaneous rewarming, average skin blood flow was also lower in AFD than in CAU [2.8 (1.6) versus 4.3 (1.0) flux mmHg -1 , P < 0.001]. These data provide further support that AFD experience an exaggerated response to hand cooling on reflection this appears to overstate findings; however, the results demonstrate that the COX pathway is not the primary reason for the exaggerated responses in AFD and increased susceptibility to NFCI. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

Sensorimotor Gating in Depressed and Euthymic Patients with Bipolar Disorder: Analysis on Prepulse Inhibition of Acoustic Startle Response Stratified by Gender and State.

PubMed

Matsuo, Junko; Ota, Miho; Hidese, Shinsuke; Teraishi, Toshiya; Hori, Hiroaki; Ishida, Ikki; Hiraishi, Moeko; Kunugi, Hiroshi

2018-01-01

Prepulse inhibition (PPI) of the acoustic startle reflex is an operational measure of sensorimotor gating. The findings on PPI deficits in bipolar disorder (BD) are inconsistent among studies due to various confounding factors such as gender. This study aimed to assess sensorimotor gating deficits in patients with BD stratified by gender and state (depressed/euthymic), and to explore related clinical variables. Subjects were 106 non-manic BD patients (26 BD I and 80 BD II; 63 with depression and 43 euthymic) and 232 age-, gender-, and ethnicity-matched (Japanese) healthy controls. Depression severity was assessed using the Hamilton Depression Rating Scale-21. The electromyographic activity of the orbicularis oculi muscle was measured by a computerized startle reflex test unit. Startle magnitude, habituation, and PPI were compared among the three clinical groups: depressed BD, euthymic BD, and healthy controls. In a second analysis, patients were divided into four groups using the quartile PPI levels of controls of each gender, and a ratio of the low-PPI group (<1st quartile of controls) was compared. Effects of psychosis and medication status were examined by the Mann-Whitney U test. Clinical correlates such as medication dosage and depression severity with startle measurements were examined by Spearman's correlation. Male patients with depression, but not euthymic male patients, showed significantly lower PPI at a prepulse of 86 dB and 120 ms lead interval than did male controls. More than half of the male patients with depression showed low-PPI. In contrast, PPI in female patients did not differ from that in female controls in either the depressed or euthymic state. Female patients with active psychosis showed significantly lower PPI than those without psychosis. Female patients on typical antipsychotics had significantly lower PPI, than those without such medication. PPI showed a significant positive correlation with lamotrigine dosage in male patients and lithium dosage in female patients. These findings suggest that sensorimotor gating is impaired in male BD patients with depression. However, we obtained no evidence for such abnormalities in female BD patients except for those with current psychosis. The observed associations between medication and startle measurements warrant further investigation.

Abnormal Neurocirculatory Control During Exercise in Humans with Chronic Renal Failure

PubMed Central

Park, Jeanie; Middlekauff, Holly R.

2014-01-01

Abnormal neurocirculatory control during exercise is one important mechanism leading to exercise intolerance in patients with both end-stage renal disease (ESRD) and earlier stages of chronic kidney disease (CKD). This review will provide an overview of mechanisms underlying abnormal neurocirculatory and hemodynamic responses to exercise in patients with kidney disease. Recent studies have shown that ESRD and CKD patients have an exaggerated increase in blood pressure (BP) during both isometric and rhythmic exercise. Subsequent studies examining the role of the exercise pressor reflex in the augmented pressor response revealed that muscle sympathetic nerve activity (MSNA) was not augmented during exercise in these patients, and metaboreflex-mediated increases in MSNA were blunted, while mechanoreflex-mediated increases were preserved under basal conditions. However, normalizing the augmented BP response during exercise via infusion of nitroprusside (NTP), and thereby equalizing baroreflex-mediated suppression of MSNA, an important modulator of the final hemodynamic response to exercise, revealed that CKD patients had an exaggerated increase in MSNA during isometric and rhythmic exercise. In addition, mechanoreflex-mediated control was augmented, and metaboreceptor blunting was no longer apparent in CKD patients with baroreflex normalization. Factors leading to mechanoreceptor sensitization, and other mechanisms underlying the exaggerated exercise pressor response, such as impaired functional sympatholysis, should be investigated in future studies. PMID:25458430

Physiological and neural correlates of worry and rumination: Support for the contrast avoidance model of worry.

PubMed

Steinfurth, Elisa C K; Alius, Manuela G; Wendt, Julia; Hamm, Alfons O

2017-02-01

The current experiments tested neural and physiological correlates of worry and rumination in comparison to thinking about neutral events. According to the avoidance model-stating that worry is a strategy to reduce intense emotions-physiological and neurobiological activity during worried thinking should not differ from activation during neutral thinking. According to the contrast avoidance model-stating that worry is a strategy to reduce abrupt shifts of emotions-activity should be increased. To test these competing models, we induced worry and neutral thinking in healthy participants using personal topics. A rumination condition was added to investigate the specificity of changes induced by the mental process. Two experiments were conducted assessing the effects on different response levels: (1) neural activation using fMRI, and (2) physiological response mobilization using startle and autonomic measures. During worry, participants showed a potentiated startle response and BOLD activity indicative of emotional network activation. These data partly support the contrast avoidance model of worry. Both mental processes showed elevated activity in a common network referred to as default network indicating self-referential activity. © 2016 Society for Psychophysiological Research.

Exaggerated response to mild stress in rats fed high-fat diet.

PubMed

Legendre, Ariadne; Harris, Ruth B S

2006-11-01

It has been suggested that high-fat (HF) diet exaggerates the stress-induced release of glucocorticoids due to activation of the hypothalamic-pituitary-adrenal (HPA) axis. In an initial experiment, in which rats were fed HF diet for 4 days, we found that HF-fed controls stopped gaining weight, indicating that they were hyperresponsive to the mild stress of tail bleeding but responded the same as low-fat (LF)-fed rats to the more severe stress of restraint. A second experiment confirmed these results when rats fed a HF diet for 4 days showed an exaggerated corticosterone release in response to an intraperitoneal injection of saline and movement to a novel cage, compared with LF-fed rats. Experiment 3 tested the same parameters as experiment 2 but interchanged the diets. This allowed us to differentiate between the effects of the dietary fat and the novelty of the diet. Additionally, this experiment determined whether hyperresponsiveness to mild stress in HF-fed rats was sustained during a prolonged exposure to diet. The results confirmed that a HF diet, not novelty, exaggerated the endocrine stress response after 9 days on the diet but that the effect was no longer present after 23 days on the diet. The hyperresponsiveness of the HPA axis in HF-fed rats is similar to that observed in animals that have been exposed to a significant chronic or acute stress, suggesting that the HF diet may initially be perceived as a stressor.

Influence of emotional states on inhibitory gating: Animals models to clinical neurophysiology

PubMed Central

Cromwell, Howard C.; Atchley, Rachel M.

2014-01-01

Integrating research efforts using a cross-domain approach could redefine traditional constructs used in behavioral and clinical neuroscience by demonstrating that behavior and mental processes arise not from functional isolation but from integration. Our research group has been examining the interface between cognitive and emotional processes by studying inhibitory gating. Inhibitory gating can be measured via changes in behavior or neural signal processing. Sensorimotor gating of the startle response is a well-used measure. To study how emotion and cognition interact during startle modulation in the animal model, we examined ultrasonic vocalization (USV) emissions during acoustic startle and prepulse inhibition. We found high rates of USV emission during the sensorimotor gating paradigm and revealed links between prepulse inhibition (PPI) and USV emission that could reflect emotional and cognitive influences. Measuring inhibitory gating as P50 event-related potential suppression has also revealed possible connections between emotional states and cognitive processes. We have examined the single unit responses during the traditional gating paradigm and found that acute and chronic stress can alter gating of neural signals in regions such as amygdala, striatum and medial prefrontal cortex. Our findings point to the need for more cross-domain research on how shifting states of emotion can impact basic mechanisms of information processing. Results could inform clinical work with the development of tools that depend upon cross-domain communication, and enable a better understanding and evaluation of psychological impairment. PMID:24861710

DISTINCT BEHAVIORAL PHENOTYPES IN MALE MICE LACKING THE THYROID HORMONE RECEPTOR α1 OR β ISOFORMS

PubMed Central

Vasudevan, Nandini; Morgan, Maria; Pfaff, Donald; Ogawa, Sonoko

2013-01-01

Thyroid hormones influence both neuronal development and anxiety via the thyroid hormone receptors (TRs). The TRs are encoded by two different genes, TRα and TRβ. The loss of TRα1 is implicated in increased anxiety in males, possibly via a hippocampal increase in GABAergic activity. We compared both social behaviors and two underlying and related non-social behaviors, state anxiety and responses to acoustic and tactile startle in the gonadally intact TRα1 knockout (α1KO) and TRβ (βKO) male mice to their wild-type counterparts. For the first time, we show an opposing effect of the two TR isoforms, TRα1 and TRβ, in the regulation of state anxiety, with α1 knockout animals (α1KO) showing higher levels of anxiety and βKO males showing less anxiety compared to respective wild-type mice. At odds with the increased anxiety in non-social environments, α1KO males also show lower levels of responsiveness to acoustic and tactile startle stimuli. Consistent with the data that T4 is inhibitory to lordosis in female mice, we show subtly increased sex behavior in α1KO male mice. These behaviors support the idea that TRα1 could be inhibitory to ERα driven transcription that ultimately impacts ERα driven behaviors such as lordosis. The behavioral phenotypes point to novel roles for the TRs, particularly in non-social behaviors such as state anxiety and startle. PMID:23567476

Exercise-induced hypertension among healthy firefighters-a comparison between two different definitions.

PubMed

Leiba, Adi; Baur, Dorothee M; Kales, Stefanos N

2013-01-01

Different studies have yielded conflicting results regarding the association of hypertensive response to exercise and cardiovascular morbidity. We compared two different definitions of exaggerated hypertensive response to exercise and their association with cardio-respiratory fitness in a population of healthy firefighters. We examined blood pressure response to exercise in 720 normotensive male career firefighters. Fitness was measured as peak metabolic equivalent tasks (METs) achieved during maximal exercise treadmill tests. Abnormal hypertensive response was defined either as systolic blood pressure ≥ 200 mm Hg; or alternatively, as responses falling in the upper tertile of blood pressure change from rest to exertion, divided by the maximal workload achieved. Using the simple definition of a 200 mm Hg cutoff at peak exercise less fit individuals (METs ≤ 12) were protected from an exaggerated hypertensive response (OR 0.45, 95%CI 0.30-0.67). However, using the definition of exercise-induced hypertension that corrects for maximal workload, less fit firefighters had almost twice the risk (OR 1.8, 95%CI 1.3-2.47). Blood pressure change corrected for maximal workload is better correlated with cardiorespiratory fitness. Systolic blood pressure elevation during peak exercise likely represents an adaptive response, whereas elevation out of proportion to the maximal workload may indicate insufficient vasodilation and a maladaptive response. Prospective studies are needed to best define exaggerated blood pressure response to exercise. Copyright © 2013 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Alarm pheromone is detected by the vomeronasal organ in male rats.

PubMed

Kiyokawa, Yasushi; Kodama, Yuka; Kubota, Takahiro; Takeuchi, Yukari; Mori, Yuji

2013-10-01

It is widely known that a stressed animal releases specific pheromones, possibly for alarming nearby conspecifics. We previously investigated an alarm pheromone in male rats and found that this alarm pheromone evokes several responses, including increases in the defensive and risk assessment behaviors in a modified open-field test, and enhancement of the acoustic startle reflex. However, the role of the vomeronasal organ in these pheromone effects remains unclear. To clarify this point, vomeronasal organ-excising or sham surgeries were performed in male rats for use in 2 experimental models, after which they were exposed to alarm pheromone. We found that the vomeronasal organ-excising surgery blocked the effects of this alarm pheromone in both the modified open-field test and acoustic startle reflex test. In addition, the results of habituation/dishabituation test and soybean agglutinin binding to the accessory olfactory bulb suggested that the vomeronasal organ-excising surgery completely ablated the vomeronasal organ while preserving the functioning of the main olfactory system. From the above results, we showed that the vomeronasal organ plays an important role in alarm pheromone effects in the modified open-field test and acoustic startle reflex test.

Clarifying the Role of Defensive Reactivity Deficits in Psychopathy and Antisocial Personality Using Startle Reflex Methodology

PubMed Central

Vaidyanathan, Uma; Hall, Jason R.; Patrick, Christopher J.; Bernat, Edward M.

2010-01-01

Prior research has demonstrated deficits in defensive reactivity (indexed by potentiation of the startle blink reflex) in psychopathic individuals. However, the basis of this association remains unclear, as diagnostic criteria for psychopathy encompass two distinct phenotypic components that may reflect differing neurobiological mechanisms – an affective-interpersonal component, and an antisocial deviance component. Likewise, the role of defensive response deficits in antisocial personality disorder (APD), a related but distinct syndrome, remains to be clarified. The current study examined affective priming deficits in relation to factors of psychopathy and symptoms of APD using startle reflex methods in 108 adult male prisoners. Deficits in blink reflex potentiation during aversive picture viewing were found in relation to the affective-interpersonal (Factor 1) component of psychopathy, and to a lesser extent in relation to the antisocial deviance (Factor 2) component of psychopathy and symptoms of APD—but only as a function of their overlap with affective-interpersonal features of psychopathy. These findings provide clear evidence that deficits in defensive reactivity are linked specifically to the affective-interpersonal features of psychopathy, and not the antisocial deviance features represented most strongly in APD. PMID:20973594

Developmental treatment with difluoromethylornithine has few effects on behavior or body weight in Sprague-Dawley rats.

PubMed

Ferguson, Sherry A; Cada, Amy M

2004-01-01

Developmental difluoromethylornithine (DFMO) treatment reduces cerebellar weight [Neuroscience 17 (1986) 399, Neurotoxicol. Teratol. 22 (2000) 415, Behav. Brain Res. 126 (2001) 135], but the functional alterations resulting from this have been little investigated. Here, Sprague-Dawley rats were subcutaneously injected with 500 mg/kg DFMO on postnatal days (PNDs) 5-12 and a comprehensive set of behavioral assessments measured early developmental behaviors (righting reflex, negative geotaxis), motor coordination, acoustic startle, short- and long-term activity, social behaviors, anxiety, and spatial learning and memory. DFMO treatment appeared to cause a decreased latency to perform the negative geotaxis behavior on PNDs 8-10 and increased latency to hang by the forelimbs on PNDs 12-14. Our previous study did not indicate similar effects, but age at testing differed between the two studies. DFMO treatment caused a decreased latency to maximum acoustic startle response in both the acoustic startle paradigm and in the pulse-alone trials of the prepulse inhibition test. This DFMO treatment paradigm induced a 10% decrease in adult cerebellar weight [Behav. Brain Res. 126 (2001) 135], but the results here imply that such developmental stunting has few functional alterations.

Acute Hydrocortisone Treatment Increases Anxiety but Not Fear in Healthy Volunteers: A Fear-Potentiated Startle Study

PubMed Central

Grillon, Christian; Heller, Randi; Hirschhorn, Elizabeth; Kling, Mitchel A.; Pine, Daniel S.; Schulkin, Jay; Vythilingam, Meena

2011-01-01

Background The debilitating effects of chronic glucocorticoids excess are well-known, but comparatively little is understood about the role of acute cortisol. Indirect evidence in rodents suggests that acute cortisone could selectively increase some forms of long-duration aversive states, such as “anxiety,” but not relatively similar, briefer aversive states, such as “fear.” However, no prior experimental studies in humans consider the unique effects of cortisol on anxiety and fear, using well-validated methods for eliciting these two similar but dissociable aversive states. The current study examines these effects, as instantiated with short- and long-duration threats. Methods Healthy volunteers (n = 18) received placebo or a low (20 mg) or a high (60 mg) dose of hydrocortisone in a double-blind crossover design. Subjects were exposed repeatedly to three 150-sec duration conditions: no shock; predictable shocks, in which shocks were signaled by a short-duration threat cue; and unpredictable shocks. Aversive states were indexed by acoustic startle. Fear was operationally defined as the increase in startle reactivity during the threat cue in the predictable condition (fear-potentiated startle). Anxiety was operationally defined as the increase in baseline startle from the no shock to the two threat conditions (anxiety-potentiated startle). Results Hydrocortisone affected neither baseline nor short-duration, fear-potentiated startle but increased long-duration anxiety-potentiated startle. Conclusions These results suggest that hydrocortisone administration in humans selectively increases anxiety but not fear. Possible mechanisms implicated are discussed in light of prior data in rodents. Specifically, hydrocortisone might increase anxiety via sensitization of corticotrophin-releasing hormones in the bed nucleus of the stria terminalis. PMID:21277566

Diagnostic Value of Electrocardiogram in Predicting Exaggerated Blood Pressure Response to Exercise Stress Testing.

PubMed

Eshraghi, Ali; Ebdali, Reyhaneh Takalloo; Sajjadi, Seyed Sajed; Golnezhad, Reza

2016-08-01

It is believed that an exaggerated blood pressure response (EBPR) to exercise stress test is associated with a higher risk of cardiovascular events. It is also assumed that QT dispersion (QT-d), which was originally proposed to measure the spatial dispersion of ventricular recovery times, may have a relationship to cardiovascular events. The objective of this study was to examine the difference of changes in QT-d, Maxi-QT, Mini-QT, and QT-c (corrected QT interval) of the electrocardiogram in two groups of patients with exaggerated blood pressure responses (EBPR group) and normal responses (control group) to exercise testing. Also, the diagnostic value of each of these criteria in the prediction of EBPR was studied. This cross-sectional study was conducted from May 2015 to February 2016 on patients suspected of coronary artery disease (CAD) undergoing exercise testing who had been referred to Ghaem and Imam Reza hospitals in Mashhad (Iran). All patients underwent a treadmill exercise test with the 12-lead ECG, which was optically scanned and digitized for analysis of QT-d, QT max, and QT min. Patients were divided into two groups of normal and EBPR to exercise testing. QT changes of ECG were compared between the two groups, and the diagnostic accuracy of QT variables for prediction of EBPR to exercise testing was studied. A multiple linear regression analysis (MLR), Pearson Chi-qquare, independent samples t-test, and receiver operating characteristic (ROC) curve were used as statistical methods in IBM SPSS version 19. Sixty patients (55% male) with a mean age of 50.48 ± 10.89 years were studied in two groups of normal (n=30) and exaggerated blood pressure response (n=30) to exercise testing. Maximum QT and QT dispersion were statistically different in individuals' exaggerated blood pressure response to exercise stress test (p < 0.05). The logistic regression analysis revealed that none of our parameters predicted the EBPR. The ROC curve showed that 50 and 345 milliseconds for QT dispersion and Maxi-QT were the optimal cut-off points for the prediction of EBPR. It seems that Maxi-QT and QT-d may be predictors of EBPR during exercise testing. Also, a significant difference in maxi-QT and QT-d was observed between two groups of patients with normal and EBPR during the exercise testing.

Trace Eyeblink Conditioning in Mice Is Dependent upon the Dorsal Medial Prefrontal Cortex, Cerebellum, and Amygdala: Behavioral Characterization and Functional Circuitry1,2,3

PubMed Central

Taylor, William; Kalmbach, Brian; Desai, Niraj S.

2015-01-01

Abstract Trace eyeblink conditioning is useful for studying the interaction of multiple brain areas in learning and memory. The goal of the current work was to determine whether trace eyeblink conditioning could be established in a mouse model in the absence of elicited startle responses and the brain circuitry that supports this learning. We show here that mice can acquire trace conditioned responses (tCRs) devoid of startle while head-restrained and permitted to freely run on a wheel. Most mice (75%) could learn with a trace interval of 250 ms. Because tCRs were not contaminated with startle-associated components, we were able to document the development and timing of tCRs in mice, as well as their long-term retention (at 7 and 14 d) and flexible expression (extinction and reacquisition). To identify the circuitry involved, we made restricted lesions of the medial prefrontal cortex (mPFC) and found that learning was prevented. Furthermore, inactivation of the cerebellum with muscimol completely abolished tCRs, demonstrating that learned responses were driven by the cerebellum. Finally, inactivation of the mPFC and amygdala in trained animals nearly abolished tCRs. Anatomical data from these critical regions showed that mPFC and amygdala both project to the rostral basilar pons and overlap with eyelid-associated pontocerebellar neurons. The data provide the first report of trace eyeblink conditioning in mice in which tCRs were driven by the cerebellum and required a localized region of mPFC for acquisition. The data further reveal a specific role for the amygdala as providing a conditioned stimulus-associated input to the cerebellum. PMID:26464998

Behavioural characterization of vitamin D receptor knockout mice.

PubMed

Burne, Thomas H J; McGrath, John J; Eyles, Darryl W; Mackay-Sim, Alan

2005-02-28

Vitamin D (calcitriol) is a nuclear transcription regulator acting via a nuclear hormone receptor (VDR). In addition to its role in the regulation of calcium and phosphate homeostasis and in bone formation, Vitamin D is also thought to be involved in brain function. The aim of this study was to behaviourally phenotype VDR knockout mice. We characterized the behaviour of VDR null mutant mice and wildtype littermate controls by subjecting them to a range of tests including a primary behavioural screen (using the SHIRPA protocol), rotarod, gait analysis, Y-maze, marble burying test, bedding test, holeboard test, elevated plus maze, open field test and prepulse inhibition of the acoustic startle response. There were no effects of genotype on most of the scores from the SHIRPA protocol except that VDR -/- mice had alopecia, were shorter and weighed less than VDR +/+ mice. VDR -/- mice had a shorter gait as well as impairments on the rotarod, in the bedding test and impaired habituation in both the open field and on the acoustic startle response. The VDR -/- mice had normal acoustic startle responses but had impaired PPI at long (256 ms) but not short (64 ms) prepulse to pulse intervals. The VDR -/- mice were less active in the open field and buried fewer marbles in the marble burying test. However, there were no differences in the time spent on the open arms of the elevated plus maze or in working memory as assessed by repeat arm entries on the Y-maze. Therefore, it appears that VDR -/- mice have muscular and motor impairments that significantly affects locomotor behaviour but seemingly no impairments in cognition as indicated by exploration, working memory or anxiety.

Variability in response to nicotine in the LSxSS RI strains: potential role of polymorphisms in alpha4 and alpha6 nicotinic receptor genes.

PubMed

Tritto, Theresa; Stitzel, Jerry A; Marks, Michael J; Romm, Elena; Collins, Allan C

2002-04-01

Several studies have shown that genetic factors influence the effects of nicotine on respiration, acoustic startle, Y-maze crosses and rears, heart rate and body temperature in the mouse. Recently, we identified restriction fragment length polymorphisms (RFLPs) associated with the alpha4 (Chrna4) and alpha6 (Chrna6) nicotinic cholinergic receptor genes in the recombinant inbred (RI) strains derived from the Long-Sleep (LS) and Short-Sleep (SS) mouse lines. The alpha4 polymorphism has been identified as a point-mutation at position 529 (threonine to alanine) and the alpha6 polymorphism has not yet been identified. The studies described here evaluated the potential role of these polymorphisms in regulating sensitivity to nicotine by constructing dose-response curves for the effects of nicotine on six responses in the LSxSS RI strains. The results obtained suggest that both of the polymorphisms may play a role in regulating variability in sensitivity to nicotine. Those RI strains carrying the LS-like alpha4 RFLP were significantly more sensitive to the effects of nicotine on Y-maze crosses and rears, temperature and respiration and were less sensitive to the effects of nicotine on acoustic startle than those strains carrying the SS-like alpha4 RFLP. Those RI strains carrying the LS-like alpha6 RFLP were more sensitive to the effects of nicotine on respiration and acoustic startle, and less sensitive to the effects of nicotine on Y-maze crosses than those strains carrying the SS-like alpha6 RFLP. These results suggest that genetically determined differences in sensitivity to nicotine may be explained, in part, by variability associated with at least two of the neuronal nicotinic receptor genes, alpha4 and alpha6.

Wistar-Kyoto rats as an animal model of anxiety vulnerability: support for a hypervigilance hypothesis.

PubMed

McAuley, J D; Stewart, A L; Webber, E S; Cromwell, H C; Servatius, R J; Pang, K C H

2009-12-01

Inbred Wistar-Kyoto (WKY) rats have been proposed as a model of anxiety vulnerability as they display behavioral inhibition and a constellation of learning and reactivity abnormalities relative to outbred Sprague-Dawley (SD) rats. Together, the behaviors of the WKY rat suggest a hypervigilant state that may contribute to its anxiety vulnerability. To test this hypothesis, open-field behavior, acoustic startle, pre-pulse inhibition and timing behavior were assessed in WKY and Sprague-Dawley (SD) rats. Timing behavior was evaluated using a modified version of the peak-interval timing procedure. Training and testing of timing first occurred without audio-visual (AV) interference. Following this initial test, AV interference was included on some trials. Overall, WKY rats took much longer to leave the center of the arena, made fewer line crossings, and reared less, than did SD rats. WKY rats showed much greater startle responses to acoustic stimuli and significantly greater pre-pulse inhibition than did the SD rats. During timing conditions without AV interference, timing accuracy for both strains was similar; peak times for WKY and SD rats were not different. During interference conditions, however, the timing behavior of the two strains was very different. Whereas peak times for SD rats were similar between non-interference and interference conditions, peak times for WKY rats were shorter and response rates higher in interference conditions than in non-interference conditions. The enhanced acoustic startle response, greater prepulse inhibition and altered timing behavior with audio-visual interference supports a characterization of WKY strain as hypervigilant and provides further evidence for the use of the WKY strain as a model of anxiety vulnerability.

Building Minds, Minding Buildings: Turning Crumbling Schools into Environments for Learning

ERIC Educational Resources Information Center

American Federation of Teachers, 2006

2006-01-01

This report was based on the responses of more than 1,000 school employees to a survey on the physical environment at their schools. Many of the responses revealed some startling building conditions, from students who have to wear coats and gloves in class to rats and mice entering classrooms through windows and cracks in walls. The report…

The cost of assuming the life history of a host: acoustic startle in the parasitoid fly Ormia ochracea

PubMed Central

Rosen, M. J.; Levin, E. C.; Hoy, R. R.

2009-01-01

In the obligatory reproductive dependence of a parasite on its host, the parasite must trade the benefit of ‘outsourcing’ functions like reproduction for the risk of assuming hazards associated with the host. In the present study, we report behavioral adaptations of a parasitic fly, Ormia ochracea, that resemble those of its cricket hosts. Ormia females home in on the male cricket's songs and deposit larvae, which burrow into the cricket, feed and emerge to pupate. Because male crickets call at night, gravid female Ormia in search of hosts are subject to bat predation, in much the same way as female crickets are when responding to male song. We show that Ormia has evolved the same evasive behavior as have crickets: an acoustic startle response to bat-like ultrasound that manifests clearly only during flight. Furthermore, like crickets, Ormia has a sharp response boundary between the frequencies of song and bat cries, resembling categorical perception first described in the context of human speech. PMID:19946084

The cost of assuming the life history of a host: acoustic startle in the parasitoid fly Ormia ochracea.

PubMed

Rosen, M J; Levin, E C; Hoy, R R

2009-12-01

In the obligatory reproductive dependence of a parasite on its host, the parasite must trade the benefit of 'outsourcing' functions like reproduction for the risk of assuming hazards associated with the host. In the present study, we report behavioral adaptations of a parasitic fly, Ormia ochracea, that resemble those of its cricket hosts. Ormia females home in on the male cricket's songs and deposit larvae, which burrow into the cricket, feed and emerge to pupate. Because male crickets call at night, gravid female Ormia in search of hosts are subject to bat predation, in much the same way as female crickets are when responding to male song. We show that Ormia has evolved the same evasive behavior as have crickets: an acoustic startle response to bat-like ultrasound that manifests clearly only during flight. Furthermore, like crickets, Ormia has a sharp response boundary between the frequencies of song and bat cries, resembling categorical perception first described in the context of human speech.

Manipulating affective state using extended picture presentations.

PubMed

Sutton, S K; Davidson, R J; Donzella, B; Irwin, W; Dottl, D A

1997-03-01

Separate, extended series of positive, negative, and neutral pictures were presented to 24 (12 men, 12 women) undergraduates. Each series was presented on a different day, with full counterbalancing of presentation orders. Affective state was measured using (a) orbicularis oculi activity in response to acoustic startle probes during picture presentation, (b) corrugator supercilii activity between and during picture presentation, and (c) changes in self-reports of positive and negative affect. Participants exhibited larger eyeblink reflex magnitudes when viewing negative than when viewing positive pictures. Corrugator activity was also greater during the negative than during the positive picture set, during both picture presentation and the period between pictures. Self-reports of negative affect increased in response to the negative picture set, and self-reports of positive affect were greatest following the positive picture set. These findings suggest that extended picture presentation is an effective method of manipulating affective state and further highlight the utility of startle probe and facial electromyographic measures in providing on-line readouts of affective state.

Endothelial dysfunction correlates with exaggerated exercise pressor response during whole body maximal exercise in chronic kidney disease.

PubMed

Downey, Ryan M; Liao, Peizhou; Millson, Erin C; Quyyumi, Arshed A; Sher, Salman; Park, Jeanie

2017-05-01

Chronic kidney disease (CKD) patients have exercise intolerance associated with increased cardiovascular mortality. Previous studies demonstrate that blood pressure (BP) and sympathetic nerve responses to handgrip exercise are exaggerated in CKD. These patients also have decreased nitric oxide (NO) bioavailability and endothelial dysfunction, which could potentially lead to an impaired ability to vasodilate during exercise. We hypothesized that CKD patients have exaggerated BP responses during maximal whole body exercise and that endothelial dysfunction correlates with greater exercise pressor responses in these patients. Brachial artery flow-mediated dilation (FMD) was assessed before maximal treadmill exercise in 56 participants: 38 CKD (56.7 ± 1.2 yr old, 38 men) and 21 controls (52.8 ± 1.8 yr old, 20 men). During maximal treadmill exercise, the slope-of-rise in systolic BP (+10.32 vs. +7.75 mmHg/stage, P < 0.001), mean arterial pressure (+3.50 vs. +2.63 mmHg/stage, P = 0.004), and heart rate (+11.87 vs. +10.69 beats·min -1 ·stage -1 , P = 0.031) was significantly greater in CKD compared with controls. Baseline FMD was significantly lower in CKD (2.76 ± 0.42% vs. 5.84 ± 0.97%, P = 0.008). Lower FMD values were significantly associated with a higher slope-of-rise in systolic BP (+11.05 vs. 8.71 mmHg/stage, P = 0.003) during exercise in CKD, as well as poorer exercise capacity measured as peak oxygen uptake (V̇o 2peak ; 19.47 ± 1.47 vs. 24.57 ± 1.51 ml·min -1 ·kg -1 , P < 0.001). These findings demonstrate that low FMD in CKD correlates with augmented BP responses during exercise and lower V̇o 2peak , suggesting that endothelial dysfunction may contribute to exaggerated exercise pressor responses and poor exercise capacity in CKD patients.

Exaggerated Exercise Blood Pressure Response and Future Cardiovascular Disease.

PubMed

Tzemos, Nikolaos; Lim, Pitt O; Mackenzie, Isla S; MacDonald, Thomas M

2015-11-01

Exaggerated blood pressure (BP) response to exercise predicts future hypertension. However, there is considerable lack of understanding regarding the mechanism of how this abnormal response is generated, and how it relates to the future establishment of cardiovascular disease. The authors studied 82 healthy male volunteers without cardiovascular risk factors. The participants were categorized into two age-matched groups depending on their exercise systolic BP (ExSBP) rise after 3 minutes of exercise using a submaximal step test: exaggerated ExSBP group (hyper-responders [peak SBP ≥ 180 mm Hg]) and low ExSBP responder group (hypo-responders [peak SBP <180 mm Hg]). Forearm venous occlusion plethysmography and intra-arterial infusions of acetylcholine (ACh), N(G)-monomethyl-L-arginine (L-NMMA), sodium nitroprusside (SNP), and norepinephrine (NE) were used to assess vascular reactivity. Proximal aortic compliance was assessed with ultrasound, and neurohormonal blood sampling was performed at rest and during peak exercise. The hyper-responder group exhibited a significantly lower increase in forearm blood flow (FBF) with ACh compared with the hypo-responder group (ΔFBF 215% [14] vs 332.3% [28], mean [standard error of the mean]; P<.001), as well as decreased proximal aortic compliance. The vasoconstrictive response to L-NMMA was significantly impaired in the hyper-responder group in comparison to the hypo-responder group (ΔFBF -40.2% [1.6] vs -50.2% [2.6]; P<.05). In contrast, the vascular response to SNP and NE were comparable in both groups. Peak exercise plasma angiotensin II levels were significantly higher in the hyper-responder group (31 [1] vs 23 [2] pg/mL, P=.01). An exaggerated BP response to exercise is related to endothelial dysfunction, decreased proximal aortic compliance, and increased exercise-related neurohormonal activation, the constellation of which may explain future cardiovascular disease. © 2015 Wiley Periodicals, Inc.

A network analysis of DSM-5 posttraumatic stress disorder symptoms and correlates in U.S. military veterans.

PubMed

Armour, Cherie; Fried, Eiko I; Deserno, Marie K; Tsai, Jack; Pietrzak, Robert H

2017-01-01

Recent developments in psychometrics enable the application of network models to analyze psychological disorders, such as PTSD. Instead of understanding symptoms as indicators of an underlying common cause, this approach suggests symptoms co-occur in syndromes due to causal interactions. The current study has two goals: (1) examine the network structure among the 20 DSM-5 PTSD symptoms, and (2) incorporate clinically relevant variables to the network to investigate whether PTSD symptoms exhibit differential relationships with suicidal ideation, depression, anxiety, physical functioning/quality of life (QoL), mental functioning/QoL, age, and sex. We utilized a nationally representative U.S. military veteran's sample; and analyzed the data from a subsample of 221 veterans who reported clinically significant DSM-5 PTSD symptoms. Networks were estimated using state-of-the-art regularized partial correlation models. Data and code are published along with the paper. The 20-item DSM-5 PTSD network revealed that symptoms were positively connected within the network. Especially strong connections emerged between nightmares and flashbacks; blame of self or others and negative trauma-related emotions, detachment and restricted affect; and hypervigilance and exaggerated startle response. The most central symptoms were negative trauma-related emotions, flashbacks, detachment, and physiological cue reactivity. Incorporation of clinically relevant covariates into the network revealed paths between self-destructive behavior and suicidal ideation; concentration difficulties and anxiety, depression, and mental QoL; and depression and restricted affect. These results demonstrate the utility of a network approach in modeling the structure of DSM-5 PTSD symptoms, and suggest differential associations between specific DSM-5 PTSD symptoms and clinical outcomes in trauma survivors. Implications of these results for informing the assessment and treatment of this disorder, are discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

IgLON5 antibody: Neurological accompaniments and outcomes in 20 patients.

PubMed

Honorat, Josephe A; Komorowski, Lars; Josephs, Keith A; Fechner, Kai; St Louis, Erik K; Hinson, Shannon R; Lederer, Sabine; Kumar, Neeraj; Gadoth, Avi; Lennon, Vanda A; Pittock, Sean J; McKeon, Andrew

2017-09-01

To describe the phenotypes, treatment response, and outcome of IgLON5 autoimmunity. Archived serum and CSF specimens from 367 patients known to harbor unclassified antibodies which stained neural synapses diffusely (mimicking amphiphysin-IgG) were reevaluated by indirect immunofluorescence assay (IFA) using a composite of mouse tissues and recombinant IgLON5-transfected cell-based assay (CBA, Euroimmun). Available specimens (serum, 25; CSF, 9) from 26/367 patients (7%) had identical IFA appearance and robust IgLON5 CBA positivity. Clinical information was available for 20/26 patients; 13 were women. Median disease-onset age was 62 years (range, 46-75 years). Most patients had insidious onset and progression of neurological symptoms affecting movement and sleep predominantly. Sleep disorders were sleep-disordered breathing (11) and parasomnias (3). Brainstem disorders were gait instability (14), dysphagia (10), abnormal eye movements (7), respiratory dysfunction (6), ataxia (5), craniocervical dystonia (3), and dysarthria (3). Findings compatible with hyperexcitability included myoclonus (3), cramps (3), fasciculations (2), and exaggerated startle (2). Neuropsychiatric disorders included cognitive dysfunction (6), psychiatric symptoms (5), and seizures (1). Dysautonomia, in 9, affected bladder function (7), gastrointestinal motility (3), thermoregulation (3), and orthostatic tolerance (1). Just 2 patients had coexisting autoimmune disease. Brain MRI findings were nonspecific and CSF was noninflammatory in all tested. Seven of 9 immunotherapy-treated patients improved: 6 of those 7 were stable at last follow-up. Three untreated patients died. Each IgLON5-IgG subclass (1-4) was readily detectable in ≥80% of specimens using CBA. IgLON5-IgG is diagnostic of a potentially treatable neurological disorder, where autoimmune clues are otherwise lacking.

