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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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

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.

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

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…

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

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.

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

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.

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.

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.

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

Lack of predictive power of trait fear and anxiety for conditioned pain modulation (CPM).

PubMed

Horn-Hofmann, Claudia; Priebe, Janosch A; Schaller, Jörg; Görlitz, Rüdiger; Lautenbacher, Stefan

2016-12-01

In recent years the association of conditioned pain modulation (CPM) with trait fear and anxiety has become a hot topic in pain research due to the assumption that such variables may explain the low CPM efficiency in some individuals. However, empirical evidence concerning this association is still equivocal. Our study is the first to investigate the predictive power of fear and anxiety for CPM by using a well-established psycho-physiological measure of trait fear, i.e. startle potentiation, in addition to two self-report measures of pain-related trait anxiety. Forty healthy, pain-free participants (female: N = 20; age: M = 23.62 years) underwent two experimental blocks in counter-balanced order: (1) a startle paradigm with affective picture presentation and (2) a CPM procedure with hot water as conditioning stimulus (CS) and contact heat as test stimulus (TS). At the end of the experimental session, pain catastrophizing (PCS) and pain anxiety (PASS) were assessed. PCS score, PASS score and startle potentiation to threatening pictures were entered as predictors in a linear regression model with CPM magnitude as criterion. We were able to show an inhibitory CPM effect in our sample: pain ratings of the heat stimuli were significantly reduced during hot water immersion. However, CPM was neither predicted by self-report of pain-related anxiety nor by startle potentiation as psycho-physiological measure of trait fear. These results corroborate previous negative findings concerning the association between trait fear/anxiety and CPM efficiency and suggest that shifting the focus from trait to state measures might be promising.

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.

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.

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.

Psychophysiological Response Patterns to Affective Film Stimuli

PubMed Central

Bos, Marieke G. N.; Jentgens, Pia; Beckers, Tom; Kindt, Merel

2013-01-01

Psychophysiological research on emotion utilizes various physiological response measures to index activation of the defense system. Here we tested 1) whether acoustic startle reflex (ASR), skin conductance response (SCR) and heart rate (HR) elicited by highly arousing stimuli specifically reflect a defensive state and 2) the relation between resting heart rate variability (HRV) and affective responding. In a within-subject design, participants viewed film clips with a positive, negative and neutral content. In contrast to SCR and HR, we show that ASR differentiated between negative, neutral and positive states and can therefore be considered as a reliable index of activation of the defense system. Furthermore, resting HRV was associated with affect-modulated characteristics of ASR, but not with SCR or HR. Interestingly, individuals with low-HRV showed less differentiation in ASR between affective states. We discuss the important value of ASR in psychophysiological research on emotion and speculate on HRV as a potential biological marker for demarcating adaptive from maladaptive responding. PMID:23646134

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.

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.

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

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.

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.

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

Prepulse inhibition of the startle reflex and its attentional modulation in the human S-ketamine and N,N-dimethyltryptamine (DMT) models of psychosis.

PubMed

Heekeren, K; Neukirch, A; Daumann, J; Stoll, M; Obradovic, M; Kovar, K-A; Geyer, M A; Gouzoulis-Mayfrank, E

2007-05-01

Patients with schizophrenia exhibit diminished prepulse inhibition (PPI) of the acoustic startle reflex and deficits in the attentional modulation of PPI. Pharmacological challenges with hallucinogens are used as models for psychosis in both humans and animals. Remarkably, in contrast to the findings in schizophrenic patients and in animal hallucinogen models of psychosis, previous studies with healthy volunteers demonstrated increased levels of PPI after administration of low to moderate doses of either the antiglutamatergic hallucinogen ketamine or the serotonergic hallucinogen psilocybin. The aim of the present study was to investigate the influence of moderate and high doses of the serotonergic hallucinogen N,N-dimethyltryptamine (DMT) and the N-methyl-D-aspartate antagonist S-ketamine on PPI and its attentional modulation in humans. Fifteen healthy volunteers were included in a double-blind cross-over study with two doses of DMT and S-ketamine. Effects on PPI and its attentional modulation were investigated. Nine subjects completed both experimental days with the two doses of both drugs. S-ketamine increased PPI in both dosages, whereas DMT had no significant effects on PPI. S-ketamine decreased and DMT tended to decrease startle magnitude. There were no significant effects of either drug on the attentional modulation of PPI. In human experimental hallucinogen psychoses, and even with high, clearly psychotogenic doses of DMT or S-ketamine, healthy subjects failed to exhibit the predicted attenuation of PPI. In contrast, PPI was augmented and the startle magnitude was decreased after S-ketamine. These data point to important differences between human hallucinogen models and both animal hallucinogen models of psychosis and naturally occurring 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

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…

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

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.

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.

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.

Affective picture modulation: valence, arousal, attention allocation and motivational significance.

PubMed

Leite, Jorge; Carvalho, Sandra; Galdo-Alvarez, Santiago; Alves, Jorge; Sampaio, Adriana; Gonçalves, Oscar F

2012-03-01

The present study analyses the modulatory effects of affective pictures in the early posterior negativity (EPN), the late positive potential (LPP) and the human startle response on both the peripheral (eye blink EMG) and central neurophysiological levels (Probe P3), during passive affective pictures viewing. The affective pictures categories were balanced in terms of valence (pleasant; unpleasant) and arousal (high; low). The data shows that EPN may be sensitive to specific stimulus characteristics (affective relevant pictures versus neutral pictures) associated with early stages of attentional processing. In later stages, the heightened attentional resource allocation as well as the motivated significance of the affective stimuli was found to elicit enhanced amplitudes of slow wave processes thought to be related to enhanced encoding, namely LPP,. Although pleasant low arousing pictures were effective in engaging the resources involved in the slow wave processes, the highly arousing affective stimuli (pleasant and unpleasant) were found to produce the largest enhancement of the LPP, suggesting that high arousing stimuli may are associated with increased motivational significance. Additionally the response to high arousing stimuli may be suggestive of increased motivational attention, given the heightened attentional allocation, as expressed in the P3 probe, especially for the pleasant pictures. The hedonic valence may then serve as a mediator of the attentional inhibition to the affective priming, potentiating or inhibiting a shift towards defensive activation, as measured by the startle reflex. Copyright © 2011 Elsevier B.V. All rights reserved.

Threatening social context facilitates pain-related fear learning.

PubMed

Karos, Kai; Meulders, Ann; Vlaeyen, Johan W S

2015-03-01

This study investigated the effects of a threatening and a safe social context on learning pain-related fear, a key factor in the development and maintenance of chronic pain. We measured self-reported pain intensity, pain expectancy, pain-related fear (verbal ratings and eyeblink startle responses), and behavioral measures of avoidance (movement-onset latency and duration) using an established differential voluntary movement fear conditioning paradigm. Participants (N = 42) performed different movements with a joystick: during fear acquisition, movement in one direction (CS+) was followed by a painful stimulus (pain-US) whereas movement in another direction (CS-) was not. For participants in the threat group, an angry face was continuously presented in the background during the task, whereas in the safe group, a happy face was presented. During the extinction phase the pain-US was omitted. As compared to the safe social context, a threatening social context led to increased contextual fear and facilitated differentiation between CS+ and CS- movements regarding self-reported pain expectancy, fear of pain, eyeblink startle responses, and movement-onset latency. In contrast, self-reported pain intensity was not affected by social context. These data support the modulation of pain-related fear by social context. A threatening social context leads to stronger acquisition of (pain-related) fear and simultaneous contextual fear but does not affect pain intensity ratings. This knowledge may aid in the prevention of chronic pain and anxiety disorders and shows that social context might modulate pain-related fear without immediately affecting pain intensity itself. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

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 emotional startle effect is disrupted by a concurrent working memory task.

PubMed

King, Rosemary; Schaefer, Alexandre

2011-02-01

Working memory (WM) processes are often thought to play an important role in the cognitive regulation of negative emotions. However, little is known about how they influence emotional processing. We report two experiments that tested whether a concurrent working memory task could modulate the emotional startle eyeblink effect, a well-known index of emotional processing. In both experiments, emotionally negative and neutral pictures were viewed in two conditions: a "cognitive load" (CL) condition, in which participants had to actively maintain information in working memory (WM) while viewing the pictures, and a control "no load" (NL) condition. Picture-viewing instructions were identical across CL and NL. In both experiments, results showed a significant reduction of the emotional modulation of the startle eyeblink reflex in the CL condition compared to the NL condition. These findings suggest that a concurrent WM task disrupts emotional processing even when participants are directing visual focus on emotionally relevant information. Copyright © 2010 Society for Psychophysiological Research.

Affective and Neuroendocrine Effects of Withdrawal from Chronic, Long-Acting Opiate Administration

PubMed Central

Hamilton, Kathryn L.; Harris, Andrew C.; Gewirtz, Jonathan C.

2013-01-01

Although the long-acting opiate methadone is commonly used to treat drug addiction, relatively little is known about effects of withdrawal from this drug in preclinical models. The current study examined affective, neuroendocrine, and somatic signs of withdrawal from the longer-acting methadone derivative l-alpha-acetylmethydol (LAAM) in rats. Anxiety-like behavior during both spontaneous and antagonist-precipitated withdrawal was measured by potentiation of the startle reflex. Withdrawal elevated corticosterone and somatic signs and blunted circadian variations in baseline startle responding. In addition, fear to an explicit, Pavlovian conditioned stimulus (fear-potentiated startle) was enhanced. These data suggest that anxiety-like behavior as measured using potentiated startle responding does not emerge spontaneously during withdrawal from chronic opiate exposure – in contrast to withdrawal from acute drug exposure – but rather is manifested as exaggerated fear in response to explicit threat cues. PMID:24076207

Acute fluoxetine modulates emotional processing in young adult volunteers.

PubMed

Capitão, L P; Murphy, S E; Browning, M; Cowen, P J; Harmer, C J

2015-08-01

Fluoxetine is generally regarded as the first-line pharmacological treatment for young people, as it is believed to show a more favourable benefit:risk ratio than other antidepressants. However, the mechanisms through which fluoxetine influences symptoms in youth have been little investigated. This study examined whether acute administration of fluoxetine in a sample of young healthy adults altered the processing of affective information, including positive, sad and anger cues. A total of 35 male and female volunteers aged between 18 and 21 years old were randomized to receive a single 20 mg dose of fluoxetine or placebo. At 6 h after administration, participants completed a facial expression recognition task, an emotion-potentiated startle task, an attentional dot-probe task and the Rapid Serial Visual Presentation. Subjective ratings of mood, anxiety and side effects were also taken pre- and post-fluoxetine/placebo administration. Relative to placebo-treated participants, participants receiving fluoxetine were less accurate at identifying anger and sadness and did not show the emotion-potentiated startle effect. There were no overall significant effects of fluoxetine on subjective ratings of mood. Fluoxetine can modulate emotional processing after a single dose in young adults. This pattern of effects suggests a potential cognitive mechanism for the greater benefit:risk ratio of fluoxetine in adolescent patients.

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.

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 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.

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.

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

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.

Emotional modulation of pain and spinal nociception in fibromyalgia

PubMed Central

Rhudy, Jamie L.; DelVentura, Jennifer L.; Terry, Ellen L.; Bartley, Emily J.; Olech, Ewa; Palit, Shreela; Kerr, Kara L.

2013-01-01

Fibromyalgia (FM) is characterized by widespread pain, as well as affective disturbance (e.g., depression). Given that emotional processes are known to modulate pain, a disruption of emotion and emotional modulation of pain and nociception may contribute to FM. The present study used a well-validated affective picture-viewing paradigm to study emotional processing and emotional modulation of pain and spinal nociception. Participants were 18 individuals with FM, 18 individuals with rheumatoid arthritis (RA), and 19 healthy pain-free controls (HC). Mutilation, neutral, and erotic pictures were presented in four blocks; two blocks assessed only physiological-emotional reactions (i.e., pleasure/arousal ratings, corrugator EMG, startle modulation, skin conductance) in the absence of pain and two blocks assessed emotional reactivity and emotional modulation of pain and the nociceptive flexion reflex (NFR, a physiological measure of spinal nociception) evoked by suprathreshold electric stimulations over the sural nerve. In general, mutilation pictures elicited displeasure, corrugator activity, subjective arousal, and sympathetic activation, whereas erotic pictures elicited pleasure, subjective arousal, and sympathetic activation. However, FM was associated with deficits in appetitive activation (e.g., reduced pleasure/arousal to erotica). Moreover, emotional modulation of pain was observed in HC and RA, but not FM, even though all three groups evidenced modulation of NFR. Additionally, NFR thresholds were not lower in the FM group, indicating a lack of spinal sensitization. Together, these results suggest that FM is associated with a disruption of supraspinal processes associated with positive affect and emotional modulation of pain, but not brain-to-spinal cord circuitry that modulates spinal nociceptive processes. PMID:23622762

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

An Anatomical Basis for Opponent Process Mechanisms of Opiate Withdrawal

PubMed Central

Radke, Anna K.; Rothwell, Patrick E.; Gewirtz, Jonathan C.

2011-01-01

Opponent process theory predicts that the first step in the induction of drug withdrawal is the activation of reward-related circuitry. Using the acoustic startle reflex as a model of anxiety-like behavior in rats, we show the emergence of a negative affective state during withdrawal after direct infusion of morphine into the ventral tegmental area (VTA), the origin of the mesolimbic dopamine system. Potentiation of startle during withdrawal from systemic morphine exposure requires a decrease in opiate receptor stimulation in the VTA and can be relieved by administration of the dopamine receptor agonist apomorphine. Together, our results suggest that the emergence of anxiety during withdrawal from acute opiate exposure begins with activation of VTA mesolimbic dopamine circuitry, providing a mechanism for the opponent process view of withdrawal. PMID:21593338

Repetitive exposure: Brain and reflex measures of emotion and attention

PubMed Central

Ferrari, Vera; Bradley, Margaret M.; Codispoti, Maurizio; Lang, Peter J.

2010-01-01

Effects of massed repetition on the modulation of the late positive potential elicited during affective picture viewing were investigated in two experiments. Despite a difference in the number of repetitions across studies (from 5 to 30), results were quite similar: the late positive potential continued to be enhanced when viewing emotional, compared to neutral, pictures. On the other hand, massed repetition did prompt a reduction in the late positive potential that was most pronounced for emotional pictures. Startle probe P3 amplitude generally increased with repetition, suggesting diminished attention allocation to repeated pictures. The blink reflex, however, continued to be modulated by hedonic valence, despite massive massed repetition. Taken together, the data suggest that the amplitude of the late positive potential during picture viewing reflects both motivational significance and attention allocation. PMID:20701711

Neuronal connectivity and interactions between the auditory and limbic systems. Effects of noise and tinnitus.

PubMed

Kraus, Kari Suzanne; Canlon, Barbara

2012-06-01

Acoustic experience such as sound, noise, or absence of sound induces structural or functional changes in the central auditory system but can also affect limbic regions such as the amygdala and hippocampus. The amygdala is particularly sensitive to sound with valence or meaning, such as vocalizations, crying or music. The amygdala plays a central role in auditory fear conditioning, regulation of the acoustic startle response and can modulate auditory cortex plasticity. A stressful acoustic stimulus, such as noise, causes amygdala-mediated release of stress hormones via the HPA-axis, which may have negative effects on health, as well as on the central nervous system. On the contrary, short-term exposure to stress hormones elicits positive effects such as hearing protection. The hippocampus can affect auditory processing by adding a temporal dimension, as well as being able to mediate novelty detection via theta wave phase-locking. Noise exposure affects hippocampal neurogenesis and LTP in a manner that affects structural plasticity, learning and memory. Tinnitus, typically induced by hearing malfunctions, is associated with emotional stress, depression and anatomical changes of the hippocampus. In turn, the limbic system may play a role in the generation as well as the suppression of tinnitus indicating that the limbic system may be essential for tinnitus treatment. A further understanding of auditory-limbic interactions will contribute to future treatment strategies of tinnitus and noise trauma. Copyright © 2012 Elsevier B.V. All rights reserved.