PURA syndrome: clinical delineation and genotype-phenotype study in 32 individuals with review of published literature

PubMed Central

Reijnders, Margot R F; Janowski, Robert; Alvi, Mohsan; Self, Jay E; van Essen, Ton J; Vreeburg, Maaike; Rouhl, Rob P W; Stevens, Servi J C; Stegmann, Alexander P A; Schieving, Jolanda; Pfundt, Rolph; van Dijk, Katinke; Smeets, Eric; Stumpel, Connie T R M; Bok, Levinus A; Cobben, Jan Maarten; Engelen, Marc; Mansour, Sahar; Whiteford, Margo; Chandler, Kate E; Douzgou, Sofia; Cooper, Nicola S; Tan, Ene-Choo; Foo, Roger; Lai, Angeline H M; Rankin, Julia; Green, Andrew; Lönnqvist, Tuula; Isohanni, Pirjo; Williams, Shelley; Ruhoy, Ilene; Carvalho, Karen S; Dowling, James J; Lev, Dorit L; Sterbova, Katalin; Lassuthova, Petra; Neupauerová, Jana; Waugh, Jeff L; Keros, Sotirios; Clayton-Smith, Jill; Smithson, Sarah F; Brunner, Han G; van Hoeckel, Ceciel; Anderson, Mel; Clowes, Virginia E; Siu, Victoria Mok; DDD study, The; Selber, Paulo; Leventer, Richard J; Nellaker, Christoffer; Niessing, Dierk; Hunt, David; Baralle, Diana

2018-01-01

Background De novo mutations in PURA have recently been described to cause PURA syndrome, a neurodevelopmental disorder characterised by severe intellectual disability (ID), epilepsy, feeding difficulties and neonatal hypotonia. Objectives To delineate the clinical spectrum of PURA syndrome and study genotype-phenotype correlations. Methods Diagnostic or research-based exome or Sanger sequencing was performed in individuals with ID. We systematically collected clinical and mutation data on newly ascertained PURA syndrome individuals, evaluated data of previously reported individuals and performed a computational analysis of photographs. We classified mutations based on predicted effect using 3D in silico models of crystal structures of Drosophila-derived Pur-alpha homologues. Finally, we explored genotype-phenotype correlations by analysis of both recurrent mutations as well as mutation classes. Results We report mutations in PURA (purine-rich element binding protein A) in 32 individuals, the largest cohort described so far. Evaluation of clinical data, including 22 previously published cases, revealed that all have moderate to severe ID and neonatal-onset symptoms, including hypotonia (96%), respiratory problems (57%), feeding difficulties (77%), exaggerated startle response (44%), hypersomnolence (66%) and hypothermia (35%). Epilepsy (54%) and gastrointestinal (69%), ophthalmological (51%) and endocrine problems (42%) were observed frequently. Computational analysis of facial photographs showed subtle facial dysmorphism. No strong genotype-phenotype correlation was identified by subgrouping mutations into functional classes. Conclusion We delineate the clinical spectrum of PURA syndrome with the identification of 32 additional individuals. The identification of one individual through targeted Sanger sequencing points towards the clinical recognisability of the syndrome. Genotype-phenotype analysis showed no significant correlation between mutation classes and disease severity. PMID:29097605

Exaggerated haemodynamic and neural responses to involuntary contractions induced by whole-body vibration in normotensive obese versus lean women.

PubMed

Dipla, Konstantina; Kousoula, Dimitra; Zafeiridis, Andreas; Karatrantou, Konstantina; Nikolaidis, Michalis G; Kyparos, Antonios; Gerodimos, Vassilis; Vrabas, Ioannis S

2016-06-01

What is the central question of this study? In obesity, the exaggerated blood pressure response to voluntary exercise is linked to hypertension, yet the mechanisms are not fully elucidated. We examined whether involuntary contractions elicit greater haemodynamic responses and altered neural control of blood pressure in normotensive obese versus lean women. What is the main finding and its importance? During involuntary contractions induced by whole-body vibration, there were augmented blood pressure and spontaneous baroreflex responses in obese compared with lean women. This finding is suggestive of an overactive mechanoreflex in the exercise-induced hypertensive response in obesity. Passive contractions did not elicit differential heart rate responses in obese compared with lean women, implying other mechanisms for the blunted heart rate response reported during voluntary exercise in obesity. In obesity, the exaggerated blood pressure (BP) response to exercise is linked to hypertension, yet the mechanisms are not fully elucidated. In this study, we examined whether involuntary mechanical oscillations, induced by whole-body vibration (WBV), elicit greater haemodynamic responses and altered neural control of BP in obese versus lean women. Twenty-two normotensive, premenopausal women (12 lean and 10 obese) randomly underwent a passive WBV (25 Hz) and a control protocol (similar posture without WVB). Beat-by-beat BP, heart rate, stroke volume, systemic vascular resistance, cardiac output, parasympathetic output (evaluated by heart rate variability) and spontaneous baroreceptor sensitivity (sBRS) were assessed. We found that during WBV, obese women exhibited an augmented systolic BP response compared with lean women that was correlated with body fat percentage (r = 0.77; P < 0.05). The exaggerated BP rise was driven mainly by the greater increase in cardiac output index in obese versus lean women, associated with a greater stroke volume index in obese women. Involuntary contractions did not elicit a differential magnitude of responses in heart rate, heart rate variability indices and systemic vascular resistance in obese versus lean women; however, they did result in greater sBRS responses (P < 0.05) in obese women. In conclusion, involuntary contractions elicited an augmented BP and sBRS response in normotensive obese versus lean women. The greater elevations in circulatory haemodynamics in obese women are suggestive of an overactive mechanoreflex in the exercise-induced hypertensive response in obesity. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.

Differences in Regional Brain Responses to Food Ingestion After Roux-en-Y Gastric Bypass and the Role of Gut Peptides: A Neuroimaging Study.

PubMed

Hunt, Katharine F; Dunn, Joel T; le Roux, Carel W; Reed, Laurence J; Marsden, Paul K; Patel, Ameet G; Amiel, Stephanie A

2016-10-01

Improved appetite control, possibly mediated by exaggerated gut peptide responses to eating, may contribute to weight loss after Roux-en-Y gastric bypass (RYGB). This study compared brain responses to food ingestion between post-RYGB (RYGB), normal weight (NW), and obese (Ob) unoperated subjects and explored the role of gut peptide responses in RYGB. Neuroimaging with [(18)F]-fluorodeoxyglucose (FDG) positron emission tomography was performed in 12 NW, 21 Ob, and 9 RYGB (18 ± 13 months postsurgery) subjects after an overnight fast, once FED (400 kcal mixed meal), and once FASTED, in random order. RYGB subjects repeated the studies with somatostatin infusion and basal insulin replacement. Fullness, sickness, and postscan ad libitum meal consumption were measured. Regional brain FDG uptake was compared using statistical parametric mapping. RYGB subjects had higher overall fullness and food-induced sickness and lower ad libitum consumption. Brain responses to eating differed in the hypothalamus and pituitary (exaggerated activation in RYGB), left medial orbital cortex (OC) (activation in RYGB, deactivation in NW), right dorsolateral frontal cortex (deactivation in RYGB and NW, absent in Ob), and regions mapping to the default mode network (exaggerated deactivation in RYGB). Somatostatin in RYGB reduced postprandial gut peptide responses, sickness, and medial OC activation. RYGB induces weight loss by augmenting normal brain responses to eating in energy balance regions, restoring lost inhibitory control, and altering hedonic responses. Altered postprandial gut peptide responses primarily mediate changes in food-induced sickness and OC responses, likely to associate with food avoidance. © 2016 by the American Diabetes Association.

Appetitive responses to sexual stimuli are attenuated in individuals with low levels of sexual desire.

PubMed

Giargiari, Tracie D; Mahaffey, Amanda L; Craighead, W Edward; Hutchison, Kent E

2005-10-01

Despite the high prevalence of sexual desire disorders, little is known about their biological underpinnings in humans. Animal studies suggest that dopamine is involved in appetitive sexual behavior; thus, one aim of this study was to elucidate that relationship in humans. This study used measurement of the acoustic startle response (ASR) and prepulse inhibition of the startle response (PPI) as psychophysiological indicators of changes in motivational states to assess the potential relation between sexual desire and appetitive motivation in humans. Responses to sexually provocative stimuli consisting of single nude men and single nude women in a sample of 153 participants (77 men, 76 women) were assessed. The results indicated that ASR was attenuated after exposure to appetitive stimuli (i.e., sexually provocative pictures of attractive individuals) to a greater extent among participants with higher levels of sexual desire, as measured by the Sexual Desire Inventory-2 (Spector, I. P., Carey, M. P., & Steinberg, L. (1996). Journal of Sex & Marital Therapy, 22, 175-190). In addition, PPI was inversely associated with subjective ratings across stimuli such that greater subjective levels of desire were correlated with lower levels of PPI. In general, these results suggest that individuals with lower levels of sexual desire may have a diminished physiological response to appetitive sexual stimuli.

DEVELOPMENTAL THYROID HORMONE INSUFFICIENCY ALTERS THE AMPLITUDE OF THE ACOUSTIC STARTLE RESPONSE IN RATS

EPA Science Inventory

Purpose: The thyroid hormone (TH) system is one of the targets of endocrine disrupting chemicals. Since TH is essential for proper brain development, disruption by exposure to chemicals during development can result in adverse neurological outcomes. Previous studies revealed th...

Chronic Anabolic Androgenic Steroid Exposure Alters Corticotropin Releasing Factor Expression and Anxiety-Like Behaviors in the Female Mouse

PubMed Central

Costine, Beth A; Oberlander, Joseph G; Davis, Matthew C; Penatti, Carlos A A; Porter, Donna M; Leaton, Robert N; Henderson, Leslie P

2010-01-01

Summary In the past several decades, the therapeutic use of anabolic androgenic steroids (AAS) has been overshadowed by illicit use of these drugs by elite athletes and a growing number of adolescents to enhance performance and body image. As with adults, AAS use by adolescents is associated with a range of behavioral effects, including increased anxiety and altered responses to stress. It has been suggested that adolescents, especially adolescent females, may be particularly susceptible to the effects of these steroids, but few experiments in animal models have been performed to test this assertion. Here we show that chronic exposure of adolescent female mice to a mixture of three commonly abused AAS (testosterone cypionate, nandrolone decanoate and methandrostenolone; 7.5 mg/kg/day for 5 days) significantly enhanced anxiety-like behavior as assessed by the acoustic startle response (ASR), but did not augment the fear-potentiated startle response (FPS) or alter sensorimotor gating as assessed by prepulse inhibition of the acoustic startle response (PPI). AAS treatment also significantly increased the levels of corticotropin releasing factor (CRF) mRNA and somal-associated CRF immunoreactivity in the central amygdala (CeA), as well as neuropil-associated immunoreactivity in the dorsal aspect of the anterolateral division of the bed nucleus of the stria terminalis (dBnST). AAS treatment did not alter CRF receptor 1 or 2 mRNA in either the CeA or the dBnST; CRF immunoreactivity in the ventral BNST, the paraventricular nucleus (PVN) or the median eminence (ME); or peripheral levels of corticosterone. These results suggest that chronic AAS treatment of adolescent female mice may enhance generalized anxiety, but not sensorimotor gating or learned fear, via a mechanism that involves increased CRF-mediated signaling from CeA neurons projecting to the dBnST. PMID:20537804

Direct and indirect nigrofugal projections to the nucleus reticularis pontis caudalis mediate in the motor execution of the acoustic startle reflex.

PubMed

Hormigo, Sebastian; López, Dolores E; Cardoso, Antonio; Zapata, Gladys; Sepúlveda, Jacqueline; Castellano, Orlando

2018-07-01

The acoustic startle reflex (ASR) is a short and intense defensive reaction in response to a loud and unexpected acoustic stimulus. In the rat, a primary startle pathway encompasses three serially connected central structures: the cochlear root neurons, the giant neurons of the nucleus reticularis pontis caudalis (PnC), and the spinal motoneurons. As a sensorimotor interface, the PnC has a central role in the ASR circuitry, especially the integration of different sensory stimuli and brain states into initiation of motor responses. Since the basal ganglia circuits control movement and action selection, we hypothesize that their output via the substantia nigra (SN) may interplay with the ASR primary circuit by providing inputs to PnC. Moreover, the pedunculopontine tegmental nucleus (PPTg) has been proposed as a functional and neural extension of the SN, so it is another goal of this study to describe possible anatomical connections from the PPTg to PnC. Here, we made 6-OHDA neurotoxic lesions of the SN pars compacta (SNc) and submitted the rats to a custom-built ASR measurement session to assess amplitude and latency of motor responses. We found that following lesion of the SNc, ASR amplitude decreased and latency increased compared to those values from the sham-surgery and control groups. The number of dopamine neurons remaining in the SNc after lesion was also estimated using a stereological approach, and it correlated with our behavioral results. Moreover, we employed neural tract-tracing techniques to highlight direct projections from the SN to PnC, and indirect projections through the PPTg. Finally, we also measured levels of excitatory amino acid neurotransmitters in the PnC following lesion of the SN, and found that they change following an ipsi/contralateral pattern. Taken together, our results identify nigrofugal efferents onto the primary ASR circuit that may modulate motor responses.

Mutations in monoamine oxidase (MAO) genes in mice lead to hypersensitivity to serotonin-enhancing drugs: implications for drug side effects in humans.

PubMed

Fox, M A; Panessiti, M G; Moya, P R; Tolliver, T J; Chen, K; Shih, J C; Murphy, D L

2013-12-01

A possible side effect of serotonin-enhancing drugs is the serotonin syndrome, which can be lethal. Here we examined possible hypersensitivity to two such drugs, the serotonin precursor 5-hydroxy-L-tryptophan (5-HTP) and the atypical opioid tramadol, in mice lacking the genes for both monoamine oxidase A (MAOA) and MAOB. MAOA/B-knockout (KO) mice displayed baseline serotonin syndrome behaviors, and these behavioral responses were highly exaggerated following 5-HTP or tramadol versus baseline and wild-type (WT) littermates. Compared with MAOA/B-WT mice, baseline tissue serotonin levels were increased ∼2.6-3.9-fold in MAOA/B-KO mice. Following 5-HTP, serotonin levels were further increased ∼4.5-6.2-fold in MAOA/B-KO mice. These exaggerated responses are in line with the exaggerated responses following serotonin-enhancing drugs that we previously observed in mice lacking the serotonin transporter (SERT). These findings provide a second genetic mouse model suggestive of possible human vulnerability to the serotonin syndrome in individuals with lesser-expressing MAO or SERT polymorphisms that confer serotonergic system changes.

Mutations in monoamine oxidase (MAO) genes in mice lead to hypersensitivity to serotonin-enhancing drugs: implications for drug side effects in humans

PubMed Central

Fox, MA; Panessiti, MG; Moya, PR; Tolliver, TJ; Chen, K; Shih, JC; Murphy, DL

2012-01-01

A possible side effect of serotonin-enhancing drugs is the serotonin syndrome, which can be lethal. Here we examined possible hypersensitivity to two such drugs, the serotonin precursor 5-hydroxy-L-tryptophan (5-HTP) and the atypical opioid tramadol, in mice lacking the genes for both monoamine oxidase A (MAOA) and MAOB. MAOA/B-knockout (KO) mice displayed baseline serotonin syndrome behaviors, and these behavioral responses were highly exaggerated following 5-HTP or tramadol versus baseline and wild-type (WT) littermates. Compared with MAOA/B-WT mice, baseline tissue serotonin levels were increased ~2.6–3.9-fold in MAOA/B-KO mice. Following 5-HTP, serotonin levels were further increased ~4.5–6.2-fold in MAOA/B-KO mice. These exaggerated responses are in line with the exaggerated responses following serotonin-enhancing drugs that we previously observed in mice lacking the serotonin transporter (SERT). These findings provide a second genetic mouse model suggestive of possible human vulnerability to the serotonin syndrome in individuals with lesser-expressing MAO or SERT polymorphisms that confer serotonergic system changes. PMID:22964922

Additive Effects of Threat-of-Shock and Picture Valence on Startle Reflex Modulation

PubMed Central

Bublatzky, Florian; Guerra, Pedro M.; Pastor, M. Carmen; Schupp, Harald T.; Vila, Jaime

2013-01-01

The present study examined the effects of sustained anticipatory anxiety on the affective modulation of the eyeblink startle reflex. Towards this end, pleasant, neutral and unpleasant pictures were presented as a continuous stream during alternating threat-of-shock and safety periods, which were cued by colored picture frames. Orbicularis-EMG to auditory startle probes and electrodermal activity were recorded. Previous findings regarding affective picture valence and threat-of-shock modulation were replicated. Of main interest, anticipating aversive events and viewing affective pictures additively modulated defensive activation. Specifically, despite overall potentiated startle blink magnitude in threat-of-shock conditions, the startle reflex remained sensitive to hedonic picture valence. Finally, skin conductance level revealed sustained sympathetic activation throughout the entire experiment during threat- compared to safety-periods. Overall, defensive activation by physical threat appears to operate independently from reflex modulation by picture media. The present data confirms the importance of simultaneously manipulating phasic-fear and sustained-anxiety in studying both normal and abnormal anxiety. PMID:23342060

The CRH1 antagonist GSK561679 increases human fear but not anxiety as assessed by startle.

PubMed

Grillon, Christian; Hale, Elizabeth; Lieberman, Lynne; Davis, Andrew; Pine, Daniel S; Ernst, Monique

2015-03-13

Fear to predictable threat and anxiety to unpredictable threat reflect distinct processes mediated by different brain structures, the central nucleus of the amygdala and the bed nucleus of the stria terminalis (BNST), respectively. This study tested the hypothesis that the corticotropin-releasing factor (CRF1) antagonist GSK561679 differentially reduces anxiety but increases fear in humans. A total of 31 healthy females received each of four treatments: placebo, 50 mg GSK561679 (low-GSK), 400 mg GSK561679 (high-GSK), and 1 mg alprazolam in a crossover design. Participants were exposed to three conditions during each of the four treatments. The three conditions included one in which predictable aversive shocks were signaled by a cue, a second during which shocks were administered unpredictably, and a third condition without shock. Fear and anxiety were assessed using the acoustic startle reflex. High-GSK had no effect on startle potentiation during unpredictable threat (anxiety) but increased startle potentiation during the predictable condition (fear). Low-GSK did not affect startle potentiation across conditions. Consistent with previous findings, alprazolam reduced startle potentiation during unpredictable threat but not during predictable threat. The increased fear by high-GSK replicates animal findings and suggests a lift of the inhibitory effect of the BNST on the amygdala by the CRF1 antagonist.

Physiological markers of anxiety are increased in children of abused mothers.

PubMed

Jovanovic, Tanja; Smith, Ami; Kamkwalala, Asante; Poole, James; Samples, Tara; Norrholm, Seth D; Ressler, Kerry J; Bradley, Bekh

2011-08-01

A growing number of studies indicate that low income, African American men and women living in urban environments are at high risk for trauma exposure, which may have intergenerational effects. The current study employed psychophysiological methods to describe biomarkers of anxiety in children of traumatized mothers. Study participants were recruited from a highly traumatized urban population, comprising mother-child pairs (n=36) that included school-age children. Mothers were assessed for childhood abuse with the Childhood Trauma Questionnaire, as well as symptoms of depression and posttraumatic stress disorder (PTSD). The children were measured for dark-enhanced startle responses and heart-rate variability. Dark-enhanced startle was found to be higher in children whose mothers had high levels of childhood physical abuse, as compared to children whose mothers had low levels of physical abuse. During the habituation phase of the startle experiment, children whose mothers had high levels of childhood emotional abuse had higher sympathetic system activation compared to children of mothers with low emotional abuse. These effects remained significant after accounting for maternal symptoms of PTSD and depression, as well as for the child's trauma exposure. These results demonstrate that children of mothers who have history of childhood physical and emotional abuse have higher dark-enhanced startle as well as greater sympathetic nervous system activation than children of mothers who do not report a history of childhood physical and emotional abuse, and emphasize the utility of physiological measures as pervasive biomarkers of psychopathology that can easily be measured in children. © 2011 The Authors. Journal of Child Psychology and Psychiatry © 2011 Association for Child and Adolescent Mental Health.

Defensive motivation and attention in anticipation of different types of predictable and unpredictable threat: A startle and event-related potential investigation.

PubMed

Nelson, Brady D; Hajcak, Greg

2017-08-01

Predictability is an important characteristic of threat that impacts defensive motivation and attentional engagement. Supporting research has primarily focused on actual threat (e.g., shocks), and it is unclear whether the predictability of less intense threat (e.g., unpleasant pictures) similarly affects motivation and attention. The present study utilized a within-subject design and examined defensive motivation (startle reflex and self-reported anxiety) and attention (probe N100 and P300) in anticipation of shocks and unpleasant pictures during a no, predictable, and unpredictable threat task. This study also examined the impact of predictability on the P300 to shocks and late positive potential (LPP) to unpleasant pictures. The startle reflex and self-reported anxiety were increased in anticipation of both types of threat relative to no threat. Furthermore, startle potentiation in anticipation of unpredictable threat was greater for shocks compared to unpleasant pictures, but there was no difference for predictable threat. The probe N100 was enhanced in anticipation of unpredictable threat relative to predictable threat and no threat, and the probe P300 was suppressed in anticipation of predictable and unpredictable threat relative to no threat. These effects did not differ between the shock and unpleasant picture trials. Finally, the P300 and early LPP component were increased in response to unpredictable relative to predictable shocks and unpleasant pictures, respectively. The present study suggests that the unpredictability of unpleasant pictures increases defensive motivation, but to a lesser degree relative to actual threat. Moreover, unpredictability enhances attentional engagement in anticipation of, and in reaction to, both types of threat. © 2017 Society for Psychophysiological Research.

Dynamics of defensive reactivity in patients with panic disorder and agoraphobia: implications for the etiology of panic disorder.

PubMed

Richter, Jan; Hamm, Alfons O; Pané-Farré, Christiane A; Gerlach, Alexander L; Gloster, Andrew T; Wittchen, Hans-Ulrich; Lang, Thomas; Alpers, Georg W; Helbig-Lang, Sylvia; Deckert, Jürgen; Fydrich, Thomas; Fehm, Lydia; Ströhle, Andreas; Kircher, Tilo; Arolt, Volker

2012-09-15

The learning perspective of panic disorder distinguishes between acute panic and anxious apprehension as distinct emotional states. Following animal models, these clinical entities reflect different stages of defensive reactivity depending upon the imminence of interoceptive or exteroceptive threat cues. The current study tested this model by investigating the dynamics of defensive reactivity in a large group of patients with panic disorder and agoraphobia (PD/AG). Three hundred forty-five PD/AG patients participated in a standardized behavioral avoidance test (being entrapped in a small, dark chamber for 10 minutes). Defense reactivity was assessed measuring avoidance and escape behavior, self-reports of anxiety and panic symptoms, autonomic arousal (heart rate and skin conductance), and potentiation of the startle reflex before and during exposure of the behavioral avoidance test. Panic disorder and agoraphobia patients differed substantially in their defensive reactivity. While 31.6% of the patients showed strong anxious apprehension during this task (as indexed by increased reports of anxiety, elevated physiological arousal, and startle potentiation), 20.9% of the patients escaped from the test chamber. Active escape was initiated at the peak of the autonomic surge accompanied by an inhibition of the startle response as predicted by the animal model. These physiological responses resembled the pattern observed during the 34 reported panic attacks. We found evidence that defensive reactivity in PD/AG patients is dynamically organized ranging from anxious apprehension to panic with increasing proximity of interoceptive threat. These data support the learning perspective of panic disorder. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Evolution of the Mauthner axon cap.

PubMed

Bierman, Hilary S; Zottoli, Steven J; Hale, Melina E

2009-01-01

Studies of vertebrate brain evolution have focused primarily on patterns of gene expression or changes in size and organization of major brain regions. The Mauthner cell, an important reticulospinal neuron that functions in the startle response of many species, provides an opportunity for evolutionary comparisons at the cellular level. Despite broad interspecific similarities in Mauthner cell morphology, the motor patterns and startle behaviors it initiates vary markedly. Response diversity has been hypothesized to result, in part, from differences in the structure and function of the Mauthner cell-associated axon cap. We used light microscopy techniques to compare axon cap morphology across a wide range of species, including all four extant basal actinopterygian orders, representatives of a variety of teleost lineages and lungfishes, and we combined our data with published descriptions of axon cap structure. The 'composite' axon cap, observed in teleosts, is an organized conglomeration of glia and fibers of inhibitory and excitatory interneurons. Lungfish, amphibian tadpoles and several basal actinopterygian fishes have 'simple' axon caps that appear to lack glia and include few fibers. Several other basal actinopterygian fishes have 'simple-dense' caps that include greater numbers of fibers than simple caps, but lack the additional elements and organization of composite caps. Phylogenetic mapping shows that through evolution there are discrete transitions in axon cap morphology occurring at the base of gnathostomes, within basal actinopterygians, and at the base of the teleost radiation. Comparing axon cap evolution to the evolution of startle behavior and motor pattern provides insight into the relationship between Mauthner cell-associated structures and their functions in behavior. Copyright 2009 S. Karger AG, Basel.

Longitudinal Health Research in the U.S. Navy.

DTIC Science & Technology

1979-12-01

while morbidity variables would be the presence or absence of a specific disease or condition, or perhaps a continuous response such S as level of...Cardiovascular routine electrocardiogram * * * * startle electrocardiogram * computer processed electrocardiogram * * exercise electrocardiogram...basal metabolic rate * other * * Anthropometry somatotype * * * measurements (in addition to height & weight) e * * Teleoroentgenograms

REFLEX MODIFICATION: AN APPROACH TO INCORPORATE INTO A DEVELOPMENTAL NEUROTOXICITY (DNT) STUDY DESIGN WITH COMMERCIAL EQUIPMENT.

EPA Science Inventory

Reflex modification (RM) of the startle response is a very useful tool for testing sensory function and the integrity of a well-defined complement of neural circuits. Advantages of this procedure include the ability to rapidly acquire objective measurements and differentiate sen...

A Constructive Response to "Where Mathematics Comes From."

ERIC Educational Resources Information Center

Schiralli, Martin; Sinclair, Nathalie

2003-01-01

Reviews the Lakoff and Nunez's book, "Where Mathematics Comes From: How the Embodied Mind Brings Mathematics into Being (2000)," which provided many mathematics education researchers with a novel and startling perspective on mathematical thinking. Suggests that several of the book's flaws can be addressed through a more rigorous establishment of…

Two-tone suppression in the cricket, Eunemobius carolinus (Gryllidae, Nemobiinae)

NASA Astrophysics Data System (ADS)

Farris, Hamilton E.; Hoy, Ronald R.

2002-03-01

Sounds with frequencies >15 kHz elicit an acoustic startle response (ASR) in flying crickets (Eunemobius carolinus). Although frequencies <15 kHz do not elicit the ASR when presented alone, when presented with ultrasound (40 kHz), low-frequency stimuli suppress the ultrasound-induced startle. Thus, using methods similar to those in masking experiments, we used two-tone suppression to assay sensitivity to frequencies in the audio band. Startle suppression was tuned to frequencies near 5 kHz, the frequency range of male calling songs. Similar to equal loudness contours measured in humans, however, equal suppression contours were not parallel, as the equivalent rectangular bandwidth of suppression tuning changed with increases in ultrasound intensity. Temporal integration of suppressor stimuli was measured using nonsimultaneous presentations of 5-ms pulses of 6 and 40 kHz. We found that no suppression occurs when the suppressing tone is >2 ms after and >5 ms before the ultrasound stimulus, suggesting that stimulus overlap is a requirement for suppression. When considered together with our finding that the intensity of low-frequency stimuli required for suppression is greater than that produced by singing males, the overlap requirement suggests that two-tone suppression functions to limit the ASR to sounds containing only ultrasound and not to broadband sounds that span the audio and ultrasound range.

Maternal buffering of fear-potentiated startle in children and adolescents with trauma exposure.

PubMed

van Rooij, Sanne J H; Cross, Dorthie; Stevens, Jennifer S; Vance, L Alexander; Kim, Ye Ji; Bradley, Bekh; Tottenham, Nim; Jovanovic, Tanja

2017-02-01

Parental availability influences fear expression and learning across species, but the effect of maternal buffering on fear learning in humans is unknown. Here we investigated the effect of maternal availability during fear conditioning in a group of children (ages 8-10) and adolescents (ages 11-13) from a low-income population with a range of trauma exposure. Acoustic startle response data were collected to measure fear-potentiated startle (FPS) in 104 participants. A total of 62 participants were tested with the mother available and 42 when the mother was not in the testing room. We observed that maternal availability during fear conditioning interacted with age to affect FPS discrimination between CS+ and CS-. In line with previous findings suggesting an absence of maternal buffering in adolescents, fear discrimination was affected by maternal availability only in children. Second, we observed that the effect of maternal buffering on FPS discrimination in children was not influenced by maternally reported warmth. In conclusion, we demonstrated that maternal availability improved discrimination in children, regardless of the quality of the relationship. Adolescents discriminated irrespective of maternal status, suggesting that childhood may be a sensitive period for environmental influences on key processes such as learning of danger and safety signals.

Behavioral Characterization of Knockin Mice with Mutations M287L and Q266I in the Glycine Receptor α1 Subunit

PubMed Central

Blednov, Yuri A.; Benavidez, Jill M.; Homanics, Gregg E.

2012-01-01

We used behavioral pharmacology to characterize heterozygous knockin mice with mutations (Q266I or M287L) in the α1 subunit of the glycine receptor (GlyR) (J Pharmacol Exp Ther 340:304–316, 2012). These mutations were designed to reduce (M287L) or eliminate (Q266I) ethanol potentiation of GlyR function. We asked which behavioral effects of ethanol would be reduced more in the Q266I mutant than the M287L and found rotarod ataxia to be the behavior that fulfilled this criterion. Compared with controls, the mutant mice also differed in ethanol consumption, ethanol-stimulated startle response, signs of acute physical dependence, and duration of loss of righting response produced by ethanol, butanol, ketamine, pentobarbital, and flurazepam. Some of these behavioral changes were mimicked in wild-type mice by acute injections of low, subconvulsive doses of strychnine. Both mutants showed increased acoustic startle response and increased sensitivity to strychnine seizures. Thus, in addition to reducing ethanol action on the GlyRs, these mutations reduced glycinergic inhibition, which may also alter sensitivity to GABAergic drugs. PMID:22037202

Learning and memory deficits in mice lacking protease activated receptor-1

PubMed Central

Almonte, Antoine G.; Hamill, Cecily E.; Chhatwal, Jasmeer P.; Wingo, Thomas S.; Barber, Jeremy A.; Lyuboslavsky, Polina N.; Sweatt, J. David; Ressler, Kerry J.; White, David A.; Traynelis, Stephen F.

2007-01-01

The roles of serine proteases and protease activated receptors have been extensively studied in coagulation, wound healing, inflammation, and neurodegeneration. More recently, serine proteases have been suggested to influence synaptic plasticity. In this context, we examined the role of protease activated receptor 1 (PAR1), which is activated following proteolytic cleavage by thrombin and plasmin, in emotionally-motivated learning. We were particularly interested in PAR1 because its activation enhances the function of NMDA receptors, which are required for some forms of synaptic plasticity. We examined several baseline behavioral measures, including locomotor activity, expression of anxiety-like behavior, motor task acquisition, nociceptive responses, and startle responses in C57Bl/6 mice in which the PAR1 receptor has been genetically deleted. In addition, we evaluated learning and memory in these mice using two memory tasks, passive avoidance and cued fear-conditioning. Whereas locomotion, pain response, startle, and measures of baseline anxiety were largely unaffected by PAR1 removal, PAR1−/− animals showed significant deficits in a passive avoidance task and in cued fear conditioning. These data suggest that PAR1 may play an important role in emotionally-motivated learning. PMID:17544303

An Auditory BCI System for Assisting CRS-R Behavioral Assessment in Patients with Disorders of Consciousness

NASA Astrophysics Data System (ADS)

Xiao, Jun; Xie, Qiuyou; He, Yanbin; Yu, Tianyou; Lu, Shenglin; Huang, Ningmeng; Yu, Ronghao; Li, Yuanqing

2016-09-01

The Coma Recovery Scale-Revised (CRS-R) is a consistent and sensitive behavioral assessment standard for disorders of consciousness (DOC) patients. However, the CRS-R has limitations due to its dependence on behavioral markers, which has led to a high rate of misdiagnosis. Brain-computer interfaces (BCIs), which directly detect brain activities without any behavioral expression, can be used to evaluate a patient’s state. In this study, we explored the application of BCIs in assisting CRS-R assessments of DOC patients. Specifically, an auditory passive EEG-based BCI system with an oddball paradigm was proposed to facilitate the evaluation of one item of the auditory function scale in the CRS-R - the auditory startle. The results obtained from five healthy subjects validated the efficacy of the BCI system. Nineteen DOC patients participated in the CRS-R and BCI assessments, of which three patients exhibited no responses in the CRS-R assessment but were responsive to auditory startle in the BCI assessment. These results revealed that a proportion of DOC patients who have no behavioral responses in the CRS-R assessment can generate neural responses, which can be detected by our BCI system. Therefore, the proposed BCI may provide more sensitive results than the CRS-R and thus assist CRS-R behavioral assessments.

An Auditory BCI System for Assisting CRS-R Behavioral Assessment in Patients with Disorders of Consciousness.

PubMed

Xiao, Jun; Xie, Qiuyou; He, Yanbin; Yu, Tianyou; Lu, Shenglin; Huang, Ningmeng; Yu, Ronghao; Li, Yuanqing

2016-09-13

The Coma Recovery Scale-Revised (CRS-R) is a consistent and sensitive behavioral assessment standard for disorders of consciousness (DOC) patients. However, the CRS-R has limitations due to its dependence on behavioral markers, which has led to a high rate of misdiagnosis. Brain-computer interfaces (BCIs), which directly detect brain activities without any behavioral expression, can be used to evaluate a patient's state. In this study, we explored the application of BCIs in assisting CRS-R assessments of DOC patients. Specifically, an auditory passive EEG-based BCI system with an oddball paradigm was proposed to facilitate the evaluation of one item of the auditory function scale in the CRS-R - the auditory startle. The results obtained from five healthy subjects validated the efficacy of the BCI system. Nineteen DOC patients participated in the CRS-R and BCI assessments, of which three patients exhibited no responses in the CRS-R assessment but were responsive to auditory startle in the BCI assessment. These results revealed that a proportion of DOC patients who have no behavioral responses in the CRS-R assessment can generate neural responses, which can be detected by our BCI system. Therefore, the proposed BCI may provide more sensitive results than the CRS-R and thus assist CRS-R behavioral assessments.

Physiological reactivity of pregnant women to evoked fetal startle

PubMed Central

DiPietro, Janet A.; Voegtline, Kristin M.; Costigan, Kathleen A.; Aguirre, Frank; Kivlighan, Katie; Chen, Ping

2013-01-01

Objective The bidirectional nature of mother-child interaction is widely acknowledged during infancy and childhood. Prevailing models during pregnancy focus on unidirectional influences exerted by the pregnant woman on the developing fetus. Prior work has indicated that the fetus also affects the pregnant woman. Our objective was to determine whether a maternal psychophysiological response to stimulation of the fetus could be isolated. Methods Using a longitudinal design, an airborne auditory stimulus was used to elicit a fetal heart rate and motor response at 24 (n = 47) and 36 weeks (n = 45) gestation. Women were blind to condition (stimulus versus sham). Maternal parameters included cardiac (heart rate) and electrodermal (skin conductance) responses. Multilevel modeling of repeated measures with 5 data points per second was used to examine fetal and maternal responses. Results As expected, compared to a sham condition, the stimulus generated a fetal motor response at both gestational ages, consistent with a mild fetal startle. Fetal stimulation was associated with significant, transient slowing of maternal heart rate coupled with increased skin conductance within 10 s of the stimulus at both gestational ages. Nulliparous women showed greater electrodermal responsiveness. The magnitude of the fetal motor response significantly corresponded to the maternal skin conductance response at 5, 10, 15, and 30 s following stimulation. Conclusion Elicited fetal movement exerts an independent influence on the maternal autonomic nervous system. This finding contributes to current models of the dyadic relationship during pregnancy between fetus and pregnant woman. PMID:24119937

Validating a human model for anxiety using startle potentiated by cue and context: the effects of alprazolam, pregabalin, and diphenhydramine

PubMed Central

Mol, N.; Kenemans, J. L.; Prinssen, E. P.; Niklson, I.; Xia-Chen, C.; Broeyer, F.; van Gerven, J.

2009-01-01

Background Fear-potentiated startle has been suggested as a translational model for evaluating efficacy of anxiolytic compounds in humans. Several known anxiolytic compounds have been tested as well as several putative anxiolytics. Because results of these studies have been equivocal, the aim of the present study was to examine another pharmacological permutation of the human potentiated startle model by comparing two anxiolytic agents to a non-anxiolytic sedative and placebo. Methods Twenty healthy volunteers participated in a double-blind, placebo-controlled, cross-over study with four sessions in which they received single doses of the anxiolytics alprazolam (1 mg) and pregabalin (200 mg), as well as diphenhydramine (50 mg) as a non-anxiolytic sedative control and placebo. The design included a cued shock condition that presumably evokes fear and an unpredictable shock context condition presumably evoking anxiety. Results None of the treatments reliably reduced either fear- or anxiety-potentiated startle. Alprazolam and diphenhydramine reduced overall baseline startle. Alprazolam was found to only affect contextual anxiety in a statistical significant way after two subjects who failed to show a contextual anxiety effect in the placebo condition were excluded from the analysis. Pregabalin did not significantly affect any of the physiological measures. Discussion The negative findings from this study are discussed in terms of methodological differences between designs and in variability of startle both between and within study participants. Conclusion Even though fear-potentiated startle may be used to translate preclinical evidence to human populations, methodological issues still hamper the application of this model to early screening of putative anxiolytic drugs. PMID:19415242

Oxytocin and Social Support as Synergistic Inhibitors of Aversive Fear Conditioning and Fear-Potentiated Startle in Male Rats

DTIC Science & Technology

2011-05-01

uring fear extinction in PTSD : an fMRI Study . CNS Neurosci Ther, print copy in press (originally published online 16 April 2010, at http://www3...alleviate one or more physiopathologies of PTSD . The effect of oxytocin on background anxiety in our fear- potentiated startle studies in rats is also...benefits for patients with PTSD . fear; anxiety; PTSD ; startle; social isolation 60 jrosen@udel.edu Table of Contents

Exaggerated neurobiological sensitivity to threat as a mechanism linking anxiety with increased risk for diseases of aging

PubMed Central

O’Donovan, Aoife; Slavich, George M; Epel, Elissa S.; Neylan, Thomas C

2015-01-01

Anxiety disorders increase risk for the early development of several diseases of aging. Elevated inflammation, a common risk factor across diseases of aging, may play a key role in the relationship between anxiety and physical disease. However, the neurobiological mechanisms linking anxiety with elevated inflammation remain unclear. In this review, we present a neurobiological model of the mechanisms by which anxiety promotes inflammation. Specifically we propose that exaggerated neurobiological sensitivity to threat in anxious individuals may lead to sustained threat perception, which is accompanied by prolonged activation of threat-related neural circuitry and threat-responsive biological systems including the hypothalamic-pituitary-adrenal (HPA) axis, autonomic nervous system (ANS), and inflammatory response. Over time, this pattern of responding can promote chronic inflammation through structural and functional brain changes, altered sensitivity of immune cell receptors, dysregulation of the HPA axis and ANS, and accelerated cellular aging. Chronic inflammation, in turn, increases risk for diseases of aging. Exaggerated neurobiological sensitivity to threat may thus be a treatment target for reducing disease risk in anxious individuals. PMID:23127296

The CRH1 Antagonist GSK561679 Increases Human Fear But Not Anxiety as Assessed by Startle

PubMed Central

Grillon, Christian; Hale, Elizabeth; Lieberman, Lynne; Davis, Andrew; Pine, Daniel S; Ernst, Monique

2015-01-01

Fear to predictable threat and anxiety to unpredictable threat reflect distinct processes mediated by different brain structures, the central nucleus of the amygdala and the bed nucleus of the stria terminalis (BNST), respectively. This study tested the hypothesis that the corticotropin-releasing factor (CRF1) antagonist GSK561679 differentially reduces anxiety but increases fear in humans. A total of 31 healthy females received each of four treatments: placebo, 50 mg GSK561679 (low-GSK), 400 mg GSK561679 (high-GSK), and 1 mg alprazolam in a crossover design. Participants were exposed to three conditions during each of the four treatments. The three conditions included one in which predictable aversive shocks were signaled by a cue, a second during which shocks were administered unpredictably, and a third condition without shock. Fear and anxiety were assessed using the acoustic startle reflex. High-GSK had no effect on startle potentiation during unpredictable threat (anxiety) but increased startle potentiation during the predictable condition (fear). Low-GSK did not affect startle potentiation across conditions. Consistent with previous findings, alprazolam reduced startle potentiation during unpredictable threat but not during predictable threat. The increased fear by high-GSK replicates animal findings and suggests a lift of the inhibitory effect of the BNST on the amygdala by the CRF1 antagonist. PMID:25430779

Anxiogenic-like effect of chronic corticosterone in the light-dark emergence task in mice.

PubMed

Ardayfio, Paul; Kim, Kwang-Soo

2006-04-01

Chronic hypercortisolemia is a hallmark of neuroendocrine and psychiatric disorders, such as Cushing's disease and depression. Whether cortisol directly contributes to the altered mood and anxiety symptoms seen in these diseases remains unclear. To address this, the authors have modeled hypercortisolemia by administering corticosterone in the drinking water of female Swiss Webster mice for 17 or 18 days (13 mg/kg). Light-dark emergence, startle habituation, and startle reactivity were measured. Chronic but not acute treatment with corticosterone increased the latency to emerge into the light compartment, an anxiogenic-like effect. Chronic corticosterone treatment did not affect startle habituation, but did reduce startle reactivity. This study suggests that chronic hypercortisolemia may contribute to anxiety-related behavior in patients with Cushing's disease and depression. ((c) 2006 APA, all rights reserved).

Male-male competition and female choice are differentially affected by male call acoustics in the serrate-legged small treefrog, Kurixalus odontotarsus.

PubMed

Zhu, Bicheng; Wang, Jichao; Zhao, Longhui; Chen, Qinghua; Sun, Zhixin; Yang, Yue; Brauth, Steven E; Tang, Yezhong; Cui, Jianguo

2017-01-01

The evolution of exaggerated vocal signals in anuran species is an important topic. Males and females have both evolved the ability to discriminate communication sounds. However, the nature of sexual dimorphism in cognition and sensory discrimination and in the evolution and limitation of sexual signal exaggeration remain relatively unexplored. In the present study, we used male calls of varied complexity in the serrate-legged small treefrog, Kurixalus odontotarsus , as probes to investigate how both sexes respond to variations in call complexity and how sex differences in signal discrimination play a role in the evolution of sexual signal exaggeration. The compound calls of male K. odontotarsus consist of a series of one or more harmonic notes (A notes) which may be followed by one or more short broadband notes (B notes). Male playback experiments and female phonotaxis tests showed that increasing the number of A notes in stimulus calls elicits increased numbers of response calls by males and increases the attractiveness of the stimulus calls to females. The addition of B notes, however, reduces male calling responses. Moreover, call stimuli which contain only B notes suppress spontaneous male calling responses. Phonotaxis experiments show that females prefer calls with greater numbers of A notes and calls containing both A notes and B notes, but do not prefer calls with only B notes. Male-male competition and female choice appear to have played different roles in the evolution and limitation of signal complexity in K. odontotarsus . These results provide new insights into how exaggerated compound signals evolve and how signal complexity may be limited in anurans.

Exaggerated Increases in Microglia Proliferation, Brain Inflammatory Response and Sickness Behaviour upon Lipopolysaccharide Stimulation in Non-Obese Diabetic Mice.

PubMed

McGuiness, Barry; Gibney, Sinead M; Beumer, Wouter; Versnel, Marjan A; Sillaber, Inge; Harkin, Andrew; Drexhage, Hemmo A

2016-01-01

The non-obese diabetic (NOD) mouse, an established model for autoimmune diabetes, shows an exaggerated reaction of pancreas macrophages to inflammatory stimuli. NOD mice also display anxiety when immune-stimulated. Chronic mild brain inflammation and a pro-inflammatory microglial activation is critical in psychiatric behaviour. To explore brain/microglial activation and behaviour in NOD mice at steady state and after systemic lipopolysaccharide (LPS) injection. Affymetrix analysis on purified microglia of pre-diabetic NOD mice (8-10 weeks) and control mice (C57BL/6 and CD1 mice, the parental non-autoimmune strain) at steady state and after systemic LPS (100 μg/kg) administration. Quantitative PCR was performed on the hypothalamus for immune activation markers (IL-1β, IFNγ and TNFα) and growth factors (BDNF and PDGF). Behavioural profiling of NOD, CD1, BALB/c and C57BL/6 mice at steady state was conducted and sickness behaviour/anxiety in NOD and CD1 mice was monitored before and after LPS injection. Genome analysis revealed cell cycle/cell death and survival aberrancies of NOD microglia, substantiated as higher proliferation on BrdU staining. Inflammation signs were absent. NOD mice had a hyper-reactive response to novel environments with some signs of anxiety. LPS injection induced a higher expression of microglial activation markers, a higher brain pro-inflammatory set point (IFNγ, IDO) and a reduced expression of BDNF and PDGF after immune stimulation in NOD mice. NOD mice displayed exaggerated and prolonged sickness behaviour after LPS administration. After stimulation with LPS, NOD mice display an increased microglial proliferation and an exaggerated inflammatory brain response with reduced BDNF and PDGF expression and increased sickness behaviour as compared to controls. © 2016 S. Karger AG, Basel.

Tramadol and another atypical opioid meperidine have exaggerated serotonin syndrome behavioral effects, but decreased analgesic effects, in genetically-deficient serotonin transporter (SERT) mice

PubMed Central

Fox, Meredith A.; Jensen, Catherine L.; Murphy, Dennis L.

2009-01-01

The serotonin syndrome is a potential side effect of serotonin-enhancing drugs, including antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs). We recently reported a genetic mouse model for the serotonin syndrome, as serotonin transporter (SERT)-deficient mice have exaggerated serotonin syndrome behavioral responses to the MAOI tranylcypromine and the serotonin precursor 5-hydroxy-L-tryptophan (5-HTP). As numerous case reports implicate the atypical opioids tramadol and meperidine in the development of the human serotonin syndrome, we examined tramadol and meperidine as possible causative drugs in the rodent model of the serotonin syndrome in SERT wildtype (+/+), heterozygous (+/−) and knockout (−/−) mice. Comparisons were made to SERT mice treated with either vehicle or morphine, an opioid not implicated in the serotonin syndrome in humans. Here we show that tramadol and meperidine, but not morphine, induce serotonin syndrome-like behaviors in mice, and we show that this response is exaggerated in mice lacking one or two copies of SERT. The exaggerated response to tramadol in SERT −/− mice was blocked by pretreatment with the 5-HT1A antagonist WAY 100635. Further, we show that morphine-, meperidine- and tramadol-induced analgesia is markedly decreased in SERT −/− mice. These studies suggest that caution seems warranted in prescribing or not warning patients receiving SSRIs or MAOIs, that dangerous side effects may occur during concurrent use of tramadol and similar agents. These findings suggest that it is conceivable that there might be increased vulnerability in individuals with SERT polymorphisms that may reduce SERT by more than 50%, the level in SERT +/− mice. PMID:19275775

Thyroxine: effects of neonatal administration on maturation, development, and behavior.

PubMed

Schapiro, S; Norman, R J

1967-03-10

Thyroxine was administered to infant rats within the first 3 days of postnatal life; controls receiving 0.01N NaOH were from the same litter. Thyroxine accelerated the maturation of the pituitary-adrenal response to elec tric shock. The "startle response" ap peared earlier in the experimental ani mals, as did the development and re sponse of the electroencephalogram to novel stimuli. The thyroxine-treated rats, when 16 to 18 days old, acquired a conditioned-avoidance response faster than did controls.

Sensory Substitution for Wounded Servicemembers

DTIC Science & Technology

2009-10-28

recently blinded individual without verbal notification (e.g., to tap his or her shoulder) can lead to a startle response as he or she can not perceive...34. WUtWt IM» 1 *• ,. .. ,„ List RtcoQWTtd °ftoflfi/n# male short a Figure 6: / eft , BrainPort® display showing stereo presentation of a

The Acoustic Startle Response and Disruption of Aiming. 1. Effect of Stimulus Repetition, Intensity, and Intensity Changes

DTIC Science & Technology

1989-11-01

PEST consisting of an approximate one-third oc- procedure described by Taylor and Creelman tave band centered at 800 Hz (cutoffs at 700 (1967...to some extent Taylor, M. M., and Creelman . C. D. (1967). PEST: Efficient estimates on probability functions. Journal of the performance disruption

Physiologic Responses to Racial Rejection Images among Young Adults from African-American Backgrounds

ERIC Educational Resources Information Center

Kiang, Lisa; Blumenthal, Terry D.; Carlson, Erika N.; Lawson, Yolanda N.; Shell, J. Clark

2009-01-01

Physiologic reactivity to racially rejecting images was assessed in 35 young adults (10 males, 25 female) from African-American backgrounds using the startle probe paradigm. In a laboratory setting, participants viewed 16 images depicting racial rejection, racial acceptance, nonracial negative, and nonracial positive themes. While viewing these…

The Role of Peer Relationships and Interactions in Preschool Bilingual Children's Responses to Picture Books

ERIC Educational Resources Information Center

Kim, So Jung

2016-01-01

In spite of the emphasis on the importance of social contexts in children's literacy development, there is still a startling scarcity of studies examining the role of peer relationships in preschool bilinguals' literary practices. This qualitative case study investigates how peer relationships and interactions among preschool, Korean-English…

Stuttering in Adults: The Acoustic Startle Response, Temperamental Traits, and Biological Factors

ERIC Educational Resources Information Center

Alm, Per A.; Risberg, Jarl

2007-01-01

The purpose of this study was to investigate the relation between stuttering and a range of variables of possible relevance, with the main focus on neuromuscular reactivity, and anxiety. The explorative analysis also included temperament, biochemical variables, heredity, preonset lesions, and altered auditory feedback (AAF). An increased level of…

Psychophysiological reactivity of currently dental phobic-, remitted dental phobic- and never-dental phobic individuals during exposure to dental-related and other affect-inducing materials.

PubMed

Wannemueller, André; Adolph, Dirk; Joehren, Hans-Peter; Blackwell, Simon E; Margraf, Jürgen

2017-03-01

Psychophysiological responses indicating the preparation of defensive behaviour, such as heart rate (HR)-increase and startle-response (SR) potentiation, have often been reported amongst individuals suffering from phobic disorders when exposed to phobia-related information. Although exposure is widely considered the 'gold standard' for treatment of Specific Phobia, it is unclear to what extent psychophysiological defensive response patterns change following treatment, and whether any changes are maintained. We assessed the acoustic SR- and HR-response to neutral, positive, negative and phobia-related pictures and sounds in 41 individuals currently suffering from dental phobia, 22 formerly dental phobic individuals who had remitted following an exposure-based treatment eight months prior to assessment, and 29 control individuals with no history of dental phobia. We observed SR-potentiation to dental-related stimuli in controls combined with HR-deceleration. In contrast, amongst phobic individuals SR-potentiation was accompanied by HR-acceleration to dental pictures. Successfully treated individuals showed inhibited startle reactivity in combination with HR-deceleration to dental related materials of both modalities. Our findings suggest inappropriate fight-flight preparation amongst individuals with dental phobia, reflecting overactivation of the defensive system. However, successful treatment results in inhibited physiological defence preparation, with remitted individuals displaying a response pattern that differed from that of phobic individuals and controls. Copyright © 2016 Elsevier Ltd. All rights reserved.

Development of fear acquisition and extinction in children: effects of age and anxiety.

PubMed

Jovanovic, Tanja; Nylocks, Karin Maria; Gamwell, Kaitlyn L; Smith, Ami; Davis, Telsie A; Norrholm, Seth Davin; Bradley, Bekh

2014-09-01

Development of anxiety disorders is associated with neurobiological changes in areas that are a critical part of the fear neurocircuitry. Fear conditioning paradigms can offer insight into the mechanisms underlying the neurobiological ontogeny of anxiety. A small number of studies have focused on the effects of age and anxiety separately in school age children. The present study aimed to investigate these effects in 8-13 year old children with higher and lower trait anxiety. We examined differential fear conditioning and extinction using skin conductance responses and fear-potentiated startle in 60 children recruited from a low-income urban population. The results indicated that children under 10 years of age show poor discrimination of conditioned stimuli, and that anxiety increases fear responses during fear acquisition. After controlling for age and trauma exposure, fear-potentiated startle to the safety cue predicted child anxiety levels suggesting that impaired safety signal learning may be a risk factor for anxiety disorders in adulthood. Identifying risk phenotypes in children may provide opportunities for early intervention and prevention of illness. Copyright © 2013 Elsevier Inc. All rights reserved.

Development of Fear Acquisition and Extinction in Children: Effects of Age and Anxiety

PubMed Central

Jovanovic, Tanja; Nylocks, Karin Maria; Gamwell, Kaitlyn L.; Smith, Ami; Davis, Telsie A.; Norrholm, Seth Davin; Bradley, Bekh

2013-01-01

Development of anxiety disorders is associated with neurobiological changes in areas that are a critical part of the fear neurocircuitry. Fear conditioning paradigms can offer insight into the mechanisms underlying the neurobiological ontogeny of anxiety. A small number of studies have focused on the effects of age and anxiety separately in school age children. The present study aimed to investigate these effects in 8-13 year old children with higher and lower trait anxiety. We examined differential fear conditioning and extinction using skin conductance responses and fear-potentiated startle in 60 children recruited from a low-income urban population. The results indicated that children under 10 years of age show poor discrimination of conditioned stimuli, and that anxiety increases fear responses during fear acquisition. After controlling for age and trauma exposure, fear-potentiated startle to the safety cue predicted child anxiety levels suggesting that impaired safety signal learning may be a risk factor for anxiety disorders in adulthood. Identifying risk phenotypes in children may provide opportunities for early intervention and prevention of illness. PMID:24183838

Prefrontal oxygenation and the acoustic startle eyeblink response during exercise: A test of the dual-mode model.

PubMed

Tempest, Gavin D; Parfitt, Gaynor

2017-07-01

The interplay between the prefrontal cortex and amygdala is proposed to explain the regulation of affective responses (pleasure/displeasure) during exercise as outlined in the dual-mode model. However, due to methodological limitations the dual-mode model has not been fully tested. In this study, prefrontal oxygenation (using near-infrared spectroscopy) and amygdala activity (reflected by eyeblink amplitude using acoustic startle methodology) were recorded during exercise standardized to metabolic processes: 80% of ventilatory threshold (below VT), at the VT, and at the respiratory compensation point (RCP). Self-reported tolerance of the intensity of exercise was assessed prior to, and affective responses recorded during exercise. The results revealed that, as the intensity of exercise became more challenging (from below VT to RCP), prefrontal oxygenation was larger and eyeblink amplitude and affective responses were reduced. Below VT and at VT, larger prefrontal oxygenation was associated with larger eyeblink amplitude. At the RCP, prefrontal oxygenation was greater in the left than right hemisphere, and eyeblink amplitude explained significant variance in affective responses (with prefrontal oxygenation) and self-reported tolerance. These findings highlight the role of the prefrontal cortex and potentially the amygdala in the regulation of affective (particularly negative) responses during exercise at physiologically challenging intensities (above VT). In addition, a psychophysiological basis of self-reported tolerance is indicated. This study provides some support of the dual-mode model and insight into the neural basis of affective responses during exercise. © 2017 Society for Psychophysiological Research.

Interactions of Stress and Nicotine on Amplitude, Pre-Pulse Inhibition and Habituation of the Acoustic Startle Reflex

DTIC Science & Technology

1992-09-24

Marquez , Armario , & Gelpi, 1988) consistent with a stress response . Restraint stress has been reported to increase the amplitude of sensory...and NE in the brain (Adell , Garcia- Marquez , Armario , & Gelpi , 1988) consistent with a stress response. Restraint stress has been reported t o...and non- reactive strains. Al coholism. Clinical and Experimental Research, ~(2), 170-174. Adell, A., Garcia - Marquez, C., Armario , A. , & Gelpi , E

Effect of "enriched environment" during development on adult rat behavior and response to the dopamine receptor agonist apomorphine.

PubMed

Hoffmann, L C; Schütte, S R M; Koch, M; Schwabe, K

2009-02-18

Enriched housing conditions (enriched environment, EE) during development has been shown to influence adult rat behavior and transmitter systems, especially dopamine function. We were interested in how different degrees of enrichment during development would affect adult rats' behavior and response to dopamine receptor challenge. Two groups of male Wistar rats (n=11-12) were raised under two different degrees of EE, i.e. "high enriched" and "low enriched" groups. A third group was kept under standard conditions and served as "non-enriched" control. As adults, rats were tested for anxiety (elevated plus-maze), for spatial learning (four-arm-baited eight-arm radial maze), and for motivation (breakpoint of the progressive ratio test). Finally, locomotor activity (activity box) and sensorimotor gating (prepulse inhibition (PPI) of the acoustic startle response (ASR)) were tested with and without challenge with the dopamine receptor agonist apomorphine. The time spent on the open or enclosed arms of the elevated plus-maze did not differ between groups, but the high enriched group showed higher rearing activity on the open arms. The breakpoint did not differ between groups. Learning and memory in the radial maze task only differed on the first few trials, but high enriched rats run faster compared with the other groups. In contrast, in the activity box enriched groups were less active, but apomorphine had the highest effect. Between groups, no difference in PPI and startle amplitude was found, but in the high and low EE group startle amplitude was enhanced after administration of apomorphine, while the PPI deficit induced by this drug was not different between groups. Altogether, we found no evidence that different amounts of environmental enrichment without differences in social EE affect rats' cognitive, emotional or motivational behavior. However, motor activity seems to be enhanced when rats are behaviorally or pharmacologically challenged by dopamine receptor agonists.

Assessment of Glutamate Transporter GLAST (EAAT1)-Deficient Mice for Phenotypes Relevant to the Negative and Executive/Cognitive Symptoms of Schizophrenia

PubMed Central

Karlsson, Rose-Marie; Tanaka, Kohichi; Saksida, Lisa M; Bussey, Timothy J; Heilig, Markus; Holmes, Andrew

2012-01-01

Glutamatergic dysfunction is increasingly implicated in the pathophysiology of schizophrenia. Current models postulate that dysfunction of glutamate and its receptors underlie many of the symptoms in this disease. However, the mechanisms involved are not well understood. Although elucidating the role for glutamate transporters in the disease has been limited by the absence of pharmacological tools that selectively target the transporter, we recently showed that glial glutamate and aspartate transporter (GLAST; excitatory amino-acid transporter 1) mutant mice exhibit abnormalities on behavioral measures thought to model the positive symptoms of schizophrenia, some of which were rescued by treatment with either haloperidol or the mGlu2/3 agonist, LY379268 the mGlu2/3 agonist, LY379268. To further determine the role of GLAST in schizophrenia-related behaviors we tested GLAST mutant mice on a series of behavioral paradigms associated with the negative (social withdrawal, anhedonia), sensorimotor gating (prepulse inhibition of startle), and executive/cognitive (discrimination learning, extinction) symptoms of schizophrenia. GLAST knockout (KO) mice showed poor nesting behavior and abnormal sociability, whereas KO and heterozygous (HET) both demonstrated lesser preference for a novel social stimulus compared to wild-type littermate controls. GLAST KO, but not HET, had a significantly reduced acoustic startle response, but no significant deficit in prepulse inhibition of startle. GLAST KO and HET showed normal sucrose preference. In an instrumental visual discrimination task, KO showed impaired learning. By contrast, acquisition and extinction of a simple instrumental response was normal. The mGlu2/3 agonist, LY379268, failed to rescue the discrimination impairment in KO mice. These findings demonstrate that gene deletion of GLAST produces select phenotypic abnormalities related to the negative and cognitive symptoms of schizophrenia. PMID:19078949

Rasch Measurement: A Response to Payanides, Robinson and Tymms

ERIC Educational Resources Information Center

Goldstein, Harvey

2015-01-01

A response is made to a paper that urges the use of the Rasch model for educational assessment. This paper argues that the model is inadequate and that claims for its efficacy are exaggerated and technically weak.

Effects of the NMDA receptor antagonist memantine on the expression and development of acute opiate dependence as assessed by withdrawal-potentiated startle and hyperalgesia.

PubMed

Harris, Andrew C; Rothwell, Patrick E; Gewirtz, Jonathan C

2008-03-01

While the N-methyl-D: -aspartate (NMDA) glutamate receptor has been strongly implicated in chronic opiate dependence, relatively few studies have examined the effects of NMDA receptor antagonists on withdrawal from acute opiate exposure. The current study examined the effects of memantine, a well-tolerated NMDA receptor antagonist, on acute opiate dependence as assessed by elevations in rodent startle responding (i.e., "withdrawal-potentiated startle") and increased pain sensitivity (i.e., hyperalgesia). Administration of memantine either attenuated (5 mg/kg) or blocked (10 mg/kg) the expression of withdrawal-potentiated startle during naloxone (2.5 mg/kg)-precipitated withdrawal from a single dose of morphine sulfate (10 mg/kg). Pre-treatment with the NMDA receptor antagonist also inhibited the exacerbation of withdrawal-potentiated startle across repeated acute opiate exposures. Memantine blocked the expression of acute dependence, but was less effective in inhibiting its escalation, when hyperalgesia was used as a measure of withdrawal. These doses of memantine did not affect startle responding or nociception in otherwise drug-free animals. Data from additional control groups indicated that the effects of memantine on the expression of withdrawal were not influenced by nonspecific interactions between the NMDA antagonist and either morphine or naloxone. These findings suggest that the NMDA receptor may play a key role in the earliest stages of opiate dependence and provide further evidence that memantine may be useful for the treatment of opiate withdrawal.

Describing the interplay between anxiety and cognition: From impaired performance under low cognitive load to reduced anxiety under high load

PubMed Central

Vytal, Katherine; Cornwell, Brian; Arkin, Nicole; Grillon, Christian

2012-01-01

Anxiety impairs the ability to think and concentrate, suggesting that the interaction between emotion and cognition may elucidate the debilitating nature of pathological anxiety. Using a verbal n-back task that parametrically modulated cognitive load, we explored the effect of experimentally-induced anxiety on task performance and the startle reflex. Findings suggest there is a crucial inflection point between moderate and high cognitive load, where resources shift from anxious apprehension to focus on task demands. Specifically, we demonstrate that anxiety impairs performance under low-load, but is reduced when subjects engage in a difficult task that occupies executive resources. We propose a two-component model of anxiety that describes a cognitive mechanism behind performance impairment and an automatic response that supports sustained anxiety-potentiated startle. Implications for therapeutic interventions and emotional pathology are discussed. PMID:22332819

Affective responsiveness, betrayal, and childhood abuse.

PubMed

Reichmann-Decker, Aimee; DePrince, Anne P; McIntosh, Daniel N

2009-01-01

Several trauma-specific and emotion theories suggest that alterations in children's typical affective responses may serve an attachment function in the context of abuse by a caregiver or close other. For example, inhibiting negative emotional responses or expressions might help the child preserve a relationship with an abusive caregiver. Past research in this area has relied on self-report methods to discover links between affective responsiveness and caregiver abuse. Extending this literature, the current study used facial electromyography to assess affective responsiveness with 2 measures: mimicry of emotional facial expressions and affective modulation of startle. We predicted that women who reported childhood abuse by close others would show alterations in affective responsiveness relative to their peers. We tested 100 undergraduate women who reported histories of (a) childhood sexual or physical abuse by someone close, such as a parent (high-betrayal); (b) childhood abuse by someone not close (low-betrayal); or (c) no abuse in childhood (no-abuse). Especially when viewing women's emotional expressions, the high-betrayal group showed more mimicry of happy and less mimicry of angry faces relative to women who reported no- or low-betrayal abuse, who showed the opposite pattern. Furthermore, women who reported high-betrayal abuse showed less affective modulation of startle during pictures depicting men threatening women than did the other two groups. Findings suggest that, as predicted by betrayal trauma theory, women who have experienced high-betrayal abuse show alterations in automatic emotional processes consistent with caregiving-maintenance goals in an abusive environment.

NEAR ROADWAYS EXPOSURE TO URBAN AIR POLLUTANTS STUDY (NEXUS)

EPA Science Inventory

The proposed research addresses both the effects and the mechanisms by which traffic-associated exposures induce exaggerated airway responses in children with asthma, and how these exposures cause biologic responses on inflammatory pathways, oxidative stress, and the frequ...

Measuring Anxious Responses to Predictable and Unpredictable Threat in Children and Adolescents

ERIC Educational Resources Information Center

Schmitz, Anja; Merikangas, Kathleen; Swendsen, Haruka; Cui, Lihong; Heaton, Leann; Grillon, Christian

2011-01-01

Research has highlighted the need for new methods to assess emotions in children on multiple levels to gain better insight into the complex processes of emotional development. The startle reflex is a unique translational tool that has been used to study physiological processes during fear and anxiety in rodents and in human participants. However,…

Comparison of Symptom Distress between World War II Ex-POWs and Vietnam Combat Veterans with Post Traumatic Stress Disorder.

ERIC Educational Resources Information Center

Miller, David J.; And Others

It has been documented that exposure to severe and prolonged stress can result in emotional disturbances which may last for decades. Research has focused on the diagnosis of Post-traumatic Stress Disorder (PTSD), symptoms of which include flashbacks, increased startle response, interpersonal withdrawal, suspiciousness, impulsivity, and…

Psychophysiological Investigation of Combat Veterans with Subthreshold Post-traumatic Stress Disorder Symptoms.

PubMed

Costanzo, Michelle; Jovanovic, Tanja; Norrholm, Seth D; Ndiongue, Rochelle; Reinhardt, Brian; Roy, Michael J

2016-08-01

Military service members (SMs) with subthreshold combat-related post-traumatic stress disorder (PTSD) symptoms often have clinically significant functional impairment, even though they do not meet full PTSD criteria. We therefore assessed the psychophysical responses of SMs, upon their return from Afghanistan or Iraq, to a fear conditioning paradigm to better understand the biological underpinnings of symptom severity. Heart rate (HR), skin conductance, electromyography startle, and respiratory rate (RR) were monitored throughout three distinct phases of the paradigm-fear acquisition, fear inhibition, and fear extinction-while plasma catecholamines (epinephrine, norepinephrine, and dopamine) were measured at the end of fear inhibition. Those with higher PTSD symptom severity demonstrated elevations in HR and startle response to danger cues; elevated self-reported depression and anxiety; impaired functional status; poor skin conductance discrimination between danger and safety; and increases in HR and RR during fear extinction. Moreover, an inverse relationship was seen between plasma dopamine and HR during fear inhibition for those with high symptoms. Overall, the physiological responses we observed in our subthreshold PTSD population parallel what has been previously observed in full PTSD, making a case for addressing subthreshold PTSD symptoms in combat veterans. Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.

The effects of flow on schooling Devario aequipinnatus: school structure, startle response and information transmission

PubMed Central

Chicoli, A.; Butail, S.; Lun, Y.; Bak-Coleman, J.; Coombs, S.; Paley, D.A.

2014-01-01

To assess how flow affects school structure and threat detection, startle response rates of solitary and small groups of giant danio Devario aequipinnatus were compared to visual looming stimuli in flow and no-flow conditions. The instantaneous position and heading of each D. aequipinnatus were extracted from high-speed videos. Behavioural results indicate that (1) school structure is altered in flow such that D. aequipinnatus orient upstream while spanning out in a crosswise direction, (2) the probability of at least one D. aequipinnatus detecting the visual looming stimulus is higher in flow than no flow for both solitary D. aequipinnatus and groups of eight D. aequipinnatus, however, (3) the probability of three or more individuals responding is higher in no flow than flow. Taken together, these results indicate a higher probability of stimulus detection in flow but a higher probability of internal transmission of information in no flow. Finally, results were well predicted by a computational model of collective fright response that included the probability of direct detection (based on signal detection theory) and indirect detection (i.e. via interactions between group members) of threatening stimuli. This model provides a new theoretical framework for analysing the collective transfer of information among groups of fishes and other organisms. PMID:24773538

The Relationship Between Facial Skin Surface Temperature Reactivity and Traditional Polygraph Measures Used in the Psychophysiological Detection of Deception: A Preliminary Investigation

DTIC Science & Technology

2002-03-01

Surface Temperature and Polygraph Measures 19 References Cook , E. and Turpin , G. ( 1997 ). Differentiating orienting, startle, and defense responses... Turpin , 1997 ). The results of the present study also suggest that, in the forehead and periorbital region, the situation is complex. A multivariate...Facial Skin Surface Temperature and Polygraph Measures 3 areas would be differentially affected by participants’ fear-induced central and ANS responses to

Role of ribonuclease L in viral pathogen-associated molecular pattern/influenza virus and cigarette smoke-induced inflammation and remodeling.

PubMed

Zhou, Yang; Kang, Min-Jong; Jha, Babal Kant; Silverman, Robert H; Lee, Chun Geun; Elias, Jack A

2013-09-01

Interactions between cigarette smoke (CS) exposure and viral infection play an important role(s) in the pathogenesis of chronic obstructive pulmonary disease and a variety of other disorders. A variety of lines of evidence suggest that this interaction induces exaggerated inflammatory, cytokine, and tissue remodeling responses. We hypothesized that the 2'-5' oligoadenylate synthetase (OAS)/RNase L system, an innate immune antiviral pathway, plays an important role in the pathogenesis of these exaggerated responses. To test this hypothesis, we characterize the activation of 2'-5' OAS in lungs from mice exposed to CS and viral pathogen-associated molecular patterns (PAMPs)/live virus, alone and in combination. We also evaluated the inflammatory and remodeling responses induced by CS and virus/viral PAMPs in lungs from RNase L null and wild-type mice. These studies demonstrate that CS and viral PAMPs/live virus interact in a synergistic manner to stimulate the production of select OAS moieties. They also demonstrate that RNase L plays a critical role in the pathogenesis of the exaggerated inflammatory, fibrotic, emphysematous, apoptotic, TGF-β1, and type I IFN responses induced by CS plus virus/viral PAMP in combination. These studies demonstrate that CS is an important regulator of antiviral innate immunity, highlight novel roles of RNase L in CS plus virus induced inflammation, tissue remodeling, apoptosis, and cytokine elaboration and highlight pathways that may be operative in chronic obstructive pulmonary disease and mechanistically related disorders.

Investigation of a central nucleus of the amygdala/dorsal raphe nucleus serotonergic circuit implicated in fear-potentiated startle

PubMed Central

Spannuth, Benjamin M.; Hale, Matthew W.; Evans, Andrew K.; Lukkes, Jodi L.; Campeau, Serge; Lowry, Christopher A.

2011-01-01

Serotonergic systems are thought to play an important role in control of motor activity and emotional states. We used a fear-potentiated startle paradigm to investigate the effects of a motor-eliciting stimulus in the presence or absence of induction of an acute fear state on serotonergic neurons in the dorsal raphe nucleus (DR) and cells in subdivisions of the central amygdaloid nucleus (CE), a structure that plays an important role in fear responses, using induction of the protein product of the immediate-early gene, c-fos. In Experiment 1 we investigated the effects of fear conditioning training, by training rats to associate a light cue (conditioned stimulus, CS; 1000 lx, 2 sec) with foot shock (0.5 s, 0.5 mA) in a single session. In Experiment 2 rats were given two training sessions identical to Experiment 1 on days 1 and 2, then tested in one of four conditions on day 3: 1) placement in the training context without exposure to either the CS or acoustic startle (AS), 2) exposure to 10 trials of the 2 s CS, 3) exposure to 40 110 dB AS trials, or 4) exposure to 40 110 dB AS trials with 10 of the trials preceded by and co-terminating with the CS. All treatments were conducted during a 20 min session. Fear conditioning training, by itself, increased c-Fos expression in multiple subdivisions of the CE and throughout the DR. In contrast, fear-potentiated startle selectively increased c-Fos expression in the medial subdivision of the CE and in serotonergic neurons in the dorsal part of the dorsal raphe nucleus (DRD). These data are consistent with previous studies demonstrating that fear-related stimuli selectively activate DRD serotonergic neurons. Further studies of this mesolimbocortical serotonergic system could have important implications for understanding mechanisms underlying vulnerability to stress-related psychiatric disorders, including anxiety and affective disorders. PMID:21277950

Developmental lead exposure causes startle response deficits in zebrafish.