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

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.

Oxytocin Reduces Background Anxiety in a Fear-Potentiated Startle Paradigm: Peripheral vs Central Administration

PubMed Central

Ayers, Luke W; Missig, Galen; Schulkin, Jay; Rosen, Jeffrey B

2011-01-01

Oxytocin is known to have anti-anxiety and anti-stress effects. Using a fear-potentiated startle paradigm in rats, we previously demonstrated that subcutaneously administered oxytocin suppressed acoustic startle following fear conditioning compared with startle before fear conditioning (termed background anxiety), but did not have an effect on cue-specific fear-potentiated startle. The findings suggest oxytocin reduces background anxiety, an anxious state not directly related to cue-specific fear, but sustained beyond the immediate threat. The goal of the present study was to compare the effects of centrally and peripherally administered oxytocin on background anxiety and cue-specific fear. Male rats were given oxytocin either subcutaneously (SC) or intracerebroventricularly (ICV) into the lateral ventricles before fear-potentiated startle testing. Oxytocin doses of 0.01 and 0.1 μg/kg SC reduced background anxiety. ICV administration of oxytocin at doses from 0.002 to 20 μg oxytocin had no effect on background anxiety or cue-specific fear-potentiated startle. The 20 μg ICV dose of oxytocin did reduce acoustic startle in non-fear conditioned rats. These studies indicate that oxytocin is potent and effective in reducing background anxiety when delivered peripherally, but not when delivered into the cerebroventricular system. Oxytocin given systemically may have anti-anxiety properties that are particularly germane to the hypervigilance and exaggerated startle typically seen in many anxiety and mental health disorder patients. PMID:21796104

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.

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.

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

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.

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.

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).

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.

Emotional modulation of pain and spinal nociception in fibromyalgia.

PubMed

Rhudy, Jamie L; DelVentura, Jennifer L; Terry, Ellen L; Bartley, Emily J; Olech, Ewa; Palit, Shreela; Kerr, Kara L

2013-07-01

Fibromyalgia (FM) is characterized by widespread pain, as well as affective disturbance (eg, depression). Given that emotional processes are known to modulate pain, a disruption of emotion and emotional modulation of pain and nociception may contribute to FM. The present study used a well-validated affective picture-viewing paradigm to study emotional processing and emotional modulation of pain and spinal nociception. Participants were 18 individuals with FM, 18 individuals with rheumatoid arthritis (RA), and 19 healthy pain-free controls (HC). Mutilation, neutral, and erotic pictures were presented in 4 blocks; 2 blocks assessed only physiological-emotional reactions (ie, pleasure/arousal ratings, corrugator electromyography, startle modulation, skin conductance) in the absence of pain, and 2 blocks assessed emotional reactivity and emotional modulation of pain and the nociceptive flexion reflex (NFR, a physiological measure of spinal nociception) evoked by suprathreshold electric stimulations over the sural nerve. In general, mutilation pictures elicited displeasure, corrugator activity, subjective arousal, and sympathetic activation, whereas erotic pictures elicited pleasure, subjective arousal, and sympathetic activation. However, FM was associated with deficits in appetitive activation (eg, reduced pleasure/arousal to erotica). Moreover, emotional modulation of pain was observed in HC and RA, but not FM, even though all 3 groups evidenced modulation of NFR. Additionally, NFR thresholds were not lower in the FM group, indicating a lack of spinal sensitization. Together, these results suggest that FM is associated with a disruption of supraspinal processes associated with positive affect and emotional modulation of pain, but not brain-to-spinal cord circuitry that modulates spinal nociceptive processes. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

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

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

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.

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

Jumping Frenchmen, Miryachit, and Latah: Culture-Specific Hyperstartle-Plus Syndromes.

PubMed

Lanska, Douglas J

2018-01-01

In the late 19th century, jumping (French Canadians in Maine, USA), miryachit (Siberia), and latah (Southeast Asia) were among a group of similar disorders described around the world, each of which manifests as an exaggerated startle response with additional late-response features that were felt by some to overlap with hysteria or tics. The later features following the exaggerated startle reaction variably include mimesis (e.g., echopraxia, echolalia) and automatic obedience. These reaction patterns tended to persist indefinitely in affected individuals. Because of their dramatic stimulus-driven behaviors, affected individuals were prone to be teased and tormented by being repeatedly and intentionally startled. Despite clinical overlap between jumping and Tourette syndrome, these entities are now recognized as distinct: in jumping, the key feature is an abnormal startle response, the abnormal reaction is always provoked, and tics are absent, whereas in Tourette syndrome, the key feature is spontaneous motor and vocal tics, although patients with Tourette syndrome may occasionally also have an exaggerated startle response. These disorders have been conceptualized from anthropological, psychodynamic, and neurobiologic perspectives, with no complete resolution to date. Attempts at treatment have been generally unsuccessful, including attempts with bromization and hypnosis, although anecdotal reports of successful deconditioning have been published. In population groups affected, these disorders are usually considered as behavioral peculiarities and not as diseases per se, and there is no apparent tendency to develop disabling mental illness or neurodegenerative disorders. The genesis of these disorders, their cultural and social components, and their interactions with the presumed underlying physiological substrate need further study. Careful descriptive and analytic epidemiological studies are also lacking for all of these disorders. © 2018 S. Karger AG, Basel.

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.

Discovery touches down after successful mission STS-95

NASA Technical Reports Server (NTRS)

1998-01-01

Orbiter Discovery startles a great white egret next to runway 33 as it touches down at the Shuttle Landing Facility. Discovery returns to Earth with its crew of seven after a successful mission STS-95 lasting nearly nine days and 3.6 million miles. The mission included research payloads such as the Spartan solar- observing deployable spacecraft, the Hubble Space Telescope Orbital Systems Test Platform, the International Extreme Ultraviolet Hitchhiker, as well as the SPACEHAB single module with experiments on space flight and the aging process.

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.

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

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.

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.

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.

Feeling worse to feel better: pain-offset relief simultaneously stimulates positive affect and reduces negative affect.

PubMed

Franklin, Joseph C; Lee, Kent M; Hanna, Eleanor K; Prinstein, Mitchell J

2013-04-01

Although pain itself induces negative affect, the removal (or offset) of pain induces a powerful state of relief. Despite being implicated in a wide range of psychological and behavioral phenomena, relief remains a poorly understood emotion. In particular, some theorists associate relief with increased positive affect, whereas others associate relief with diminished negative affect. In the present study, we examined the affective nature of relief in a pain-offset paradigm with psychophysiological measures that were specific to negative valence (startle eyeblink reactivity) and positive valence (startle postauricular reactivity). Results revealed that pain offset simultaneously stimulates positive affect and diminishes negative affect for at least several seconds. Results also indicated that pain intensity differentially affects the positive and negative valence aspects of relief. These findings clarify the affective nature of relief and provide insight into why people engage in both normal and abnormal behaviors associated with relief.

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

Parvalbumin and GAD65 Interneuron Inhibition in the Ventral Hippocampus Induces Distinct Behavioral Deficits Relevant to Schizophrenia

PubMed Central

Nguyen, Robin; Morrissey, Mark D.; Mahadevan, Vivek; Cajanding, Janine D.; Woodin, Melanie A.; Yeomans, John S.; Takehara-Nishiuchi, Kaori

2014-01-01

Hyperactivity within the ventral hippocampus (vHPC) has been linked to both psychosis in humans and behavioral deficits in animal models of schizophrenia. A local decrease in GABA-mediated inhibition, particularly involving parvalbumin (PV)-expressing GABA neurons, has been proposed as a key mechanism underlying this hyperactive state. However, direct evidence is lacking for a causal role of vHPC GABA neurons in behaviors associated with schizophrenia. Here, we probed the behavioral function of two different but overlapping populations of vHPC GABA neurons that express either PV or GAD65 by selectively inhibiting these neurons with the pharmacogenetic neuromodulator hM4D. We show that acute inhibition of vHPC GABA neurons in adult mice results in behavioral changes relevant to schizophrenia. Inhibiting either PV or GAD65 neurons produced distinct behavioral deficits. Inhibition of PV neurons, affecting ∼80% of the PV neuron population, robustly impaired prepulse inhibition of the acoustic startle reflex (PPI), startle reactivity, and spontaneous alternation, but did not affect locomotor activity. In contrast, inhibiting a heterogeneous population of GAD65 neurons, affecting ∼40% of PV neurons and 65% of cholecystokinin neurons, increased spontaneous and amphetamine-induced locomotor activity and reduced spontaneous alternation, but did not alter PPI. Inhibition of PV or GAD65 neurons also produced distinct changes in network oscillatory activity in the vHPC in vivo. Together, these findings establish a causal role for vHPC GABA neurons in controlling behaviors relevant to schizophrenia and suggest a functional dissociation between the GABAergic mechanisms involved in hippocampal modulation of sensorimotor processes. PMID:25378161

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

Increased positive versus negative affective perception and memory in healthy volunteers following selective serotonin and norepinephrine reuptake inhibition.

PubMed

Harmer, Catherine J; Shelley, Nicholas C; Cowen, Philip J; Goodwin, Guy M

2004-07-01

Antidepressants that inhibit the reuptake of serotonin (SSRIs) or norepinephrine (SNRIs) are effective in the treatment of disorders such as depression and anxiety. Cognitive psychological theories emphasize the importance of correcting negative biases of information processing in the nonpharmacological treatment of these disorders, but it is not known whether antidepressant drugs can directly modulate the neural processing of affective information. The present study therefore assessed the actions of repeated antidepressant administration on perception and memory for positive and negative emotional information in healthy volunteers. Forty-two male and female volunteers were randomly assigned to 7 days of double-blind intervention with the SSRI citalopram (20 mg/day), the SNRI reboxetine (8 mg/day), or placebo. On the final day, facial expression recognition, emotion-potentiated startle response, and memory for affect-laden words were assessed. Questionnaires monitoring mood, hostility, and anxiety were given before and after treatment. In the facial expression recognition task, citalopram and reboxetine reduced the identification of the negative facial expressions of anger and fear. Citalopram also abolished the increased startle response found in the context of negative affective images. Both antidepressants increased the relative recall of positive (versus negative) emotional material. These changes in emotional processing occurred in the absence of significant differences in ratings of mood and anxiety. However, reboxetine decreased subjective ratings of hostility and elevated energy. Short-term administration of two different antidepressant types had similar effects on emotion-related tasks in healthy volunteers, reducing the processing of negative relative to positive emotional material. Such effects of antidepressants may ameliorate the negative biases in information processing that characterize mood and anxiety disorders. They also suggest a mechanism of action potentially compatible with cognitive theories of anxiety and depression.

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.

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

Extensive epistasis for olfactory behaviour, sleep and waking activity in Drosophila melanogaster.

PubMed

Swarup, Shilpa; Harbison, Susan T; Hahn, Lauren E; Morozova, Tatiana V; Yamamoto, Akihiko; Mackay, Trudy F C; Anholt, Robert R H

2012-02-01

Epistasis is an important feature of the genetic architecture of quantitative traits, but the dynamics of epistatic interactions in natural populations and the relationship between epistasis and pleiotropy remain poorly understood. Here, we studied the effects of epistatic modifiers that segregate in a wild-derived Drosophila melanogaster population on the mutational effects of P-element insertions in Semaphorin-5C (Sema-5c) and Calreticulin (Crc), pleiotropic genes that affect olfactory behaviour and startle behaviour and, in the case of Crc, sleep phenotypes. We introduced Canton-S B (CSB) third chromosomes with or without a P-element insertion at the Crc or Sema-5c locus in multiple wild-derived inbred lines of the Drosophila melanogaster Genetic Reference Panel (DGRP) and assessed the effects of epistasis on the olfactory response to benzaldehyde and, for Crc, also on sleep. In each case, we found substantial epistasis and significant variation in the magnitude of epistasis. The predominant direction of epistatic effects was to suppress the mutant phenotype. These observations support a previous study on startle behaviour using the same D. melanogaster chromosome substitution lines, which concluded that suppressing epistasis may buffer the effects of new mutations. However, epistatic effects are not correlated among the different phenotypes. Thus, suppressing epistasis appears to be a pervasive general feature of natural populations to protect against the effects of new mutations, but different epistatic interactions modulate different phenotypes affected by mutations at the same pleiotropic gene.

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.

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.

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

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.

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.

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.

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.

Triarchic dimensions of psychopathy in young adulthood: Associations with clinical and physiological measures after accounting for adolescent psychopathic traits.

PubMed

Kyranides, Melina Nicole; Fanti, Kostas A; Sikki, Maria; Patrick, Christopher J

2017-04-01

This study examined associations of psychopathy facets of boldness, meanness, and disinhibition with clinically relevant variables and physiological reactivity to affective stimuli. These associations were examined after accounting for developmental associations with adolescent psychopathic traits, namely callous-unemotional traits, narcissism, and impulsivity. Psychopathic traits were assessed during adolescence using the Antisocial Process Screening Device and the Inventory of Callous Unemotional traits and during young adulthood via the Triarchic Psychopathy Measure. Clinical variables (N = 99, Mage = 15.91, 53% female), as well as affective and physiological responses (heart rate, skin conductance, startle modulation) to violent and erotic videos (N = 88, Mage = 19.92, 50% female) were also assessed during adulthood. After accounting for adolescent psychopathic traits, boldness was associated with high cognitive reappraisal and low anxiety, fear, and hostility, and meanness was related to callous-unemotional traits, hostility, less sympathy to victims, and less use of cognitive reappraisal. Disinhibition, by contrast, was associated with impulsivity, increased anxiety, and hostile and aggressive tendencies, as well as conduct disorder, antisocial personality disorder symptoms, and cognitive suppression. In addition, evidence was found for different physiological measures operating as biological indicators of these distinctive dimensions, with reduced resting heart rate and cardiac reactivity to violent stimuli indicative of boldness, above and beyond adolescent psychopathic traits, and low startle potentiation for violent stimuli indicative of callous-unemotional traits and meanness. These findings provide evidence for the value of a multidomain approach for clarifying neurobiological mechanisms of psychopathic tendencies that can inform prevention and treatment efforts. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

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

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

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.

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...

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.

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.

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.

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

Relationships between hostility, affective ratings of pictures, and state affects during task-induced stress.

PubMed

Heponiemi, Tarja; Ravaja, Niklas; Elovainio, Marko; Keltikangas-Järvinen, Liisa

2007-03-01

The authors examined the relationship of hostility with (a) affective ratings of pictures and (b) state affects evoked by task-induced stress in 95 healthy men and women 22-37 years of age. Pictures were from the International Affective Picture System (IAPS; P. J. Lang, M. M. Bradley, & B. N. Cuthbert, 1999). Stressors included a startle task, mental arithmetic task, and choice-deadline reaction time task. The circumplex model of affect was used to structure the self-reported state affects. The authors found that hostility was associated with displeasure, high arousal, and low dominance ratings of IAPS pictures. Hostility was related to unpleasant affect and unactivated unpleasant affect during the experiment, and subscale paranoia was related to activated unpleasant affect. Findings suggest that participants scoring high on hostility are prone to negative emotional reactions.