PubMed

Rice, Clinton; Ghorai, Jugal K; Zalewski, Kathryn; Weber, Daniel N

2011-10-01

Lead (Pb(2+)) exposure continues to be an important concern for fish populations. Research is required to assess the long-term behavioral effects of low-level concentrations of Pb(2+) and the physiological mechanisms that control those behaviors. Newly fertilized zebrafish embryos (<2h post fertilization; hpf) were exposed to one of three concentrations of lead (as PbCl(2)): 0, 10, or 30 nM until 24 hpf. (1) Response to a mechanosensory stimulus: Individual larvae (168 hpf) were tested for response to a directional, mechanical stimulus. The tap frequency was adjusted to either 1 or 4 taps/s. Startle response was recorded at 1000 fps. Larvae responded in a concentration-dependent pattern for latency to reaction, maximum turn velocity, time to reach V(max) and escape time. With increasing exposure concentrations, a larger number of larvae failed to respond to even the initial tap and, for those that did respond, ceased responding earlier than control larvae. These differences were more pronounced at a frequency of 4 taps/s. (2) Response to a visual stimulus: Fish, exposed as embryos (2-24 hpf) to Pb(2+) (0-10 μM) were tested as adults under low light conditions (≈ 60 μW/m(2)) for visual responses to a rotating black bar. Visual responses were significantly degraded at Pb(2+) concentrations of 30 nM. These data suggest that zebrafish are viable models for short- and long-term sensorimotor deficits induced by acute, low-level developmental Pb(2+) exposures. Copyright © 2011 Elsevier B.V. All rights reserved.

Altered insula response to sweet taste processing after recovery from anorexia and bulimia nervosa

PubMed Central

Oberndorfer, Tyson A.; Frank, Guido K.W.; Simmons, Alan N.; Wagner, Angela; McCurdy, Danyale; Fudge, Julie L.; Yang, Tony T.; Paulus, Martin P.; Kaye, Walter H.

2014-01-01

Objective Recent studies suggest that altered function of higher-order appetitive neural circuitry may contribute to restricted eating in anorexia nervosa and overeating in bulimia nervosa. This study used sweet tastes to interrogate gustatory neurocircuitry involving the anterior insula and related regions that modulate sensory-interoceptive-reward signals in response to palatable foods. Method Subjects recovered from anorexia and bulimia were studied to avoid confounding effects of altered nutritional state. Functional magnetic resonance imaging measured brain response to repeated tastes of sucrose and sucralose to disentangle neural processing of caloric and non-caloric sweet tastes. Whole-brain functional analysis was constrained to anatomical regions of interest. Results Compared to matched control women (n=14), women recovered from anorexia (n=14) had diminished (F(1,27)=7.79, p=0.01) and women recovered from bulimia (n=14) had exaggerated (F(1,27)=6.12, p=0.02) right anterior insula hemodynamic response to tastes of sucrose. Furthermore, anterior insula responses to sucrose compared to sucralose was exaggerated in recovered subjects (lower in women recovered from anorexia and higher in women recovered from bulimia). Conclusions The anterior insula integrates sensory/reward aspects of taste in the service of nutritional homeostasis. For example, one possibility is that restricted eating and weight loss occur in anorexia nervosa because of a failure to accurately recognize hunger signals, whereas overeating in bulimia nervosa could represent an exaggerated perception of hunger signals. This response may reflect the altered calibration of signals related to sweet taste and the caloric content of food and may offer a pathway to novel and more effective treatments. PMID:23732817

Baseline psychophysiological and cortisol reactivity as a predictor of PTSD treatment outcome in virtual reality exposure therapy

PubMed Central

Norrholm, Seth Davin; Jovanovic, Tanja; Gerardi, Maryrose; Breazeale, Kathryn G.; Price, Matthew; Davis, Michael; Duncan, Erica; Ressler, Kerry J.; Bradley, Bekh; Rizzo, Albert; Tuerk, Peter W.; Rothbaum, Barbara O.

2017-01-01

Baseline cue-dependent physiological reactivity may serve as an objective measure of posttraumatic stress disorder (PTSD) symptoms. Additionally, prior animal model and psychological studies would suggest that subjects with greatest symptoms at baseline may have the greatest violation of expectancy to danger when undergoing exposure based psychotherapy; thus treatment approaches which enhanced the learning under these conditions would be optimal for those with maximal baseline cue-dependent reactivity. However methods to study this hypothesis objectively are lacking. Virtual reality (VR) methodologies have been successfully employed as an enhanced form of imaginal prolonged exposure therapy for the treatment of PTSD. Our goal was to examine the predictive nature of initial psychophysiological (e.g., startle, skin conductance, heart rate) and stress hormone responses (e.g., cortisol) during presentation of VR-based combat-related stimuli on PTSD treatment outcome. Combat veterans with PTSD underwent 6 weeks of VR exposure therapy combined with either D-cycloserine (DCS), alprazolam (ALP), or placebo (PBO). In the DCS group, startle response to VR scenes prior to initiation of treatment accounted for 76% of the variance in CAPS change scores, p < 0.001, in that higher responses predicted greater changes in symptom severity over time. Additionally, baseline cortisol reactivity was inversely associated with treatment response in the ALP group, p = 0.04. We propose that baseline cue-activated physiological measures will be sensitive to predicting patients’ level of response to exposure therapy, in particular in the presence of enhancement (e.g., DCS). PMID:27183343

Intrinsic Properties of Larval Zebrafish Neurons in Ethanol

PubMed Central

Ikeda, Hiromi; Delargy, Alison H.; Yokogawa, Tohei; Urban, Jason M.; Burgess, Harold A.; Ono, Fumihito

2013-01-01

The behavioral effects of ethanol have been studied in multiple animal models including zebrafish. Locomotion of zebrafish larvae is resistant to high concentrations of ethanol in bath solution. This resistance has been attributed to a lower systemic concentration of ethanol in zebrafish when compared with bath solution, although the mechanism to maintain such a steep gradient is unclear. Here we examined whether the intrinsic properties of neurons play roles in this resistance. In order to minimize the contribution of metabolism and diffusional barriers, larvae were hemisected and the anterior half immersed in a range of ethanol concentrations thereby ensuring the free access of bath ethanol to the brain. The response to vibrational stimuli of three types of reticulospinal neurons: Mauthner neurons, vestibulospinal neurons, and MiD3 neurons were examined using an intracellular calcium indicator. The intracellular [Ca2+] response in MiD3 neurons decreased in 100 mM ethanol, while Mauthner neurons and vestibulospinal neurons required >300 mM ethanol to elicit similar effects. The ethanol effect in Mauthner neurons was reversible following removal of ethanol. Interestingly, activities of MiD3 neurons displayed spontaneous recovery in 300 mM ethanol, suggestive of acute tolerance. Finally, we examined with mechanical vibration the startle response of free-swimming larvae in 300 mM ethanol. Ethanol treatment abolished long latency startle responses, suggesting a functional change in neural processing. These data support the hypothesis that individual neurons in larval zebrafish brains have distinct patterns of response to ethanol dictated by specific molecular targets. PMID:23658822

Cigarette smoke silences innate lymphoid cell function and facilitates an exacerbated type I interleukin-33-dependent response to infection.

PubMed

Kearley, Jennifer; Silver, Jonathan S; Sanden, Caroline; Liu, Zheng; Berlin, Aaron A; White, Natalie; Mori, Michiko; Pham, Tuyet-Hang; Ward, Christine K; Criner, Gerard J; Marchetti, Nathaniel; Mustelin, Tomas; Erjefalt, Jonas S; Kolbeck, Roland; Humbles, Alison A

2015-03-17

Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease and is presumed to be central to the altered responsiveness to recurrent infection in these patients. We examined the effects of smoke priming underlying the exacerbated response to viral infection in mice. Lack of interleukin-33 (IL-33) signaling conferred complete protection during exacerbation and prevented enhanced inflammation and exaggerated weight loss. Mechanistically, smoke was required to upregulate epithelial-derived IL-33 and simultaneously alter the distribution of the IL-33 receptor ST2. Specifically, smoke decreased ST2 expression on group 2 innate lymphoid cells (ILC2s) while elevating ST2 expression on macrophages and natural killer (NK) cells, thus altering IL-33 responsiveness within the lung. Consequently, upon infection and release, increased local IL-33 significantly amplified type I proinflammatory responses via synergistic modulation of macrophage and NK cell function. Therefore, in COPD, smoke alters the lung microenvironment to facilitate an alternative IL-33-dependent exaggerated proinflammatory response to infection, exacerbating disease. Copyright © 2015 Elsevier Inc. All rights reserved.

20 CFR 220.14 - Weighing of evidence.

Code of Federal Regulations, 2013 CFR

2013-04-01

... capacity evaluation is based upon functional objective tests with high validity and reliability; (2) The... exam findings which is indicative of exaggerated or potential malingering response; (6) The evidence...

20 CFR 220.14 - Weighing of evidence.

Code of Federal Regulations, 2011 CFR

2011-04-01

... capacity evaluation is based upon functional objective tests with high validity and reliability; (2) The... exam findings which is indicative of exaggerated or potential malingering response; (6) The evidence...

20 CFR 220.14 - Weighing of evidence.

Code of Federal Regulations, 2014 CFR

2014-04-01

... capacity evaluation is based upon functional objective tests with high validity and reliability; (2) The... exam findings which is indicative of exaggerated or potential malingering response; (6) The evidence...

20 CFR 220.14 - Weighing of evidence.

Code of Federal Regulations, 2012 CFR

2012-04-01

... capacity evaluation is based upon functional objective tests with high validity and reliability; (2) The... exam findings which is indicative of exaggerated or potential malingering response; (6) The evidence...

Valuing Teachers: How Much Is a Good Teacher Worth?

ERIC Educational Resources Information Center

Hanushek, Eric A.

2011-01-01

The magnitude of variation in the quality of teachers, even within each school, is startling. Teachers who work in a given school, and therefore teach students with similar demographic characteristics, can be responsible for increases in math and reading levels that range from a low of one-half year to a high of one and a half years of learning…

AX+, BX- Discrimination Learning in the Fear-Potentiated Startle Paradigm: Possible Relevance to Inhibitory Fear Learning in Extinction

ERIC Educational Resources Information Center

Myers, Karyn M.; Davis, Michael

2004-01-01

The neural mechanisms of fear suppression most commonly are studied through the use of extinction, a behavioral procedure in which a feared stimulus (i.e., one previously paired with shock) is nonreinforced repeatedly, leading to a reduction or elimination of the fear response. Although extinction is perhaps the most convenient index of fear…

How do anthropogenic contaminants (ACs) affect behaviour? Multi-level analysis of the effects of copper on boldness in hermit crabs.

PubMed

White, Stephen J; Briffa, Mark

2017-02-01

Natural animal populations are increasingly exposed to human impacts on the environment, which could have consequences for their behaviour. Among these impacts is exposure to anthropogenic contaminants. Any environmental variable that influences internal state could impact behaviour across a number of levels: at the sample mean, at the level of among-individual differences in behaviour ('animal personality') and at the level of within-individual variation in behaviour (intra-individual variation, 'IIV'). Here we examined the effect of exposure to seawater-borne copper on the startle response behaviour of European hermit crabs, Pagurus bernhardus across these levels. Copper exposure rapidly led to longer startle responses on average, but did not lead to any change in repeatability indicating that individual differences were present and equally consistent in the presence and absence of copper. There was no strong evidence that copper exposure led to changes in IIV. Our data show that exposure to copper for 1 week produces sample mean level changes in the behaviour of hermit crabs. However, there is no evidence that this exposure led to changes in repeatability through feedback loops.

Short-term and persistent impacts on behaviors related to locomotion, anxiety, and startle responses of Japanese medaka (Oryzias latipes) induced by acute, sublethal exposure to chlorpyrifos.

PubMed

Qiu, Xuchun; Nomichi, Sayaka; Chen, Kun; Honda, Masato; Kang, Ik Joon; Shimasaki, Yohei; Oshima, Yuji

2017-11-01

Although most exposures to chlorpyrifos (CPF) in natural flowing waters are brief and episodic, there have been a few reports of the persistence of abnormal fish behaviors caused by such acute exposure. The present study focused on the behavioral and biochemical responses of Japanese medaka (Oryzias latipes) to acute, sublethal exposure to CPF, as well as the persistence of the effects during a 3-week recovery test in CPF-free water. The medaka became hyperactive and exhibited an elevated anxiety state after a 4-day exposure to 0.024mg/L of CPF, but they recovered from these abnormal behavioral responses within 7days of recovery treatment. In contrast, persistent impacts on some startle responses to a sudden stimulation (induced by a ball drop) were observed in medaka exposed to CPF. The reaction latency did not change immediately after the 4-day exposure, but was significantly prolonged by as much as 21days after the termination of exposure. The post-stimulus swimming distance within 5s significantly decreased on the day immediately after the 4-day exposure, but it significantly increased after 7days of recovery treatment. The activity of acetylcholinesterase (AChE) in the brains of medaka was significantly inhibited on the day immediately after the 4-day exposure, but it returned to 80% and 110% of that in control fish on days 7 and 21 of the recovery period, respectively. However, AChE activities in the eyes of exposed medaka were persistently inhibited and declined to 33%, 71%, and 72% of that in control fish on days 0 (immediately after the 4-day exposure), 7, and 21 of recovery, respectively. Correlation analysis suggested that the changes of AChE activities in the brains of medaka may underlie some of the observed acute behavioral changes, and the changes of AChE activities in the eyes may contribute to the persistence of the abnormalities in the reaction latency of the startle response. Our findings suggest that medaka need a long time to recover from acute, sublethal exposure to CPF, and the persistence of the behavioral abnormalities might affect their fitness in natural habitats. Copyright © 2017 Elsevier B.V. All rights reserved.

Psychometric properties for the Balanced Inventory of Desirable Responding: dichotomous versus polytomous conventional and IRT scoring.

PubMed

Vispoel, Walter P; Kim, Han Yi

2014-09-01

[Correction Notice: An Erratum for this article was reported in Vol 26(3) of Psychological Assessment (see record 2014-16017-001). The mean, standard deviation and alpha coefficient originally reported in Table 1 should be 74.317, 10.214 and .802, respectively. The validity coefficients in the last column of Table 4 are affected as well. Correcting this error did not change the substantive interpretations of the results, but did increase the mean, standard deviation, alpha coefficient, and validity coefficients reported for the Honesty subscale in the text and in Tables 1 and 4. The corrected versions of Tables 1 and Table 4 are shown in the erratum.] Item response theory (IRT) models were applied to dichotomous and polytomous scoring of the Self-Deceptive Enhancement and Impression Management subscales of the Balanced Inventory of Desirable Responding (Paulhus, 1991, 1999). Two dichotomous scoring methods reflecting exaggerated endorsement and exaggerated denial of socially desirable behaviors were examined. The 1- and 2-parameter logistic models (1PLM, 2PLM, respectively) were applied to dichotomous responses, and the partial credit model (PCM) and graded response model (GRM) were applied to polytomous responses. For both subscales, the 2PLM fit dichotomous responses better than did the 1PLM, and the GRM fit polytomous responses better than did the PCM. Polytomous GRM and raw scores for both subscales yielded higher test-retest and convergent validity coefficients than did PCM, 1PLM, 2PLM, and dichotomous raw scores. Information plots showed that the GRM provided consistently high measurement precision that was superior to that of all other IRT models over the full range of both construct continuums. Dichotomous scores reflecting exaggerated endorsement of socially desirable behaviors provided noticeably weak precision at low levels of the construct continuums, calling into question the use of such scores for detecting instances of "faking bad." Dichotomous models reflecting exaggerated denial of the same behaviors yielded much better precision at low levels of the constructs, but it was still less precision than that of the GRM. These results support polytomous over dichotomous scoring in general, alternative dichotomous scoring for detecting faking bad, and extension of GRM scoring to situations in which IRT offers additional practical advantages over classical test theory (adaptive testing, equating, linking, scaling, detecting differential item functioning, and so forth). PsycINFO Database Record (c) 2014 APA, all rights reserved.

Dissociative identity disorder and prepulse inhibition of the acoustic startle reflex

PubMed Central

Dale, Karl Yngvar; Flaten, Magne Arve; Elden, Åke; Holte, Arne

2008-01-01

A group of persons with dissociative identity disorder (DID) was compared with a group of persons with other dissociative disorders, and a group of nondiagnosed controls with regard to prepulse inhibition (PPI) of the acoustic startle reflex. The findings suggest maladaptive attentional processes at a controlled level, but not at a preattentive automatic level, in persons with DID. The prepulse occupied more controlled attentional resources in the DID group compared with the other two groups. Preattentive automatic processing, on the other hand, was normal in the DID group. Moreover, startle reflexes did not habituate in the DID group. In conclusion, increased PPI and delayed habituation is consistent with increased vigilance in individuals with DID. The present findings of reduced habituation of startle reflexes and increased PPI in persons with DID suggest the operation of a voluntary process that directs attention away from unpleasant or threatening stimuli. Aberrant voluntary attentional processes may thus be a defining characteristic in DID. PMID:18830396

Dissociating response systems: erasing fear from memory.

PubMed

Soeter, Marieke; Kindt, Merel

2010-07-01

In addition to the extensive evidence in animals, we previously showed that disrupting reconsolidation by noradrenergic blockade produced amnesia for the original fear response in humans. Interestingly, the declarative memory for the fear association remained intact. These results asked for a solid replication. Moreover, given the constructive nature of memories, the intact recollection of the fear association could eventually 'rebuild' the fear memory, resulting in the spontaneous recovery of the fear response. Yet, perseverance of the amnesic effects would have substantial clinical implications, as even the most effective treatments for psychiatric disorders display high percentages of relapse. Using a differential fear conditioning procedure in humans, we replicated our previous findings by showing that administering propranolol (40mg) prior to memory reactivation eliminated the startle fear response 24h later. But most importantly, this effect persisted at one month follow-up. Notably, the propranolol manipulation not only left the declarative memory for the acquired contingency untouched, but also skin conductance discrimination. In addition, a close association between declarative knowledge and skin conductance responses was found. These findings are in line with the supposed double dissociation of fear conditioning and declarative knowledge relative to the amygdala and hippocampus in humans. They support the view that skin conductance conditioning primarily reflects contingency learning, whereas the startle response is a rather specific measure of fear. Furthermore, the results indicate the absence of a causal link between the actual knowledge of a fear association and its fear response, even though they often operate in parallel. Interventions targeting the amygdalar fear memory may be essential in specifically and persistently dampening the emotional impact of fear. From a clinical and ethical perspective, disrupting reconsolidation points to promising interventions persistently erasing fear responses from trauma memory without affecting the actual recollection.

Human fear extinction and return of fear using reconsolidation update mechanisms: The contribution of on-line expectancy ratings

PubMed Central

Warren, Victor Taylor; Anderson, Kemp M.; Kwon, Cliffe; Bosshardt, Lauren; Jovanovic, Tanja; Bradley, Bekh; Norrholm, Seth Davin

2015-01-01

Disruption of the reconsolidation of conditioned fear memories has been suggested as a non-pharmacological means of preventing the return of learned fear in human populations. A reconsolidation update paradigm was developed in which a reconsolidation window is opened by a single isolated retrieval trial of a previously reinforced CS+ which is then followed by Extinction Training within that window. However, follow-up studies in humans using multi-methods fear conditioning indices (e.g., fear-potentiated startle, skin conductance, US-expectancy) have failed to replicate the retrieval + extinction effects. In the present study, we further investigated the retrieval + extinction reconsolidation update paradigm by directly comparing the acquisition, extinction, and return of fear-potentiated startle in the absence or presence of US-expectancy measures (using a trial-by-trial response keypad) with and without retrieval of a previously acquired CS-US association. Participants were fear conditioned to two visual cue CS+'s, one of which was presented as a single, isolated retrieval trial before Extinction Training and one that was extinguished as usual. The results show that the inclusion of US-expectancy measures strengthens the CS–US association to provide enhanced fear conditioning and maintenance of fear memories over the experimental sessions. In addition, in the groups that used on-line US-expectancy measures, the retrieval + extinction procedure reduced reinstatement of fear-potentiated startle to both previously reinforced CS+'s, as compared to the extinction as usual group. PMID:24183839

Startle Potentiation to Uncertain Threat as a Psychophysiological Indicator of Fear-based Psychopathology: An Examination across Multiple Internalizing Disorders

PubMed Central

Gorka, Stephanie M.; Lieberman, Lynne; Shankman, Stewart A.; Phan, K. Luan

2016-01-01

Heightened reactivity to uncertain threat (U-threat) is an important individual difference factor that may characterize fear-based internalizing psychopathologies (IPs) and distinguish them from distress/misery IPs. To date, however, the majority of existing research examining reactivity to U-threat has been within individuals with panic disorder and major depressive disorder (MDD) and no prior study has directly tested this hypothesis across multiple IPs. The current study therefore explored whether heightened reactivity to U-threat is a psychophysiological indicator of fear-based psychopathology across five groups: current 1) social anxiety disorder (SAD), 2) specific phobia (SP), 3) generalized anxiety disorder (GAD), 4) MDD, and 5) individuals with no history of psychopathology (controls). All 160 adults completed a well-validated threat-of-shock task designed to probe responses to predictable (P-) and U-threat. Startle eyeblink potentiation was recorded as an index of aversive arousal. Results indicated that individuals with SAD and SP evidenced greater startle potentiation to U-threat, but not P-threat, relative to individuals with GAD, MDD and controls (who did not differ). The current findings, along with the prior panic disorder and MDD literature, suggest that heightened reactivity to U-threat is a psychophysiological indicator of fear-based disorders and could represent a neurobiological organizing principle for internalizing psychopathology. The findings also suggest that individuals with fear disorders generally display a hypersensitivity to uncertain aversive events, which could contribute to their psychopathology. PMID:27868423

Exaggerated gonadotropin response to luteinizing hormone-releasing hormone in amenorrheic runners.

PubMed

Yahiro, J; Glass, A R; Fears, W B; Ferguson, E W; Vigersky, R A

1987-03-01

Most studies of exercise-induced amenorrhea have compared amenorrheic athletes (usually runners) with sedentary control subjects. Such comparisons will identify hormonal changes that develop as a result of exercise training but cannot determine which of these changes play a role in causing amenorrhea. To obviate this problem, we assessed reproductive hormone status in a group of five amenorrheic runners and compared them to a group of six eumenorrheic runners matched for body fatness, training intensity, and exercise performance. Compared to the eumenorrheic runners, the amenorrheic runners had lower serum estradiol concentrations, similar basal serum luteinizing hormone and follicle-stimulating hormone concentrations, and exaggerated responses of serum gonadotropins after administration of luteinizing hormone-releasing hormone (100 micrograms intravenous bolus). Serum prolactin levels, both basally and after thyrotropin-releasing hormone administration (500 micrograms intravenous bolus) or treadmill exercise, was similar in the two groups, as were serum thyroid function tests (including thyrotropin response to thyrotropin-releasing hormone). Changes in serum cortisol levels after short-term treadmill exercise were similar in both groups, and serum testosterone levels increased after exercise only in the eumenorrheic group. In neither group did such exercise change serum luteinizing hormone, follicle-stimulating hormone, or thyrotropin levels. We concluded that exercise-induced amenorrhea is not solely related to the development of increased prolactin output after exercise training. The exaggerated gonadotropin response to luteinizing hormone-releasing hormone seen in amenorrheic runners in comparison with matched eumenorrheic runners is consistent with a hypothalamic etiology for the menstrual dysfunction, analogous to that previously described in "stress-induced" or "psychogenic" amenorrhea.

Differences in response to corticotropin-releasing factor after short- and long-term consumption of a high-fat diet.

PubMed

Legendre, Ariadne; Papakonstantinou, Emilia; Roy, Marie-Claude; Richard, Denis; Harris, Ruth B S

2007-09-01

We previously reported an exaggerated endocrine and weight loss response to stress in rats fed a high-fat (HF) diet for 5 days. Others report blunted stress-induced anxiety in rats made obese on a HF diet. Experiments described here tested whether sensitivity to stress-related peptides was changed in obese and nonobese HF-fed rats. Third ventricle infusion of corticotropin-releasing factor (CRF) in rats made obese on HF diet (40% kcal fat) produced an exaggerated hypophagia, which is thought to be mediated by CRF(2) receptors. Obese rats responded to a lower dose of CRF for a longer time than rats fed a low-fat (LF) diet (12% kcal fat). CRF-induced release of corticosterone, which is thought to be mediated by CRF(1) receptors, was not exaggerated in obese HF-fed rats. In contrast, rats fed HF diet for 5 days showed the same food intake and corticosterone response to CRF as LF-fed rats. CRF mRNA expression in the paraventricular nucleus of the hypothalamus was stimulated by mild stress (ip saline injection and placement in a novel cage) in LF-fed rats but not in rats fed HF diet for 5 days because of a nonsignificant increase in expression in nonstressed HF-fed rats. In addition, nonstressed levels of urocortin (UCN) I mRNA expression in the Edinger-Westphal nucleus were significantly inhibited in HF-fed rats. These data suggest that rats that have become obese on a HF diet show a change in responsiveness to stress peptides, whereas the increased stress response in nonobese HF-fed rats may be associated with changes in basal CRF and UCN I mRNA expression.

Lesions of the anteroventral third ventricle region exaggerate neuroendocrine and thermogenic but not behavioral responses to a novel environment.

PubMed

Whyte, Douglas G; Johnson, Alan Kim

2007-01-01

Mild psychological stressors provoke an acute rise in core temperature (T(C)), stimulate the hypothalamo-pituitary-adrenocortical (HPA) axis, and induce various stress-related behaviors. In the present study, we examined the effect of ablation of the anteroventral third ventricle region (AV3V) on both physiological and behavioral responses to a novel environment. T(C) was monitored in male Sprague-Dawley rats, with either sham or AV3V lesions, during a 5-h exposure to a novel environment. Trunk blood was collected, in a second group of rats, for the assessment of plasma levels of ACTH and corticosterone. Novelty-induced grooming and rearing behaviors were assessed in a third group of animals. T(C) was elevated in all animals after 30 min in the novel environment, but the rise was exaggerated in rats with AV3V lesions ( approximately 0.5 degrees C). AV3V-lesion rats maintained a higher core temperature for 2 h before it returned to the same level as the control group. Plasma levels of ACTH and corticosterone were also exaggerated in the AV3V lesion group after 30 min in a novel environment. In contrast to the physiological responses, the behavioral measures of grooming and rearing revealed no differences between the groups. The results from the current study suggest that neurons within the AV3V region exert an inhibitory influence on the HPA axis and fever developed in response to stressful psychological stimuli. They also confirm that the physiological and hormonal components of the stress response are independent of certain behavioral measures of stress.

Exaggerated cardiovascular effects of cocaine in conscious dogs with pacing-induced dilated cardiomyopathy.

PubMed

Mathier, Michael A; Shen, You-Tang; Shannon, Richard P

2002-12-01

The aim of this study was to explore the characteristics and mechanisms of the cardiovascular effects of cocaine in dilated cardiomyopathy. We studied the cardiovascular responses to acute intravenous cocaine (1 mg/kg) in 8 conscious, chronically instrumented dogs before and after the development of dilated cardiomyopathy induced by rapid ventricular pacing. To help elucidate the role of altered baroreflex function in mediating the cardiovascular effects of cocaine, we also studied responses in 3 conscious, chronically instrumented dogs that had undergone surgical sinoaortic baroreceptor denervation. Cocaine produced greater increases in heart rate (+57 +/- 8% from 112 +/- 5 beats/min versus +28 +/- 3% from 100 +/- 4 beats/min; P <.01), first derivative of left ventricular pressure (+30 +/- 5% from 1,714 +/- 147 mm Hg/sec versus +15 +/- 3% from 3,032 +/- 199 mm Hg/sec; P <.01), coronary vascular resistance (+28 +/- 5% from 2.3 +/- 0.3 mm Hg/mL/min versus +11 +/- 5% from 2.2 +/- 0.3 mm Hg/mL/min; P <.05) and plasma norepinephrine concentration (+130 +/- 31% from 462 +/- 102 pg/mL versus +86 +/- 32% from 286 +/- 77 pg/mL; P <.05) in dogs with dilated cardiomyopathy as compared to controls. In addition, responses were much more rapid in onset following the development of dilated cardiomyopathy. Chronotropic and inotropic responses to cocaine were similarly rapid and exaggerated in dogs after baroreceptor denervation. Cocaine produces rapid and exaggerated chronotropic, inotropic, and coronary vasoconstrictor responses in conscious dogs with pacing-induced dilated cardiomyopathy. Alterations in arterial baroreflex function may play a role in these observations, which in turn may underlie the clinically observed association between cocaine and heart failure.

Male rats with the testicular feminization mutation of the androgen receptor display elevated anxiety-related behavior and corticosterone response to mild stress

PubMed Central

Zuloaga, Damian G.; Poort, Jessica E.; Jordan, Cynthia L.; Breedlove, S. Marc

2011-01-01

Testosterone influences the hypothalamic-pituitary-adrenal axis, anxiety-related behavior, and sensorimotor gating in rodents, but little is known about the role of the androgen receptor (AR) in mediating these influences. We compared levels of the stress hormone corticosterone at baseline and following exposure to a novel object in an open field in wild type (wt) male and female rats, and male rats with the testicular feminization mutation (Tfm) of the AR, which disables its function. Basal corticosterone was equivalent in all groups, but exposure to a novel object in an open field elicited a greater increase in corticosterone in Tfm males and wt females than in wt males. Tfm males also showed increased behavioral indices of anxiety compared to wt males and females in the test. Analysis of the immediate early gene c-Fos expression after exposure to a novel object revealed greater activation in Tfm males than wt males in some regions (medial preoptic area) and lesser activation in others (dentate gyrus, posterodorsal medial amygdala). No differences were found in a measure of sensorimotor gating (prepulse inhibition of the acoustic startle response), although Tfm males had an increased acoustic startle response compared to wt males and females. These findings demonstrate that ARs play a role in regulating anxiety-related behaviors, as well as corticosterone responses and neural activation following exposure to a mild stressor in rats. PMID:21801726

Brain stimulation in posttraumatic stress disorder

PubMed Central

Novakovic, Vladan; Sher, Leo; Lapidus, Kyle A.B.; Mindes, Janet; A.Golier, Julia; Yehuda, Rachel

2011-01-01

Posttraumatic stress disorder (PTSD) is a complex, heterogeneous disorder that develops following trauma and often includes perceptual, cognitive, affective, physiological, and psychological features. PTSD is characterized by hyperarousal, intrusive thoughts, exaggerated startle response, flashbacks, nightmares, sleep disturbances, emotional numbness, and persistent avoidance of trauma-associated stimuli. The efficacy of available treatments for PTSD may result in part from relief of associated depressive and anxiety-related symptoms in addition to treatment of core symptoms that derive from reexperiencing, numbing, and hyperarousal. Diverse, heterogeneous mechanisms of action and the ability to act broadly or very locally may enable brain stimulation devices to address PTSD core symptoms in more targeted ways. To achieve this goal, specific theoretical bases derived from novel, well-designed research protocols will be necessary. Brain stimulation devices include both long-used and new electrical and magnetic devices. Electroconvulsive therapy (ECT) and Cranial electrotherapy stimulation (CES) have both been in use for decades; transcranial magnetic stimulation (TMS), magnetic seizure therapy (MST), deep brain stimulation (DBS), transcranial Direct Current Stimulation (tDCS), and vagus nerve stimulation (VNS) have been developed recently, over approximately the past twenty years. The efficacy of brain stimulation has been demonstrated as a treatment for psychiatric and neurological disorders such as anxiety (CES), depression (ECT, CES, rTMS, VNS, DBS), obsessive-compulsive disorder (OCD) (DBS), essential tremor, dystonia (DBS), epilepsy (DBS, VNS), Parkinson Disease (DBS), pain (CES), and insomnia (CES). To date, limited data on brain stimulation for PTSD offer only modest guidance. ECT has shown some efficacy in reducing comorbid depression in PTSD patients but has not been demonstrated to improve most core PTSD symptoms. CES and VNS have shown some efficacy in reducing anxiety, findings that may suggest possible utility in relieving PTSD-associated anxiety. Treatment of animal models of PTSD with DBS suggests potential human benefit. Additional research and novel treatment options for PTSD are urgently needed. The potential usefulness of brain stimulation in treating PTSD deserves further exploration. PMID:22893803

Habituation in acoustic startle reflex: individual differences in personality.

PubMed

Blanch, Angel; Balada, Ferran; Aluja, Anton

2014-03-01

This study analyzed the relationship of individual differences in personality with habituation in the acoustic startle response (ASR). Data from nine trials in ASR to white noise bursts and a personality questionnaire based on the alternative big five personality approach were modelled with a latent growth curve (LCM) including intercept and slope habituation growth factors. There was a negative correlation between the intercept and slope, indicating that individuals with higher initial ASR levels had also a more pronounced and faster decrease in the ASR. Contrary to expectations, Extraversion and Sensation Seeking did not relate with habituation in ASR. Neuroticism and Aggressiveness related asymmetrically with the habituation rate in ASR. Higher levels of Neuroticism were related with faster habituation, whereas higher levels of Aggressiveness were related with slower habituation. Further studies with the LCM should be undertaken to clarify in a greater extent the association of personality with habituation in ASR. Copyright © 2014 Elsevier B.V. All rights reserved.

The Onset of Puberty: Effects on the Psychophysiology of Defensive and Appetitive Motivation

PubMed Central

Quevedo, Karina; Benning, Stephen D; Gunnar, Megan R; Dahl, Ronald E

2010-01-01

We examined puberty-specific effects on affect-related behavior and on the psychophysiology of defensive and appetitive motivation while controlling for age. Adolescents (N=94, ages=12 and 13 years), viewed 75 pictures (IAPS: pleasant, neutral and aversive) while listening to auditory probes. Startle response and postauricular (PA) reflex were collected as measures of defensive and appetitive motivation respectively. Pubertal status and measures of anxiety/stress reaction and sensation/thrill seeking were obtained. Mid/late pubertal adolescents showed enhanced startle amplitude across all picture valences. A puberty by valence interaction revealed that mid/late pubertal adolescents showed appetitive potentiation of the PA, while pre/early pubertal adolescents showed no modulation of the PA reflex. Mid/late pubertal adolescents also scored significantly higher on measures of sensation/thrill seeking than did their pre/early pubertal peers and puberty moderated the association between psychophysiology and behavioral measures, suggesting that it plays a role in reorganizing defensive and appetitive motivational systems. PMID:19144221

Deficient aversive-potentiated startle and the triarchic model of psychopathy: The role of boldness.

PubMed

Esteller, Àngels; Poy, Rosario; Moltó, Javier

2016-05-01

This study examined the contribution of the phenotypic domains of boldness, meanness, and disinhibition of the triarchic conceptualization of psychopathy (Patrick, Fowles, & Krueger, 2009) to deficient aversive-potentiated startle in a mixed-gender sample of 180 undergraduates. Eyeblink responses to noise probes were recorded during a passive picture-viewing task (erotica, neutral, threat, and mutilation). Deficient threat vs. neutral potentiation was uniquely related to increased boldness scores, thus suggesting that the diminished defensive reaction to aversive stimulation is specifically linked to the charm, social potency and venturesomeness features of psychopathy (boldness), but not to features such as callousness, coldheartedness and cruelty traits (meanness), even though both phenotypes theoretically share the same underlying low-fear disposition. Our findings provide further evidence of the differential association between distinct psychopathy components and deficits in defensive reactivity and strongly support the validity of the triarchic model of psychopathy in disentangling the etiology of this personality disorder. Copyright © 2016 Elsevier B.V. All rights reserved.

Impaired fear inhibition learning predicts the persistence of symptoms of posttraumatic stress disorder (PTSD).

PubMed

Sijbrandij, Marit; Engelhard, Iris M; Lommen, Miriam J J; Leer, Arne; Baas, Johanna M P

2013-12-01

Recent cross-sectional studies have shown that the inability to suppress fear under safe conditions is a key problem in people with posttraumatic stress disorder (PTSD). The current longitudinal study examined whether individual differences in fear inhibition predict the persistence of PTSD symptoms. Approximately 2 months after deployment to Afghanistan, 144 trauma-exposed Dutch soldiers were administered a conditional discrimination task (AX+/BX-). In this paradigm, A, B, and X are neutral stimuli. X combined with A is paired with a shock (AX+ trials); X combined with B is not (BX- trials). Fear inhibition was measured (AB trials). Startle electromyogram responses and shock expectancy ratings were recorded. PTSD symptoms were measured at 2 months and at 9 months after deployment. Results showed that greater startle responses during AB trials in individuals who discriminated between danger (AX+) and safety (BX-) during conditioning, predicted higher PTSD symptoms at 2 months and 9 months post-deployment. The predictive effect at 9 months remained significant after controlling for critical incidents during previous deployments and PTSD symptoms at 2 months. Responses to AX+ or BX- trials, or discrimination learning (AX+ minus BX-) did not predict PTSD symptoms. It is concluded that impaired fear inhibition learning seems to be involved in the persistence of PTSD symptoms. Copyright © 2013 Elsevier Ltd. All rights reserved.

Fabp7 Maps to a Quantitative Trait Locus for a Schizophrenia Endophenotype

PubMed Central

Watanabe, Akiko; Toyota, Tomoko; Owada, Yuji; Hayashi, Takeshi; Iwayama, Yoshimi; Matsumata, Miho; Ishitsuka, Yuichi; Nakaya, Akihiro; Maekawa, Motoko; Ohnishi, Tetsuo; Arai, Ryoichi; Sakurai, Katsuyasu; Yamada, Kazuo; Kondo, Hisatake; Hashimoto, Kenji; Osumi, Noriko; Yoshikawa, Takeo

2007-01-01

Deficits in prepulse inhibition (PPI) are a biological marker for schizophrenia. To unravel the mechanisms that control PPI, we performed quantitative trait loci (QTL) analysis on 1,010 F2 mice derived by crossing C57BL/6 (B6) animals that show high PPI with C3H/He (C3) animals that show low PPI. We detected six major loci for PPI, six for the acoustic startle response, and four for latency to response peak, some of which were sex-dependent. A promising candidate on the Chromosome 10-QTL was Fabp7 (fatty acid binding protein 7, brain), a gene with functional links to the N-methyl-D-aspartic acid (NMDA) receptor and expression in astrocytes. Fabp7-deficient mice showed decreased PPI and a shortened startle response latency, typical of the QTL's proposed effects. A quantitative complementation test supported Fabp7 as a potential PPI-QTL gene, particularly in male mice. Disruption of Fabp7 attenuated neurogenesis in vivo. Human FABP7 showed altered expression in schizophrenic brains and genetic association with schizophrenia, which were both evident in males when samples were divided by sex. These results suggest that FABP7 plays a novel and crucial role, linking the NMDA, neurodevelopmental, and glial theories of schizophrenia pathology and the PPI endophenotype, with larger or overt effects in males. We also discuss the results from the perspective of fetal programming. PMID:18001149

The effects of Eph-ephrin mutations on pre-pulse inhibition in mice.

PubMed

Liuzzo, Andrea; Gray, Lincoln; Wallace, Matthew; Gabriele, Mark

2014-08-01

Eph-ephrin signaling is known to be important in directing topographic projections in the afferent auditory pathway, including connections to various subdivisions of the inferior colliculus (IC). The acoustic startle-response (ASR) is a reliable reflexive behavioral response in mammals elicited by an unexpected intense acoustic startle-eliciting stimulus (ES). It is mediated by a sub-cortical pathway that includes the IC. The ASR amplitude can be measured with an accelerometer under the subject and can be decreased in amplitude by presenting a less intense, non-startling stimulus 5-300ms before the ES. This reflexive decrement in ASR is called pre-pulse inhibition (PPI) and indicates that the relatively soft pre-pulse was heard. PPI is a general trait among mammals. Mice have been used recently to study this response and to reveal how genetic mutations affect neural circuits and hence the ASR and PPI. In this experiment, we measured the effect of Eph-ephrin mutations using control mice (C57BL/6J), mice with compromised EphA4 signaling (EphA4(lacZ/+), EphA4(lacZ/lacZ)), and knockout ephrin-B3 mice (ephrin-B3 (+/-, -/-)). Control and EphA4(lacZ/+s)trains showed robust PPI (up to 75% decrement in ASR) to an offset of a 70dB SPL background noise at 50ms before the ES. Ephrin-B3 knockout mice and EphA4 homozygous mutants were only marginally significant in PPI (<25% decrement and <33% decrement, respectively) to the same conditions. This decrement in PPI highlights the importance of ephrin-B3 and EphA4 interactions in ordering auditory behavioral circuits. Thus, different mutations in certain members of the signaling family produce a full range of changes in PPI, from minimal to nearly maximal. This technique can be easily adapted to study other aspects of hearing in a wider range of mutations. Along with ongoing neuroanatomical studies, this allows careful quantification of how the auditory anatomical, physiological and now behavioral phenotype is affected by changes in Eph-ephrin expression and functionality. Copyright © 2014 Elsevier Inc. All rights reserved.

Dominant tree species are at risk from exaggerated drought under climate change.

PubMed

Fensham, Roderick J; Fraser, Josie; MacDermott, Harry J; Firn, Jenifer

2015-10-01

Predicting the consequences of climate change on forest systems is difficult because trees may display species-specific responses to exaggerated droughts that may not be reflected by the climatic envelope of their geographic range. Furthermore, few studies have examined the postdrought recovery potential of drought-susceptible tree species. This study develops a robust ranking of the drought susceptibility of 21 tree species based on their mortality after two droughts (1990s and 2000s) in the savanna of north-eastern Australia. Drought-induced mortality was positively related to species dominance, negatively related to the ratio of postdrought seedlings to adults and had no relationship to the magnitude of extreme drought within the species current geographic ranges. These results suggest that predicting the consequences of exaggerated drought on species' geographic ranges is difficult, but that dominant species like Eucalyptus with relatively slow rates of population recovery and dispersal are the most susceptible. The implications for savanna ecosystems are lower tree densities and basal area. © 2015 John Wiley & Sons Ltd.

A mechanism of extreme growth and reliable signaling in sexually selected ornaments and weapons.

PubMed

Emlen, Douglas J; Warren, Ian A; Johns, Annika; Dworkin, Ian; Lavine, Laura Corley

2012-08-17

Many male animals wield ornaments or weapons of exaggerated proportions. We propose that increased cellular sensitivity to signaling through the insulin/insulin-like growth factor (IGF) pathway may be responsible for the extreme growth of these structures. We document how rhinoceros beetle horns, a sexually selected weapon, are more sensitive to nutrition and more responsive to perturbation of the insulin/IGF pathway than other body structures. We then illustrate how enhanced sensitivity to insulin/IGF signaling in a growing ornament or weapon would cause heightened condition sensitivity and increased variability in expression among individuals--critical properties of reliable signals of male quality. The possibility that reliable signaling arises as a by-product of the growth mechanism may explain why trait exaggeration has evolved so many different times in the context of sexual selection.

Airborne Acoustic Perception by a Jumping Spider.

PubMed

Shamble, Paul S; Menda, Gil; Golden, James R; Nitzany, Eyal I; Walden, Katherine; Beatus, Tsevi; Elias, Damian O; Cohen, Itai; Miles, Ronald N; Hoy, Ronald R

2016-11-07

Jumping spiders (Salticidae) are famous for their visually driven behaviors [1]. Here, however, we present behavioral and neurophysiological evidence that these animals also perceive and respond to airborne acoustic stimuli, even when the distance between the animal and the sound source is relatively large (∼3 m) and with stimulus amplitudes at the position of the spider of ∼65 dB sound pressure level (SPL). Behavioral experiments with the jumping spider Phidippus audax reveal that these animals respond to low-frequency sounds (80 Hz; 65 dB SPL) by freezing-a common anti-predatory behavior characteristic of an acoustic startle response. Neurophysiological recordings from auditory-sensitive neural units in the brains of these jumping spiders showed responses to low-frequency tones (80 Hz at ∼65 dB SPL)-recordings that also represent the first record of acoustically responsive neural units in the jumping spider brain. Responses persisted even when the distances between spider and stimulus source exceeded 3 m and under anechoic conditions. Thus, these spiders appear able to detect airborne sound at distances in the acoustic far-field region, beyond the near-field range often thought to bound acoustic perception in arthropods that lack tympanic ears (e.g., spiders) [2]. Furthermore, direct mechanical stimulation of hairs on the patella of the foreleg was sufficient to generate responses in neural units that also responded to airborne acoustic stimuli-evidence that these hairs likely play a role in the detection of acoustic cues. We suggest that these auditory responses enable the detection of predators and facilitate an acoustic startle response. VIDEO ABSTRACT. Copyright © 2016 Elsevier Ltd. All rights reserved.

Infrasound initiates directional fast-start escape responses in juvenile roach Rutilus rutilus.

PubMed

Karlsen, Hans E; Piddington, Robert W; Enger, Per S; Sand, Olav

2004-11-01

Acoustic stimuli within the sonic range are effective triggers of C-type escape behaviours in fish. We have previously shown that fish have an acute sensitivity to infrasound also, with acceleration thresholds in the range of 10(-5) m s(-2). In addition, infrasound at high intensities around 10(-2) m s(-2) elicits strong and sustained avoidance responses in several fish species. In the present study, the possible triggering of C-escapes by infrasonic single-cycle vibrations was examined in juvenile roach Rutilus rutilus. The fish were accelerated in a controlled and quantifiable manner using a swing system. The applied stimuli simulated essential components of the accelerations that a small fish would encounter in the hydrodynamic flow field produced by a predatory fish. Typical C- and S-type escape responses were induced by accelerations within the infrasonic range with a threshold of 0.023 m s(-2) for an initial acceleration at 6.7 Hz. Response trajectories were on average in the same direction as the initial acceleration. Unexpectedly, startle behaviours mainly occurred in the trailing half of the test chamber, in which the fish were subjected to linear acceleration in combination with compression, i.e. the expected stimuli produced by an approaching predator. Very few responses were observed in the leading half of the test chamber, where the fish were subjected to acceleration and rarefaction, i.e. the stimuli expected from a suction type of predator. We conclude that particle acceleration is essential for the directionality of the startle response to infrasound, and that the response is triggered by the synergistic effects of acceleration and compression.

Unilateral block of NMDA receptors in the amygdala prevents predator stress-induced lasting increases in anxiety-like behavior and unconditioned startle--effective hemisphere depends on the behavior.

PubMed

Adamec, R E; Burton, P; Shallow, T; Budgell, J

Lasting increases in anxiety-like behavior (ALB) in the elevated plus-maze are produced by a single 5-min exposure of a rat to a cat. Rats become more anxious in the plus-maze for up to 3 weeks after the exposure. The first study in this series demonstrated that blockade of NMDA receptors in rats with MK-801, AP7, or CPP, given systemically 30 min prior to exposure to a cat prevents the increase in ALB assessed 1 week later in the elevated plus-maze. To localize the site of action of systemic MK-801, MK-801 was injected in the amygdala 30 min prior to predator stress. Injections were given either unilaterally in either hemisphere, or bilaterally in both hemispheres. The target of the injection was the basolateral amygdala. The effects of injection depended on both the type of behavior and the hemisphere of injection. Injections of MK-801 in a variety of sites in the basolateral amygdala had no effect on the suppression of open-arm exploration produced by predator stress. Other amygdala nuclei or other limbic sites likely mediate the effects of systemically administered MK-801 on this behavior. In contrast, NMDA receptors in the left lateral amygdala mediate lasting suppression of risk assessment. MK-801, in a variety of sites in the left but not right lateral amygdala, blocked the effects of predator stress on risk assessment. This is clear evidence of separability of neural mechanisms controlling open-arm exploration and risk assessment. Different NMDA-dependent amygdala circuitry mediated effects of predator stress on unconditioned acoustic startle 1 week after cat exposure. The data indicate that integrity of the left lateral amygdala is necessary for potentiation of startle amplitude by predator stress, though NMDA receptors are not involved in this function. Nevertheless, NMDA receptors in the right, but not the left lateral amygdala, mediate initiation of changes in startle. The data also suggest that the right amygdala action is "downstream" from the left amygdala contribution. These findings are consistent with the view that NMDA receptors are involved in initiation, but not maintenance, of neural changes mediating lasting increases in anxiety following severe stress. Finally, the findings of the importance of the right amygdala in stress-induced enhancement of the startle response provides neurobiological face validity to predator stress as a model of aspects of posttraumatic stress disorder.

Animal models of 'anxiety': where next?

PubMed

Rodgers, R J

1997-11-01

Numerous procedures have been developed to facilitate preclinical research on the behavioural pharmacology of anxiety and, as a result of this application, are often referred to as animal models of 'anxiety'. This is an unfortunate misnomer, not only because of the apparent inability of many tests to detect novel anxiolytics consistently, but also because the term implies that anxiety is a unitary emotion. Such difficulties have arisen largely as a consequence of test development strategies which, by emphasizing pharmacological (i.e. benzodiazepine) validation, have yielded models predictive of a specific type of anxiolytic activity. The present review argues that the refinement of existing tests as well as the development of new procedures requires urgent attention to the much neglected issue of behavioural validation. From an evolutionary perspective, normal human anxiety may be conceptualized as a repertoire of defence reactions tailored to meet different forms of threats, and disorders of anxiety as the inappropriate activation or exaggeration of these usually adaptive response patterns. In this context, consideration of the defensive reactions typically observed in our animal models reveals substantially greater commonality in the behavioural effects of benzodiazepine and 5-HT1A anxiolytics than would otherwise be apparent. Therefore, with the exception of the conventional plus-maze paradigm (discussed at some length), better correspondence is seen in tests involving unconditioned response to potential threat (e.g. social interaction, distress vocalizations and light/dark exploration) than in tests of conditioned fear reactions. Even within the latter grouping, however, greater commonality is seen in procedures based on reactions to proximal threat (e.g. freezing, startle, ultrasonic vocalizations, burying) than those involving reactions to distal threat (e.g. avoidance/flight). Significantly, very similar findings have been reported in tests specifically designed to study defensive reactions (e.g. rat and mouse defence test batteries) or which incorporate a more detailed knowledge of defence into established procedures (e.g. ethological plus-maze and defensive burying paradigms). Furthermore, recent evidence also suggests that drugs with proved clinical efficacy in panic attacks/panic disorder have reliably stronger effects on flight responses than other components of the defensive repertoire. It is concluded that a focus on defensive behaviour patterns improves test validity (predictive/face/construct), offers a more rational basis for test selection in drug development programmes, and provides a firmer theoretical framework for future methodological and therapeutic advance.

Baseline psychophysiological and cortisol reactivity as a predictor of PTSD treatment outcome in virtual reality exposure therapy.

PubMed

Norrholm, Seth Davin; Jovanovic, Tanja; Gerardi, Maryrose; Breazeale, Kathryn G; Price, Matthew; Davis, Michael; Duncan, Erica; Ressler, Kerry J; Bradley, Bekh; Rizzo, Albert; Tuerk, Peter W; Rothbaum, Barbara O

2016-07-01

Baseline cue-dependent physiological reactivity may serve as an objective measure of posttraumatic stress disorder (PTSD) symptoms. Additionally, prior animal model and psychological studies would suggest that subjects with greatest symptoms at baseline may have the greatest violation of expectancy to danger when undergoing exposure based psychotherapy; thus treatment approaches which enhanced the learning under these conditions would be optimal for those with maximal baseline cue-dependent reactivity. However methods to study this hypothesis objectively are lacking. Virtual reality (VR) methodologies have been successfully employed as an enhanced form of imaginal prolonged exposure therapy for the treatment of PTSD. Our goal was to examine the predictive nature of initial psychophysiological (e.g., startle, skin conductance, heart rate) and stress hormone responses (e.g., cortisol) during presentation of VR-based combat-related stimuli on PTSD treatment outcome. Combat veterans with PTSD underwent 6 weeks of VR exposure therapy combined with either d-cycloserine (DCS), alprazolam (ALP), or placebo (PBO). In the DCS group, startle response to VR scenes prior to initiation of treatment accounted for 76% of the variance in CAPS change scores, p < 0.001, in that higher responses predicted greater changes in symptom severity over time. Additionally, baseline cortisol reactivity was inversely associated with treatment response in the ALP group, p = 0.04. We propose that baseline cue-activated physiological measures will be sensitive to predicting patients' level of response to exposure therapy, in particular in the presence of enhancement (e.g., DCS). Published by Elsevier Ltd.

Toll-like receptor 9 deficiency impacts sensory and motor behaviors.

PubMed

Khariv, Veronika; Pang, Kevin; Servatius, Richard J; David, Brian T; Goodus, Matthew T; Beck, Kevin D; Heary, Robert F; Elkabes, Stella

2013-08-01

Toll-like receptors (TLRs) mediate the induction of the innate immune system in response to pathogens, injury and disease. However, they also play non-immune roles and are expressed in the central nervous system (CNS) during prenatal and postnatal stages including adulthood. Little is known about their roles in the CNS in the absence of pathology. Several members of the TLR family have been implicated in the development of neural and cognitive function although the contribution of TLR9 to these processes has not been well defined. The current studies were undertaken to determine whether developmental TLR9 deficiency affects motor, sensory or cognitive functions. We report that TLR9 deficient (TLR9(-/-)) mice show a hyper-responsive sensory and motor phenotype compared to wild type (TLR9(+/+)) controls. This is indicated by hypersensitivity to thermal stimuli in the hot plate paw withdrawal test, enhanced motor-responsivity under anxious conditions in the open field test and greater sensorimotor reactivity in the acoustic startle response. Prepulse inhibition (PPI) of the acoustic startle response was also enhanced, which indicates abnormal sensorimotor gating. In addition, subtle, but significant, gait abnormalities were noted in the TLR9(-/-) mice on the horizontal balance beam test with higher foot slip numbers than TLR9(+/+) controls. In contrast, spatial learning and memory, assessed by the Morris water maze, was similar in the TLR9(-/-) and TLR9(+/+) mice. These findings support the notion that TLR9 is important for the appropriate development of sensory and motor behaviors. Copyright © 2013 Elsevier Inc. All rights reserved.

Lead exposure and fear-potentiated startle in the VA Normative Aging Study: a pilot study of a novel physiological approach to investigating neurotoxicant effects.

PubMed

Grashow, Rachel; Miller, Mark W; McKinney, Ann; Nie, Linda H; Sparrow, David; Hu, Howard; Weisskopf, Marc G

2013-01-01

Physiologically-based indicators of neural plasticity in humans could provide mechanistic insights into toxicant actions on learning in the brain, and perhaps prove more objective and sensitive measures of such effects than other methods. We explored the association between lead exposure and classical conditioning of the acoustic startle reflex (ASR)-a simple form of associative learning in the brain-in a population of elderly men. Fifty-one men from the VA Normative Aging Study with cumulative bone lead exposure measurements made with K-X-Ray-Fluorescence participated in a fear-conditioning protocol. The mean age of the men was 75.5years (standard deviation [sd]=5.9) and mean patella lead concentration was 22.7μg/g bone (sd=15.9). Baseline ASR eyeblink response decreased with age, but was not associated with subsequent conditioning. Among 37 men with valid responses at the end of the protocol, higher patella lead was associated with decreased awareness of the conditioning contingency (declarative learning; adjusted odds ratio [OR] per 20μg/g patella lead=0.91, 95% confidence interval [CI]: 0.84, 0.99, p=0.03). Eyeblink conditioning (non-declarative learning) was 0.44sd less (95% CI: -0.91, 0.02; p=0.06) per 20μg/g patella lead after adjustment. Each result was stronger when correcting for the interval between lead measurement and startle testing (awareness: OR=0.88, 95% CI: 0.78, 0.99, p=0.04; conditioning: -0.79sd less, 95% CI: -1.56, 0.03, p=0.04). This initial exploration suggests that lead exposure interferes with specific neural mechanisms of learning and offers the possibility that the ASR may provide a new approach to physiologically explore the effects of neurotoxicant exposures on neural mechanisms of learning in humans with a paradigm that is directly comparable to animal models. Copyright © 2013 Elsevier Inc. All rights reserved.

The common neural parasite Pseudoloma neurophilia is associated with altered startle response habituation in adult zebrafish (Danio rerio): Implications for the zebrafish as a model organism

PubMed Central

Spagnoli, Sean; Xue, Lan; Kent, Michael L.

2015-01-01

The zebrafish’s potential as a model for human neurobehavioral research appears nearly limitless despite its relatively recent emergence as an experimental organism. Since the zebrafish has only been part of the research community for a handful of decades, pathogens from its commercial origins continue to plague laboratory stocks. One such pathogen is Pseudoloma neurophilia, a common microparasite in zebrafish laboratories world-wide that generally produces subclinical infections. Given its high prevalence, its predilection for the host’s brain and spinal cord, and the delicate nature of neurobehavioral research, the behavioral consequences of subclinical P. neurophilia infection must be explored. Fish infected via cohabitation were tested for startle response habituation in parallel with controls in a device that administered ten taps over ten minutes along with taps at 18 and 60 minutes to evaluate habituation extinction. After testing, fish were euthanized and evaluated for infection via histopathology. Infected fish had a significantly smaller reduction in startle velocity during habituation compared to uninfected tankmates and controls. Habituation was eliminated in infected and control fish at 18 minutes, whereas exposed negative fish retained partial habituation at 18 minutes. Infection was also associated with enhanced capture evasion: Despite the absence of external symptoms, infected fish tended to be caught later than uninfected fish netted from the same tank. The combination of decreased overall habituation, early extinction of habituation compared to uninfected cohorts, and enhanced netting evasion indicates that P. neurophilia infection is associated with a behavioral phenotype distinct from that of controls and uninfected cohorts. Because of its prevalence in zebrafish facilities, P. neurophilia has the potential to insidiously influence a wide range of neurobehavioral studies if these associations are causative. Rigorous health screening is therefore vital to the improvement of the zebrafish as a translational model for human behavior. PMID:26028515

The common neural parasite Pseudoloma neurophilia is associated with altered startle response habituation in adult zebrafish (Danio rerio): Implications for the zebrafish as a model organism.

PubMed

Spagnoli, Sean; Xue, Lan; Kent, Michael L

2015-09-15

The zebrafish's potential as a model for human neurobehavioral research appears nearly limitless despite its relatively recent emergence as an experimental organism. Since the zebrafish has only been part of the research community for a handful of decades, pathogens from its commercial origins continue to plague laboratory stocks. One such pathogen is Pseudoloma neurophilia, a common microparasite in zebrafish laboratories world-wide that generally produces subclinical infections. Given its high prevalence, its predilection for the host's brain and spinal cord, and the delicate nature of neurobehavioral research, the behavioral consequences of subclinical P. neurophilia infection must be explored. Fish infected via cohabitation were tested for startle response habituation in parallel with controls in a device that administered ten taps over 10 min along with taps at 18 and 60 min to evaluate habituation extinction. After testing, fish were euthanized and evaluated for infection via histopathology. Infected fish had a significantly smaller reduction in startle velocity during habituation compared to uninfected tankmates and controls. Habituation was eliminated in infected and control fish at 18 min, whereas exposed negative fish retained partial habituation at 18 min. Infection was also associated with enhanced capture evasion: Despite the absence of external symptoms, infected fish tended to be caught later than uninfected fish netted from the same tank. The combination of decreased overall habituation, early extinction of habituation compared to uninfected cohorts, and enhanced netting evasion indicates that P. neurophilia infection is associated with a behavioral phenotype distinct from that of controls and uninfected cohorts. Because of its prevalence in zebrafish facilities, P. neurophilia has the potential to insidiously influence a wide range of neurobehavioral studies if these associations are causative. Rigorous health screening is therefore vital to the improvement of the zebrafish as a translational model for human behavior. Copyright © 2015 Elsevier B.V. All rights reserved.

The benefits of expanding studies of trait exaggeration to hemimetabolous insects and beyond morphology.

PubMed

Toubiana, William; Khila, Abderrahman

2016-08-01

Trait exaggeration, well known to naturalists and evolutionary biologists, has recently become a prominent research subject in the modern field of Evolutionary Developmental Biology. A large number of traits that can be considered as cases of exaggeration exist in nature. Yet, the field has almost exclusively focused on the study of growth-related exaggerated traits in a selection of holometabolous insects. The absence of the hemimetabola from studies of exaggeration leaves a significant gap in our understanding of the development and evolution of such traits. Here we argue that efforts to understand the mechanisms of trait exaggeration would benefit from expanding the study subjects to include other kinds of exaggeration and other model species. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

The association between exaggeration in health related science news and academic press releases: retrospective observational study

PubMed Central

Vivian-Griffiths, Solveiga; Boivin, Jacky; Williams, Andy; Venetis, Christos A; Davies, Aimée; Ogden, Jack; Whelan, Leanne; Hughes, Bethan; Dalton, Bethan; Boy, Fred

2014-01-01

Objective To identify the source (press releases or news) of distortions, exaggerations, or changes to the main conclusions drawn from research that could potentially influence a reader’s health related behaviour. Design Retrospective quantitative content analysis. Setting Journal articles, press releases, and related news, with accompanying simulations. Sample Press releases (n=462) on biomedical and health related science issued by 20 leading UK universities in 2011, alongside their associated peer reviewed research papers and news stories (n=668). Main outcome measures Advice to readers to change behaviour, causal statements drawn from correlational research, and inference to humans from animal research that went beyond those in the associated peer reviewed papers. Results 40% (95% confidence interval 33% to 46%) of the press releases contained exaggerated advice, 33% (26% to 40%) contained exaggerated causal claims, and 36% (28% to 46%) contained exaggerated inference to humans from animal research. When press releases contained such exaggeration, 58% (95% confidence interval 48% to 68%), 81% (70% to 93%), and 86% (77% to 95%) of news stories, respectively, contained similar exaggeration, compared with exaggeration rates of 17% (10% to 24%), 18% (9% to 27%), and 10% (0% to 19%) in news when the press releases were not exaggerated. Odds ratios for each category of analysis were 6.5 (95% confidence interval 3.5 to 12), 20 (7.6 to 51), and 56 (15 to 211). At the same time, there was little evidence that exaggeration in press releases increased the uptake of news. Conclusions Exaggeration in news is strongly associated with exaggeration in press releases. Improving the accuracy of academic press releases could represent a key opportunity for reducing misleading health related news. PMID:25498121

The association between exaggeration in health related science news and academic press releases: retrospective observational study.

PubMed

Sumner, Petroc; Vivian-Griffiths, Solveiga; Boivin, Jacky; Williams, Andy; Venetis, Christos A; Davies, Aimée; Ogden, Jack; Whelan, Leanne; Hughes, Bethan; Dalton, Bethan; Boy, Fred; Chambers, Christopher D

2014-12-09

To identify the source (press releases or news) of distortions, exaggerations, or changes to the main conclusions drawn from research that could potentially influence a reader's health related behaviour. Retrospective quantitative content analysis. Journal articles, press releases, and related news, with accompanying simulations. Press releases (n = 462) on biomedical and health related science issued by 20 leading UK universities in 2011, alongside their associated peer reviewed research papers and news stories (n = 668). Advice to readers to change behaviour, causal statements drawn from correlational research, and inference to humans from animal research that went beyond those in the associated peer reviewed papers. 40% (95% confidence interval 33% to 46%) of the press releases contained exaggerated advice, 33% (26% to 40%) contained exaggerated causal claims, and 36% (28% to 46%) contained exaggerated inference to humans from animal research. When press releases contained such exaggeration, 58% (95% confidence interval 48% to 68%), 81% (70% to 93%), and 86% (77% to 95%) of news stories, respectively, contained similar exaggeration, compared with exaggeration rates of 17% (10% to 24%), 18% (9% to 27%), and 10% (0% to 19%) in news when the press releases were not exaggerated. Odds ratios for each category of analysis were 6.5 (95% confidence interval 3.5 to 12), 20 (7.6 to 51), and 56 (15 to 211). At the same time, there was little evidence that exaggeration in press releases increased the uptake of news. Exaggeration in news is strongly associated with exaggeration in press releases. Improving the accuracy of academic press releases could represent a key opportunity for reducing misleading health related news. © Sumner et al 2014.

[Immortal time bias in pharmacoepidemiological studies: definition, solutions and examples].

PubMed

Faillie, Jean-Luc; Suissa, Samy

2015-01-01

Among the observational studies of drug effects in chronic diseases, many of them have found effects that were exaggerated or wrong. Among bias responsible for these errors, the immortal time bias, concerning the definition of exposure and exposure periods, is relevantly important as it usually tends to wrongly attribute a significant benefit to the study drug (or exaggerate a real benefit). In this article, we define the mechanism of immortal time bias, we present possible solutions and illustrate its consequences through examples of pharmacoepidemiological studies of drug effects. © 2014 Société Française de Pharmacologie et de Thérapeutique.

In the Blink of an Eye: Investigating the Role of Awareness in Fear Responding by Measuring the Latency of Startle Potentiation

PubMed Central

Åsli, Ole; Flaten, Magne A.

2012-01-01

The latency of startle reflex potentiation may shed light on the aware and unaware processes underlying associative learning, especially associative fear learning. We review research suggesting that single-cue delay classical conditioning is independent of awareness of the contingency between the conditioned stimulus (CS) and the unconditioned stimulus (US). Moreover, we discuss research that argues that conditioning independent of awareness has not been proven. Subsequently, three studies from our lab are presented that have investigated the role of awareness in classical conditioning, by measuring the minimum latency from CS onset to observed changes in reflexive behavior. In sum, research using this method shows that startle is potentiated 30 to 100 ms after CS onset following delay conditioning. Following trace fear conditioning, startle is potentiated 1500 ms after CS presentation. These results indicate that the process underlying delay conditioned responding is independent of awareness, and that trace fear conditioned responding is dependent on awareness. Finally, this method of investigating the role of awareness is discussed and future research possibilities are proposed. PMID:24962686

Forms of attention and attentional disorders.

PubMed

O'Donnell, Brian F

2002-05-01

Difficulties in attention or concentration are observed in many clinical syndromes. Cognitive studies of normal attention and neuropsychological studies of brain dysfunction indicate that attention reflects a variety of mechanisms. These processes include the startle response, the orienting response, selective attention, vigilance, and divided attention. Understanding the specific mechanisms involved in attention deficits or lapses may be helpful in planning and evaluating remediation programs and in altering patients' environments to compensate for specific attention deficits. In this article, forms of attention and disorders of attention are discussed, with emphasis on their importance to every day activities.

The neural basis of visual behaviors in the larval zebrafish

PubMed Central

Portugues, Ruben; Engert, Florian

2015-01-01

We review visually guided behaviors in larval zebrafish and summarise what is known about the neural processing that results in these behaviors, paying particular attention to the progress made in the last 2 years. Using the examples of the optokinetic reflex, the optomotor response, prey tracking and the visual startle response, we illustrate how the larval zebrafish presents us with a very promising model vertebrate system that allows neurocientists to integrate functional and behavioral studies and from which we can expect illuminating insights in the near future. PMID:19896836

Inhibitory Control in Anxious and Healthy Adolescents Is Modulated by Incentive and Incidental Affective Stimuli

ERIC Educational Resources Information Center

Hardin, Michael G.; Mandell, Darcy; Mueller, Sven C.; Dahl, Ronald E.; Pine, Daniel S.; Ernst, Monique

2009-01-01

Background: Anxiety disorders are characterized by elevated, sustained responses to threat, that manifest as threat attention biases. Recent evidence also suggests exaggerated responses to incentives. How these characteristics influence cognitive control is under debate and is the focus of the present study. Methods: Twenty-five healthy…

Modification of Fear Memory by Pharmacological and Behavioural Interventions during Reconsolidation.

PubMed

Thome, Janine; Koppe, Georgia; Hauschild, Sophie; Liebke, Lisa; Schmahl, Christian; Lis, Stefanie; Bohus, Martin

2016-01-01

Dysfunctional fear responses play a central role in many mental disorders. New insights in learning and memory suggest that pharmacological and behavioural interventions during the reconsolidation of reactivated fear memories may increase the efficacy of therapeutic interventions. It has been proposed that interventions applied during reconsolidation may modify the original fear memory, and thus prevent the spontaneous recovery and reinstatement of the fear response. We investigated whether pharmacological (propranolol) and behavioural (reappraisal, multisensory stimulation) interventions reduce fear memory, and prevent reinstatement of fear in comparison to a placebo control group. Eighty healthy female subjects underwent a differential fear conditioning procedure with three stimuli (CS). Two of these (CS+) were paired with an electric shock on day 1. On day 2, 20 subjects were pseudo-randomly assigned to either the propranolol or placebo condition, or underwent one of the two behavioural interventions after one of the two CS+ was reactivated. On day 3, all subjects underwent an extinction phase, followed by a reinstatement test. Dependent variables were US expectancy ratings, fear-potentiated startle, and skin conductance response. Differential fear responses to the reactivated and non-reactivated CS+ were observed only in the propranolol condition. Here, the non-reactivated CS+ evoked stronger fear-potentiated startle-responses compared to the placebo group. None of the interventions prevented the return of the extinguished fear response after re-exposure to the unconditioned stimulus. Our data are in line with an increasing body of research stating that the occurrence of reconsolidation may be constrained by boundary conditions such as subtle differences in experimental manipulations and instructions. In conclusion, our findings do not support a beneficial effect in using reconsolidation processes to enhance effects of psychotherapeutic interventions. This implies that more research is required before therapeutic interventions may benefit from a combination with reconsolidation processes.

The exaggerated inflammatory response in Behçet's syndrome: identification of dysfunctional post-transcriptional regulation of the IFN-γ/CXCL10 IP-10 pathway

PubMed Central

Ambrose, N; Khan, E; Ravindran, R; Lightstone, L; Abraham, S; Botto, M; Johns, M; Haskard, D O

2015-01-01

The mechanisms underlying the exaggerated inflammatory response in Behçet's syndrome (BS) remain poorly understood. We investigated the response of CD14+ blood monocytes to interferon (IFN)-γ, focusing on the chemokine CXCL10. Chemokine synthesis and release were analysed at a protein and mRNA level following stimulation with IFN-γ. Findings in BS patients were compared with 25 healthy controls (HC), 15 rheumatoid arthritis (RA) and 15 systemic lupus erythematosus (SLE) disease control patients. BS monocytes produced significantly more CXCL10 protein than HC monocytes from 2 h following IFN-γ stimulation, despite equivalent quantities of mRNA, suggesting more efficient translation. This was significantly more pronounced in BS with high disease activity and in those with ocular and neurological clinical manifestations. The imbalance between CXCL10 protein and mRNA expression was not observed in either RA or SLE patients, and was not seen with other chemokines studied (CXCL9, CXCL11 and CCL2). Furthermore, BS monocytes treated with an alternative stimulant (LPS) did not show abnormal tumour necrosis factor (TNF)-α release. Sucrose density gradients to segregate monocyte CXCL10 mRNA into free RNA or polysome-associated RNA showed equal proportions in BS and HC samples, suggesting that the difference between BS and HC may be due to reduced negative control of CXCL10 translation in BS at a post-initiation level. We conclude that BS monocytes have dysfunctional post-transcriptional regulation of CXCL10 mRNA, resulting in over-expression of CXCL10 protein upon IFN-γ stimulation. As CXCL10 is a chemokine that recruits mononuclear cells, this abnormality may contribute to the exaggerated inflammatory responses that characterizes BS. PMID:25982097

The exaggerated inflammatory response in Behçet's syndrome: identification of dysfunctional post-transcriptional regulation of the IFN-γ/CXCL10 IP-10 pathway.

PubMed

Ambrose, N; Khan, E; Ravindran, R; Lightstone, L; Abraham, S; Botto, M; Johns, M; Haskard, D O

2015-09-01

The mechanisms underlying the exaggerated inflammatory response in Behçet's syndrome (BS) remain poorly understood. We investigated the response of CD14(+) blood monocytes to interferon (IFN)-γ, focusing on the chemokine CXCL10. Chemokine synthesis and release were analysed at a protein and mRNA level following stimulation with IFN-γ. Findings in BS patients were compared with 25 healthy controls (HC), 15 rheumatoid arthritis (RA) and 15 systemic lupus erythematosus (SLE) disease control patients. BS monocytes produced significantly more CXCL10 protein than HC monocytes from 2 h following IFN-γ stimulation, despite equivalent quantities of mRNA, suggesting more efficient translation. This was significantly more pronounced in BS with high disease activity and in those with ocular and neurological clinical manifestations. The imbalance between CXCL10 protein and mRNA expression was not observed in either RA or SLE patients, and was not seen with other chemokines studied (CXCL9, CXCL11 and CCL2). Furthermore, BS monocytes treated with an alternative stimulant (LPS) did not show abnormal tumour necrosis factor (TNF)-α release. Sucrose density gradients to segregate monocyte CXCL10 mRNA into free RNA or polysome-associated RNA showed equal proportions in BS and HC samples, suggesting that the difference between BS and HC may be due to reduced negative control of CXCL10 translation in BS at a post-initiation level. We conclude that BS monocytes have dysfunctional post-transcriptional regulation of CXCL10 mRNA, resulting in over-expression of CXCL10 protein upon IFN-γ stimulation. As CXCL10 is a chemokine that recruits mononuclear cells, this abnormality may contribute to the exaggerated inflammatory responses that characterizes BS. © 2015 British Society for Immunology.

Developmental Programming: Priming Disease Susceptibility for Subsequent Generations.