Genetic variation in serotonin transporter function affects human fear expression indexed by fear-potentiated startle.

PubMed

Klumpers, Floris; Heitland, Ivo; Oosting, Ronald S; Kenemans, J Leon; Baas, Johanna M P

2012-02-01

The serotonin transporter (SERT) plays a crucial role in anxiety. Accordingly, variance in SERT functioning appears to constitute an important pathway to individual differences in anxiety. The current study tested the hypothesis that genetic variation in SERT function is associated with variability in the basic reflex physiology of defense. Healthy subjects (N=82) were presented with clearly instructed cues of shock threat and safety to induce robust anxiety reactions. Subjects carrying at least one short allele for the 5-HTTLPR polymorphism showed stronger fear-potentiated startle compared to long allele homozygotes. However, short allele carriers showed no deficit in the downregulation of fear after the offset of threat. These results suggest that natural variation in SERT function affects the magnitude of defensive reactions while not affecting the capacity for fear regulation. Copyright © 2011 Elsevier B.V. All rights reserved.

Startle stimuli reduce the internal model control in discrete movements.

PubMed

Wright, Zachary A; Rogers, Mark W; MacKinnon, Colum D; Patton, James L

2009-01-01

A well known and major component of movement control is the feedforward component, also known as the internal model. This model predicts and compensates for expected forces seen during a movement, based on recent experience, so that a well-learned task such as reaching to a target can be executed in a smooth straight manner. It has recently been shown that the state of preparation of planned movements can be tested using a startling acoustic stimulus (SAS). SAS, presented 500, 250 or 0 ms before the expected "go" cue resulted in the early release of the movement trajectory associated with the after-effects of the force field training (i.e. the internal model). In a typical motor adaptation experiment with a robot-applied force field, we tested if a SAS stimulus influences the size of after-effects that are typically seen. We found that in all subjects the after-effect magnitudes were significantly reduced when movements were released by SAS, although this effect was not further modulated by the timing of SAS. Reduced after-effects reveal at least partial existence of learned preparatory control, and identify startle effects that could influence performance in tasks such as piloting, teleoperation, and sports.

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

Effects of the novel endocannabinoid uptake inhibitor, LY2183240, on fear-potentiated startle and alcohol-seeking behaviors in mice selectively bred for high alcohol preference.

PubMed

Powers, Matthew S; Barrenha, Gustavo D; Mlinac, Nate S; Barker, Eric L; Chester, Julia A

2010-12-01

Alcohol-use disorders often occur together with anxiety disorders in humans which may be partly due to common inherited genetic factors. Evidence suggests that the endocannabinoid system (ECS) is a promising therapeutic target for the treatment of individuals with anxiety and/or alcohol-use disorders. The present study assessed the effects of a novel endocannabinoid uptake inhibitor, LY2183240, on anxiety- and alcohol-seeking behaviors in a unique animal model that may represent increased genetic risk to develop co-morbid anxiety and alcohol-use disorders in humans. Mice selectively bred for high alcohol preference (HAP) show greater fear-potentiated startle (FPS) than mice selectively bred for low alcohol preference (LAP). We examined the effects of LY2183240 on the expression of FPS in HAP and LAP mice and on alcohol-induced conditioned place preference (CPP) and limited-access alcohol drinking behavior in HAP mice. Repeated administration of LY2183240 (30 mg/kg) reduced the expression of FPS in HAP but not LAP mice when given prior to a second FPS test 48 h after fear conditioning. Both the 10 and 30 mg/kg doses of LY2183240 enhanced the expression of alcohol-induced CPP and this effect persisted in the absence of the drug. LY2183240 did not alter limited-access alcohol drinking behavior, unconditioned startle responding, or locomotor activity. These findings suggest that ECS modulation influences both conditioned fear and conditioned alcohol reward behavior. LY2183240 may be an effective pharmacotherapy for individuals with anxiety disorders, such as post-traumatic stress disorder, but may not be appropriate for individuals with co-morbid anxiety and alcohol-use disorders.

The CB1 Receptor as an Important Mediator of Hedonic Reward Processing

PubMed Central

Friemel, Chris M; Zimmer, Andreas; Schneider, Miriam

2014-01-01

The endocannabinoid (ECB) system has emerged recently as a key mediator for reward processing. It is well known that cannabinoids affect appetitive learning processes and can induce reinforcing and rewarding effects. However, the involvement of the ECB system in hedonic aspects of reward-related behavior is not completely understood. With the present study, we investigated the modulatory role of the ECB system on hedonic perception, measured by the pleasure attenuated startle (PAS) paradigm for a palatable food reward. Here, a conditioned odor is thought to induce a pleasant affective state that attenuates an aversive reflex—the acoustic startle response. Modulatory effects of the CB1 receptor antagonist/inverse agonist SR1411716 and the cannabinoid agonist WIN 55 212-2 on PAS were examined in rats. PAS was also measured in CB1 receptor knockout (KO) and wild-type (WT) mice. Pharmacological inhibition as well as the absence of CB1 receptors was found to reduce PAS, whereas WIN 55 212-2 administration increased PAS. Finally, presentation of a conditioned reward cue was found to induce striatal FosB/ΔFosB expression in WT mice, but not in KO mice, indicating a reduced stimulation of reward-related brain regions in conditioned KO mice by odor presentation. We here show that in addition to our previous studies in rats, PAS may also serve as a valuable and suitable measure to assess hedonic processing in mice. Our data further indicate that the ECB system, and in particular CB1 receptor signaling, appears to be highly important for the mediation of hedonic aspects of reward processing. PMID:24718372

SALICYLATE INCREASES THE GAIN OF THE CENTRAL AUDITORY SYSTEM

PubMed Central

Sun, W.; Lu, J.; Stolzberg, D.; Gray, L.; Deng, A.; Lobarinas, E.; Salvi, R. J.

2009-01-01

High doses of salicylate, the anti-inflammatory component of aspirin, induce transient tinnitus and hearing loss. Systemic injection of 250 mg/kg of salicylate, a dose that reliably induces tinnitus in rats, significantly reduced the sound evoked output of the rat cochlea. Paradoxically, salicylate significantly increased the amplitude of the sound-evoked field potential from the auditory cortex (AC) of conscious rats, but not the inferior colliculus (IC). When rats were anesthetized with isoflurane, which increases GABA-mediated inhibition, the salicylate-induced AC amplitude enhancement was abolished, whereas ketamine, which blocks N-methyl-d-aspartate receptors, further increased the salicylate-induced AC amplitude enhancement. Direct application of salicylate to the cochlea, however, reduced the response amplitude of the cochlea, IC and AC, suggesting the AC amplitude enhancement induced by systemic injection of salicylate does not originate from the cochlea. To identify a behavioral correlate of the salicylate-induced AC enhancement, the acoustic startle response was measured before and after salicylate treatment. Salicylate significantly increased the amplitude of the startle response. Collectively, these results suggest that high doses of salicylate increase the gain of the central auditory system, presumably by down-regulating GABA-mediated inhibition, leading to an exaggerated acoustic startle response. The enhanced startle response may be the behavioral correlate of hyperacusis that often accompanies tinnitus and hearing loss. Published by Elsevier Ltd on behalf of IBRO. PMID:19154777

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.

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.

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

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…

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.

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.

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 ...

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.

Exercise is associated with reduction in the anxiogenic effect of mCPP on acoustic startle.

PubMed

Fox, James H; Hammack, Sayamwong E; Falls, William A

2008-08-01

Voluntary exercise has been associated with reduced anxiety across several animal models. Manipulation of central 5-HT can alter anxiety-like behaviors and administration of the 5-HT agonist metachlorophenylpiperazine (mCPP) increases anxiety in rodents and humans. To examine whether the anxiolytic effect of exercise is associated with an alteration in 5-HT systems, we examined the anxiogenic effect of mCPP in exercising and nonexercising mice. C57BL/6J mice were given 2 weeks of free access to either a functioning or nonfunctioning running wheel. Mice were then tested for acoustic startle following systemic injection of either 0, 0.1, 0.3, or 1 mg/kg of mCPP. Consistent with its anxiogenic properties, mCPP produced a dose-dependent increase in acoustic startle in nonexercising mice. However, this anxiogenic effect was blunted in exercising mice. These findings suggest that exercise may help to reduce anxiety by altering 5-HT systems, perhaps by down-regulating postsynaptic 5HT 2B/2C receptors.

Anger and aggression problems in veterans are associated with an increased acoustic startle reflex.

PubMed

Heesink, Lieke; Kleber, Rolf; Häfner, Michael; van Bedaf, Laury; Eekhout, Iris; Geuze, Elbert

2017-02-01

Anger and aggression are frequent problems in deployed military personnel. A lowered threshold of perceiving and responding to threat can trigger impulsive aggression. This can be indicated by an exaggerated startle response. Fifty-two veterans with anger and aggression problems (Anger group) and 50 control veterans were tested using a startle experiment with 10 startle probes and 10 prepulse trials, presented in a random order and with a random interval between the trials. Predictors (demographics, Trait Anger, State Anger, Harm Avoidance and Anxious Arousal) for the startle response within the Anger group were tested. Increased EMG responses were found to the startle probes in the Anger Group compared to the Control group, but not to the prepulse trials. Furthermore, Harm Avoidance and State Anger predicted the increased startle reflex within the Anger group, whereas Trait Anger was negatively related to the startle reflex. These findings indicate that threat reactivity is increased in anger and aggression problems. These problems are not only caused by an anxious predisposition, the degree of anger also predicts the startle reflex. Copyright © 2016 Elsevier B.V. All rights reserved.

Visual Complexity Attenuates Emotional Processing in Psychopathy: Implications for Fear-Potentiated Startle Deficits

PubMed Central

Sadeh, Naomi; Verona, Edelyn

2012-01-01

A long-standing debate is the extent to which psychopathy is characterized by a fundamental deficit in attention or emotion. We tested the hypothesis that the interplay of emotional and attentional systems is critical for understanding processing deficits in psychopathy. Sixty-three offenders were assessed using the Psychopathy Checklist: Screening Version. Event-related brain potentials (ERPs) and fear-potentiated startle (FPS) were collected while participants viewed pictures selected to disentangle an existing confound between perceptual complexity and emotional content in the pictures typically used to study fear deficits in psychopathy. As predicted, picture complexity moderated emotional processing deficits. Specifically, the affective-interpersonal features of psychopathy were associated with greater allocation of attentional resources to processing emotional stimuli at initial perception (visual N1) but only when picture stimuli were visually-complex. Despite this, results for the late positive potential indicated that emotional pictures were less attentionally engaging and held less motivational significance for individuals high in affective-interpersonal traits. This deficient negative emotional processing was observed later in their reduced defensive fear reactivity (FPS) to high-complexity unpleasant pictures. In contrast, the impulsive-antisocial features of psychopathy were associated with decreased sensitivity to picture complexity (visual N1) and unrelated to emotional processing as assessed by ERP and FPS. These findings are the first to demonstrate that picture complexity moderates FPS deficits and implicate the interplay of attention and emotional systems as deficient in psychopathy. PMID:22187225

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

Disturbed prepulse inhibition in patients with schizophrenia is consequential to dysfunction of selective attention.

PubMed

Scholes, Kirsty E; Martin-Iverson, Mathew T

2010-03-01

Controversy exists as to the cause of disturbed prepulse inhibition (PPI) in patients with schizophrenia. This study aimed to clarify the nature of PPI in schizophrenia using improved methodology. Startle and PPI were measured in 44 patients with schizophrenia and 32 controls across a range of startling stimulus intensities under two conditions, one while participants were attending to the auditory stimuli (ATTEND condition) and one while participants completed a visual task in order to ensure they were ignoring the auditory stimuli (IGNORE condition). Patients showed reduced PPI of R(MAX) (reflex capacity) and increased PPI of Hillslope (reflex efficacy) only under the INGORE condition, and failed to show the same pattern of attentional modulation of the reflex parameters as controls. In conclusion, disturbed PPI in schizophrenia appears to result from deficits in selective attention, rather than from preattentive dysfunction.

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

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.

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.

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

CRF receptor blockade prevents initiation and consolidation of stress effects on affect in the predator stress model of PTSD.

PubMed

Adamec, Robert; Fougere, Dennis; Risbrough, Victoria

2010-07-01

Post traumatic stress disorder (PTSD) is a chronic anxiety disorder initiated by an intensely threatening, traumatic event. There is a great need for more efficacious pharmacotherapy and preventive treatments for PTSD. In animals, corticotropin-releasing factor (CRF) and the CRF1 receptor play a critical role in behavioural and neuroendocrine responses to stress. We tested the hypothesis that CRF1 activation is required for initiation and consolidation of long-term effects of trauma on anxiety-like behaviour in the predator exposure (predator stress) model of PTSD. Male C57BL6 mice were treated with the selective CRF1 antagonist CRA0450 (2, 20 mg/kg) 30 min before or just after predator stress. Long-term effects of stress on rodent anxiety were measured 7 d later using acoustic startle, elevated plus maze (EPM), light/dark box, and hole-board tests. Predator stress increased startle amplitude and delayed startle habituation, increased time in and decreased exits from the dark chamber in the light/dark box test, and decreased risk assessment in the EPM. CRF1 antagonism had limited effects on these behaviours in non-stressed controls, with the high dose decreasing risk assessment in the EPM. However, in stressed animals CRF1 antagonism blocked initiation and consolidation of stressor effects on startle, and returned risk assessment to baseline levels in predator-stressed mice. These findings implicate CRF1 activation in initiation and post-trauma consolidation of predator stress effects on anxiety-like behaviour, specifically on increased arousal as measured by exaggerated startle behaviours. These data support further research of CRF1 antagonists as potential prophylactic treatments for PTSD.

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.

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.

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.

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.

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.

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

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

"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.

Context and explicit threat cue modulation of the startle reflex: Preliminary evidence of distinctions between adolescents with principal fear disorders versus distress disorders

PubMed Central

Waters, Allison M.; Nazarian, Maria; Mineka, Susan; Zinbarg, Richard E.; Griffith, James W.; Naliboff, Bruce; Ornitz, Edward M.; Craske, Michelle G.

2014-01-01

Anxiety and depression are prevalent, impairing disorders. High comorbidity has raised questions about how to define and classify them. Structural models emphasise distinctions between “fear” and “distress” disorders while other initiatives propose they be defined by neurobiological indicators that cut across disorders. This study examined startle reflex (SR) modulation in adolescents with principal fear disorders (specific phobia; social phobia) (n = 20), distress disorders (unipolar depressive disorders, dysthymia, generalized anxiety disorder; post-traumatic stress disorder) (n = 9), and controls (n = 29) during (a) baseline conditions, (b) threat context conditions (presence of contraction pads over the biceps muscle), and (c) an explicit threat cue paradigm involving phases that signalled safety from aversive stimuli (early and late stages of safe phases; early stages of danger phases) and phases that signalled immediate danger of an aversive stimulus (late stages of danger phases). Adolescents with principal fear disorders showed larger SRs than other groups throughout safe phases and early stages of danger phases. SRs did not differ between groups during late danger phases. Adolescents with principal distress disorders showed attenuated SRs during baseline and context conditions compared to other groups. Preliminary findings support initiatives to redefine emotional disorders based on neurobiological functioning. PMID:24679992

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

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.