PubMed

Messer, L C; Boone-Heinonen, J; Mponwane, L; Wallack, L; Thornburg, K L

2015-03-01

Racial and/or ethnic minorities carry the highest burden of many adverse health outcomes intergenerationally We propose a paradigm in which developmental programming exacerbates the effects of racial patterning of adverse environmental conditions, thereby contributing to health disparity persistence. Evidence that developmental programming induces a heightened response to adverse exposures ("second hits") encountered later in life is considered. We evaluated the evidence for the second hit phenomenon reported in animal and human studies from three domains (air, stress, nutrition). Original research including a gestational exposure and a childhood or adulthood second hit exposure was reviewed. Evidence from animal studies suggest that prenatal exposure to air pollutants is associated with an exaggerated reaction to postnatal air pollution exposure, which results in worse health outcomes. It also indicates offspring exposed to prenatal maternal stress produce an exaggerated response to subsequent stressors, including anxiety and hyper-responsiveness of the hypothalamic-pituitary-adrenal axis. Similarly, prenatal and postnatal Western-style diets induce synergistic effects on weight gain, metabolic dysfunction, and atherosclerotic risk. Cross-domain second hits (e.g., gestational air pollution followed by childhood stressor) were also considered. Suboptimal gestational environments induce exaggerated offspring responses to subsequent environmental and social exposures. These developmental programming effects may result in enhanced sensitivity of ongoing, racially patterned, adverse exposures in race/ethnic minorities, thereby exacerbating health disparities from one generation to the next. Empirical assessment of the hypothesized role of priming processes in the propagation of health disparities is needed. Future social epidemiology research must explicitly consider synergistic relationships among social environmental conditions to which gestating females are exposed and offspring exposures when assessing causes for persistent health disparities.

Developmental Programming: Priming Disease Susceptibility for Subsequent Generations

PubMed Central

Boone-Heinonen, J.; Mponwane, L.; Wallack, L.; Thornburg, K. L.

2015-01-01

Racial and/or ethnic minorities carry the highest burden of many adverse health outcomes intergenerationally We propose a paradigm in which developmental programming exacerbates the effects of racial patterning of adverse environmental conditions, thereby contributing to health disparity persistence. Evidence that developmental programming induces a heightened response to adverse exposures (“second hits”) encountered later in life is considered. We evaluated the evidence for the second hit phenomenon reported in animal and human studies from three domains (air, stress, nutrition). Original research including a gestational exposure and a childhood or adulthood second hit exposure was reviewed. Evidence from animal studies suggest that prenatal exposure to air pollutants is associated with an exaggerated reaction to postnatal air pollution exposure, which results in worse health outcomes. It also indicates offspring exposed to prenatal maternal stress produce an exaggerated response to subsequent stressors, including anxiety and hyper-responsiveness of the hypothalamic–pituitary–adrenal axis. Similarly, prenatal and postnatal Western-style diets induce synergistic effects on weight gain, metabolic dysfunction, and atherosclerotic risk. Cross-domain second hits (e.g., gestational air pollution followed by childhood stressor) were also considered. Suboptimal gestational environments induce exaggerated offspring responses to subsequent environmental and social exposures. These developmental programming effects may result in enhanced sensitivity of ongoing, racially patterned, adverse exposures in race/ethnic minorities, thereby exacerbating health disparities from one generation to the next. Empirical assessment of the hypothesized role of priming processes in the propagation of health disparities is needed. Future social epidemiology research must explicitly consider synergistic relationships among social environmental conditions to which gestating females are exposed and offspring exposures when assessing causes for persistent health disparities. PMID:26366336

Quantitative representations of an exaggerated anxiety response in the brain of female spider phobics-a parametric fMRI study.

PubMed

Zilverstand, Anna; Sorger, Bettina; Kaemingk, Anita; Goebel, Rainer

2017-06-01

We employed a novel parametric spider picture set in the context of a parametric fMRI anxiety provocation study, designed to tease apart brain regions involved in threat monitoring from regions representing an exaggerated anxiety response in spider phobics. For the stimulus set, we systematically manipulated perceived proximity of threat by varying a depicted spider's context, size, and posture. All stimuli were validated in a behavioral rating study (phobics n = 20; controls n = 20; all female). An independent group participated in a subsequent fMRI anxiety provocation study (phobics n = 7; controls n = 7; all female), in which we compared a whole-brain categorical to a whole-brain parametric analysis. Results demonstrated that the parametric analysis provided a richer characterization of the functional role of the involved brain networks. In three brain regions-the mid insula, the dorsal anterior cingulate, and the ventrolateral prefrontal cortex-activation was linearly modulated by perceived proximity specifically in the spider phobia group, indicating a quantitative representation of an exaggerated anxiety response. In other regions (e.g., the amygdala), activation was linearly modulated in both groups, suggesting a functional role in threat monitoring. Prefrontal regions, such as dorsolateral prefrontal cortex, were activated during anxiety provocation but did not show a stimulus-dependent linear modulation in either group. The results confirm that brain regions involved in anxiety processing hold a quantitative representation of a pathological anxiety response and more generally suggest that parametric fMRI designs may be a very powerful tool for clinical research in the future, particularly when developing novel brain-based interventions (e.g., neurofeedback training). Hum Brain Mapp 38:3025-3038, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Reinstatement of contextual conditioned anxiety in virtual reality and the effects of transcutaneous vagus nerve stimulation in humans.

PubMed

Genheimer, Hannah; Andreatta, Marta; Asan, Esther; Pauli, Paul

2017-12-20

Since exposure therapy for anxiety disorders incorporates extinction of contextual anxiety, relapses may be due to reinstatement processes. Animal research demonstrated more stable extinction memory and less anxiety relapse due to vagus nerve stimulation (VNS). We report a valid human three-day context conditioning, extinction and return of anxiety protocol, which we used to examine effects of transcutaneous VNS (tVNS). Seventy-five healthy participants received electric stimuli (unconditioned stimuli, US) during acquisition (Day1) when guided through one virtual office (anxiety context, CTX+) but never in another (safety context, CTX-). During extinction (Day2), participants received tVNS, sham, or no stimulation and revisited both contexts without US delivery. On Day3, participants received three USs for reinstatement followed by a test phase. Successful acquisition, i.e. startle potentiation, lower valence, higher arousal, anxiety and contingency ratings in CTX+ versus CTX-, the disappearance of these effects during extinction, and successful reinstatement indicate validity of this paradigm. Interestingly, we found generalized reinstatement in startle responses and differential reinstatement in valence ratings. Altogether, our protocol serves as valid conditioning paradigm. Reinstatement effects indicate different anxiety networks underlying physiological versus verbal responses. However, tVNS did neither affect extinction nor reinstatement, which asks for validation and improvement of the stimulation protocol.

Involvement of the opioid system in the hypokinetic state induced in cockroaches by a parasitoid wasp.

PubMed

Gavra, Tali; Libersat, Frederic

2011-03-01

The parasitoid wasp Ampulex compressa stings and injects venom into the cockroach brain to induce a long-lasting hypokinetic state. This state is characterized by decreased responsiveness to aversive stimuli, suggesting the manipulation of a neuromodulatory system in the cockroach's central nervous system. A likely candidate is the opioid system, which is known to affect responsiveness to stimuli in insects. To explore this possibility, we injected cockroaches with different opioid receptor agonists or antagonists before they were stung by a wasp and tested the escape behavior of these cockroaches to electric foot shocks. Antagonists significantly decreased the startle threshold in stung individuals, whereas agonists led to an increased startle threshold in controls. Yet, neither agonists nor antagonists had any effect on grooming. To further characterize the interaction between the venom and opioid receptors, we used an antenna-heart preparation. In un-stung individuals external application of crude venom completely inhibits antenna-heart contractions. In stung individuals the antenna-heart showed no contractions. Although acetylcholine restored contractions, the opioid receptor antagonist naloxone was unable to antagonize the venom inhibition. These results suggest that the venom of A. compressa might contribute to the manipulation of cockroach behavior by affecting the opioid system.

Investigation of a central nucleus of the amygdala/dorsal raphe nucleus serotonergic circuit implicated in fear-potentiated startle.

PubMed

Spannuth, B M; Hale, M W; Evans, A K; Lukkes, J L; Campeau, S; Lowry, C A

2011-04-14

Serotonergic systems are thought to play an important role in control of motor activity and emotional states. We used a fear-potentiated startle paradigm to investigate the effects of a motor-eliciting stimulus in the presence or absence of induction of an acute fear state on serotonergic neurons in the dorsal raphe nucleus (DR) and cells in subdivisions of the central amygdaloid nucleus (CE), a structure that plays an important role in fear responses, using induction of the protein product of the immediate-early gene, c-Fos. In Experiment 1 we investigated the effects of fear conditioning training, by training rats to associate a light cue (conditioned stimulus, CS; 1000 lx, 2 s) with foot shock (0.5 s, 0.5 mA) in a single session. In Experiment 2 rats were given two training sessions identical to Experiment 1 on days 1 and 2, then tested in one of four conditions on day 3: (1) placement in the training context without exposure to either the CS or acoustic startle (AS), (2) exposure to 10 trials of the 2 s CS, (3) exposure to 40 110 dB AS trials, or (4) exposure to 40 110 dB AS trials with 10 of the trials preceded by and co-terminating with the CS. All treatments were conducted during a 20 min session. Fear conditioning training, by itself, increased c-Fos expression in multiple subdivisions of the CE and throughout the DR. In contrast, fear-potentiated startle selectively increased c-Fos expression in the medial subdivision of the CE and in serotonergic neurons in the dorsal part of the dorsal raphe nucleus (DRD). These data are consistent with previous studies demonstrating that fear-related stimuli selectively activate DRD serotonergic neurons. Further studies of this mesolimbocortical serotonergic system could have important implications for understanding mechanisms underlying vulnerability to stress-related psychiatric disorders, including anxiety and affective disorders. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Association between problematic alcohol use and reactivity to uncertain threat in two independent samples

PubMed Central

Gorka, Stephanie M.; Lieberman, Lynne; Phan, K. Luan; Shankman, Stewart A.

2016-01-01

Background Recent laboratory studies have shown that acute alcohol intoxication selectively and effectively dampens aversive responding to an uncertain threat. An emerging hypothesis is that individuals who exhibit heightened reactivity to an uncertain threat may be especially motivated to use alcohol to dampen their distress, setting the stage for negative reinforcement processes to drive excessive alcohol use. However, no study to date has directly examined whether current problematic drinkers exhibit heightened reactivity to an uncertain threat as would be expected. Methods The present study was therefore designed to examine the association between current problematic alcohol use and reactivity to an uncertain threat during sobriety in two, independent samples. In Study 1 (n = 221) and Study 2 (n = 74), adult participants completed the same well-validated threat-of-shock task which separately probes responses to temporally predictable and unpredictable threat. Startle potentiation was measured as an index of aversive responding. Problematic alcohol use was defined as number of binge episodes within the past 30 days in Study 1 and total scores on a self-report measure of hazardous drinking in Study 2. Results As hypothesized, across both studies greater levels of problematic drinking were associated with greater startle potentiation to an unpredictable threat. In Study 2, hazardous drinking scores were also positively associated with startle potentiation to predictable threat. Conclusions The findings are notably consistent with the notion that heightened reactivity to an uncertain threat is an important individual difference factor associated with the onset and/or maintenance of problematic drinking behaviors and may therefore be a novel prevention and intervention target. PMID:27173662

Excitability of pontine startle processing neurones is regulated by the two-pore-domain K+ channel TASK-3 coupled to 5-HT2C receptors.

PubMed

Weber, Maruschka; Schmitt, Angelika; Wischmeyer, Erhard; Döring, Frank

2008-09-01

The mammalian startle reflex is a fast response to sudden intense sensory stimuli that can be increased by anxiety or decreased by reward. The cellular integration of sensory and modulatory information takes place in giant neurones of the caudal pontine reticular formation (PnC). The startle reflex is known to be enhanced by 5-hydroxytryptamine (5-HT); however, signalling mechanisms that change the excitability of the PnC giant neurones are poorly understood. Possible molecular candidates are two-pore-domain K(+) (K(2)P) channels that generate a variable K(+) background conductance and control neuronal excitability upon activation of G-protein-coupled receptors. We demonstrate by in situ hybridization that the K(2)P channel TASK-3 is substantially expressed in PnC giant neurones. Brain slice recordings revealed a corresponding background K(+) current in these cells that forms about 30% of the outward current at -30 mV. Inactivation of TASK-3 at pH 6.4 and by ruthenium red depolarized the cells by about 7 mV and increased the action potential frequency as well as duration. Specific activation of Galpha(q)-coupled 5-HT(2) receptors with alpha-methyl 5-HT evoked a similar increase of neuronal excitability. Consistently, we measured afferent synaptic inputs from serotonergic raphe neurones and detected 5-HT(2C) receptors in PnC giant neurones by immunohistochemistry. Thus, neuronal excitability of PnC giant neurones in vivo is most likely increased by serotonergic projections via the K(2)P channel TASK-3.

Aversive imagery in panic disorder: agoraphobia severity, comorbidity, and defensive physiology.

PubMed

McTeague, Lisa M; Lang, Peter J; Laplante, Marie-Claude; Bradley, Margaret M

2011-09-01

Panic is characterized as a disorder of interoceptive physiologic hyperarousal, secondary to persistent anticipation of panic attacks. The novel aim of this research was to investigate whether severity of agoraphobia within panic disorder covaries with the intensity of physiological reactions to imagery of panic attacks and other aversive scenarios. A community sample of principal panic disorder (n = 112; 41 without agoraphobia, 71 with agoraphobia) and control (n = 76) participants imagined threatening and neutral events while acoustic startle probes were presented and the eye-blink response (orbicularis oculi) recorded. Changes in heart rate, skin conductance level, and facial expressivity were also measured. Overall, panic disorder patients exceeded control participants in startle reflex and heart rate during imagery of standard panic attack scenarios, concordant with more extreme ratings of aversion and emotional arousal. Accounting for the presence of agoraphobia revealed that both panic disorder with and without situational apprehension showed the pronounced heart rate increases during standard panic attack imagery observed for the sample as a whole. In contrast, startle potentiation to aversive imagery was more robust in those without versus with agoraphobia. Reflex diminution was most dramatic in those with the most pervasive agoraphobia, coincident with the most extreme levels of comorbid broad negative affectivity, disorder chronicity, and functional impairment. Principal panic disorder may represent initial, heightened interoceptive fearfulness and concomitant defensive hyperactivity, which through progressive generalization of anticipatory anxiety ultimately transitions to a disorder of pervasive agoraphobic apprehension and avoidance, broad dysphoria, and compromised mobilization for defensive action. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Startle potentiation to uncertain threat as a psychophysiological indicator of fear-based psychopathology: An examination across multiple internalizing disorders.

PubMed

Gorka, Stephanie M; Lieberman, Lynne; Shankman, Stewart A; Phan, K Luan

2017-01-01

Heightened reactivity to uncertain threat (U-threat) is an important individual difference factor that may characterize fear-based internalizing psychopathologies (IPs) and distinguish them from distress/misery IPs. To date, however, the majority of existing research examining reactivity to U-threat has been within individuals with panic disorder and major depressive disorder (MDD) and no prior study has directly tested this hypothesis across multiple IPs. The current study therefore explored whether heightened reactivity to U-threat is a psychophysiological indicator of fear-based psychopathology across 5 groups: current (a) social anxiety disorder (SAD); (b) specific phobia (SP); (c) generalized anxiety disorder (GAD); (d) MDD; and (c) individuals with no history of psychopathology (controls). All 160 adults completed a well-validated threat-of-shock task designed to probe responses to predictable (P-) and U-threat. Startle eyeblink potentiation was recorded as an index of aversive arousal. Results indicated that individuals with SAD and SP evidenced greater startle potentiation to U-threat, but not P-threat, relative to individuals with GAD, MDD, and controls (who did not differ). The current findings, along with the prior panic disorder and MDD literature, suggest that heightened reactivity to U-threat is a psychophysiological indicator of fear-based disorders and could represent a neurobiological organizing principle for internalizing psychopathology. The findings also suggest that individuals with fear disorders generally display a hypersensitivity to uncertain aversive events, which could contribute to their psychopathology. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Aversive imagery in panic disorder: Agoraphobia severity, comorbidity and defensive physiology

PubMed Central

McTeague, Lisa M.; Lang, Peter J.; Laplante, Marie-Claude; Bradley, Margaret M.

2011-01-01

Background Panic is characterized as a disorder of interoceptive physiological hyperarousal, secondary to persistent anticipation of panic attacks. The novel aim of the present research was to investigate whether severity of agoraphobia within panic disorder covaries with the intensity of physiological reactions to imagery of panic attacks and other aversive scenarios. Methods A community sample of principal panic disorder (n=112; 41 without agoraphobia, 71 with agoraphobia) and control (n=76) participants imagined threatening and neutral events while acoustic startle probes were presented and the eye-blink response (orbicularis oculi) recorded. Changes in heart rate, skin conductance level, and facial expressivity were also measured. Results Overall panic disorder patients exceeded controls in startle reflex and heart rate during imagery of standard panic attack scenarios, concordant with more extreme ratings of aversion and emotional arousal. Accounting for the presence of agoraphobia revealed that both panic disorder with and without situational apprehension showed the pronounced heart rate increases during standard panic attack imagery observed for the sample as a whole. In contrast, startle potentiation to aversive imagery was more robust in those without versus with agoraphobia. Reflex diminution was most dramatic in those with the most pervasive agoraphobia, coincident with the most extreme levels of comorbid broad negative affectivity, disorder chronicity, and functional impairment. Conclusions Principal panic disorder may represent initial, heightened interoceptive fearfulness and concomitant defensive hyperactivity, which through progressive generalization of anticipatory anxiety, ultimately transitions to a disorder of pervasive agoraphobic apprehension and avoidance, broad dysphoria and compromised mobilization for defensive action. PMID:21550590

Exaggerating Accessible Differences: When Gender Stereotypes Overestimate Actual Group Differences.

PubMed

Eyal, Tal; Epley, Nicholas

2017-09-01

Stereotypes are often presumed to exaggerate group differences, but empirical evidence is mixed. We suggest exaggeration is moderated by the accessibility of specific stereotype content. In particular, because the most accessible stereotype contents are attributes perceived to differ between groups, those attributes are most likely to exaggerate actual group differences due to regression to the mean. We tested this hypothesis using a highly accessible gender stereotype: that women are more socially sensitive than men. We confirmed that the most accessible stereotype content involves attributes perceived to differ between groups (pretest), and that these stereotypes contain some accuracy but significantly exaggerate actual gender differences (Experiment 1). We observe less exaggeration when judging less accessible stereotype content (Experiment 2), or when judging individual men and women (Experiment 3). Considering the accessibility of specific stereotype content may explain when stereotypes exaggerate actual group differences and when they do not.

Behavioral, autonomic, and subjective reactions to low- and moderate-level simulated sonic booms : a report of two experiments and a general evaluation of sonic boom startle effects.

DOT National Transportation Integrated Search

1974-09-01

Two separate studies are reported. The first attempted to determine a sonic boom exposure level below which startle reactions would not occur. Subjects were exposed indoors to six simulated sonic booms having various outside overpressures. In the sec...

Evidence of Fearlessness in Behaviourally Disordered Children: A Study on Startle Reflex Modulation

ERIC Educational Resources Information Center

van Goozen, Stephanie H. M.; Snoek, Heddeke; Matthys, Walter; van Rossum, Inge; van Engeland, Herman

2004-01-01

Background: Patterns of low heart rate, skin conductance and cortisol seem to characterise children with disruptive behaviour disorder (DBD). Until now, the startle paradigm has not been used in DBD children. We investigated whether DBD children, like adult psychopaths, process emotional stimuli in an abnormal way. Method: Twenty-one DBD and 33…

Creatine Kinase Clinical Considerations: Ethnicity, Gender and Genetics

DTIC Science & Technology

2009-10-01

reported that the CC genotype was associated with exaggerated CK responses to exercise (37), inspection of their data and a letter to the editor (19...variation, response to eccentric exercise , and association of inflammatory mediators with muscle damage variables. J Appl Physiol. 104:451-458, 2008...174) and TNFA (-308) promoter polymorphisms are associated with systemic creatine kinase response to eccentric exercise . Eur J Appl Physiol. 104

Development of the acoustically evoked behavioral response in larval plainfin midshipman fish, Porichthys notatus.

PubMed

Alderks, Peter W; Sisneros, Joseph A

2013-01-01

The ontogeny of hearing in fishes has become a major interest among bioacoustics researchers studying fish behavior and sensory ecology. Most fish begin to detect acoustic stimuli during the larval stage which can be important for navigation, predator avoidance and settlement, however relatively little is known about the hearing capabilities of larval fishes. We characterized the acoustically evoked behavioral response (AEBR) in the plainfin midshipman fish, Porichthys notatus, and used this innate startle-like response to characterize this species' auditory capability during larval development. Age and size of larval midshipman were highly correlated (r(2) = 0.92). The AEBR was first observed in larvae at 1.4 cm TL. At a size ≥ 1.8 cm TL, all larvae responded to a broadband stimulus of 154 dB re1 µPa or -15.2 dB re 1 g (z-axis). Lowest AEBR thresholds were 140-150 dB re 1 µPa or -33 to -23 dB re 1 g for frequencies below 225 Hz. Larval fish with size ranges of 1.9-2.4 cm TL had significantly lower best evoked frequencies than the other tested size groups. We also investigated the development of the lateral line organ and its function in mediating the AEBR. The lateral line organ is likely involved in mediating the AEBR but not necessary to evoke the startle-like response. The midshipman auditory and lateral line systems are functional during early development when the larvae are in the nest and the auditory system appears to have similar tuning characteristics throughout all life history stages.

Behavioural and cognitive abnormalities in an imprinting centre deletion mouse model for Prader-Willi syndrome.

PubMed

Relkovic, Dinko; Doe, Christine M; Humby, Trevor; Johnstone, Karen A; Resnick, James L; Holland, Anthony J; Hagan, Jim J; Wilkinson, Lawrence S; Isles, Anthony R

2010-01-01

The genes in the imprinted cluster on human chromosome 15q11-q13 are known to contribute to psychiatric conditions such as schizophrenia and autism. Major disruptions of this interval leading to a lack of paternal allele expression give rise to Prader-Willi syndrome (PWS), a neurodevelopmental disorder with core symptoms of a failure to thrive in infancy and, on emergence from infancy, learning disabilities and over-eating. Individuals with PWS also display a number of behavioural problems and an increased incidence of neuropsychiatric abnormalities, which recent work indicates involve aspects of frontal dysfunction. To begin to examine the contribution of genes in this interval to relevant psychological and behavioural phenotypes, we exploited the imprinting centre (IC) deletion mouse model for PWS (PWS-IC(+/-)) and the five-choice serial reaction time task (5-CSRTT), which is primarily an assay of visuospatial attention and response control that is highly sensitive to frontal manipulations. Locomotor activity, open-field behaviour and sensorimotor gating were also assessed. PWS-IC(+/-) mice displayed reduced locomotor activity, increased acoustic startle responses and decreased prepulse inhibition of startle responses. In the 5-CSRTT, the PWS-IC(+/-) mice showed deficits in discriminative response accuracy, increased correct reaction times and increased omissions. Task manipulations confirmed that these differences were likely to be due to impaired attention. Our data recapitulate several aspects of the PWS clinical condition, including findings consistent with frontal abnormalities, and may indicate novel contributions of the imprinted genes found in 15q11-q13 to behavioural and cognitive function generally.

Effects of instructed emotion regulation on valence, arousal, and attentional measures of affective processing.

PubMed

Bernat, Edward M; Cadwallader, Meredith; Seo, Dongju; Vizueta, Nathalie; Patrick, Christopher J

2011-01-01

Cognitive control of emotion has been investigated using tasks prompting participants to increase or decrease emotional responding to affective pictures. This study provides a more comprehensive evaluation of responding in this task by including: pleasant and unpleasant pictures, increase and decrease instructions, additional physiological measures, and a fully randomized design. Findings suggest that control efforts did modulate higher-level affective responses indexed by self-reported valence and expressive facial muscles, but not lower-level affective responses indexed by startle blink and heart rate. Similarly, electrocortical measures evidenced expectable affective responses and control-related activity, but no modulation of affective patterns due to the control efforts.

Positive Response Distortion by Police Officer Applicants: Association of Paulhus Deception Scales with MMPI-2 and Inwald Personality Inventory Validity Scales

ERIC Educational Resources Information Center

Detrick, Paul; Chibnall, John T.

2008-01-01

Interpretation of positive response distortion (socially desirable responding) in employment evaluations is an important validity issue. This study of police officer applicants examined the construct validity of the Paulhus Deception Scales (PDS)--Moralistic Bias (MB; exaggerated adjustment/agreeableness) and Egoistic Bias (EB; exaggerated…

Resting RSA Is Associated with Natural and Self-Regulated Responses to Negative Emotional Stimuli

ERIC Educational Resources Information Center

Demaree, Heath A.; Robinson, Jennifer L.; Everhart, D. Erik; Schmeichel, Brandon J.

2004-01-01

Resting respiratory sinus arrhythmia (RSA) was assessed among 111 adult participants. These individuals were then asked to watch a positive or negative affective film in either a natural manner or while exaggerating their facial response. Facial reactions to the film were video-recorded and subsequently rated in terms of facial affect.…

Localized blastomycosis-like pyoderma with good response to cotrimoxazol and cryotherapy.

PubMed

Su, Ozlem; Demirkesen, Cuyan; Onsun, Nahide

2004-05-01

Blastomycosis-like pyoderma is an unusual, exaggerated, vegetative-tissue reaction to a prolonged primary or secondary bacterial infection. It is a rare disease, usually seen in immunocompromized patients. We report a case of localized blastomycosis-like pyoderma responding poorly to classic treatments, but that gave a dramatic response to a combination treatment of cotrimoxazol and cryotherapy.

Elevated Acoustic Startle Responses in Humans: Relationship to Reduced Loudness Discomfort Level, but not Self-Report of Hyperacusis.

PubMed

Knudson, Inge M; Melcher, Jennifer R

2016-06-01

Increases in the acoustic startle response (ASR) of animals have been reported following experimental manipulations to induce tinnitus, an auditory disorder defined by phantom perception of sound. The increases in ASR have been proposed to signify the development of hyperacusis, a clinical condition defined by intolerance of normally tolerable sound levels. To test this proposal, the present study compared ASR amplitude to measures of sound-level tolerance (SLT) in humans, the only species in which SLT can be directly assessed. Participants had clinically normal/near-normal hearing thresholds, were free of psychotropic medications, and comprised people with tinnitus and without. ASR was measured as eyeblink-related electromyographic activity in response to a noise pulse presented at a range of levels and in two background conditions (noise and quiet). SLT was measured as loudness discomfort level (LDL), the lowest level of sound deemed uncomfortable, and via a questionnaire on the loudness of sounds in everyday life. Regardless of tinnitus status, ASR amplitude at a given stimulus level increased with decreasing LDL, but showed no relationship to SLT self-reported via the questionnaire. These relationships (or lack thereof) could not be attributed to hearing threshold, age, anxiety, or depression. The results imply that increases in ASR in the animal work signify decreases in LDL specifically and may not correspond to the development of hyperacusis as would be self-reported by a clinic patient.

Defensive responses of cuttlefish to different teleost predators.

PubMed

Staudinger, Michelle D; Buresch, Kendra C; Mäthger, Lydia M; Fry, Charlie; McAnulty, Sarah; Ulmer, Kimberly M; Hanlon, Roger T

2013-12-01

We evaluated cuttlefish (Sepia officinalis) responses to three teleost predators: bluefish (Pomatomus saltatrix), summer flounder (Paralichthys dentatus), and black seabass (Centropristis striata). We hypothesized that the distinct body shapes, swimming behaviors, and predation tactics exhibited by the three fishes would elicit markedly different antipredator responses by cuttlefish. Over the course of 25 predator-prey behavioral trials, 3 primary and 15 secondary defense behaviors of cuttlefish were shown to predators. In contrast, secondary defenses were not shown during control trials in which predators were absent. With seabass-a benthic, sit-and-pursue predator-cuttlefish used flight and spent more time swimming in the water column than with other predators. With bluefish-an active, pelagic searching predator-cuttlefish remained closely associated with the substrate and relied more on cryptic behaviors. Startle (deimatic) displays were the most frequent secondary defense shown to seabass and bluefish, particularly the Dark eye ring and Deimatic spot displays. We were unable to evaluate secondary defenses by cuttlefish to flounder-a lie-and-wait predator-because flounder did not pursue cuttlefish or make attacks. Nonetheless, cuttlefish used primary defense during flounder trials, alternating between cryptic still and moving behaviors. Overall, our results suggest that cuttlefish may vary their behavior in the presence of different teleost predators: cryptic behaviors may be more important in the presence of active searching predators (e.g., bluefish), while conspicuous movements such as swimming in the water column and startle displays may be more prevalent with relatively sedentary, bottom-associated predators (e.g., seabass).

Probing for Neuroadaptations to Unpredictable Stressors in Addiction: Translational Methods and Emerging Evidence

PubMed Central

Kaye, Jesse T.; Bradford, Daniel E.; Magruder, Katherine P.; Curtin, John J.

2017-01-01

Stressors clearly contribute to addiction etiology and relapse in humans, but our understanding of specific mechanisms remains limited. Rodent models of addiction offer the power, flexibility, and precision necessary to delineate the causal role and specific mechanisms through which stressors influence alcohol and other drug use. This review describes a program of research using startle potentiation to unpredictable stressors that is well positioned to translate between animal models and clinical research with humans on stress neuroadaptations in addiction. This research rests on a solid foundation provided by three separate pillars of evidence from (a) rodent behavioral neuroscience on stress neuroadaptations in addiction, (b) rodent affective neuroscience on startle potentiation, and (c) human addiction and affective science with startle potentiation. Rodent stress neuroadaptation models implicate adaptations in corticotropin-releasing factor and norepinephrine circuits within the central extended amygdala following chronic alcohol and other drug use that mediate anxious behaviors and stress-induced reinstatement among drug-dependent rodents. Basic affective neuroscience indicates that these same neural mechanisms are involved in startle potentiation to unpredictable stressors in particular (vs. predictable stressors). We believe that synthesis of these evidence bases should focus us on the role of unpredictable stressors in addiction etiology and relapse. Startle potentiation in unpredictable stressor tasks is proposed to provide an attractive and flexible test bed to encourage tight translation and reverse translation between animal models and human clinical research on stress neuroadaptations. Experimental therapeutics approaches focused on unpredictable stressors hold high promise to identify, repurpose, or refine pharmacological and psychosocial interventions for addiction. PMID:28499100

Modulation of the N170 with Classical Conditioning: The Use of Emotional Imagery and Acoustic Startle in Healthy and Depressed Participants

PubMed Central

Camfield, David A.; Mills, Jessica; Kornfeld, Emma J.; Croft, Rodney J.

2016-01-01

Recent studies have suggested that classical conditioning may be capable of modulating early sensory processing in the human brain, and that there may be differences in the magnitude of the conditioned changes for individuals with major depressive disorder. The effect of conditioning on the N170 event-related potential was investigated using neutral faces as conditioned stimuli (CS+) and emotional imagery and acoustic startle as unconditioned stimuli (UCS). In the first experiment, electroencephalogram was recorded from 24 undergraduate students (M = 21.07 years, SD = 3.38 years) under the following conditions: (i) CS+/aversive imagery, (ii) CS+/aversive imagery and acoustic startle, (iii) CS+/acoustic startle, and (iv) CS+/pleasant imagery. The amplitude of the N170 was enhanced following conditioning with aversive imagery as well as acoustic startle. In the second experiment, 26 healthy control participants were tested (17 females and 9 males, age M = 25.97 years, SD = 9.42) together with 18 depressed participants (13 females and 5 males, age M = 23.26 years, SD = 4.01) and three conditions were used: CS+/aversive imagery, CS+/pleasant imagery, and CS-. N170 amplitude at P7 was increased for the CS+/aversive condition in comparison to CS- in the conditioning blocks versus baseline. No differences between depressed and healthy participants were found. Across both experiments, evaluative conditioning was absent. It was concluded that aversive UCS are capable of modulating early sensory processing of faces, although further research is also warranted in regards to positive UCS. PMID:27445773

Probing for Neuroadaptations to Unpredictable Stressors in Addiction: Translational Methods and Emerging Evidence.

PubMed

Kaye, Jesse T; Bradford, Daniel E; Magruder, Katherine P; Curtin, John J

2017-05-01

Stressors clearly contribute to addiction etiology and relapse in humans, but our understanding of specific mechanisms remains limited. Rodent models of addiction offer the power, flexibility, and precision necessary to delineate the causal role and specific mechanisms through which stressors influence alcohol and other drug use. This review describes a program of research using startle potentiation to unpredictable stressors that is well positioned to translate between animal models and clinical research with humans on stress neuroadaptations in addiction. This research rests on a solid foundation provided by three separate pillars of evidence from (a) rodent behavioral neuroscience on stress neuroadaptations in addiction, (b) rodent affective neuroscience on startle potentiation, and (c) human addiction and affective science with startle potentiation. Rodent stress neuroadaptation models implicate adaptations in corticotropin-releasing factor and norepinephrine circuits within the central extended amygdala following chronic alcohol and other drug use that mediate anxious behaviors and stress-induced reinstatement among drug-dependent rodents. Basic affective neuroscience indicates that these same neural mechanisms are involved in startle potentiation to unpredictable stressors in particular (vs. predictable stressors). We believe that synthesis of these evidence bases should focus us on the role of unpredictable stressors in addiction etiology and relapse. Startle potentiation in unpredictable stressor tasks is proposed to provide an attractive and flexible test bed to encourage tight translation and reverse translation between animal models and human clinical research on stress neuroadaptations. Experimental therapeutics approaches focused on unpredictable stressors hold high promise to identify, repurpose, or refine pharmacological and psychosocial interventions for addiction.

Callous-unemotional, impulsive-irresponsible, and grandiose-manipulative traits: Distinct associations with heart rate, skin conductance, and startle responses to violent and erotic scenes.

PubMed

Fanti, Kostas A; Kyranides, Melina N; Georgiou, Giorgos; Petridou, Maria; Colins, Olivier F; Tuvblad, Catherine; Andershed, Henrik

2017-05-01

The present study aimed to examine whether callous-unemotional, grandiose-manipulative, and impulsive-irresponsible dimensions of psychopathy are differentially related to various affective and physiological measures, assessed at baseline and in response to violent and erotic movie scenes. Data were collected from young adults (N = 101) at differential risk for psychopathic traits. Findings from regression analyses revealed a unique predictive contribution of grandiose-manipulative traits in particular to higher ratings of positive valence for violent scenes. Callous-unemotional traits were uniquely associated with lower levels of sympathy toward victims and lower ratings of fear and sadness during violent scenes. All three psychopathy dimensions and the total psychopathy scale showed negative zero-order correlations with heart rate at baseline, but regression analyses revealed that only grandiose manipulation was uniquely predictive of lower baseline heart rate. Grandiose manipulation was also significantly associated with lower baseline skin conductance. Regarding autonomic activity, findings resulted in a unique negative association between grandiose manipulation and heart rate activity in response to violent scenes. In contrast, the impulsive-irresponsible dimension was positively related with heart rate activity to violent scenes. Finally, findings revealed that only callous-unemotional traits were negatively associated with startle potentiation in response to violent scenes. No associations during erotic scenes were identified. These findings point to unique associations between the three assessed dimensions of psychopathy with physiological measures, indicating that grandiose manipulation is associated with hypoarousal, impulsive irresponsibility with hyperarousal, and callous-unemotional traits with low emotional and fear responses to violent scenes. © 2017 Society for Psychophysiological Research.

Neural Systems Involved in Fear and Anxiety Measured with Fear-Potentiated Startle

ERIC Educational Resources Information Center

Davis, Michael

2006-01-01

A good deal is now known about the neural circuitry involved in how conditioned fear can augment a simple reflex (fear-potentiated startle). This involves visual or auditory as well as shock pathways that project via the thalamus and perirhinal or insular cortex to the basolateral amygdala (BLA). The BLA projects to the central (CeA) and medial…

Contextual-Specificity of Short-Delay Extinction in Humans: Renewal of Fear-Potentiated Startle in a Virtual Environment

ERIC Educational Resources Information Center

Alvarez, Ruben P.; Johnson, Linda; Grillon, Christian

2007-01-01

A recent fear-potentiated startle study in rodents suggested that extinction was not context dependent when extinction was conducted after a short delay following acquisition, suggesting that extinction can lead to erasure of fear learning in some circumstances. The main objective of this study was to attempt to replicate these findings in humans…

1996 Toxic Hazards Research Annual Report.

DTIC Science & Technology

1998-01-01

gasoline , diesel fuel, and jet propulsion (JP) fuel (Staats, 1994). Millions of dollars are spent each year at petroleum contaminated sites for remediation...of locomotor activity and auditory startle reflex tests will be provided in the detailed technical report (in progress). Body Weights and Food...Olfactory Sensitization, Acoustic Startle, Prepulse Inhibition and Habituation, Total Locomotor Activity, Tail Flick Analgesia, and the Treadmill Test of

Stress and PTSD Mechanisms as Targets for Pharmacotherapy of Alcohol Abuse, Addiction, and Relapse

DTIC Science & Technology

2015-10-01

AWARD NUMBER: W81XWH-13-1-0126 TITLE: Stress and PTSD Mechanisms as Targets for Pharmacotherapy of Alcohol Abuse, Addiction, and Relapse...DATES COVERED 30 Sep 2014 - 29 Sep 2015 4. TITLE AND SUBTITLE Stress and PTSD Mechanisms as Targets for Pharmacotherapy of Alcohol Abuse, Addiction...demonstrated that alcohol -na"ive rats exhibiting high acoustic startle response (which is associated with increased anxiety-like behavior) develop

The gap-startle paradigm to assess auditory temporal processing: Bridging animal and human research.