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.

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.

Facing two faces: Defense activation varies as a function of personal relevance.

PubMed

Bublatzky, Florian; Alpers, Georg W

2017-04-01

It can be unsettling to be watched by a group of people, and when they express anger or hostility, this can prime defensive behavior. In contrast, when others smile at us, this may be comforting. This study tested to which degree the impact of facial expressions (happy, neutral, and angry) varies with the personal relevance of a social situation. Modelling a triadic situation, two faces looked either directly at the participant, faced each other, or they were back to back. Results confirmed that this variation constitutes a gradient of personal relevance (directed frontally > towards > away), as reflected by corresponding defensive startle modulation and autonomic nervous system activity. This gradient was particularly pronounced for angry faces and it was steeper in participants with higher levels of social anxiety. Thus, sender-recipient constellations modulate the processing of facial emotions in favor of adequate behavioral responding (e.g., avoidance) in group settings. Copyright © 2017 Elsevier B.V. All rights reserved.

Ontogeny of sensorimotor gating and short-term memory processing throughout the adolescent period in rats.

PubMed

Goepfrich, Anja A; Friemel, Chris M; Pauen, Sabina; Schneider, Miriam

2017-06-01

Adolescence and puberty are highly susceptible developmental periods during which the neuronal organization and maturation of the brain is completed. The endocannabinoid (eCB) system, which is well known to modulate cognitive processing, undergoes profound and transient developmental changes during adolescence. With the present study we were aiming to examine the ontogeny of cognitive skills throughout adolescence in male rats and clarify the potential modulatory role of CB1 receptor signalling. Cognitive skills were assessed repeatedly every 10th day in rats throughout adolescence. All animals were tested for object recognition memory and prepulse inhibition of the acoustic startle reflex. Although cognitive performance in short-term memory as well as sensorimotor gating abilities were decreased during puberty compared to adulthood, both tasks were found to show different developmental trajectories throughout adolescence. A low dose of the CB1 receptor antagonist/inverse agonist SR141716 was found to improve recognition memory specifically in pubertal animals while not affecting behavioral performance at other ages tested. The present findings demonstrate that the developmental trajectory of cognitive abilities does not occur linearly for all cognitive processes and is strongly influenced by pubertal maturation. Developmental alterations within the eCB system at puberty onset may be involved in these changes in cognitive processing. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

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.

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.

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.

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.

Fear-Potential Startle as a Model System for Analyzing Learning and Memory

DTIC Science & Technology

1988-09-21

connection between the central nucleus of the amygdala and the nucleus reticularis pontis caudalis, an obligatory part of the startle pathway. Because we...Miserendino, M and Davis, M. A direct pathway from the central nucleus of the amygdala to the region of the nucleus reticularis pontis caudalis critical for...blocked by drugs that decrease anxiety in humans as well as by lesions of the central nucleus of the amygdala, an area of the brain known to be critical for

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.

Double dissociation in the neural substrates of acute opiate dependence as measured by withdrawal-potentiated startle.

PubMed

Harris, A C; Atkinson, D M; Aase, D M; Gewirtz, J C

2006-01-01

The basolateral amygdala and portions of the "extended" amygdala (i.e. central nucleus of the amygdala, bed nucleus of the stria terminalis and shell of the nucleus accumbens) have been implicated in the aversive aspects of withdrawal from chronic opiate administration. Given that similar withdrawal signs are observed following a single opiate exposure, these structures may also play a role in "acute opiate dependence." In the current study, drug-naïve rats underwent naloxone-precipitated withdrawal from acute morphine (10 mg/kg) exposure on two successive days. On either the first or second day of testing, the basolateral amygdala, central nucleus of the amygdala, bed nucleus of the stria terminalis, or nucleus accumbens was temporarily inactivated immediately prior to naloxone injection by microinfusion of the glutamatergic alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid receptor antagonist 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo(f)quinoxaline-7-sulfonamide (3 microg/0.5 microl). On the first day, inactivation of the basolateral amygdala, central nucleus of the amygdala, or bed nucleus of the stria terminalis, but not the nucleus accumbens blocked withdrawal-potentiated startle, a behavioral measure of the anxiogenic effects of withdrawal. On the second day, inactivation of the nucleus accumbens, but not the basolateral amygdala, central nucleus of the amygdala, or bed nucleus of the stria terminalis disrupted the withdrawal effect. Effects of structural inactivations on withdrawal-potentiated startle were not influenced by differences in withdrawal severity on the two days of testing. A fear-potentiated startle procedure provided functional confirmation of correct cannulae placement in basolateral amygdale- and central nucleus of the amygdala-implanted animals. Our findings indicate a double dissociation in the neural substrates of withdrawal-potentiated startle following a first versus second morphine exposure, and may reflect a reorganization of the neural circuitry underlying the expression of withdrawal-induced negative affect during the earliest stages of opiate dependence.

Stimulation of nicotinic acetylcholine alpha7 receptors rescue schizophrenia-like cognitive impairments in rats.

PubMed

Potasiewicz, Agnieszka; Nikiforuk, Agnieszka; Hołuj, Małgorzata; Popik, Piotr

2017-02-01

Alpha7 nicotinic acetylcholine receptor (α7 nAChR) dysfunction plays an important role in schizophrenia. Positive allosteric modulators of α7 nAChR have emerged as a promising therapeutic approach to manage cognitive deficits that are inadequately treated in schizophrenic patients. The aim of the present study was to evaluate the ability of type I (CCMI) and type II (PNU120596) α7 nAChR positive allosteric modulators to counteract MK-801-induced cognitive and sensorimotor gating deficits. The activity of these compounds was compared with the action of the α7 nAChR agonist A582941. CCMI, PNU120596 and A582941 reversed the sensorimotor gating impairment evoked by MK-801 based on the prepulse inhibition of the startle response. Additionally, no MK-801-evoked working memory deficits were observed with α7 nAChR ligand pretreatment as assessed in a discrete paired-trial delayed alternation task. However, these compounds did not affect the rats' attentional performances in the five-choice serial reaction time test. The α7 nAChR agents demonstrated a beneficial effect on sensorimotor gating and some aspects of cognition tested in a rat model of schizophrenia. Therefore, these results support the use of α7 nAChR positive allosteric modulators as a potential treatment strategy in schizophrenia.

The Effect of Oxytocin on Social and Non-Social Behaviour and Striatal Protein Expression in C57BL/6N Mice

PubMed Central

Zhang, Xiaofan; Li, Qi; Zhang, Min; Lam, Sylvia; Sham, Pak Chung; Bu, Bitao; Chua, Siew Eng; Wang, Wei; McAlonan, Grainne Mary

2015-01-01

Oxytocin has been suggested as a promising new treatment for neurodevelopmental disorders. However, important gaps remain in our understanding of its mode of action, in particular, to what extent oxytocin modulates social and non-social behaviours and whether its effects are generalizable across both sexes. Here we investigated the effects of a range of oxytocin doses on social and non-social behaviours in C57BL/6N mice of both sexes. As the striatum modulates social and non-social behaviours, and is implicated in neurodevelopmental disorders, we also conducted a pilot exploration of changes in striatal protein expression elicited by oxytocin. Oxytocin increased prepulse inhibition of startle but attenuated the recognition memory in male C57BL/6N mice. It increased social interaction time and suppressed the amphetamine locomotor response in both sexes. The striatum proteome following oxytocin exposure could be clearly discriminated from saline controls. With the caveat that these results are preliminary, oxytocin appeared to alter individual protein expression in directions similar to conventional anti-psychotics. The proteins affected by oxytocin could be broadly categorized as those that modulate glutamatergic, GABAergic or dopaminergic signalling and those that mediate cytoskeleton dynamics. Our results here encourage further research into the clinical application of this peptide hormone, which may potentially extend treatment options across a spectrum of neurodevelopmental conditions. PMID:26716999

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

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

A large single ethnicity study of prepulse inhibition in schizophrenia: Separate analysis by sex focusing on effect of symptoms.

PubMed

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

2016-11-01

Deficits in sensorimotor gating, as measured with prepulse inhibition (PPI), have been considered an endophenotype of schizophrenia. However, the question remains whether these deficits are related to current symptoms. This single site study aimed to explore clinical features related to the modulation of startle reflex in a large sample of Japanese patients with schizophrenia (DSM-IV). The subjects comprised 181 patients and 250 healthy controls matched for age and sex. Schizophrenia symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Startle reflex to acoustic stimuli was recorded using a startle stimulus of 115 dB and a prepulse of four different conditions (intensity: 86 dB or 90 dB; lead interval: 60 ms or 120 ms). Patients exhibited significantly reduced startle magnitude (p < 0.001), habituation (p = 0.001), and PPI (90 dB, 60 ms, p = 0.016; 90 dB, 120 ms, p = 0.001) compared with controls. Patients of both sexes exhibited significantly lower habituation and PPI (90 dB, 120 ms) compared with the same sex controls. We could not detect a significant correlation with any clinical variable in the entire patients, however, when men and women were examined separately, there was a negative correlation with the PANSS cognitive domain (ρ = -0.33, p = 0.008) in men, but not in women. Moreover, when patients were subdivided into four clusters, two clusters with high positive symptoms showed significant PPI deficits in men. Our results suggest that sensorimotor gating is impaired in schizophrenia of both sexes, and PPI deficits may be related to thought disturbance and disorganization in male patients with schizophrenia. Copyright © 2016 Elsevier Ltd. All rights reserved.

Conditioned fear in low- and high-anxious rats is differentially regulated by cortical subcortical and midbrain 5-HT(1A) receptors.

PubMed

Ferreira, R; Nobre, M J

2014-05-30

Interactions between the prelimbic cortex and the basolateral amygdala underlie fear memory processing, mostly through acquiring and consolidating the learning of a conditioned fear. More recently, studies highlighted the role of the dorsal periaqueductal gray (DPAG) in the modulation of learning fear responses. In addition, extensive data in the literature have signaled the importance of serotonin (5-HT) on fear and anxiety. In the present study, the role of 5-HT neurotransmission of the prelimbic cortex, basolateral amygdala or the DPAG on the unconditioned and conditioned fear responses in rats previously selected as low- (LA) or high-anxious (HA) were assessed through local infusions of 5-HT itself (10nmol/0.2μl) or the selective 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT - 0.3μg/0.2μl). Behavioral analysis was conducted using the fear-potentiated startle (FPS) procedure. Dependent variables recorded were the latency and amplitude of the unconditioned startle response and FPS. Our findings suggest that, on the prelimbic cortex, 5-HT modulates the expression of conditioned fear response in HA rats and this modulation is dependent on 5-HT1A receptors. This is not true, however, for the basolateral amygdala or the DPAG. In these regions LA but not HA rats were susceptible to the anxiolytic-like effect of 5-HT1A receptor activation. It is thought that the expression of conditioned fear in HA subjects may be dependent on other 5-HT receptors, as the 5-HT1B subtype, and/or changes in other systems such as the GABA and glutamate neurotransmitters. These results increase our understanding of the rostrocaudal influence of 5-HT on the unconditioned and conditioned fear responses in LA and HA subjects and, to some extent, are in disagreement with the theoretical current that emphasizes the role of 5-HT on anxiety, mainly at the subcortical and midbrain levels. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

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

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...

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

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

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

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

Animal models of tinnitus.

PubMed

Brozoski, Thomas J; Bauer, Carol A

2016-08-01

Presented is a thematic review of animal tinnitus models from a functional perspective. Chronic tinnitus is a persistent subjective sound sensation, emergent typically after hearing loss. Although the sensation is experientially simple, it appears to have central a nervous system substrate of unexpected complexity that includes areas outside of those classically defined as auditory. Over the past 27 years animal models have significantly contributed to understanding tinnitus' complex neurophysiology. In that time, a diversity of models have been developed, each with its own strengths and limitations. None has clearly become a standard. Animal models trace their origin to the 1988 experiments of Jastreboff and colleagues. All subsequent models derive some of their features from those experiments. Common features include behavior-dependent psychophysical determination, acoustic conditions that contrast objective sound and silence, and inclusion of at least one normal-hearing control group. In the present review, animal models have been categorized as either interrogative or reflexive. Interrogative models use emitted behavior under voluntary control to indicate hearing. An example would be pressing a lever to obtain food in the presence of a particular sound. In this type of model animals are interrogated about their auditory sensations, analogous to asking a patient, "What do you hear?" These models require at least some training and motivation management, and reflect the perception of tinnitus. Reflexive models, in contrast, employ acoustic modulation of an auditory reflex, such as the acoustic startle response. An unexpected loud sound will elicit a reflexive motor response from many species, including humans. Although involuntary, acoustic startle can be modified by a lower-level preceding event, including a silent sound gap. Sound-gap modulation of acoustic startle appears to discriminate tinnitus in animals as well as humans, and requires no training or motivational manipulation, but its sensitivity, reliability, mechanism, and optimal implementation are incompletely understood. While to date animal models have significantly expanded the neuroscience of tinnitus, they have been limited to examining sensory features. In the human condition, emotional and cognitive factors are also important. It is not clear that the emotional features of tinnitus can be further understood using animal models, but models may be applied to examine cognitive factors. A recently developed model is described that reveals an interaction between tinnitus and auditory attention. This research suggests that effective tinnitus therapy could rely on modifying attention to the sensation rather than modifying the sensation itself. This article is part of a Special Issue entitled . Copyright © 2015 Elsevier B.V. All rights reserved.

Extreme startle and photomyoclonic response in severe hypocalcaemia.

PubMed

Moccia, Marcello; Erro, Roberto; Nicolella, Elvira; Striano, Pasquale; Striano, Salvatore

2014-03-01

We report the case of 62-year-old woman referred to our department because of a clinical suspicion of tonic-clonic seizures. Clinical examination revealed an exaggerated startle reflex, EEG showed a photomyoclonic response, and blood tests indicated severe hypocalcaemia. Additional clinical data, treatment strategies, and long-term follow-up visits were reported. The present report discusses the difficulties in distinguishing between epileptic and non-epileptic startles, and shows, for the first time, exaggerated startle reflex and extreme photomyoclonic response due to severe hypocalcaemia.

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

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.

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.

Cerebral Developmental Abnormalities in a Mouse with Systemic Pyruvate Dehydrogenase Deficiency

PubMed Central

Pliss, Lioudmila; Hausknecht, Kathryn A.; Stachowiak, Michal K.; Dlugos, Cynthia A.; Richards, Jerry B.; Patel, Mulchand S.

2013-01-01

Pyruvate dehydrogenase (PDH) complex (PDC) deficiency is an inborn error of pyruvate metabolism causing a variety of neurologic manifestations. Systematic analyses of development of affected brain structures and the cellular processes responsible for their impairment have not been performed due to the lack of an animal model for PDC deficiency. METHODS: In the present study we investigated a murine model of systemic PDC deficiency by interrupting the X-linked Pdha1 gene encoding the α subunit of PDH to study its role on brain development and behavioral studies. RESULTS: Male embryos died prenatally but heterozygous females were born. PDC activity was reduced in the brain and other tissues in female progeny compared to age-matched control females. Immunohistochemical analysis of several brain regions showed that approximately 40% of cells were PDH−. The oxidation of glucose to CO2 and incorporation of glucose-carbon into fatty acids were reduced in brain slices from 15 day-old PDC-deficient females. Histological analyses showed alterations in several structures in white and gray matters in 35 day-old PDC-deficient females. Reduction in total cell number and reduced dendritic arbors in Purkinje neurons were observed in PDC-deficient females. Furthermore, cell proliferation, migration and differentiation into neurons by newly generated cells were reduced in the affected females during pre- and postnatal periods. PDC-deficient mice had normal locomotor activity in a novel environment but displayed decreased startle responses to loud noises and there was evidence of abnormal pre-pulse inhibition of the startle reflex. CONCLUSIONS: The results show that a reduction in glucose metabolism resulting in deficit in energy production and fatty acid biosynthesis impairs cellular differentiation and brain development in PDC-deficient mice. PMID:23840713

"Time Out"

ERIC Educational Resources Information Center

Pluviose, David

2007-01-01

According to recent statistics from the University of Central Florida's Institute for Diversity and Ethics in Sport, Blacks hold just 6.2 percent of newspaper sports department jobs--a startling disparity when considering that 78 percent of NBA players and 66 percent of NFL players are Black. How does this disparity affect the coverage of top…

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.

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

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.

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).

Effects of acute or repeated paroxetine and fluoxetine treatment on affective behavior in male and female adolescent rats

PubMed Central

Amodeo, Leslie R.; Greenfield, Venuz Y.; Humphrey, Danielle E.; Varela, Veronica; Pipkin, Joseph A.; Eaton, Shannon E.; Johnson, Jelesa D.; Plant, Christopher P.; Harmony, Zachary R.; Wang, Li; Crawford, Cynthia A.

2015-01-01

Rationale The SSRI antidepressant fluoxetine is one of the few drugs that is effective at treating depression in adolescent humans. In contrast, the SSRI paroxetine has limited efficacy and is more at risk for inducing suicidal behavior. Objective The purpose of the present study was to more fully characterize the differential actions of paroxetine and fluoxetine. Methods In Experiment 1, male and female rats were injected with paroxetine (2.5 or 10 mg/kg), fluoxetine (10 mg/kg), or vehicle for 10 days starting on postnatal day (PD) 35, and affective behaviors were assessed using sucrose preference and elevated plus maze tasks. A separate set of rats were used to examine monoamine levels. In Experiment 2, rats were injected with paroxetine (2.5, 5 or 10 mg/kg), fluoxetine (5, 10 or 20 mg/kg), or vehicle during the same time frame as Experiment 1 and anxiety-like behaviors were measured using elevated plus maze, light/dark box, and acoustic startle. Results Repeated SSRI treatment failed to alter sucrose preference, although both paroxetine and fluoxetine reduced time spent in the open arms of the elevated plus maze and light compartment of the light/dark box. Paroxetine, but not fluoxetine, enhanced acoustic startle and interfered with habituation. Serotonin turnover was decreased by both acute and repeated fluoxetine treatment but unaltered by paroxetine administration. Discussion These results show that repeated treatment with paroxetine and fluoxetine has dissociable actions in adolescent rats. In particular, paroxetine, but not fluoxetine, increases acoustic startle at low doses and may increase sensitivity to environmental stressors. PMID:26141193

Effects of acute or repeated paroxetine and fluoxetine treatment on affective behavior in male and female adolescent rats.

PubMed

Amodeo, Leslie R; Greenfield, Venuz Y; Humphrey, Danielle E; Varela, Veronica; Pipkin, Joseph A; Eaton, Shannon E; Johnson, Jelesa D; Plant, Christopher P; Harmony, Zachary R; Wang, Li; Crawford, Cynthia A

2015-10-01

The SSRI antidepressant fluoxetine is one of the few drugs that is effective at treating depression in adolescent humans. In contrast, the SSRI paroxetine has limited efficacy and is more at risk for inducing suicidal behavior. The purpose of the present study was to more fully characterize the differential actions of paroxetine and fluoxetine. In experiment 1, male and female rats were injected with paroxetine (2.5 or 10 mg/kg), fluoxetine (10 mg/kg), or vehicle for 10 days starting on postnatal day (PD) 35, and affective behaviors were assessed using sucrose preference and elevated plus maze tasks. A separate set of rats were used to examine monoamine levels. In experiment 2, rats were injected with paroxetine (2.5, 5, or 10 mg/kg), fluoxetine (5, 10, or 20 mg/kg), or vehicle during the same time frame as experiment 1, and anxiety-like behaviors were measured using elevated plus maze, light/dark box, and acoustic startle. Repeated SSRI treatment failed to alter sucrose preference, although both paroxetine and fluoxetine reduced time spent in the open arms of the elevated plus maze and light compartment of the light/dark box. Paroxetine, but not fluoxetine, enhanced acoustic startle and interfered with habituation. Serotonin turnover was decreased by both acute and repeated fluoxetine treatment but unaltered by paroxetine administration. These results show that repeated treatment with paroxetine and fluoxetine has dissociable actions in adolescent rats. In particular, paroxetine, but not fluoxetine, increases acoustic startle at low doses and may increase sensitivity to environmental stressors.

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 ...

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

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

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.

[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.

Lifelong disturbance of serotonin transporter functioning results in fear learning deficits: Reversal by blockade of CRF1 receptors.

PubMed

Bijlsma, Elisabeth Y; Hendriksen, Hendrikus; Baas, Johanna M P; Millan, Mark J; Groenink, Lucianne

2015-10-01

The inability to associate aversive events with relevant cues (i.e. fear learning) may lead to maladaptive anxiety. To further study the role of the serotonin transporter (SERT) in fear learning, classical fear conditioning was studied in SERT knockout rats (SERT(-/-)) using fear potentiation of the startle reflex. Next, fear acquisition and concomitant development of contextual conditioned fear were monitored during training. To differentiate between developmental and direct effects of reduced SERT functioning, effects of acute and chronic SSRI treatment were studied in adult rats. Considering the known interactions between serotonin and corticotropin-releasing factor (CRF), we studied the effect of the CRFR1 antagonist CP154,526 on behavioral changes observed and determined CRF1 receptor levels in SERT(-/-) rats. SERT(-/-) showed blunted fear potentiation and enhanced contextual fear, which resulted from a deficit in fear acquisition. Paroxetine treatment did not affect acquisition or expression of fear-potentiated startle, suggesting that disturbed fear learning in SERT(-/-) results from developmental changes and not from reduced SERT functioning. Although CRF1 receptor levels did not differ significantly between genotypes, CP154,526 treatment normalized both cue- and contextual fear in SERT(-/-) during acquisition, but not expression of fear-potentiated startle. The disrupted fear acquisition and concomitant increase in contextual conditioned fear-potentiated startle fear in SERT(-/-) resembles the associative learning deficit seen in patients with panic disorder and suggests that normal SERT functioning is crucial for the development of an adequate fear neuro-circuitry. Moreover, the normalization of fear acquisition by CP154,526 suggests a role for central CRF signaling in the generalization of fear. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

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.

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.

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

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.

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

Neural, Hormonal, and Cognitive Correlates of Metabolic Dysfunction and Emotional Reactivity.

PubMed

Wolf, Tovah; Tsenkova, Vera; Ryff, Carol D; Davidson, Richard J; Willette, Auriel A

2018-06-01

Prediabetes and type 2 diabetes (i.e., hyperglycemia) are characterized by insulin resistance. These problems with energy metabolism may exacerbate emotional reactivity to negatively valenced stimuli and related phenomena such as predisposition toward negative affect, as well as cognitive deficits. Higher emotional reactivity is seen with hyperglycemia and insulin resistance. However, it is largely unknown how metabolic dysfunction correlates with related neural, hormonal, and cognitive outcomes. Among 331 adults from the Midlife in the United States study, eye-blink response (EBR) we cross sectionally examined to gauge reactivity to negative, positive, or neutrally valenced pictures from international affect picture system stimuli proximal to an acoustic startle probe. Increased EBR to negative stimuli was considered an index of stress reactivity. Frontal alpha asymmetry, a biomarker of negative affect predisposition, was determined using resting electroencephalography. Baseline urinary cortisol output was collected. Cognitive performance was gauged using the Brief Test of Adult Cognition by telephone. Fasting glucose and insulin characterized hyperglycemia or the homeostatic model assessment of insulin resistance. Higher homeostatic model assessment of insulin resistance corresponded to an increased startle response, measured by EBR magnitude, for negative versus positive stimuli (R = 0.218, F(1,457) = 5.48, p = .020, euglycemia: M(SD) = .092(.776), hyperglycemia: M(SD) = .120(.881)). Participants with hyperglycemia versus euglycemia showed greater right frontal alpha asymmetry (F(1,307) = 6.62, p = .011, euglycemia: M(SD) = .018(.167), hyperglycemia: M(SD) = -.029(.160)), and worse Brief Test of Adult Cognition by telephone arithmetic performance (F(1,284) = 4.25, p = .040, euglycemia: M(SD) = 2.390(1.526), hyperglycemia: M(SD) = 1.920(1.462)). Baseline urinary cortisol (log10 μg/12 hours) was also dysregulated in individuals with hyperglycemia (F(1,324) = 5.09, p = .025, euglycemia: M(SD) = 1.052 ± .332, hyperglycemia: M(SD) = .961 (.362)). These results suggest that dysmetabolism is associated with increased emotional reactivity, predisposition toward negative affect, and specific cognitive deficits.

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.

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.

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.

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

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.

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.

Iron Deficiency with or without Anemia Impairs Prepulse Inhibition of the Startle Reflex

PubMed Central

Pisansky, Marc T.; Wickham, Robert J.; Su, Jianjun; Fretham, Stephanie; Yuan, Li-Lian; Sun, Mu; Gewirtz, Jonathan C.; Georgieff, Michael K.

2013-01-01

Iron deficiency (ID) during early life causes long-lasting detrimental cognitive sequelae, many of which are linked to alterations in hippocampus function, dopamine synthesis, and the modulation of dopaminergic circuitry by the hippocampus. These same features have been implicated in the origins of schizophrenia, a neuropsychiatric disorder with significant cognitive impairments. Deficits in sensorimotor gating represent a reliable endophenotype of schizophrenia that can be measured by prepulse inhibition (PPI) of the acoustic startle reflex. Using two rodent model systems, we investigated the influence of early-life ID on PPI in adulthood. To isolate the role of hippocampal iron in PPI, our mouse model utilized a timed (embryonic day 18.5), hippocampus-specific knockout of Slc11a2, a gene coding an important regulator of cellular iron uptake, the divalent metal transport type 1 protein (DMT-1). Our second model used a classic rat dietary-based global ID during gestation, a condition that closely mimics human gestational ID anemia (IDA). Both models exhibited impaired PPI in adulthood. Furthermore, our DMT-1 knockout model displayed reduced long-term potentiation (LTP) and elevated paired pulse facilitation (PPF), electrophysiological results consistent with previous findings in the IDA rat model. These results, in combination with previous findings demonstrating impaired hippocampus functioning and altered dopaminergic and glutamatergic neurotransmission, suggest that iron availability within the hippocampus is critical for the neurodevelopmental processes underlying sensorimotor gating. Ultimately, evidence of reduced PPI in both of our models may offer insights into the roles of fetal ID and the hippocampus in the pathophysiology of schizophrenia. PMID:23733517

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.

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.

Serotonergic systems in the balance: CRHR1 and CRHR2 differentially control stress-induced serotonin synthesis.

PubMed

Donner, Nina C; Siebler, Philip H; Johnson, Danté T; Villarreal, Marcos D; Mani, Sofia; Matti, Allison J; Lowry, Christopher A

2016-01-01

Anxiety and affective disorders are often associated with hypercortisolism and dysfunctional serotonergic systems, including increased expression of TPH2, the gene encoding the rate-limiting enzyme of neuronal serotonin synthesis. We previously reported that chronic glucocorticoid exposure is anxiogenic and increases rat Tph2 mRNA expression, but it was still unclear if this also translates to increased TPH2 protein levels and in vivo activity of the enzyme. Here, we found that adult male rats treated with corticosterone (CORT, 100 μg/ml) via the drinking water for 21 days indeed show increased TPH2 protein expression in the dorsal and ventral part of the dorsal raphe nucleus (DRD, DRV) during the light phase, abolishing the enzyme's diurnal rhythm. In a second study, we systemically blocked the conversion of 5-hydroxytryptophan (5-HTP) to serotonin immediately before rats treated with CORT or vehicle were either exposed to 30 min acoustic startle stress or home cage control conditions. This allowed us to measure 5-HTP accumulation as a direct readout of basal versus stress-induced in vivo TPH2 activity. As expected, basal TPH2 activity was elevated in the DRD, DRV and MnR of CORT-treated rats. In response to stress, a multitude of serotonergic systems reacted with increased TPH2 activity, but the stress-, anxiety-, and learned helplessness-related dorsal and caudal DR (DRD/DRC) displayed stress-induced increases in TPH2 activity only after chronic CORT-treatment. To address the mechanisms underlying this region-specific CORT-dependent sensitization, we stereotaxically implanted CORT-treated rats with cannulae targeting the DR, and pharmacologically blocked either corticotropin-releasing hormone receptor type 1 (CRHR1) or type 2 (CRHR2) 10 min prior to acoustic startle stress. CRHR2 blockade prevented stress-induced increases of TPH2 activity within the DRD/DRC, while blockade of CRHR1 potentiated stress-induced TPH2 activity in the entire DR. Stress-induced TPH2 activity in the DRD/DRC furthermore predicted TPH2 activity in the amygdala and in the caudal pontine reticular nucleus (PnC), while serotonin synthesis in the PnC was strongly correlated with the maximum startle response. Our data demonstrate that chronically elevated glucocorticoids sensitize stress- and anxiety-related serotonergic systems, and for the first time reveal competing roles of CRHR1 and CRHR2 on stress-induced in vivo serotonin synthesis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Serotonergic systems in the balance: CRHR1 and CRHR2 differentially control stress-induced serotonin synthesis

PubMed Central

Donner, Nina C.; Siebler, Philip H.; Johnson, Danté T.; Villarreal, Marcos D.; Mani, Sofia; Matti, Allison J.; Lowry, Christopher A.

2015-01-01

Anxiety and affective disorders are often associated with hypercortisolism and dysfunctional serotonergic systems, including increased expression of TPH2, the gene encoding the rate-limiting enzyme of neuronal serotonin synthesis. We previously reported that chronic glucocorticoid exposure is anxiogenic and increases rat Tph2 mRNA expression, but it was still unclear if this also translates to increased TPH2 protein levels and in vivo activity of the enzyme. Here, we found that adult male rats treated with corticosterone (CORT, 100 μg/ml) via the drinking water for 21 days indeed show increased TPH2 protein expression in the dorsal and ventral part of the dorsal raphe nucleus (DRD, DRV) during the light phase, abolishing the enzyme’s diurnal rhythm. In a second study, we systemically blocked the conversion of 5-hydroxytryptophan (5-HTP) to serotonin immediately before rats treated with CORT or vehicle were either exposed to 30 min acoustic startle stress or home cage control conditions. This allowed us to measure 5-HTP accumulation as a direct readout of basal versus stress-induced in vivo TPH2 activity. As expected, basal TPH2 activity was elevated in the DRD, DRV and MnR of CORT-treated rats. In response to stress, a multitude of serotonergic systems reacted with increased TPH2 activity, but the stress-, anxiety-, and learned helplessness-related dorsal and caudal DR (DRD/DRC) displayed stress-induced increases in TPH2 activity only after chronic CORT-treatment. To address the mechanisms underlying this region-specific CORT-dependent sensitization, we stereotaxically implanted CORT-treated rats with cannulae targeting the DR, and pharmacologically blocked either corticotropin-releasing hormone receptor type 1 (CRHR1) or type 2 (CRHR2) 10 min prior to acoustic startle stress. CRHR2 blockade prevented stress-induced increases of TPH2 activity within the DRD/DRC, while blockade of CRHR1 potentiated stress-induced TPH2 activity in the entire DR. Stress-induced TPH2 activity in the DRD/DRC furthermore predicted TPH2 activity in the amygdala and in the caudal pontine reticular nucleus (PnC), while serotonin synthesis in the PnC was strongly correlated with the maximum startle response. Our data demonstrate that chronically elevated glucocorticoids sensitize stress- and anxiety-related serotonergic systems, and for the first time reveal competing roles of CRHR1 and CRHR2 on stress-induced in vivo serotonin synthesis. PMID:26454419

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.