PubMed

Fournier, Philippe; Hébert, Sylvie

2016-05-01

The gap-prepulse inhibition of the acoustic startle (GPIAS) paradigm is the primary test used in animal research to identify gap detection thresholds and impairment. When a silent gap is presented shortly before a loud startling stimulus, the startle reflex is inhibited and the extent of inhibition is assumed to reflect detection. Here, we applied the same paradigm in humans. One hundred and fifty-seven normal-hearing participants were tested using one of five gap durations (5, 25, 50, 100, 200 ms) in one of the following two paradigms-gap-embedded in or gap-following-the continuous background noise. The duration-inhibition relationship was observable for both conditions but followed different patterns. In the gap-embedded paradigm, GPIAS increased significantly with gap duration up to 50 ms and then more slowly up to 200 ms (trend only). In contrast, in the gap-following paradigm, significant inhibition-different from 0--was observable only at gap durations from 50 to 200 ms. The finding that different patterns are found depending on gap position within the background noise is compatible with distinct mechanisms underlying each of the two paradigms. © 2016 Society for Psychophysiological Research.

Psychopathy, startle blink modulation, and electrodermal reactivity in twin men

PubMed Central

BENNING, STEPHEN D.; PATRICK, CHRISTOPHER J.; IACONO, WILLIAM G.

2008-01-01

Psychopathy is a personality disorder with interpersonal–emotional and antisocial deviance facets. This study investigated these facets of psychopathy prospectively using normal-range personality traits in a community sample of young adult men who completed a picture-viewing task that included startle blink and skin conductance measures, like tasks used to study psychopathy in incarcerated men. Consistent with prior research, scores on the interpersonal–emotional facet of psychopathy (“fearless dominance”) were associated with deficient fear-potentiated startle. Conversely, scores on the social deviance facet of psychopathy (“impulsive antisociality”) were associated with smaller overall skin conductance magnitudes. Participants high in fearless dominance also exhibited deficient skin conductance magnitudes specifically to aversive pictures. Findings encourage further investigation of psychopathy and its etiology in community samples. PMID:16364071

Loss-of-function mutations in the ethylene receptor ETR1 cause enhanced sensitivity and exaggerated response to ethylene in Arabidopsis.

PubMed

Cancel, Jesse D; Larsen, Paul B

2002-08-01

Ethylene signaling in Arabidopsis begins at a family of five ethylene receptors that regulate activity of a downstream mitogen-activated protein kinase kinase kinase, CTR1. Triple and quadruple loss-of-function ethylene receptor mutants display a constitutive ethylene response phenotype, indicating they function as negative regulators in this pathway. No ethylene-related phenotype has been described for single loss-of-function receptor mutants, although it was reported that etr1 loss-of-function mutants display a growth defect limiting plant size. In actuality, this apparent growth defect results from enhanced responsiveness to ethylene; a phenotype manifested in all tissues tested. The phenotype displayed by etr1 loss-of-function mutants was rescued by treatment with an inhibitor of ethylene perception, indicating that it is ethylene dependent. Identification of an ethylene-dependent phenotype for a loss-of-function receptor mutant gave a unique opportunity for genetic and biochemical analysis of upstream events in ethylene signaling, including demonstration that the dominant ethylene-insensitive phenotype of etr2-1 is partially dependent on ETR1. This work demonstrates that mutational loss of the ethylene receptor ETR1 alters responsiveness to ethylene in Arabidopsis and that enhanced ethylene response in Arabidopsis not only results in increased sensitivity but exaggeration of response.

Loss-of-Function Mutations in the Ethylene Receptor ETR1 Cause Enhanced Sensitivity and Exaggerated Response to Ethylene in Arabidopsis

PubMed Central

Cancel, Jesse D.; Larsen, Paul B.

2002-01-01

Ethylene signaling in Arabidopsis begins at a family of five ethylene receptors that regulate activity of a downstream mitogen-activated protein kinase kinase kinase, CTR1. Triple and quadruple loss-of-function ethylene receptor mutants display a constitutive ethylene response phenotype, indicating they function as negative regulators in this pathway. No ethylene-related phenotype has been described for single loss-of-function receptor mutants, although it was reported that etr1 loss-of-function mutants display a growth defect limiting plant size. In actuality, this apparent growth defect results from enhanced responsiveness to ethylene; a phenotype manifested in all tissues tested. The phenotype displayed by etr1 loss-of-function mutants was rescued by treatment with an inhibitor of ethylene perception, indicating that it is ethylene dependent. Identification of an ethylene-dependent phenotype for a loss-of-function receptor mutant gave a unique opportunity for genetic and biochemical analysis of upstream events in ethylene signaling, including demonstration that the dominant ethylene-insensitive phenotype of etr2-1 is partially dependent on ETR1. This work demonstrates that mutational loss of the ethylene receptor ETR1 alters responsiveness to ethylene in Arabidopsis and that enhanced ethylene response in Arabidopsis not only results in increased sensitivity but exaggeration of response. PMID:12177468

Prenatal methyl-donor supplementation augments colitis in young adult mice

USDA-ARS?s Scientific Manuscript database

Inflammatory bowel diseases have become highly prevalent in developed countries. Environmentally triggered exaggerated immune responses against the intestinal microbiome are thought to mediate the disorders. The potential dietary origins of the disease group have been implicated. However, the effect...

Dipeptides as effective prodrugs of the unnatural amino acid (+)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (LY354740), a selective group II metabotropic glutamate receptor agonist.

PubMed

Bueno, Ana Belén; Collado, Iván; de Dios, Alfonso; Domínguez, Carmen; Martín, José Alfredo; Martín, Luisa M; Martínez-Grau, María Angeles; Montero, Carlos; Pedregal, Concepción; Catlow, John; Coffey, D Scott; Clay, Michael P; Dantzig, Anne H; Lindstrom, Terry; Monn, James A; Jiang, Haiyan; Schoepp, Darryle D; Stratford, Robert E; Tabas, Linda B; Tizzano, Joseph P; Wright, Rebecca A; Herin, Marc F

2005-08-11

(+)-2-Aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (1), also known as LY354740, is a highly potent and selective agonist for group II metabotropic glutamate receptors (mGlu receptors 2 and 3) tested in clinical trials. It has been shown to block anxiety in the fear-potentiated startle model. Its relatively low bioavailability in different animal species drove the need for an effective prodrug form that would produce a therapeutic response at lower doses for the treatment of anxiety disorders. We have investigated the increase of intestinal absorption of this compound by targeting the human peptide transporter hPepT1 for active transport of di- and tripeptides derived from 1. We have found that oral administration of an N dipeptide derivative of 1 (12a) in rats shows up to an 8-fold increase in drug absorption and a 300-fold increase in potency in the fear-potentiated startle model in rats when compared with the parent drug 1.

Hawkmoths produce anti-bat ultrasound

PubMed Central

Barber, Jesse R.; Kawahara, Akito Y.

2013-01-01

Bats and moths have been engaged in aerial warfare for nearly 65 Myr. This arms race has produced a suite of counter-adaptations in moths, including bat-detecting ears. One set of defensive strategies involves the active production of sound; tiger moths' ultrasonic replies to bat attack have been shown to startle bats, warn the predators of bad taste and jam their biosonar. Here, we report that hawkmoths in the Choerocampina produce entirely ultrasonic sounds in response to tactile stimulation and the playback of biosonar attack sequences. Males do so by grating modified scraper scales on the outer surface of the genital valves against the inner margin of the last abdominal tergum. Preliminary data indicate that females also produce ultrasound to touch and playback of echolocation attack, but they do so with an entirely different mechanism. The anti-bat function of these sounds is unknown but might include startling, cross-family acoustic mimicry, warning of unprofitability or physical defence and/or jamming of echolocation. Hawkmoths present a novel and tractable system to study both the function and evolution of anti-bat defences. PMID:23825084

[The effect of neonatal administration of monosodium glutamate on behavior and blood corticosterone level].

PubMed

Kuznetsova, E G; Amstislavskaia, T G; Bulygina, V V; Il'nitskaia, S I; Tibeĭkina, M A; Skrinskaia, Iu A

2006-06-01

DBA/2 male mice were treated with monosodium glutamate (MSG) in a dose of 4 mg/g on 1, 3, 5, 7, 9 days after birth. Saline treated and intact males were used as control groups. MSG treated males displayed decreased number of crossed squares, rearings, entries in the centre and time in the centre of open field in comparison with saline-treated but not intact animals. Time in the light compartment of the light-dark box was increased in MSG-treated mice versus both saline treated and intact animals. MSG administration reduced acoustic startle response but did not affect the magnitude of prepulse inhibition of the startle reflex. Sexual motivation in male mice was reduced by MSG, the same trend was observed after saline treatment. MSG administration increased corticosterone basal level 4-fold while saline treatment did not affect it. These data suggest that neonatal administration of MSG decreases locomotion, exploratory activity, anxiety in male mice, while corticosterone level is increased. Saline treatment increases these parameters (except sexual motivation), and this augmentation is not connected to changes in corticosterone basal level.

Neurochemical, behavioral and physiological effects of pharmacologically enhanced serotonin levels in serotonin transporter (SERT)-deficient mice

PubMed Central

Fox, Meredith A.; Jensen, Catherine L.; French, Helen T.; Stein, Alison R.; Huang, Su-Jan; Tolliver, Teresa J.; Murphy, Dennis L.

2008-01-01

Rationale Serotonin transporter (SERT) knockout (−/−) mice have an altered phenotype in adulthood, including high baseline anxiety and depressive-like behaviors, associated with increased baseline extracellular serotonin levels throughout life. Objectives To examine the effects of increases in serotonin following administration of the serotonin precursor 5-hydroxy-L-tryptophan (5-HTP) in SERT wildtype (+/+), heterozygous (+/−) and −/− mice. Results 5-HTP increased serotonin in all five brain areas examined, with ~2–5-fold increases in SERT +/+ and +/− mice, and greater 4.5–11.7-fold increases in SERT −/− mice. Behaviorally, 5-HTP induced exaggerated serotonin syndrome behaviors in SERT −/− mice, with similar effects in male and female mice. Studies suggest promiscuous serotonin uptake by the dopamine transporter (DAT) in SERT −/− mice, and here, the DAT blocker GBR 12909 enhanced 5-HTP-induced behaviors in SERT −/− mice. Physiologically, 5-HTP induced exaggerated temperature effects in SERT-deficient mice. The 5-HT1A antagonist WAY 100635 decreased 5-HTP-induced hypothermia in SERT +/+ and +/− mice, with no effect in SERT −/− mice, whereas the 5-HT7 antagonist SB 269970 decreased this exaggerated response in SERT −/− mice only. WAY 100635 and SB 269970 together completely blocked 5-HTP-induced hypothermia in SERT +/− and −/− mice. Conclusions These studies demonstrate that SERT −/− mice have exaggerated neurochemical, behavioral and physiological responses to further increases in serotonin, and provide the first evidence of intact 5-HT7 receptor function in SERT −/− mice, with interesting interactions between 5-HT1A and 5-HT7 receptors. As roles for 5-HT7 receptors in anxiety and depression were recently established, the current findings have implications for understanding the high anxiety and depressive-like phenotype of SERT-deficient mice. PMID:18712364

Behavioral-Physiological Effects of Red Phosphorus Smoke Inhalation on Two Wildlife Species. Task 3. (RP/BR Aerosol Effects upon the Spontaneous Activity, Startle Response, Pulmonary Function and Blood Chemistry/Hematology of Black-Tailed Prairie Dogs (Cynomys ludovicianus) and Rock Doves (Columba livia)

DTIC Science & Technology

1989-09-01

physiological effects of multiple exposures~-to..a red phosphorus- butyl rubber (RP/BR) military smoke product in 2 wildlife species -- bhack-tailed...effects on any pulmonary function variable of prairie dogs. There was a significant Concentration X Day interaction effect for carbon dioxide production ...dioxide production (Vco 2), respiratory exchange ratio (RER), and metabolic rate (MR) of rock doves. The interactions were associated with responses of

The neural basis of visual behaviors in the larval zebrafish.

PubMed

Portugues, Ruben; Engert, Florian

2009-12-01

We review visually guided behaviors in larval zebrafish and summarise what is known about the neural processing that results in these behaviors, paying particular attention to the progress made in the last 2 years. Using the examples of the optokinetic reflex, the optomotor response, prey tracking and the visual startle response, we illustrate how the larval zebrafish presents us with a very promising model vertebrate system that allows neurocientists to integrate functional and behavioral studies and from which we can expect illuminating insights in the near future. Copyright 2009 Elsevier Ltd. All rights reserved.

Neurocircuitry models of posttraumatic stress disorder and extinction: human neuroimaging research--past, present, and future.

PubMed

Rauch, Scott L; Shin, Lisa M; Phelps, Elizabeth A

2006-08-15

The prevailing neurocircuitry models of anxiety disorders have been amygdalocentric in form. The bases for such models have progressed from theoretical considerations, extrapolated from research in animals, to in vivo human imaging data. For example, one current model of posttraumatic stress disorder (PTSD) has been highly influenced by knowledge from rodent fear conditioning research. Given the phenomenological parallels between fear conditioning and the pathogenesis of PTSD, we have proposed that PTSD is characterized by exaggerated amygdala responses (subserving exaggerated acquisition of fear associations and expression of fear responses) and deficient frontal cortical function (mediating deficits in extinction and the capacity to suppress attention/response to trauma-related stimuli), as well as deficient hippocampal function (mediating deficits in appreciation of safe contexts and explicit learning/memory). Neuroimaging studies have yielded convergent findings in support of this model. However, to date, neuroimaging investigations of PTSD have not principally employed conditioning and extinction paradigms per se. The recent development of such imaging probes now sets the stage for directly testing hypotheses regarding the neural substrates of fear conditioning and extinction abnormalities in PTSD.

A study evaluating if targeted training for startle effect can improve pilot reactions in handling unexpected situations in a flight simulator

NASA Astrophysics Data System (ADS)

Gillen, Michael William

Recent airline accidents point to a crew's failure to make correct and timely decisions following a sudden and unusual event that startled the crew. This study sought to determine if targeted training could augment decision making during a startle event. Following a startle event cognitive function is impaired for a short duration of time (30-90 seconds). In aviation, critical decisions are often required to be made during this brief, but critical, time frame. A total of 40 volunteer crews (80 individual pilots) were solicited from a global U.S. passenger airline. Crews were briefed that they would fly a profile in the simulator but were not made aware of what the profile would entail. The study participants were asked to complete a survey on their background and flying preferences. Every other crew received training on how to handle a startle event. The training consisted of a briefing and simulator practice. Crew members (subjects) were either presented a low altitude or high altitude scenario to fly in a full-flight simulator. The maneuver scenarios were analyzed using a series of one-way ANOVAs, t-tests and regression for the main effect of training on crew performance. The data indicated that the trained crews flew the maneuver profiles significantly better than the untrained crews and significantly better than the Federal Aviation Administration (FAA) Airline Transport Pilot (ATP) standards. Each scenario's sub factors were analyzed using regression to examine for specific predictors of performance. The results indicate that in the case of the high altitude profile, problem diagnosis was a significant factor, in the low altitude profile, time management was also a significant factor. These predicators can be useful in further targeting training. The study's findings suggest that targeted training can help crews manage a startle event, leading to a potential reduction of inflight loss of control accidents. The training was broad and intended to cover an overall aircraft handling approach rather than being aircraft specific. Inclusion of this type of training by airlines has the potential to better aid crews in handling sudden and unusual events.

Thyroid function during the spontaneous course of subacute thyroiditis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Teixeira, V.L.; Romaldini, J.H.; Rodrigues, H.F.

1985-05-01

A study of changes in serum T/sub 4/, T/sub 3/, and Tg as well as of serum TSH response to TRH was done in ten patients with subacute thyroiditis, from the acute phase up to 56 mo. All patients had symptoms of thyrotoxicosis. The mean serum T/sub 4/, T/sub 3/, and Tg concentration were significantly higher than in normal subjects. The basal TSH concentrations failed to increase in response to TRH. Mean serum T/sub 3/ and serum Tg levels remained higher than in normal subjects until 4 to 5 mo after the acute phase. Thyroid autoantibodies were absent during themore » whole period of study. An exaggerated response of TSH to TRH in six out of seven patients was observed from a 2 to 3 mo period until the end of follow-up. All patients with T/sub 3/ to T/sub 4/ ratio above the normal range (7-24 ng/..mu..g) showed also an exaggerated response of TSH to TRH. These data suggest that the spontaneous course of subacute thyroiditis may lead to a low thyroid reserve detectable even 5 yr following the acute phase of the disease.« less

Altered brain response to reward and punishment in adolescents with Anorexia Nervosa

PubMed Central

Bischoff-Grethe, Amanda; McCurdy, Danyale; Grenesko-Stevens, Emily; (Zoe) Irvine, Laura E.; Wagner, Angela; Yau, Wai-Ying Wendy; Fennema-Notestine, Christine; Wierenga, Christina E.; Fudge, Julie L.; Delgado, Mauricio R.; Kaye, Walter H.

2013-01-01

Adults recovered from anorexia nervosa (AN) have altered reward modulation within striatal limbic regions associated with the emotional significance of stimuli, and executive regions concerned with planning and consequences. We hypothesized that adolescents with AN would show similar disturbed reward modulation within the striatum and the anterior cingulate cortex, a region connected to the striatum and involved in reward-guided action selection. Using functional magnetic resonance imaging, twenty-two adolescent females (10 restricting-type AN, 12 healthy volunteers) performed a monetary guessing task. Time series data associated with monetary wins and losses within striatal and cingulate regions of interest were subjected to a linear mixed effects analysis. All participants responded more strongly to wins versus losses in limbic and anterior executive striatal territories. However, AN participants exhibited an exaggerated response to losses compared to wins in posterior executive and sensorimotor striatal regions, suggesting altered function in circuitry responsible for coding the affective context of stimuli and action selection based upon these valuations. As AN individuals are particularly sensitive to criticism, failure, and making mistakes, these findings may reflect the neural processes responsible for a bias in those with AN to exaggerate negative consequences. PMID:24148909

Altered brain response to reward and punishment in adolescents with Anorexia nervosa.

PubMed

Bischoff-Grethe, Amanda; McCurdy, Danyale; Grenesko-Stevens, Emily; Irvine, Laura E Zoe; Wagner, Angela; Yau, Wai-Ying Wendy; Fennema-Notestine, Christine; Wierenga, Christina E; Fudge, Julie L; Delgado, Mauricio R; Kaye, Walter H

2013-12-30

Adults recovered from Anorexia nervosa (AN) have altered reward modulation within striatal limbic regions associated with the emotional significance of stimuli, and executive regions concerned with planning and consequences. We hypothesized that adolescents with AN would show similar disturbed reward modulation within the striatum and the anterior cingulate cortex, a region connected to the striatum and involved in reward-guided action selection. Using functional magnetic resonance imaging, twenty-two adolescent females (10 restricting-type AN, 12 healthy volunteers) performed a monetary guessing task. Time series data associated with monetary wins and losses within striatal and cingulate regions of interest were subjected to a linear mixed effects analysis. All participants responded more strongly to wins versus losses in limbic and anterior executive striatal territories. However, AN participants exhibited an exaggerated response to losses compared to wins in posterior executive and sensorimotor striatal regions, suggesting altered function in circuitry responsible for coding the affective context of stimuli and action selection based upon these valuations. As AN individuals are particularly sensitive to criticism, failure, and making mistakes, these findings may reflect the neural processes responsible for a bias in those with AN to exaggerate negative consequences. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The effects of the preferential 5-HT2A agonist psilocybin on prepulse inhibition of startle in healthy human volunteers depend on interstimulus interval.

PubMed

Vollenweider, Franz X; Csomor, Philipp A; Knappe, Bernhard; Geyer, Mark A; Quednow, Boris B

2007-09-01

Schizophrenia patients exhibit impairments in prepulse inhibition (PPI) of the startle response. Hallucinogenic 5-HT(2A) receptor agonists are used for animal models of schizophrenia because they mimic some symptoms of schizophrenia in humans and induce PPI deficits in animals. Nevertheless, one report indicates that the 5-HT(2A) receptor agonist psilocybin increases PPI in healthy humans. Hence, we investigated these inconsistent results by assessing the dose-dependent effects of psilocybin on PPI in healthy humans. Sixteen subjects each received placebo or 115, 215, and 315 microg/kg of psilocybin at 4-week intervals in a randomized and counterbalanced order. PPI at 30-, 60-, 120-, 240-, and 2000-ms interstimulus intervals (ISIs) was measured 90 and 165 min after drug intake, coinciding with the peak and post-peak effects of psilocybin. The effects of psilocybin on psychopathological core dimensions and sustained attention were assessed by the Altered States of Consciousness Rating Scale (5D-ASC) and the Frankfurt Attention Inventory (FAIR). Psilocybin dose-dependently reduced PPI at short (30 ms), had no effect at medium (60 ms), and increased PPI at long (120-2000 ms) ISIs, without affecting startle reactivity or habituation. Psilocybin dose-dependently impaired sustained attention and increased all 5D-ASC scores with exception of Auditory Alterations. Moreover, psilocybin-induced impairments in sustained attention performance were positively correlated with reduced PPI at the 30 ms ISI and not with the concomitant increases in PPI observed at long ISIs. These results confirm the psilocybin-induced increase in PPI at long ISIs and reveal that psilocybin also produces a decrease in PPI at short ISIs that is correlated with impaired attention and consistent with deficient PPI in schizophrenia.

Putative antipsychotics with pronounced agonism at serotonin 5-HT1A and partial agonist activity at dopamine D2 receptors disrupt basal PPI of the startle reflex in rats.

PubMed

Auclair, Agnès L; Galinier, Alexandra; Besnard, Joël; Newman-Tancredi, Adrian; Depoortère, Ronan

2007-07-01

Prepulse inhibition (PPI) of the startle reflex has been extensively studied because it is disrupted in several psychiatric diseases, most notably schizophrenia. In rats, and to a lesser extent, in humans, PPI can be diminished by dopamine (DA) D(2)/D(3) and serotonin 5-HT(1A) receptor agonists. A novel class of potential antipsychotics (SSR181507, bifeprunox, and SLV313) possess partial agonist/antagonist properties at D(2) receptors and various levels of 5-HT(1A) activation. It thus appeared warranted to assess, in Sprague-Dawley rats, the effects of these antipsychotics on basal PPI. SSR181507, sarizotan, and bifeprunox decreased PPI, with a near-complete abolition at 2.5-10 mg/kg; SLV313 had a significant effect at 0.16 mg/kg only. Co-treatment with the 5-HT(1A) receptor antagonist WAY100,635 (0.63 mg/kg) showed that the 5-HT(1A) agonist activity of SSR181507 was responsible for its effect. By contrast, antipsychotics with low affinity and/or efficacy at 5-HT(1A) receptors, such as aripiprazole (another DA D(2)/D(3) and 5-HT(1A) ligand), and established typical and atypical antipsychotics (haloperidol, clozapine, risperidone, olanzapine, quetiapine, and ziprasidone) had no effect on basal PPI (0.01-2.5 to 2.5-40 mg/kg). The present data demonstrate that some putative antipsychotics with pronounced 5-HT(1A) agonist activity, coupled with partial agonist activity at DA D(2) receptors, markedly diminish PPI of the startle reflex in rats. These data raise the issue of the influence of such compounds on sensorimotor gating in humans.

History of chronic stress modifies acute stress-evoked fear memory and acoustic startle in male rats.

PubMed

Schmeltzer, Sarah N; Vollmer, Lauren L; Rush, Jennifer E; Weinert, Mychal; Dolgas, Charles M; Sah, Renu

2015-01-01

Chronicity of trauma exposure plays an important role in the pathophysiology of posttraumatic stress disorder (PTSD). Thus, exposure to multiple traumas on a chronic scale leads to worse outcomes than acute events. The rationale for the current study was to investigate the effects of a single adverse event versus the same event on a background of chronic stress. We hypothesized that a history of chronic stress would lead to worse behavioral outcomes than a single event alone. Male rats (n = 14/group) were exposed to either a single traumatic event in the form of electric foot shocks (acute shock, AS), or to footshocks on a background of chronic stress (chronic variable stress-shock, CVS-S). PTSD-relevant behaviors (fear memory and acoustic startle responses) were measured following 7 d recovery. In line with our hypothesis, CVS-S elicited significant increases in fear acquisition and conditioning versus the AS group. Unexpectedly, CVS-S elicited reduced startle reactivity to an acoustic stimulus in comparison with the AS group. Significant increase in FosB/ΔFosB-like immunostaining was observed in the dentate gyrus, basolateral amygdala and medial prefrontal cortex of CVS-S rats. Assessments of neuropeptide Y (NPY), a stress-regulatory transmitter associated with chronic PTSD, revealed selective reduction in the hippocampus of CVS-S rats. Collectively, our data show that cumulative stress potentiates delayed fear memory and impacts defensive responding. Altered neuronal activation in forebrain limbic regions and reduced NPY may contribute to these phenomena. Our preclinical studies support clinical findings reporting worse PTSD outcomes stemming from cumulative traumatization in contrast to acute trauma.

Interaction of threat and verbal working memory in adolescents.

PubMed

Patel, Nilam; Vytal, Katherine; Pavletic, Nevia; Stoodley, Catherine; Pine, Daniel S; Grillon, Christian; Ernst, Monique

2016-04-01

Threat induces a state of sustained anxiety that can disrupt cognitive processing, and, reciprocally, cognitive processing can modulate an anxiety response to threat. These effects depend on the level of cognitive engagement, which itself varies as a function of task difficulty. In adults, we recently showed that induced anxiety impaired working memory accuracy at low and medium but not high load. Conversely, increasing the task load reduced the physiological correlates of anxiety (anxiety-potentiated startle). The present work examines such threat-cognition interactions as a function of age. We expected threat to more strongly impact working memory in younger individuals by virtue of putatively restricted cognitive resources and weaker emotion regulation. This was tested by examining the influence of age on the interaction of anxiety and working memory in 25 adolescents (10 to 17 years) and 25 adults (22 to 46 years). Working memory load was manipulated using a verbal n-back task. Anxiety was induced using the threat of an aversive loud scream and measured via eyeblink startle. Findings revealed that, in both age groups, accuracy was lower during threat than safe conditions at low and medium but not high load, and reaction times were faster during threat than safe conditions at high load but did not differ at other loads. Additionally, anxiety-potentiated startle was greater during low and medium than high load. Thus, the interactions of anxiety with working memory appear similar in adolescents and adults. Whether these similarities reflect common neural mechanisms would need to be assessed using functional neuroimaging. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

Altered cerebellar development in nuclear receptor TAK1/ TR4 null mice is associated with deficits in GLAST(+) glia, alterations in social behavior, motor learning, startle reactivity, and microglia.

PubMed

Kim, Yong-Sik; Harry, G Jean; Kang, Hong Soon; Goulding, David; Wine, Rob N; Kissling, Grace E; Liao, Grace; Jetten, Anton M

2010-09-01

Previously, deficiency in the expression of the nuclear orphan receptor TAK1 was found to be associated with delayed cerebellar granule cell migration and Purkinje cell maturation with a permanent deficit in foliation of lobules VI–VII, suggesting a role for TAK1 in cerebellum development. In this study, we confirm that TAK1-deficient (TAK1(−/−)) mice have a smaller cerebellum and exhibit a disruption of lobules VI–VII. We extended these studies and show that at postnatal day 7, TAK1(−/−) mice exhibit a delay in monolayer maturation of dysmorphic calbindin 28K-positive Purkinje cells. The astrocyte-specific glutamate transporter (GLAST) was expressed within Bergmann fibers and internal granule cell layer at significantly lower levels in the cerebellum of TAK1(−/−) mice. At PND21, Golgi-positive Purkinje cells in TAK1(−/−) mice displayed a smaller soma (18%) and shorter distance to first branch point (35%). Neuronal death was not observed in TAK1(−/−) mice at PND21; however, activated microglia were present in the cerebellum, suggestive of earlier cell death. These structural deficits in the cerebellum were not sufficient to alter motor strength, coordination, or activity levels; however, deficits in acoustic startle response, prepulse startle inhibition, and social interactions were observed. Reactions to a novel environment were inhibited in a light/dark chamber, open-field, and home-cage running wheel. TAK1(−/−) mice displayed a plateau in performance on the running wheel, suggesting a deficit in learning to coordinate performance on a motor task. These data indicate that TAK1 is an important transcriptional modulator of cerebellar development and neurodevelopmentally regulated behavior.

BK Channels Mediate Synaptic Plasticity Underlying Habituation in Rats.

PubMed

Zaman, Tariq; De Oliveira, Cleusa; Smoka, Mahabba; Narla, Chakravarthi; Poulter, Michael O; Schmid, Susanne

2017-04-26

Habituation is a basic form of implicit learning and represents a sensory filter that is disrupted in autism, schizophrenia, and several other mental disorders. Despite extensive research in the past decades on habituation of startle and other escape responses, the underlying neural mechanisms are still not fully understood. There is evidence from previous studies indicating that BK channels might play a critical role in habituation. We here used a wide array of approaches to test this hypothesis. We show that BK channel activation and subsequent phosphorylation of these channels are essential for synaptic depression presumably underlying startle habituation in rats, using patch-clamp recordings and voltage-sensitive dye imaging in slices. Furthermore, positive modulation of BK channels in vivo can enhance short-term habituation. Although results using different approaches do not always perfectly align, together they provide convincing evidence for a crucial role of BK channel phosphorylation in synaptic depression underlying short-term habituation of startle. We also show that this mechanism can be targeted to enhance short-term habituation and therefore to potentially ameliorate sensory filtering deficits associated with psychiatric disorders. SIGNIFICANCE STATEMENT Short-term habituation is the most fundamental form of implicit learning. Habituation also represents a filter for inundating sensory information, which is disrupted in autism, schizophrenia, and other psychiatric disorders. Habituation has been studied in different organisms and behavioral models and is thought to be caused by synaptic depression in respective pathways. The underlying molecular mechanisms, however, are poorly understood. We here identify, for the first time, a BK channel-dependent molecular synaptic mechanism leading to synaptic depression that is crucial for habituation, and we discuss the significance of our findings for potential treatments enhancing habituation. Copyright © 2017 the authors 0270-6474/17/374540-12$15.00/0.

Benefits of Stimulus Exposure: Developmental Learning Independent of Task Performance

PubMed Central

Green, David B.; Ohlemacher, Jocelyn; Rosen, Merri J.

2016-01-01

Perceptual learning (training-induced performance improvement) can be elicited by task-irrelevant stimulus exposure in humans. In contrast, task-irrelevant stimulus exposure in animals typically disrupts perception in juveniles while causing little to no effect in adults. This may be due to the extent of exposure, which is brief in humans while chronic in animals. Here we assessed the effects of short bouts of passive stimulus exposure on learning during development in gerbils, compared with non-passive stimulus exposure (i.e., during testing). We used prepulse inhibition of the acoustic startle response, a method that can be applied at any age, to measure gap detection thresholds across four age groups, spanning development. First, we showed that both gap detection thresholds and gap detection learning across sessions displayed a long developmental trajectory, improving throughout the juvenile period. Additionally, we demonstrated larger within- and across-animal performance variability in younger animals. These results are generally consistent with results in humans, where there are extended developmental trajectories for both the perception of temporally-varying signals, and the effects of perceptual training, as well as increased variability and poorer performance consistency in children. We then chose an age (mid-juveniles) that displayed clear learning over sessions in order to assess effects of brief passive stimulus exposure on this learning. We compared learning in mid-juveniles exposed to either gap detection testing (gaps paired with startles) or equivalent gap exposure without testing (gaps alone) for three sessions. Learning was equivalent in both these groups and better than both naïve age-matched animals and controls receiving no gap exposure but only startle testing. Thus, short bouts of exposure to gaps independent of task performance is sufficient to induce learning at this age, and is as effective as gap detection testing. PMID:27378837

Exaggerated perception of facial expressions is increased in individuals with schizotypal traits

PubMed Central

Uono, Shota; Sato, Wataru; Toichi, Motomi

2015-01-01

Emotional facial expressions are indispensable communicative tools, and social interactions involving facial expressions are impaired in some psychiatric disorders. Recent studies revealed that the perception of dynamic facial expressions was exaggerated in normal participants, and this exaggerated perception is weakened in autism spectrum disorder (ASD). Based on the notion that ASD and schizophrenia spectrum disorder are at two extremes of the continuum with respect to social impairment, we hypothesized that schizophrenic characteristics would strengthen the exaggerated perception of dynamic facial expressions. To test this hypothesis, we investigated the relationship between the perception of facial expressions and schizotypal traits in a normal population. We presented dynamic and static facial expressions, and asked participants to change an emotional face display to match the perceived final image. The presence of schizotypal traits was positively correlated with the degree of exaggeration for dynamic, as well as static, facial expressions. Among its subscales, the paranoia trait was positively correlated with the exaggerated perception of facial expressions. These results suggest that schizotypal traits, specifically the tendency to over-attribute mental states to others, exaggerate the perception of emotional facial expressions. PMID:26135081

Exaggerated perception of facial expressions is increased in individuals with schizotypal traits.

PubMed

Uono, Shota; Sato, Wataru; Toichi, Motomi

2015-07-02

Emotional facial expressions are indispensable communicative tools, and social interactions involving facial expressions are impaired in some psychiatric disorders. Recent studies revealed that the perception of dynamic facial expressions was exaggerated in normal participants, and this exaggerated perception is weakened in autism spectrum disorder (ASD). Based on the notion that ASD and schizophrenia spectrum disorder are at two extremes of the continuum with respect to social impairment, we hypothesized that schizophrenic characteristics would strengthen the exaggerated perception of dynamic facial expressions. To test this hypothesis, we investigated the relationship between the perception of facial expressions and schizotypal traits in a normal population. We presented dynamic and static facial expressions, and asked participants to change an emotional face display to match the perceived final image. The presence of schizotypal traits was positively correlated with the degree of exaggeration for dynamic, as well as static, facial expressions. Among its subscales, the paranoia trait was positively correlated with the exaggerated perception of facial expressions. These results suggest that schizotypal traits, specifically the tendency to over-attribute mental states to others, exaggerate the perception of emotional facial expressions.

A novel pentadecapeptide, BPC 157, blocks the stereotypy produced acutely by amphetamine and the development of haloperidol-induced supersensitivity to amphetamine.

PubMed

Jelovac, N; Sikirić, P; Rucman, R; Petek, M; Perović, D; Konjevoda, P; Marović, A; Seiwerth, S; Grabarević, Z; Sumajstorcić, J; Dodig, G; Perić, J

1998-04-01

A novel gastric pentadecapeptide, BPC 157, has been shown to attenuate different lesions (i.e., gastrointestinal tract, liver, pancreas, somatosensory neurons). This suggests an interaction with the dopamine system. When used alone, BPC 157 does not affect gross behavior or induce stereotypy. We first investigated the effect of pentadecapeptide BPC 157 on stereotypy and acoustic startle response in rats, given as either a prophylactic (10 micrograms/kg i.p.) or therapeutic (10 ng/kg i.p.) regimen, with the dopamine indirect agonist amphetamine (10 mg/kg i.p.). There was a marked attenuation of stereotypic behavior and acoustic startle response. When the medication was given at the time of maximum amphetamine-induced excitability, there was a reversal of this behavior. A further focus was on the effect of this pentadecapeptide on increased climbing behavior in mice pretreated with the dopamine antagonist haloperidol (5.0 mg/kg i.p.), and subsequently treated with amphetamine (20 mg/kg i.p. challenge 1, 2, 4, and 10 days after haloperidol pretreatment). This protocol is usually used for the study of behavioral supersensitivity to the amphetamine stimulating effect. An almost complete reversal was noted when pentadecapeptide was coadministered with haloperidol. Together, these data provide compelling evidence for the interaction of pentadecapeptide BPC 157 with the dopamine system.

Perinatal asphyxia in the guinea pig leads to morphologic but not neurologic, cognitive, or behavioral changes.