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.

Mutations in the human GlyT2 gene define a presynaptic component of human startle disease

PubMed Central

Rees, Mark I.; Harvey, Kirsten; Pearce, Brian R.; Chung, Seo-Kyung; Duguid, Ian C.; Thomas, Philip; Beatty, Sarah; Graham, Gail E.; Armstrong, Linlea; Shiang, Rita; Abbott, Kim J.; Zuberi, Sameer M.; Stephenson, John B.P.; Owen, Michael J.; Tijssen, Marina A.J.; van den Maagdenberg, Arn M.J.M.; Smart, Trevor G.; Supplisson, Stéphane; Harvey, Robert J.

2011-01-01

Hyperekplexia is a human neurological disorder characterized by an excessive startle response and is typically caused by missense and nonsense mutations in the gene encoding the inhibitory glycine receptor (GlyR) α1 subunit (GLRA1)1-3. Genetic heterogeneity has been confirmed in isolated sporadic cases with mutations in other postsynaptic glycinergic proteins including the GlyR β subunit (GLRB)4, gephyrin (GPHN)5 and RhoGEF collybistin (ARHGEF9)6. However, many sporadic patients diagnosed with hyperekplexia do not carry mutations in these genes2-7. Here we reveal that missense, nonsense and frameshift mutations in the presynaptic glycine transporter 2 (GlyT2) gene (SLC6A5)8 also cause hyperekplexia. Patients harbouring mutations in SLC6A5 presented with hypertonia, an exaggerated startle response to tactile or acoustic stimuli, and life-threatening neonatal apnoea episodes. GlyT2 mutations result in defective subcellular localisation and/or decreased glycine uptake, with selected mutations affecting predicted glycine and Na+ binding sites. Our results demonstrate that SLC6A5 is a major gene for hyperekplexia and define the first neurological disorder linked to mutations in a Na+/Cl−-dependent transporter for a classical fast neurotransmitter. By analogy, we suggest that in other human disorders where defects in postsynaptic receptors have been identified, similar symptoms could result from defects in the cognate presynaptic neurotransmitter transporter. PMID:16751771

KSC-07pd2258

NASA Image and Video Library

2007-08-08

KENNEDY SPACE CENTER, FLA. -- A spider suspended between trees in the foreground has a perfect view of Space Shuttle Endeavour as it roars into the sky on mission STS-118. The rumbling sound of liftoff startles birds flying above. Liftoff of Endeavour from Launch Pad 39A was on time at 6:36 p.m. EDT. The mission is the 22nd shuttle flight to the International Space Station. It will continue space station construction by delivering a third starboard truss segment, S5, and other payloads such as the SPACEHAB module and the external stowage platform 3. The 11-day mission may be extended to as many as 14 depending on the test of the Station-to-Shuttle Power Transfer System that will allow the docked shuttle to draw electrical power from the station and extend its visits to the orbiting lab. Photo credit: NASA/Sandra Joseph, Tony Gray, Robert Murray

KSC-98pc1549

NASA Image and Video Library

1998-11-07

Orbiter Discovery startles a great white egret (below) next to runway 33 as it touches down at the Shuttle Landing Facility. Main gear touchdown was at 12:04 p.m. EST, landing on orbit 135. Discovery returns to Earth with its crew of seven after successfully completing mission STS-95, lasting nearly nine days and 3.6 million miles. The crew consists of Mission Commander Curtis L. Brown Jr.; Pilot Steven W. Lindsey; Mission Specialist Scott E. Parazynski; Mission Specialist Stephen K. Robinson; Payload Specialist John H. Glenn Jr., a senator from Ohio; Mission Specialist Pedro Duque of Spain, with the European Space Agency (ESA); and Payload Specialist Chiaki Mukai, M.D., with the National Space Development Agency of Japan (NASDA). The mission included research payloads such as the Spartan solar-observing deployable spacecraft, the Hubble Space Telescope Orbital Systems Test Platform, the International Extreme Ultraviolet Hitchhiker, as well as the SPACEHAB single module with experiments on space flight and the aging process

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

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.

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.

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.

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.

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

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

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.

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

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.

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

Dopamine modulates acute responses to cocaine, nicotine and ethanol in Drosophila.

PubMed

Bainton, R J; Tsai, L T; Singh, C M; Moore, M S; Neckameyer, W S; Heberlein, U

2000-02-24

Drugs of abuse have a common property in mammals, which is their ability to facilitate the release of the neurotransmitter and neuromodulator dopamine in specific brain regions involved in reward and motivation. This increase in synaptic dopamine levels is believed to act as a positive reinforcer and to mediate some of the acute responses to drugs. The mechanisms by which dopamine regulates acute drug responses and addiction remain unknown. We present evidence that dopamine plays a role in the responses of Drosophila to cocaine, nicotine or ethanol. We used a startle-induced negative geotaxis assay and a locomotor tracking system to measure the effect of psychostimulants on fly behavior. Using these assays, we show that acute responses to cocaine and nicotine are blunted by pharmacologically induced reductions in dopamine levels. Cocaine and nicotine showed a high degree of synergy in their effects, which is consistent with an action through convergent pathways. In addition, we found that dopamine is involved in the acute locomotor-activating effect, but not the sedating effect, of ethanol. We show that in Drosophila, as in mammals, dopaminergic pathways play a role in modulating specific behavioral responses to cocaine, nicotine or ethanol. We therefore suggest that Drosophila can be used as a genetically tractable model system in which to study the mechanisms underlying behavioral responses to multiple drugs of abuse.

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.

GluN2C/GluN2D subunit-selective NMDA receptor potentiator CIQ reverses MK-801-induced impairment in prepulse inhibition and working memory in Y-maze test in mice

PubMed Central

Suryavanshi, P S; Ugale, R R; Yilmazer-Hanke, D; Stairs, D J; Dravid, S M

2014-01-01

Background and Purpose Despite ample evidence supporting the N-methyl-d-aspartate receptor (NMDAR) hypofunction hypothesis of schizophrenia, progress in the development of effective therapeutics based on this hypothesis has been limited. Facilitation of NMDA receptor function by co-agonists (d-serine or glycine) only partially alleviates the symptoms in schizophrenia; other means to facilitate NMDA receptors are required. NMDA receptor sub-types differ in their subunit composition, with varied GluN2 subunits (GluN2A-GluN2D) imparting different physiological, biochemical and pharmacological properties. CIQ is a positive allosteric modulator that is selective for GluN2C/GluN2D-containing NMDA receptors (Mullasseril et al.). Experimental Approach The effect of systemic administration of CIQ was tested on impairment in prepulse inhibition (PPI), hyperlocomotion and stereotypy induced by i.p. administration of MK-801 and methamphetamine. The effect of CIQ was also tested on MK-801-induced impairment in working memory in Y-maze spontaneous alternation test. Key Results We found that systemic administration of CIQ (20 mg·kg−1, i.p.) in mice reversed MK-801 (0.15 mg·kg−1, i.p.)-induced, but not methamphetamine (3 mg·kg−1, i.p.)-induced, deficit in PPI. MK-801 increased the startle amplitude to pulse alone, which was not reversed by CIQ. In contrast, methamphetamine reduced the startle amplitude to pulse alone, which was reversed by CIQ. CIQ also partially attenuated MK-801- and methamphetamine-induced hyperlocomotion and stereotyped behaviours. Additionally, CIQ reversed the MK-801-induced working memory deficit in spontaneous alternation in a Y-maze. Conclusion and Implications Together, these results suggest that facilitation of GluN2C/GluN2D-containing receptors may serve as an important therapeutic strategy for treating positive and cognitive symptoms in schizophrenia. PMID:24236947

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.

Defensive mobilization in specific phobia: Fear specificity, negative affectivity and diagnostic prominence

PubMed Central

McTeague, Lisa M.; Lang, Peter J.; Wangelin, Bethany C.; Laplante, Marie-Claude; Bradley, Margaret M.

2012-01-01

Background Understanding of exaggerated responsivity in specific phobia—its physiology and neural mediators—has advanced considerably. However, despite strong phenotypic evidence that prominence of specific phobia relative to co-occurring conditions (i.e., principal versus non-principal disorder) is associated with dramatic differences in subjective distress, there is yet no consideration of such comorbidity issues on objective defensive reactivity. Methods A community sample of specific phobia (N=74 principal phobia; N=86 non-principal phobia) and control (n=76) participants imagined threatening and neutral events while acoustic startle probes were presented and eye-blink responses (orbicularis occuli) recorded. Changes in heart rate, skin conductance level, and facial expressivity were also measured. Results Principal specific phobia patients far exceeded controls in startle reflex and autonomic reactivity during imagery of idiographic fear scenes. Distinguishing between single and multiple phobias within principal phobia and comparing these to non-principal phobia revealed a continuum of decreasing defensive mobilization: single phobia patients were strongly reactive, multiple phobia intermediate, and non-principal patients reliably attenuated—the inverse of measures of pervasive anxiety and dysphoria (i.e., negative affectivity). Further, as more disorders supplanted specific phobia from principal disorder, overall defensive mobilization was systematically more impaired. Conclusions The exaggerated responsivity considered characteristic of specific phobia is limited to those patients for whom circumscribed fear is the most impairing condition, and coincident with little additional affective psychopathology. As specific phobia is superseded in severity by broad and chronic negative affectivity, defensive reactivity progressively diminishes. Focal fears may still be clinically-significant, but not reflected in objective measures of defensive mobilization. PMID:22386377

Defensive mobilization in specific phobia: fear specificity, negative affectivity, and diagnostic prominence.

PubMed

McTeague, Lisa M; Lang, Peter J; Wangelin, Bethany C; Laplante, Marie-Claude; Bradley, Margaret M

2012-07-01

Understanding of exaggerated responsivity in specific phobia-its physiology and neural mediators-has advanced considerably. However, despite strong phenotypic evidence that prominence of specific phobia relative to co-occurring conditions (i.e., principal versus nonprincipal disorder) is associated with dramatic differences in subjective distress, there is yet no consideration of such comorbidity issues on objective defensive reactivity. A community sample of specific phobia (n = 74 principal; n = 86 nonprincipal) and control (n = 76) participants imagined threatening and neutral events while acoustic startle probes were presented and eyeblinks (orbicularis occuli) recorded. Changes in heart rate, skin conductance level, and facial expressivity were also measured. Principal specific phobia patients far exceeded control participants in startle reflex and autonomic reactivity during idiographic fear imagery. Distinguishing between single and multiple phobias within principal phobia and comparing these with nonprincipal phobia revealed a continuum of decreasing defensive mobilization: single patients were strongly reactive, multiple patients were intermediate, and nonprincipal patients were attenuated-the inverse of measures of pervasive anxiety and dysphoria (i.e., negative affectivity). Further, as more disorders supplanted specific phobia from principal disorder, overall defensive mobilization was systematically more impaired. The exaggerated responsivity characteristic of specific phobia is limited to those patients for whom circumscribed fear is the most impairing condition and coincident with little additional affective psychopathology. As specific phobia is superseded in severity by broad and chronic negative affectivity, defensive reactivity progressively diminishes. Focal fears may still be clinically significant but not reflected in objective defensive mobilization. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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

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

Dynamic networks of PTSD symptoms during conflict.

PubMed

Greene, Talya; Gelkopf, Marc; Epskamp, Sacha; Fried, Eiko

2018-02-28

Conceptualizing posttraumatic stress disorder (PTSD) symptoms as a dynamic system of causal elements could provide valuable insights into the way that PTSD develops and is maintained in traumatized individuals. We present the first study to apply a multilevel network model to produce an exploratory empirical conceptualization of dynamic networks of PTSD symptoms, using data collected during a period of conflict. Intensive longitudinal assessment data were collected during the Israel-Gaza War in July-August 2014. The final sample (n = 96) comprised a general population sample of Israeli adult civilians exposed to rocket fire. Participants completed twice-daily reports of PTSD symptoms via smartphone for 30 days. We used a multilevel vector auto-regression model to produce contemporaneous and temporal networks, and a partial correlation network model to obtain a between-subjects network. Multilevel network analysis found strong positive contemporaneous associations between hypervigilance and startle response, avoidance of thoughts and avoidance of reminders, and between flashbacks and emotional reactivity. The temporal network indicated the central role of startle response as a predictor of future PTSD symptomatology, together with restricted affect, blame, negative emotions, and avoidance of thoughts. There were some notable differences between the temporal and contemporaneous networks, including the presence of a number of negative associations, particularly from blame. The between-person network indicated flashbacks and emotional reactivity to be the most central symptoms. This study suggests various symptoms that could potentially be driving the development of PTSD. We discuss clinical implications such as identifying particular symptoms as targets for interventions.

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.

Long-lasting changes in stress-induced corticosterone response and anxiety-like behaviors as a consequence of neonatal maternal separation in Long-Evans rats.

PubMed

Kalinichev, Mikhail; Easterling, Keith W; Plotsky, Paul M; Holtzman, Stephen G

2002-08-01

Early neonatal environmental factors appear to have powerful and long-lasting influences on an organism's physiology and behavior. Long-Evans male rats separated from their dam for 3 h daily over the first 2 weeks of life (maternally separated, MS rats) when tested as adults exhibit exaggerated behavioral and neuroendocrine responses to stress compared to 15-min separated (handled, H) animals. The purpose of this study was to compare male and female adult rats that were MS, H or were undisturbed (nonhandled, NH) as neonates in anxiety-like behaviors, in the elevated plus-maze, and in response to startle-inducing auditory stimuli. We confirmed that MS males oversecrete corticosterone (CORT; 2.5-5 times) in response to mild handling stress. MS males and females were less likely to explore open arms of the plus-maze. MS males exhibited 35% higher startle amplitudes compared to controls. Furthermore, MS males were more likely to emit ultrasonic vocalizations in response to startle than were H controls. However, MS and control females did not differ in auditory startle response or in startle-induced ultrasonic vocalizations. Therefore, experiencing maternal separation results in a long-lasting increase in anxiety-like behaviors that occurs in a sex-dependent manner.

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.

The role of the read through variant of acetylcholinesterase in anxiogenic effects of predator stress in mice.

PubMed

Adamec, Robert; Head, David; Soreq, Hermona; Blundell, Jacqueline

2008-05-16

This study examined the role of the read through variant of acetylcholinesterase (AChE-R) in lasting changes in murine affective behavior produced by a brief predator stress. AChE-R is elevated by stress in limbic cholinergic circuits implicated in anxiogenic effects of predator stress. The expression of AChE-R was blocked with a systemically administered central acting antisense oligonucleotide for AChE-R (EN101). EN101 was injected at multiple points prior to and after a predator stress in male C57 mice. Seven days after the last injection, behavior was tested. Predator stress caused a significant increase in startle amplitude, which EN101 blocked. This effect was specific to EN101, as the negative control inactive form of EN101, INVEN101 was without effect on stress effects on startle. Neither EN101 nor INVEN101 altered the anxiogenic effects of predator stress on behavior in the elevated plus maze, and both drugs partially reduced stress suppression of time active in the hole board. In the light dark box test, INVEN101 exhibited a weak block of stress effects on behavior for reasons which are unclear. Taken together, findings support the view that multiple neural systems are responsible for the different changes in behavior produced by predator stress. Present findings also suggest a role for AChE-R in specific anxiogenic (hyperarousal) effects following predator stress. Since AChE-R manipulations took place starting 23 h prior to predator stress and continued 48 h after predator stress, further research is necessary to determine the role of AChE-R in initiation and/or consolidation of hyperarousal effects of predator stress.

Deimatic display in the European swallowtail butterfly as a secondary defence against attacks from great tits.

PubMed

Olofsson, Martin; Eriksson, Stephan; Jakobsson, Sven; Wiklund, Christer

2012-01-01

Many animals reduce the risk of being attacked by a predator through crypsis, masquerade or, alternatively, by advertising unprofitability by means of aposematic signalling. Behavioural attributes in prey employed after discovery, however, signify the importance of also having an effective secondary defence if a predator uncovers, or is immune to, the prey's primary defence. In butterflies, as in most animals, secondary defence generally consists of escape flights. However, some butterfly species have evolved other means of secondary defence such as deimatic displays/startle displays. The European swallowtail, Papilio machaon, employs what appears to be a startle display by exposing its brightly coloured dorsal wing surface upon disturbance and, if the disturbance continues, by intermittently protracting and relaxing its wing muscles generating a jerky motion of the wings. This display appears directed towards predators but whether it is effective in intimidating predators so that they refrain from attacks has never been tested experimentally. In this study we staged encounters between a passerine predator, the great tit, Parus major, and live and dead swallowtail butterflies in a two-choice experiment. Results showed that the dead butterfly was virtually always attacked before the live butterfly, and that it took four times longer before a bird attacked the live butterfly. When the live butterfly was approached by a bird this generally elicited the butterfly's startle display, which usually caused the approaching bird to flee. We also performed a palatability test of the butterflies and results show that the great tits seemed to find them palatable. We conclude that the swallowtail's startle display of conspicuous coloration and jerky movements is an efficient secondary defence against small passerines. We also discuss under what conditions predator-prey systems are likely to aid the evolution of deimatic behaviours in harmless and palatable prey.

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.

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 ...

Fearing shades of grey: individual differences in fear responding towards generalisation stimuli.

PubMed

Arnaudova, Inna; Krypotos, Angelos-Miltiadis; Effting, Marieke; Kindt, Merel; Beckers, Tom

2017-09-01

Individual differences in fear generalisation have been proposed to play a role in the aetiology and/or maintenance of anxiety disorders, but few data are available to directly support that claim. The research that is available has focused mostly on generalisation of peripheral and central physiological fear responses. Far less is known about the generalisation of avoidance, the behavioural component of fear. In two experiments, we evaluated how neuroticism, a known vulnerability factor for anxiety, modulates an array of fear responses, including avoidance tendencies, towards generalisation stimuli (GS). Participants underwent differential fear conditioning, in which one conditioned stimulus (CS+) was repeatedly paired with an aversive outcome (shock; unconditioned stimulus, US), whereas another was not (CS-). Fear generalisation was observed across measures in Experiment 1 (US expectancy and evaluative ratings) and Experiment 2 (US expectancy, evaluative ratings, skin conductance, startle responses, safety behaviours), with overall highest responding to the CS+, lowest to the CS- and intermediate responding to the GSs. Neuroticism had very little impact on fear generalisation (but did affect GS recognition rates in Experiment 1), in line with the idea that fear generalisation is largely an adaptive process.

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.

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.

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

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

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

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.

Effect of the Putative Lithium Mimetic Ebselen on Brain Myo-Inositol, Sleep, and Emotional Processing in Humans.

PubMed

Singh, Nisha; Sharpley, Ann L; Emir, Uzay E; Masaki, Charles; Herzallah, Mohammad M; Gluck, Mark A; Sharp, Trevor; Harmer, Catherine J; Vasudevan, Sridhar R; Cowen, Philip J; Churchill, Grant C

2016-06-01

Lithium remains the gold standard in treating bipolar disorder but has unwanted toxicity and side effects. We previously reported that ebselen inhibits inositol monophosphatase (IMPase) and exhibits lithium-like effects in animal models through lowering of inositol. Ebselen has been tested in clinical trials for other disorders, enabling us to determine for the first time the effect of a blood-brain barrier-penetrant IMPase inhibitor on human central nervous system (CNS) function. We now report that in a double-blind, placebo-controlled trial with healthy participants, acute oral ebselen reduced brain myo-inositol in the anterior cingulate cortex, consistent with CNS target engagement. Ebselen decreased slow-wave sleep and affected emotional processing by increasing recognition of some emotions, decreasing latency time in the acoustic startle paradigm, and decreasing the reinforcement of rewarding stimuli. In summary, ebselen affects the phosphoinositide cycle and has CNS effects on surrogate markers that may be relevant to the treatment of bipolar disorder that can be tested in future clinical trials.

The Intellectual Supermarket.

ERIC Educational Resources Information Center

Demb, Ada

2002-01-01

Discusses how separating undergraduate education into its two primary components--general education and the major--and then applying the perspective of a supermarket analogy leads to startling conclusions about possible transformations of the production and distribution system for higher education at the undergraduate level and for implementing…

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

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.

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.

Failure to extinguish fear and genetic variability in the human cannabinoid receptor 1.

PubMed

Heitland, I; Klumpers, F; Oosting, R S; Evers, D J J; Leon Kenemans, J; Baas, J M P

2012-09-25

Failure to extinguish fear can lead to persevering anxiety and has been postulated as an important mechanism in the pathogenesis of human anxiety disorders. In animals, it is well documented that the endogenous cannabinoid system has a pivotal role in the successful extinction of fear, most importantly through the cannabinoid receptor 1. However, no human studies have reported a translation of this preclinical evidence yet. Healthy medication-free human subjects (N=150) underwent a fear conditioning and extinction procedure in a virtual reality environment. Fear potentiation of the eyeblink startle reflex was measured to assess fear-conditioned responding, and subjective fear ratings were collected. Participants were genotyped for two polymorphisms located within the promoter region (rs2180619) and the coding region (rs1049353) of cannabinoid receptor 1. As predicted from the preclinical literature, acquisition and expression of conditioned fear did not differ between genotypes. Crucially, whereas both homozygote (G/G, N=23) and heterozygote (A/G, N=68) G-allele carriers of rs2180619 displayed robust extinction of fear, extinction of fear-potentiated startle was absent in A/A homozygotes (N=51). Additionally, this resistance to extinguish fear left A/A carriers of rs2180619 with significantly higher levels of fear-potentiated startle at the end of the extinction training. No effects of rs1049353 genotype were observed regarding fear acquisition and extinction. These results suggest for the first time involvement of the human endocannabinoid system in fear extinction. Implications are that genetic variability in this system may underlie individual differences in anxiety, rendering cannabinoid receptor 1 a potential target for novel pharmacological treatments of anxiety disorders.

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...

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

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...

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...

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...

Rivastigmine improves isolation rearing-induced prepulse inhibition deficits via muscarinic acetylcholine receptors in mice.

PubMed

Higashino, Kosuke; Ago, Yukio; Umeki, Takahiro; Hasebe, Shigeru; Onaka, Yusuke; Hashimoto, Hitoshi; Takuma, Kazuhiro; Matsuda, Toshio

2016-02-01

The acetylcholinesterase inhibitors donepezil, galantamine, and rivastigmine are used for the treatment of Alzheimer's disease. We previously demonstrated that donepezil and galantamine differentially affect isolation rearing-induced prepulse inhibition (PPI) deficits and that this might be due to differential effects on brain muscarinic acetylcholine (mACh) receptor function in mice. We examined the effects of rivastigmine on isolation rearing-induced PPI deficits, brain ACh levels, and mACh receptor function in mice. Acoustic startle responses were measured in a startle chamber. Microdialysis was performed, and the levels of dopamine and ACh in the prefrontal cortex were measured. Rivastigmine (0.3 mg/kg) improved PPI deficits, and this improvement was antagonized by the mACh receptor antagonist telenzepine but not by the nicotinic ACh receptor antagonist mecamylamine. Rivastigmine increased extracellular ACh levels by approximately 2-3-fold, less than the increase produced by galantamine. Rivastigmine enhanced the effect of the mACh receptor agonist N-desmethylclozapine on prefrontal dopamine release, a marker of mACh receptor function, and this increase was blocked by telenzepine. In contrast, galantamine did not affect N-desmethylclozapine-induced dopamine release. Furthermore, rivastigmine did not affect cortical dopamine release induced by the serotonin1A receptor agonist osemozotan, suggesting that the effect of rivastigmine has specificity for mACh receptors. Taken together with our previous finding that marked increases in ACh levels are required for the PPI deficit improvement induced by galantamine, our present results suggest that rivastigmine improves isolation rearing-induced PPI deficits by increasing ACh levels and by concomitantly enhancing mACh receptor function.

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...

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.

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.

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.

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

Suppressed acoustic startle response in traumatic brain injury masks post-traumatic stress disorder hyper-responsivity.

PubMed

Liska, Grant M; Lee, Jea-Young; Xu, Kaya; Sanberg, Paul R; Borlongan, Cesario V

2018-05-21

An exaggerated acoustic startle reflex (ASR) is a clinical indicator of anxiety disorders, such as post-traumatic stress disorder (PTSD). Given the prevalence of PTSD following traumatic brain injury (TBI), we studied the effects of TBI on ASR. Adult Sprague Dawley rats exposed to moderate controlled cortical impact injury model of TBI displayed suppression of ASR intensity and sensitivity. As patients with PTSD have been shown to display hyperactive startle responses, the present discrepant observation of TBI-induced suppression of ASR has clinical implications, in that the reduced, instead of elevated, startle response in patients with comorbid TBI/PTSD could be owing to a masking effect of TBI.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/.

When seeing outweighs feeling: a role for prefrontal cortex in passive control of negative affect in blindsight.

PubMed

Anders, Silke; Eippert, Falk; Wiens, Stefan; Birbaumer, Niels; Lotze, Martin; Wildgruber, Dirk

2009-11-01

Affective neuroscience has been strongly influenced by the view that a 'feeling' is the perception of somatic changes and has consequently often neglected the neural mechanisms that underlie the integration of somatic and other information in affective experience. Here, we investigate affective processing by means of functional magnetic resonance imaging in nine cortically blind patients. In these patients, unilateral postgeniculate lesions prevent primary cortical visual processing in part of the visual field which, as a result, becomes subjectively blind. Residual subcortical processing of visual information, however, is assumed to occur in the entire visual field. As we have reported earlier, these patients show significant startle reflex potentiation when a threat-related visual stimulus is shown in their blind visual field. Critically, this was associated with an increase of brain activity in somatosensory-related areas, and an increase in experienced negative affect. Here, we investigated the patients' response when the visual stimulus was shown in the sighted visual field, that is, when it was visible and cortically processed. Despite the fact that startle reflex potentiation was similar in the blind and sighted visual field, patients reported significantly less negative affect during stimulation of the sighted visual field. In other words, when the visual stimulus was visible and received full cortical processing, the patients' phenomenal experience of affect did not closely reflect somatic changes. This decoupling of phenomenal affective experience and somatic changes was associated with an increase of activity in the left ventrolateral prefrontal cortex and a decrease of affect-related somatosensory activity. Moreover, patients who showed stronger left ventrolateral prefrontal cortex activity tended to show a stronger decrease of affect-related somatosensory activity. Our findings show that similar affective somatic changes can be associated with different phenomenal experiences of affect, depending on the depth of cortical processing. They are in line with a model in which the left ventrolateral prefrontal cortex is a relay station that integrates information about subcortically triggered somatic responses and information resulting from in-depth cortical stimulus processing. Tentatively, we suggest that the observed decoupling of somatic responses and experienced affect, and the reduction of negative phenomenal experience, can be explained by a left ventrolateral prefrontal cortex-mediated inhibition of affect-related somatosensory activity.

When seeing outweighs feeling: a role for prefrontal cortex in passive control of negative affect in blindsight

PubMed Central

Eippert, Falk; Wiens, Stefan; Birbaumer, Niels; Lotze, Martin; Wildgruber, Dirk

2009-01-01

Affective neuroscience has been strongly influenced by the view that a ‘feeling’ is the perception of somatic changes and has consequently often neglected the neural mechanisms that underlie the integration of somatic and other information in affective experience. Here, we investigate affective processing by means of functional magnetic resonance imaging in nine cortically blind patients. In these patients, unilateral postgeniculate lesions prevent primary cortical visual processing in part of the visual field which, as a result, becomes subjectively blind. Residual subcortical processing of visual information, however, is assumed to occur in the entire visual field. As we have reported earlier, these patients show significant startle reflex potentiation when a threat-related visual stimulus is shown in their blind visual field. Critically, this was associated with an increase of brain activity in somatosensory-related areas, and an increase in experienced negative affect. Here, we investigated the patients’ response when the visual stimulus was shown in the sighted visual field, that is, when it was visible and cortically processed. Despite the fact that startle reflex potentiation was similar in the blind and sighted visual field, patients reported significantly less negative affect during stimulation of the sighted visual field. In other words, when the visual stimulus was visible and received full cortical processing, the patients’ phenomenal experience of affect did not closely reflect somatic changes. This decoupling of phenomenal affective experience and somatic changes was associated with an increase of activity in the left ventrolateral prefrontal cortex and a decrease of affect-related somatosensory activity. Moreover, patients who showed stronger left ventrolateral prefrontal cortex activity tended to show a stronger decrease of affect-related somatosensory activity. Our findings show that similar affective somatic changes can be associated with different phenomenal experiences of affect, depending on the depth of cortical processing. They are in line with a model in which the left ventrolateral prefrontal cortex is a relay station that integrates information about subcortically triggered somatic responses and information resulting from in-depth cortical stimulus processing. Tentatively, we suggest that the observed decoupling of somatic responses and experienced affect, and the reduction of negative phenomenal experience, can be explained by a left ventrolateral prefrontal cortex-mediated inhibition of affect-related somatosensory activity. PMID:19767414

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.

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.

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.

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.

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

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.

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.

Rushing Roulette

PubMed Central

Scanlan, Larry

1976-01-01

In a Canada-wide survey, CANADIAN FAMILY PHYSICIAN found a startling divergence in provincial standards for ambulance crews and vehicles. While some provinces had developed a well-integrated ambulance system with central dispatching, rigorous standards for attendants and advanced paramedical training programs, in some the ambulances are run almost entirely by local undertakers. PMID:21308032

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

Stressor-specific effects of sex on HPA axis hormones and activation of stress-related neurocircuitry.