PubMed

Hoeger, Harald; Bubna-Littitz, Herrmann; Engelmann, Mario; Schwerdtner, Ingrid; Schmid, Diethard; Lahoda, Robert; Seidl, Rainer; Lubec, Gert; Lubec, Barbara

2003-07-01

In a recent publication, we described neurodegeneration along with neurotransmitter deficits and impaired differentiation in the guinea pig 3 months following severe perinatal asphyxia (PA). We were therefore interested in the clinical features in terms of neurology, cognitive functions, and behavior. We tested the long-term effects of PA in an animal model, which in the rat are well documented and resemble the clinical situation. Examinations consisted of an observational battery for motor and reflex functions and the acoustic startle response setting. We tested cognitive functions in the multiple T-maze and evaluated behavior using the elevated plus maze and open field studies. No neurologic deficits were observed in the observational battery, including the acoustic startle response. Cognitive functions of memory and learning were not impaired in the multiple T-maze. In the open field and in the elevated plus maze, the system to test anxiety-related behavior, guinea pigs performed well. Our findings of patent neurology, cognitive functions, and behavior do not reflect the prominent morphologic findings of neurodegeneration. This is in agreement with corresponding studies on PA in the rat at the identical time point. We learned from this study that both test systems, although representing the standard in neuroscience, are either not sensitive enough or central nervous system lesions are clinically fully compensated.

A double-blind, placebo-controlled study on the effects of Gotu Kola (Centella asiatica) on acoustic startle response in healthy subjects.

PubMed

Bradwejn, J; Zhou, Y; Koszycki, D; Shlik, J

2000-12-01

Investigations of the pharmacologic profile of medicinal plants have revealed that a number of plants with purported anxiolytic activity bind to cholecystokinin (CCK) receptors. This finding is intriguing in view of the proposed involvement of CCK in the pathophysiology of fear and anxiety. This double-blind, placebo-controlled study was undertaken to evaluate the anxiolytic activity of Gotu Kola (Centella asiatica) in healthy subjects. Gotu Kola has been used for centuries in Ayurvedic and traditional Chinese medicine to alleviate symptoms of depression and anxiety. Recent studies in the rat have shown that long-term pretreatment with Gotu Kola decreases locomotor activity, enhances elevated-plus maze performance, and attenuates the acoustic startle response (ASR). In this study, the authors evaluated the effects of Gotu Kola on the ASR in humans. Subjects were randomly assigned to receive either a single 12-g orally administered dose of Gotu Kola (N = 20) or placebo (N = 20). The results revealed that compared with placebo, Gotu Kola significantly attenuated the peak ASR amplitude 30 and 60 minutes after treatment. Gotu Kola had no significant effect on self-rated mood, heart rate, or blood pressure. These preliminary findings suggest that Gotu Kola has anxiolytic activity in humans as revealed by the ASR. It remains to be seen whether this herb has therapeutic efficacy in the treatment of anxiety syndromes.

Identification of a pheromone that increases anxiety in rats

PubMed Central

Inagaki, Hideaki; Kiyokawa, Yasushi; Tamogami, Shigeyuki; Watanabe, Hidenori; Takeuchi, Yukari; Mori, Yuji

2014-01-01

Chemical communication plays an important role in the social lives of various mammalian species. Some of these chemicals are called pheromones. Rats release a specific odor into the air when stressed. This stress-related odor increases the anxiety levels of other rats; therefore, it is possible that the anxiety-causing molecules are present in the stress-related odorants. Here, we have tried to identify the responsible molecules by using the acoustic startle reflex as a bioassay system to detect anxiogenic activity. After successive fractionation of the stress-related odor, we detected 4-methylpentanal and hexanal in the final fraction that still possessed anxiogenic properties. Using synthetic molecules, we found that minute amounts of the binary mixture, but not either molecule separately, increased anxiety in rats. Furthermore, we determined that the mixture increased a specific type of anxiety and evoked anxiety-related behavioral responses in an experimental model that was different from the acoustic startle reflex. Analyses of neural mechanisms proposed that the neural circuit related to anxiety was only activated when the two molecules were simultaneously perceived by two olfactory systems. We concluded that the mixture is a pheromone that increases anxiety in rats. To our knowledge, this is the first study identifying a rat pheromone. Our results could aid further research on rat pheromones, which would enhance our understanding of chemical communication in mammals. PMID:25512532

Association between violent behaviour and impaired prepulse inhibition of the startle response in antisocial personality disorder and schizophrenia.

PubMed

Kumari, Veena; Das, Mrigen; Hodgins, Sheilagh; Zachariah, Elizabeth; Barkataki, Ian; Howlett, Michael; Sharma, Tonmoy

2005-03-07

Violent behaviour has a strong association with antisocial personality disorder (APD) and schizophrenia. Although developments in the understanding of socio-environmental factors associated with violence should not be ignored, advances in prevention and treatment of violent behaviour would benefit by improved understanding of its neurobiological and cognitive basis. The authors, therefore, investigated prepulse inhibition (PPI) of the startle response in APD and schizophrenia in relation to a history of serious violence. The neural substrates of PPI, especially the hippocampus, amygdala, thalamus and basal ganglia, are implicated in violence as well as in APD and schizophrenia. The study included four groups: (i) patients with APD and a history of violence, (ii) patients with schizophrenia and a history of violence, (iii) patients with schizophrenia without a history of violence, and (iv) healthy subjects with no history of violence or a mental disorder. All subjects were assessed identically on acoustic PPI. Compared to healthy subjects, significantly reduced PPI occurred in APD, violent schizophrenia and non-violent schizophrenia patients. Although PPI did not significantly differentiate the three clinical groups, high ratings of violence were modestly associated with reduced PPI across the entire study sample. Violent patients with impulsive and premeditated violence showed comparable PPI. The association between violent behaviour and impaired PPI suggests that neural structures and functions underlying PPI are implicated in (inhibition of) violence.

Increased whole-body auditory startle reflex and autonomic reactivity in children with anxiety disorders

PubMed Central

Bakker, Mirte J.; Tijssen, Marina A.J.; van der Meer, Johan N.; Koelman, Johannes H.T.M.; Boer, Frits

2009-01-01

Background Young patients with anxiety disorders are thought to have a hypersensitive fear system, including alterations of the early sensorimotor processing of threatening information. However, there is equivocal support in auditory blink response studies for an enlarged auditory startle reflex (ASR) in such patients. We sought to investigate the ASR measured over multiple muscles (whole-body) in children and adolescents with anxiety disorders. Methods Between August and December 2006, we assessed ASRs (elicited by 8 consecutive tones of 104 dB, interstimulus interval of about 2 min) in 25 patients and 25 matched controls using a case–control design and in 9 nonaffected siblings. We recorded the electromyographic activity of 6 muscles and the sympathetic skin response. We investigated response occurrence (probability %) and response magnitude (area under the curve in μV × ms) of the combined response of 6 muscles and of the single blink response. Results In patients (17 girls, mean age 12 years; 13 social phobia, 9 generalized anxiety, 3 other), the combined response probability (p = 0.027) of all muscles, the combined area under the curve of all muscles (p = 0.011) and the sympathetic skin response (p = 0.006) were enlarged compared with matched controls. The response probability (p = 0.48) and area under the curve (p = 0.07) of the blink response were normal in patients compared with controls. The ASR pattern was normal with normal latencies in patients compared with controls. In nonaffected siblings, the sympathetic skin response (p = 0.038), but not the combined response probability of all muscles (p = 0.15), was enlarged compared with controls. Limitations Limitations are the sample size and restricted comparison to the psychophysiological ASR paradigm. Conclusion The results point toward a hypersensitive central nervous system (fear system), including early sensorimotor processing alterations and autonomic hyperreactivity. The multiple muscle (whole-body) ASR is suggested to be a better tool to detect ASR abnormalities in patients with anxiety disorders than the blink response alone. Abnormalities in ASR serve as a candidate endophenotype of anxiety disorders. PMID:19568483

[Hypertension, cardiovascular reactivity to stress and sensibility to pain].

PubMed

Conde-Guzón, P A; Bartolomé-Albistegui, M T; Quirós-Expósito, P; Grzib-Schlosky, G

To provide a review of empirical evidence of decreased pain perception in hypertensive persons or exaggerated cardiovascular reactivity to stress. To following article will briefly review the existing literature on the association between hypoalgesia and high blood pressure. In particular, evidence of hypoalgesia in normotensive individuals at increased risk for hypertension (exaggerated cardiovascular reactivity to stress) will be offered in support of the notion that high cardiovascular reactivity to stress and decreased pain perception may result from a common physiological dysfunction. Cardiovascular reactivity refers to changes in cardiovascular activity associated primarily with exposure to psychological stress. Different individuals show different amounts of reactivity under the same conditions. The greater cardiovascular reactivity to behavioral stressors may play some role in the development of sustained arterial hypertension. Central opioid hyposensitivity is hypothesized as a mechanism of both hypoalgesia and exaggerated autonomic and neuroendocrine responses to stress in individuals at risk for hypertension. The paraventricular nucleus of the hypothalamus (PVN) serves the crucial function of integrating cardiovascular and painful responses. The central opioid hyposensitivity model of hypoalgesia asserts that attenuation of inhibitory opioid input to the PVN may have important consequences for pain modulation. These consequences includes: 1) greater activation of baroreceptor reflex arcs, 2) enhanced release of endogenous opioids during stress, and 3) increased stimulation of descending pain modulation pathways. High elevated thresholds to painful thermal stressors might serve as a behavioral marker of risk for hypertension before the onset of high blood pressure levels.

Jasmonate and Phytochrome A Signaling in Arabidopsis Wound and Shade Responses Are Integrated through JAZ1 Stability[C][W

PubMed Central

Robson, Frances; Okamoto, Haruko; Patrick, Elaine; Harris, Sue-Ré; Wasternack, Claus; Brearley, Charles; Turner, John G.

2010-01-01

Jasmonate (JA) activates plant defense, promotes pollen maturation, and suppresses plant growth. An emerging theme in JA biology is its involvement in light responses; here, we examine the interdependence of the JA- and light-signaling pathways in Arabidopsis thaliana. We demonstrate that mutants deficient in JA biosynthesis and signaling are deficient in a subset of high irradiance responses in far-red (FR) light. These mutants display exaggerated shade responses to low, but not high, R/FR ratio light, suggesting a role for JA in phytochrome A (phyA) signaling. Additionally, we demonstrate that the FR light–induced expression of transcription factor genes is dependent on CORONATINE INSENSITIVE1 (COI1), a central component of JA signaling, and is suppressed by JA. phyA mutants had reduced JA-regulated growth inhibition and VSP expression and increased content of cis-(+)-12-oxophytodienoic acid, an intermediate in JA biosynthesis. Significantly, COI1-mediated degradation of JASMONATE ZIM DOMAIN1-β-glucuronidase (JAZ1-GUS) in response to mechanical wounding and JA treatment required phyA, and ectopic expression of JAZ1-GUS resulted in exaggerated shade responses. Together, these results indicate that JA and phyA signaling are integrated through degradation of the JAZ1 protein, and both are required for plant responses to light and stress. PMID:20435902

Neonatal (+)-methamphetamine exposure in rats alters adult locomotor responses to dopamine D1 and D2 agonists and to a glutamate NMDA receptor antagonist, but not to serotonin agonists

PubMed Central

Graham, Devon L.; Amos-Kroohs, Robyn M.; Braun, Amanda A.; Grace, Curtis E.; Schaefer, Tori L.; Skelton, Matthew R.; Williams, Michael T.; Vorhees, Charles V.

2015-01-01

Neonatal exposure to (+)-methamphetamine (Meth) results in long-term behavioural abnormalities but its developmental mechanisms are unknown. In a series of experiments, rats were treated from post-natal days (PD) 11–20 (stage that approximates human development from the second to third trimester) with Meth or saline and assessed using locomotor activity as the readout following pharmacological challenge doses with dopamine, serotonin and glutamate agonists or antagonists during adulthood. Exposure to Meth early in life resulted in an exaggerated adult locomotor hyperactivity response to the dopamine D1 agonist SKF-82958 at multiple doses, a high dose only under-response activating effect of the D2 agonist quinpirole, and an exaggerated under-response to the activating effect of the N-methyl-D-aspartic acid (NMDA) receptor antagonist, MK-801. No change in locomotor response was seen following challenge with the 5-HT releaser p-chloroamphetamine or the 5-HT2/3 receptor agonist, quipazine. These are the first data to show that PD 11-20 Meth exposure induces long-lasting alterations to dopamine D1, D2 and glutamate NMDA receptor function and may suggest how developmental Meth exposure leads to many of its long-term adverse effects. PMID:22391043

Clinical utility of the Neurobehavioral Symptom Inventory validity scales to screen for symptom exaggeration following traumatic brain injury.

PubMed

Lange, Rael T; Brickell, Tracey A; Lippa, Sara M; French, Louis M

2015-01-01

The purpose of this study was to examine the clinical utility of three recently developed validity scales (Validity-10, NIM5, and LOW6) designed to screen for symptom exaggeration using the Neurobehavioral Symptom Inventory (NSI). Participants were 272 U.S. military service members who sustained a mild, moderate, severe, or penetrating traumatic brain injury (TBI) and who were evaluated by the neuropsychology service at Walter Reed Army Medical Center within 199 weeks post injury. Participants were divided into two groups based on the Negative Impression Management scale of the Personality Assessment Inventory: (a) those who failed symptom validity testing (SVT-fail; n = 27) and (b) those who passed symptom validity testing (SVT-pass; n = 245). Participants in the SVT-fail group had significantly higher scores (p<.001) on the Validity-10, NIM5, LOW6, NSI total, and Personality Assessment Inventory (PAI) clinical scales (range: d = 0.76 to 2.34). Similarly high sensitivity, specificity, positive predictive power (PPP), and negative predictive (NPP) values were found when using all three validity scales to differentiate SVT-fail versus SVT-pass groups. However, the Validity-10 scale consistently had the highest overall values. The optimal cutoff score for the Validity-10 scale to identify possible symptom exaggeration was ≥19 (sensitivity = .59, specificity = .89, PPP = .74, NPP = .80). For the majority of people, these findings provide support for the use of the Validity-10 scale as a screening tool for possible symptom exaggeration. When scores on the Validity-10 exceed the cutoff score, it is recommended that (a) researchers and clinicians do not interpret responses on the NSI, and (b) clinicians follow up with a more detailed evaluation, using well-validated symptom validity measures (e.g., Minnesota Multiphasic Personality Inventory-2 Restructured Form, MMPI-2-RF, validity scales), to seek confirmatory evidence to support an hypothesis of symptom exaggeration.

CGRP Antagonist Infused into the Bed Nucleus of the Stria Terminalis Impairs the Acquisition and Expression of Context but Not Discretely Cued Fear

ERIC Educational Resources Information Center

Sink, Kelly S.; Davis, Michael; Walker, David L.

2013-01-01

Calcitonin gene-related peptide (CGRP) infusions into the bed nucleus of the stria terminalis (BNST) evoke increases in startle amplitude and increases in anxiety-like behavior in the plus maze. Conversely, intra-BNST infusions of the CGRP antagonist CGRP[subscript 8-37] block unconditioned startle increases produced by fox odor. Here we evaluate…

Addressing variability in the acoustic startle reflex for accurate gap detection assessment.

PubMed

Longenecker, Ryan J; Kristaponyte, Inga; Nelson, Gregg L; Young, Jesse W; Galazyuk, Alexander V

2018-06-01

The acoustic startle reflex (ASR) is subject to substantial variability. This inherent variability consequently shapes the conclusions drawn from gap-induced prepulse inhibition of the acoustic startle reflex (GPIAS) assessments. Recent studies have cast doubt as to the efficacy of this methodology as it pertains to tinnitus assessment, partially, due to variability in and between data sets. The goal of this study was to examine the variance associated with several common data collection variables and data analyses with the aim to improve GPIAS reliability. To study this the GPIAS tests were conducted in adult male and female CBA/CaJ mice. Factors such as inter-trial interval, circadian rhythm, sex differences, and sensory adaptation were each evaluated. We then examined various data analysis factors which influence GPIAS assessment. Gap-induced facilitation, data processing options, and assessments of tinnitus were studied. We found that the startle reflex is highly variable in CBA/CaJ mice, but this can be minimized by certain data collection factors. We also found that careful consideration of temporal fluctuations of the ASR and controlling for facilitation can lead to more accurate GPIAS results. This study provides a guide for reducing variance in the GPIAS methodology - thereby improving the diagnostic power of the test. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of acute exposure of permethrin in adult and developing Sprague-Dawley rats on acoustic startle response and brain and plasma concentrations.

PubMed

Williams, Michael T; Gutierrez, Arnold; Vorhees, Charles V

2018-06-08

Permethrin is a Type I (non-cyano) pyrethroid that induces tremors at high concentrations and increases acoustic startle responses (ASR) in adult rodents, however its effects in young rats have been investigated to a limited extent. ASR and tremor were assessed in adult and postnatal day (P)15 Sprague-Dawley rats at oral doses of 60, 90, or 120 mg/kg over an 8 h period. Permethrin increased ASR in adults, regardless of dose, and 20% of the high-dose rats showed tremor at later time points. For the P15 rats all doses induced tremor at all time points, and ASR was increased at 2 h in the 90 and 120 mg/kg groups with a trend in the 60 mg/kg group compared with controls. The 60 mg/kg group showed increased ASR at 4 and 6 h, whereas the 90 mg/kg group showed no differences from the controls at these times. The 120 mg/kg group showed decreased ASR from 4-8 h post-treatment. P15 and adult rats both showed plasma and brain cis- and trans-permethrin increases after dosing. After the same dose of permethrin, P15 rats had greater cis- and trans-permethrin in brain and plasma compared with adults. P15 rats had an increased tremor response compared with adults even at comparable brain permethrin concentrations. For ASR, P15 rats responded sooner and showed a biphasic pattern ranging from increased to decreased response as a function of dose and time, unlike adults that only showed increases. Overall, young rats showed greater effects from permethrin compared with adults.

Development of the Acoustically Evoked Behavioral Response in Larval Plainfin Midshipman Fish, Porichthys notatus

PubMed Central

Alderks, Peter W.; Sisneros, Joseph A.

2013-01-01

The ontogeny of hearing in fishes has become a major interest among bioacoustics researchers studying fish behavior and sensory ecology. Most fish begin to detect acoustic stimuli during the larval stage which can be important for navigation, predator avoidance and settlement, however relatively little is known about the hearing capabilities of larval fishes. We characterized the acoustically evoked behavioral response (AEBR) in the plainfin midshipman fish, Porichthys notatus, and used this innate startle-like response to characterize this species' auditory capability during larval development. Age and size of larval midshipman were highly correlated (r2 = 0.92). The AEBR was first observed in larvae at 1.4 cm TL. At a size ≥1.8 cm TL, all larvae responded to a broadband stimulus of 154 dB re1 µPa or −15.2 dB re 1 g (z-axis). Lowest AEBR thresholds were 140–150 dB re 1 µPa or −33 to −23 dB re 1 g for frequencies below 225 Hz. Larval fish with size ranges of 1.9–2.4 cm TL had significantly lower best evoked frequencies than the other tested size groups. We also investigated the development of the lateral line organ and its function in mediating the AEBR. The lateral line organ is likely involved in mediating the AEBR but not necessary to evoke the startle-like response. The midshipman auditory and lateral line systems are functional during early development when the larvae are in the nest and the auditory system appears to have similar tuning characteristics throughout all life history stages. PMID:24340003

Self-Reported Trait Mindfulness and Affective Reactivity: A Motivational Approach Using Multiple Psychophysiological Measures

PubMed Central

Cosme, Danielle; Wiens, Stefan

2015-01-01

As a form of attention, mindfulness is qualitatively receptive and non-reactive, and is thought to facilitate adaptive emotional responding. One suggested mechanism is that mindfulness facilitates disengagement from an affective stimulus and thereby decreases affective reactivity. However, mindfulness has been conceptualized as a state, intervention, and trait. Because evidence is mixed as to whether self-reported trait mindfulness decreases affective reactivity, we used a multi-method approach to study the relationship between individual differences in self-reported trait mindfulness and electrocortical, electrodermal, electromyographic, and self-reported responses to emotional pictures. Specifically, while participants (N = 51) passively viewed pleasant, neutral, and unpleasant IAPS pictures, we recorded high-density (128 channels) electrocortical, electrodermal, and electromyographic data to the pictures as well as to acoustic startle probes presented during the pictures. Afterwards, participants rated their subjective valence and arousal while viewing the pictures again. If trait mindfulness spontaneously reduces general emotional reactivity, then for individuals reporting high rather than low mindfulness, response differences between emotional and neutral pictures would show relatively decreased early posterior negativity (EPN) and late positive potential (LPP) amplitudes, decreased skin conductance responses, and decreased subjective ratings for valence and arousal. High mindfulness would also be associated with decreased emotional modulation of startle eyeblink and P3 amplitudes. Although results showed clear effects of emotion on the dependent measures, in general, mindfulness did not moderate these effects. For most measures, effect sizes were small with rather narrow confidence intervals. These data do not support the hypothesis that individual differences in self-reported trait mindfulness are related to spontaneous emotional responses during picture viewing. PMID:25749431

Targeting Nuclear Receptors to Treat Fibrostenotic Crohn’s Disease

DTIC Science & Technology

2017-08-01

feedback loop . 15. SUBJECT TERMS Crohn’s disease, intestinal smooth muscle, intestinal fibroblasts, NR4A1, 6-MP, Cytosporone B, proliferation, inflammation...whether the exaggerated tissue remodelling observed in our studies reflects a hyper -fibrotic response, versus a hyper -inflammatory phenotype

Enhanced striatal sensitivity to aversive reinforcement in adolescents versus adults.

PubMed

Galván, Adriana; McGlennen, Kristine M

2013-02-01

Neurodevelopmental changes in mesolimbic regions are associated with adolescent risk-taking behavior. Numerous studies have shown exaggerated activation in the striatum in adolescents compared with children and adults during reward processing. However, striatal sensitivity to aversion remains elusive. Given the important role of the striatum in tracking both appetitive and aversive events, addressing this question is critical to understanding adolescent decision-making, as both positive and negative factors contribute to this behavior. In this study, human adult and adolescent participants performed a task in which they received squirts of appetitive or aversive liquid while undergoing fMRI, a novel approach in human adolescents. Compared with adults, adolescents showed greater behavioral and striatal sensitivity to both appetitive and aversive stimuli, an effect that was exaggerated in response to delivery of the aversive stimulus. Collectively, these findings contribute to understanding how neural responses to positive and negative outcomes differ between adolescents and adults and how they may influence adolescent behavior.

Exaggerated blood pressure response to exercise--a new portent of masked hypertension.

PubMed

Kayrak, Mehmet; Bacaksiz, Ahmet; Vatankulu, Mehmet Akif; Ayhan, Selim S; Kaya, Zeynettin; Ari, Hatem; Sonmez, Osman; Gok, Hasan

2010-01-01

Masked hypertension (MHT) is a popular entity with increased risk of developing sustained hypertension, heart attack, stroke, and death. Subjects have normal blood pressure (BP) at office but elevated values at night so it is difficult to diagnose. Exaggerated blood pressure response to exercise (EBPR) is also a predictor of future hypertension. To investigate the relationship between these two entities, we evaluated 61 normotensive subjects with EBPR. The subjects underwent 24-h ambulatory blood pressure monitoring (ABPM). The prevalence of masked hypertension among subjects with EBPR was 41%. Body mass index (BMI), non-high density lipoprotein (HDL) cholesterol, diastolic blood pressure (DBP) at peak exercise and recovery, nondipping DBP pattern, and elevated early morning average BPs were associated with masked hypertension. In multivariate logistic regression analysis, the DBP measured at peak exercise was detected as an independent predictor of MHT in subjects with EBPR. Subjects with abnormally elevated BP during exercise are prone to MHT, necessitate medical assessment and close follow-up for hypertension.

Audiological Evaluation for Exaggerated Hearing Level.

ERIC Educational Resources Information Center

Engelberg, Marvin W.

Described are clinical techniques and procedures useful in evaluations for exaggerated hearing levels. Discussed are considerations of the audiologist, his equipment, and erroneous findings; patient cooperation, anticipated hearing handicaps, detection of exaggeration, and order of test presentation; voluntary aid conduction audiometry,…

PFOS induces behavioral alterations, including spontaneous hyperactivity that is corrected by dexamfetamine in zebrafish larvae.

PubMed

Spulber, Stefan; Kilian, Pascal; Wan Ibrahim, Wan Norhamidah; Onishchenko, Natalia; Ulhaq, Mazhar; Norrgren, Leif; Negri, Sara; Di Tuccio, Marcello; Ceccatelli, Sandra

2014-01-01

Perfluorooctane sulfonate (PFOS) is a widely spread environmental contaminant. It accumulates in the brain and has potential neurotoxic effects. The exposure to PFOS has been associated with higher impulsivity and increased ADHD prevalence. We investigated the effects of developmental exposure to PFOS in zebrafish larvae, focusing on the modulation of activity by the dopaminergic system. We exposed zebrafish embryos to 0.1 or 1 mg/L PFOS (0.186 or 1.858 µM, respectively) and assessed swimming activity at 6 dpf. We analyzed the structure of spontaneous activity, the hyperactivity and the habituation during a brief dark period (visual motor response), and the vibrational startle response. The findings in zebrafish larvae were compared with historical data from 3 months old male mice exposed to 0.3 or 3 mg/kg/day PFOS throughout gestation. Finally, we investigated the effects of dexamfetamine on the alterations in spontaneous activity and startle response in zebrafish larvae. We found that zebrafish larvae exposed to 0.1 mg/L PFOS habituate faster than controls during a dark pulse, while the larvae exposed to 1 mg/L PFOS display a disorganized pattern of spontaneous activity and persistent hyperactivity. Similarly, mice exposed to 0.3 mg/kg/day PFOS habituated faster than controls to a new environment, while mice exposed to 3 mg/kg/day PFOS displayed more intense and disorganized spontaneous activity. Dexamfetamine partly corrected the hyperactive phenotype in zebrafish larvae. In conclusion, developmental exposure to PFOS in zebrafish induces spontaneous hyperactivity mediated by a dopaminergic deficit, which can be partially reversed by dexamfetamine in zebrafish larvae.

A startling acoustic stimulus facilitates voluntary lower extremity movements and automatic postural responses in people with chronic stroke.

PubMed

Coppens, Milou J M; Roelofs, Jolanda M B; Donkers, Nicole A J; Nonnekes, Jorik; Geurts, Alexander C H; Weerdesteyn, Vivian

2018-05-14

A startling acoustic stimulus (SAS) involuntary releases prepared movements at accelerated latencies, known as the StartReact effect. Previous work has demonstrated intact StartReact in paretic upper extremity movements in people after stroke, suggesting preserved motor preparation. The question remains whether motor preparation of lower extremity movements is also unaffected after stroke. Here, we investigated StartReact effects on ballistic lower extremity movements and on automatic postural responses (APRs) following perturbations to standing balance. These APRs are particularly interesting as they are critical to prevent a fall following balance perturbations, but show substantial delays and poor muscle coordination after stroke. Twelve chronic stroke patients and 12 healthy controls performed voluntary ankle dorsiflexion movements in response to a visual stimulus, and responded to backward balance perturbations evoking APRs. Twenty-five percent of all trials contained a SAS (120 dB) simultaneously with the visual stimulus or balance perturbation. As expected, in the absence of a SAS muscle and movement onset latencies at the paretic side were delayed compared to the non-paretic leg and to controls. The SAS accelerated ankle dorsiflexion onsets in both the legs of the stroke subjects and in controls. Following perturbations, the SAS accelerated bilateral APR onsets not only in controls, but for the first time, we also demonstrated this effect in people after stroke. Moreover, APR inter- and intra-limb muscle coordination was rather weak in our stroke subjects, but substantially improved when the SAS was applied. These findings show preserved movement preparation, suggesting that there is residual (subcortical) capacity for motor recovery.

The Influence of Work-Related Chronic Stress on the Regulation of Emotion and on Functional Connectivity in the Brain

PubMed Central

Golkar, Armita; Johansson, Emilia; Kasahara, Maki; Osika, Walter; Perski, Aleksander; Savic, Ivanka

2014-01-01

Despite mounting reports about the negative effects of chronic occupational stress on cognitive and emotional functions, the underlying mechanisms are unknown. Recent findings from structural MRI raise the question whether this condition could be associated with a functional uncoupling of the limbic networks and an impaired modulation of emotional stress. To address this, 40 subjects suffering from burnout symptoms attributed to chronic occupational stress and 70 controls were investigated using resting state functional MRI. The participants' ability to up- regulate, down-regulate, and maintain emotion was evaluated by recording their acoustic startle response while viewing neutral and negatively loaded images. Functional connectivity was calculated from amygdala seed regions, using explorative linear correlation analysis. Stressed subjects were less capable of down-regulating negative emotion, but had normal acoustic startle responses when asked to up-regulate or maintain emotion and when no regulation was required. The functional connectivity between the amygdala and the anterior cingulate cortex correlated with the ability to down-regulate negative emotion. This connectivity was significantly weaker in the burnout group, as was the amygdala connectivity with the dorsolateral prefrontal cortex and the motor cortex, whereas connectivity from the amygdala to the cerebellum and the insular cortex were stronger. In subjects suffering from chronic occupational stress, the functional couplings within the emotion- and stress-processing limbic networks seem to be altered, and associated with a reduced ability to down-regulate the response to emotional stress, providing a biological substrate for a further facilitation of the stress condition. PMID:25184294

The handicap process favors exaggerated, rather than reduced, sexual ornaments.

PubMed

Tazzyman, Samuel J; Iwasa, Yoh; Pomiankowski, Andrew

2014-09-01

Why are traits that function as secondary sexual ornaments generally exaggerated in size compared to the naturally selected optimum, and not reduced? Because they deviate from the naturally selected optimum, traits that are reduced in size will handicap their bearer, and could thus provide an honest signal of quality to a potential mate. Thus if secondary sexual ornaments evolve via the handicap process, current theory suggests that reduced ornamentation should be as frequent as exaggerated ornamentation, but this is not the case. To try to explain this discrepancy, we analyze a simple model of the handicap process. Our analysis shows that asymmetries in costs of preference or ornament with regard to exaggeration and reduction cannot fully explain the imbalance. Rather, the bias toward exaggeration can be best explained if either the signaling efficacy or the condition dependence of a trait increases with size. Under these circumstances, evolution always leads to more extreme exaggeration than reduction: although the two should occur just as frequently, exaggerated secondary sexual ornaments are likely to be further removed from the naturally selected optimum than reduced ornaments. © 2014 The Authors. Evolution published by Wiley Periodicals, Inc. on behalf of The Society for the Study of Evolution.

Student Online Plagiarism: How Do We Respond?

ERIC Educational Resources Information Center

Scanlon, Patrick M.

2003-01-01

The perception that Internet plagiarism by university students is on the rise has alarmed college teachers, leading to the adoption of electronic plagiarism checkers, among other responses. Although some recent studies suggest that estimates of online plagiarism may be exaggerated, cause for concern remains. This article reviews quantitative…

Magnetic Resonance and Spectroscopy of the Human Brain in Gulf War Illness

DTIC Science & Technology

2005-08-01

relationship between GWI and stress . Acoustic startle is a hallmark feature of PTSD . Past studies have shown that PTSD subjects have an increased startle...brain, neuro- psychological testing, audio vestibular testing, PTSD 16. SECURITY CLASSIFICATION OF: 17. LIMITATION 18. NUMBER 19a. NAME OF...such as PTSD , depression, or alcohol abuse. 2) Reduced NAA in the basal ganglia and pons correlates with central nervous system signs and symptoms of

Microglial Priming and Enhanced Reactivity to Secondary Insult in Aging, and Traumatic CNS injury, and Neurodegenerative Disease

PubMed Central

Norden, Diana M.; Muccigrosso, Megan M.; Godbout, Jonathan P.

2014-01-01

Glia of the central nervous system (CNS) help to maintain homeostasis in the brain and support efficient neuronal function. Microglia are innate immune cells of the brain that mediate responses to pathogens and injury. They have key roles in phagocytic clearing, surveying the local microenvironment and propagating inflammatory signals. An interruption in homeostasis induces a cascade of conserved adaptive responses in glia. This response involves biochemical, physiological and morphological changes and is associated with the production of cytokines and secondary mediators that influence synaptic plasticity, cognition and behavior. This reorganization of host priorities represents a beneficial response that is normally adaptive but may become maladaptive when the profile of microglia is compromised. For instance, microglia can develop a primed or pro-inflammatory mRNA, protein and morphological profile with aging, traumatic brain injury and neurodegenerative disease. As a result, primed microglia exhibit an exaggerated inflammatory response to secondary and sub-threshold challenges. Consequences of exaggerated inflammatory responses by microglia include the development of cognitive deficits, impaired synaptic plasticity and accelerated neurodegeneration. Moreover, impairments in regulatory systems in these circumstances may make microglia more resistant to negative feedback and important functions of glia can become compromised and dysfunctional. Overall, the purpose of this review is to discuss key concepts of microglial priming and immune-reactivity in the context of aging, traumatic CNS injury and neurodegenerative disease. PMID:25445485

Modification of Fear Memory by Pharmacological and Behavioural Interventions during Reconsolidation

PubMed Central

Thome, Janine; Koppe, Georgia; Hauschild, Sophie; Liebke, Lisa; Schmahl, Christian; Lis, Stefanie; Bohus, Martin

2016-01-01

Background Dysfunctional fear responses play a central role in many mental disorders. New insights in learning and memory suggest that pharmacological and behavioural interventions during the reconsolidation of reactivated fear memories may increase the efficacy of therapeutic interventions. It has been proposed that interventions applied during reconsolidation may modify the original fear memory, and thus prevent the spontaneous recovery and reinstatement of the fear response. Methods We investigated whether pharmacological (propranolol) and behavioural (reappraisal, multisensory stimulation) interventions reduce fear memory, and prevent reinstatement of fear in comparison to a placebo control group. Eighty healthy female subjects underwent a differential fear conditioning procedure with three stimuli (CS). Two of these (CS+) were paired with an electric shock on day 1. On day 2, 20 subjects were pseudo-randomly assigned to either the propranolol or placebo condition, or underwent one of the two behavioural interventions after one of the two CS+ was reactivated. On day 3, all subjects underwent an extinction phase, followed by a reinstatement test. Dependent variables were US expectancy ratings, fear-potentiated startle, and skin conductance response. Results Differential fear responses to the reactivated and non-reactivated CS+ were observed only in the propranolol condition. Here, the non-reactivated CS+ evoked stronger fear-potentiated startle-responses compared to the placebo group. None of the interventions prevented the return of the extinguished fear response after re-exposure to the unconditioned stimulus. Conclusions Our data are in line with an increasing body of research stating that the occurrence of reconsolidation may be constrained by boundary conditions such as subtle differences in experimental manipulations and instructions. In conclusion, our findings do not support a beneficial effect in using reconsolidation processes to enhance effects of psychotherapeutic interventions. This implies that more research is required before therapeutic interventions may benefit from a combination with reconsolidation processes. PMID:27537364

Role of Sleep Deprivation in Fear Conditioning and Extinction: Implications for Treatment of PTSD

DTIC Science & Technology

2014-10-01

The auditory stimulus during the NA trials, a brief (40 ms) pulse of 108 dB is used to induce a startle response, the magnitude of which is the...processing in humans and rodents would aid in mechanistic studies examining SD- induced inattention. We assessed the effects of 36 hours of: 1) Total SD...were required to inhibit from responding. TSD- induced effects on human Psychomotor Vigilance Test (PVT) were also examined. Effects of SD were also

Adaptation aftereffects in the perception of gender from biological motion.

PubMed

Troje, Nikolaus F; Sadr, Javid; Geyer, Henning; Nakayama, Ken

2006-07-28

Human visual perception is highly adaptive. While this has been known and studied for a long time in domains such as color vision, motion perception, or the processing of spatial frequency, a number of more recent studies have shown that adaptation and adaptation aftereffects also occur in high-level visual domains like shape perception and face recognition. Here, we present data that demonstrate a pronounced aftereffect in response to adaptation to the perceived gender of biological motion point-light walkers. A walker that is perceived to be ambiguous in gender under neutral adaptation appears to be male after adaptation with an exaggerated female walker and female after adaptation with an exaggerated male walker. We discuss this adaptation aftereffect as a tool to characterize and probe the mechanisms underlying biological motion perception.

Experiencing and Regulating Sadness: Physiological and Cognitive Effects

ERIC Educational Resources Information Center

Robinson, Jennifer L.; Demaree, Heath A.

2009-01-01

No prior study has examined the two most prominent response-focused regulation strategies (suppression and exaggeration) using a within-subjects design. Utilizing this design allows for a direct comparison of physiological patterns and cognitive impairment associated with such efforts. One hundred and nine participants were asked to view a series…

Exaggerated Claims for Interactive Stories

NASA Astrophysics Data System (ADS)

Thue, David; Bulitko, Vadim; Spetch, Marcia; Webb, Michael

As advertising becomes more crucial to video games' success, developers risk promoting their products beyond the features that they can actually include. For features of interactive storytelling, the effects of making such exaggerations are not well known, as reports from industry have been anecdotal at best. In this paper, we explore the effects of making exaggerated claims for interactive stories, in the context of the theory of advertising. Results from a human user study show that female players find linear and branching stories to be significantly less enjoyable when they are advertised with exaggerated claims.