PubMed

Babb, Jessica A; Masini, Cher V; Day, Heidi E W; Campeau, Serge

2013-11-01

Experiencing stress can be physically and psychologically debilitating to an organism. Women have a higher prevalence of some stress-related mental illnesses, the reasons for which are unknown. These experiments explore differential HPA axis hormone release in male and female rats following acute stress. Female rats had a similar threshold of HPA axis hormone release following low intensity noise stress as male rats. Sex did not affect the acute release, or the return of HPA axis hormones to baseline following moderate intensity noise stress. Sensitive indices of auditory functioning obtained by modulation of the acoustic startle reflex by weak pre-pulses did not reveal any sexual dimorphism. Furthermore, male and female rats exhibited similar c-fos mRNA expression in the brain following noise stress, including several sex-influenced stress-related regions. The HPA axis response to noise stress was not affected by stage of estrous cycle, and ovariectomy significantly increased hormone release. Direct comparison of HPA axis hormone release to two different stressors in the same animals revealed that although female rats exhibit robustly higher HPA axis hormone release after restraint stress, the same effect was not observed following moderate and high intensity loud noise stress. Finally, the differential effect of sex on HPA axis responses to noise and restraint stress cannot readily be explained by differential social cues or general pain processing. These studies suggest the effect of sex on acute stress-induced HPA axis hormone activity is highly dependent on the type of stressor.

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.

Cannabinoids and traumatic stress modulation of contextual fear extinction and GR expression in the amygdala-hippocampal-prefrontal circuit.

PubMed

Ganon-Elazar, Eti; Akirav, Irit

2013-09-01

Considerable evidence suggests that cannabinoids modulate the behavioral and physiological response to stressful events. We have recently shown that activating the cannabinoid system using the CB1/CB2 receptor agonist WIN55,212-2 (WIN) in proximity to exposure to single-prolonged stress (SPS), a rat model of emotional trauma, prevented the stress-induced enhancement of acoustic startle response, the impairment in avoidance extinction and the enhanced negative feedback on the hypothalamic-pituitary-adrenal (HPA) axis (Ganon-Elazar and Akirav, 2012). Some of the effects were found to be mediated by CB1 receptors in the basolateral amygdala (BLA). Here we examined whether cannabinoid receptor activation in a putative brain circuit that includes the BLA, hippocampus and prefrontal cortex (PFC), could prevent the effects of traumatic stress on contextual fear extinction and alterations in glucocorticoid receptor (GR) protein levels. We found that: (i) SPS impaired contextual fear extinction tested one week after trauma exposure and that WIN prevented the stress-induced impairment of extinction when microinjected immediately after trauma exposure into the BLA or hippocampus (5 μg), but not when microinjected into the PFC, (ii) the ameliorating effects of WIN on contextual extinction were prevented by blocking GRs in the BLA and hippocampus, and (iii) SPS up regulated GRs in the BLA, PFC and hippocampus and systemic WIN administration (0.5 mg/kg) after trauma exposure normalized GR levels in the BLA and hippocampus, but not in the PFC. Cannabinoid receptor activation in the aftermath of trauma exposure may regulate the emotional response to the trauma and prevent stress-induced impairment of extinction and GR up regulation through the mediation of CB1 receptors in the BLA and hippocampus. Taken together, the findings suggest that the interaction between the cannabinoid and glucocorticoid systems is crucial in the modulation of emotional trauma. Copyright © 2013 Elsevier Ltd. All rights reserved.

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...

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...

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…

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

Deimatic Display in the European Swallowtail Butterfly as a Secondary Defence against Attacks from Great Tits

PubMed Central

Olofsson, Martin; Eriksson, Stephan; Jakobsson, Sven; Wiklund, Christer

2012-01-01

Background Many animals reduce the risk of being attacked by a predator through crypsis, masquerade or, alternatively, by advertising unprofitability by means of aposematic signalling. Behavioural attributes in prey employed after discovery, however, signify the importance of also having an effective secondary defence if a predator uncovers, or is immune to, the prey’s primary defence. In butterflies, as in most animals, secondary defence generally consists of escape flights. However, some butterfly species have evolved other means of secondary defence such as deimatic displays/startle displays. The European swallowtail, Papilio machaon, employs what appears to be a startle display by exposing its brightly coloured dorsal wing surface upon disturbance and, if the disturbance continues, by intermittently protracting and relaxing its wing muscles generating a jerky motion of the wings. This display appears directed towards predators but whether it is effective in intimidating predators so that they refrain from attacks has never been tested experimentally. Methodology/Principal Findings In this study we staged encounters between a passerine predator, the great tit, Parus major, and live and dead swallowtail butterflies in a two-choice experiment. Results showed that the dead butterfly was virtually always attacked before the live butterfly, and that it took four times longer before a bird attacked the live butterfly. When the live butterfly was approached by a bird this generally elicited the butterfly’s startle display, which usually caused the approaching bird to flee. We also performed a palatability test of the butterflies and results show that the great tits seemed to find them palatable. Conclusions/Significance We conclude that the swallowtail’s startle display of conspicuous coloration and jerky movements is an efficient secondary defence against small passerines. We also discuss under what conditions predator-prey systems are likely to aid the evolution of deimatic behaviours in harmless and palatable prey. PMID:23056590

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.

Worrying affects associative fear learning: a startle fear conditioning study.

PubMed

Gazendam, Femke J; Kindt, Merel

2012-01-01

A valuable experimental model for the pathogenesis of anxiety disorders is that they originate from a learned association between an intrinsically non-aversive event (Conditioned Stimulus, CS) and an anticipated disaster (Unconditioned Stimulus, UCS). Most anxiety disorders, however, do not evolve from a traumatic experience. Insights from neuroscience show that memory can be modified post-learning, which may elucidate how pathological fear can develop after relatively mild aversive events. Worrying--a process frequently observed in anxiety disorders--is a potential candidate to strengthen the formation of fear memory after learning. Here we tested in a discriminative fear conditioning procedure whether worry strengthens associative fear memory. Participants were randomly assigned to either a Worry (n = 23) or Control condition (n = 25). After fear acquisition, the participants in the Worry condition processed six worrisome questions regarding the personal aversive consequences of an electric stimulus (UCS), whereas the Control condition received difficult but neutral questions. Subsequently, extinction, reinstatement and re-extinction of fear were tested. Conditioned responding was measured by fear-potentiated startle (FPS), skin conductance (SCR) and UCS expectancy ratings. Our main results demonstrate that worrying resulted in increased fear responses (FPS) to both the feared stimulus (CS(+)) and the originally safe stimulus (CS(-)), whereas FPS remained unchanged in the Control condition. In addition, worrying impaired both extinction and re-extinction learning of UCS expectancy. The implication of our findings is that they show how worry may contribute to the development of anxiety disorders by affecting associative fear learning.

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

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.

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.

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.

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

On-Line Learning and the Implications for School Design

ERIC Educational Resources Information Center

Stack, Greg

2011-01-01

"Disrupting Class," published in 2008, is the story of how disruptive innovation, innovation that changes the business model organizations, will fundamentally change the American school system. The book's most startling prediction is that half of all high school classes will be on-line by 2019. In considering these predictions, the author began to…

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

Effect of the Putative Lithium Mimetic Ebselen on Brain Myo-Inositol, Sleep, and Emotional Processing in Humans

PubMed Central

Singh, Nisha; Sharpley, Ann L; Emir, Uzay E; Masaki, Charles; Herzallah, Mohammad M; Gluck, Mark A; Sharp, Trevor; Harmer, Catherine J; Vasudevan, Sridhar R; Cowen, Philip J; Churchill, Grant C

2016-01-01

Lithium remains the gold standard in treating bipolar disorder but has unwanted toxicity and side effects. We previously reported that ebselen inhibits inositol monophosphatase (IMPase) and exhibits lithium-like effects in animal models through lowering of inositol. Ebselen has been tested in clinical trials for other disorders, enabling us to determine for the first time the effect of a blood–brain barrier-penetrant IMPase inhibitor on human central nervous system (CNS) function. We now report that in a double-blind, placebo-controlled trial with healthy participants, acute oral ebselen reduced brain myo-inositol in the anterior cingulate cortex, consistent with CNS target engagement. Ebselen decreased slow-wave sleep and affected emotional processing by increasing recognition of some emotions, decreasing latency time in the acoustic startle paradigm, and decreasing the reinforcement of rewarding stimuli. In summary, ebselen affects the phosphoinositide cycle and has CNS effects on surrogate markers that may be relevant to the treatment of bipolar disorder that can be tested in future clinical trials. PMID:26593266

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.

Neurophysiological evidence of an association between cognitive control and defensive reactivity processes in young children.

PubMed

Lo, Sharon L; Schroder, Hans S; Moran, Tim P; Durbin, C Emily; Moser, Jason S

2015-10-01

Interactions between cognitive control and affective processes, such as defensive reactivity, are intimately involved in healthy and unhealthy human development. However, cognitive control and defensive reactivity processes are often studied in isolation and rarely examined in early childhood. To address these gaps, we examined the relationships between multiple neurophysiological measures of cognitive control and defensive reactivity in young children. Specifically, we assessed two event-related potentials thought to index cognitive control processes--the error-related negativity (ERN) and error positivity (Pe)--measured across two tasks, and two markers of defensive reactivity processes--startle reflex and resting parietal asymmetry--in a sample of 3- to 7-year old children. Results revealed that measures of cognitive control and defensive reactivity were related such that evidence of poor cognitive control (smaller ERN) was associated with high defensive reactivity (larger startle and greater right relative to left parietal activity). The strength of associations between the ERN and measures of defensive reactivity did not vary by age, providing evidence that poor cognitive control relates to greater defensive reactivity across early childhood years. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Assessing Anxiety in Nonhuman Primates

PubMed Central

Coleman, Kristine; Pierre, Peter J.

2014-01-01

Anxiety can be broadly described as a psychological state in which normally innocuous environmental stimuli trigger negative emotional expectations. Human anxiety disorders are multidimensional and may be organic or acquired, situational or pervasive. The broad ranging nature of the anxiety phenotype speaks to the need for models that identify its various components and root causes to develop effective clinical treatments. The cross-species comparative approach to modeling anxiety disorders in animals aims to understand mechanisms that both contribute to and modulate anxiety. Nonhuman primate models provide an important bridge from nonprimate model systems because of the complexity of nonhuman primates’ biobehavioral capacities and their commonalities with human emotion. The broad goal of this review is to provide an overview of various procedures available to study anxiety in the nonhuman primate, with a focus on the behavioral aspects of anxiety. Commonly used methods covered in this review include assessing animals in their home environment or in response to an ethologically relevant threat, associative conditioning and startle response tests, and cognitive bias tests. We also discuss how these procedures can help veterinarians and researchers care for captive nonhuman primates. PMID:25225310

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

Affective brain-computer music interfacing

NASA Astrophysics Data System (ADS)

Daly, Ian; Williams, Duncan; Kirke, Alexis; Weaver, James; Malik, Asad; Hwang, Faustina; Miranda, Eduardo; Nasuto, Slawomir J.

2016-08-01

Objective. We aim to develop and evaluate an affective brain-computer music interface (aBCMI) for modulating the affective states of its users. Approach. An aBCMI is constructed to detect a user's current affective state and attempt to modulate it in order to achieve specific objectives (for example, making the user calmer or happier) by playing music which is generated according to a specific affective target by an algorithmic music composition system and a case-based reasoning system. The system is trained and tested in a longitudinal study on a population of eight healthy participants, with each participant returning for multiple sessions. Main results. The final online aBCMI is able to detect its users current affective states with classification accuracies of up to 65% (3 class, p\\lt 0.01) and modulate its user's affective states significantly above chance level (p\\lt 0.05). Significance. Our system represents one of the first demonstrations of an online aBCMI that is able to accurately detect and respond to user's affective states. Possible applications include use in music therapy and entertainment.

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.

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.

Objective Measures of Emotion Related to Brand Attitude: A New Way to Quantify Emotion-Related Aspects Relevant to Marketing

PubMed Central

Walla, Peter; Brenner, Gerhard; Koller, Monika

2011-01-01

With this study we wanted to test the hypothesis that individual like and dislike as occurring in relation to brand attitude can be objectively assessed. First, individuals rated common brands with respect to subjective preference. Then, they volunteered in an experiment during which their most liked and disliked brand names were visually presented while three different objective measures were taken. Participant's eye blinks as responses to acoustic startle probes were registered with electromyography (EMG) (i) and their skin conductance (ii) and their heart rate (iii) were recorded. We found significantly reduced eye blink amplitudes related to liked brand names compared to disliked brand names. This finding suggests that visual perception of liked brand names elicits higher degrees of pleasantness, more positive emotion and approach-oriented motivation than visual perception of disliked brand names. Also, skin conductance and heart rate were both reduced in case of liked versus disliked brand names. We conclude that all our physiological measures highlight emotion-related differences depending on the like and dislike toward individual brands. We suggest that objective measures should be used more frequently to quantify emotion-related aspects of brand attitude. In particular, there might be potential interest to introduce startle reflex modulation to measure emotion-related impact during product development, product design and various further fields relevant to marketing. Our findings are discussed in relation to the idea that self reported measures are most often cognitively polluted. PMID:22073192

Objective measures of emotion related to brand attitude: a new way to quantify emotion-related aspects relevant to marketing.

PubMed

Walla, Peter; Brenner, Gerhard; Koller, Monika

2011-01-01

With this study we wanted to test the hypothesis that individual like and dislike as occurring in relation to brand attitude can be objectively assessed. First, individuals rated common brands with respect to subjective preference. Then, they volunteered in an experiment during which their most liked and disliked brand names were visually presented while three different objective measures were taken. Participant's eye blinks as responses to acoustic startle probes were registered with electromyography (EMG) (i) and their skin conductance (ii) and their heart rate (iii) were recorded. We found significantly reduced eye blink amplitudes related to liked brand names compared to disliked brand names. This finding suggests that visual perception of liked brand names elicits higher degrees of pleasantness, more positive emotion and approach-oriented motivation than visual perception of disliked brand names. Also, skin conductance and heart rate were both reduced in case of liked versus disliked brand names. We conclude that all our physiological measures highlight emotion-related differences depending on the like and dislike toward individual brands. We suggest that objective measures should be used more frequently to quantify emotion-related aspects of brand attitude. In particular, there might be potential interest to introduce startle reflex modulation to measure emotion-related impact during product development, product design and various further fields relevant to marketing. Our findings are discussed in relation to the idea that self reported measures are most often cognitively polluted.

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.

Chronic stress increases pituitary adenylate cyclase-activating peptide (PACAP) and brain-derived neurotrophic factor (BDNF) mRNA expression in the bed nucleus of the stria terminalis (BNST): roles for PACAP in anxiety-like behavior

PubMed Central

Hammack, Sayamwong E.; Cheung, Joseph; Rhodes, Kimberly M.; Schutz, Kristin C.; Falls, William A.; Braas, Karen M.; May, Victor

2009-01-01

Exposure to chronic stress has been argued to produce maladaptive anxiety-like behavioral states, and many of the brain regions associated with stressor responding also mediate anxiety-like behavior. Pituitary adenylate cyclase activating polypeptide (PACAP) and its specific G protein-coupled PAC1 receptor have been associated with many of these stress- and anxiety-associated brain regions, and signaling via this peptidergic system may facilitate the neuroplasticity associated with pathological affective states. Here we investigated whether chronic stress increased transcript expression for PACAP, PAC1 receptor, brain-derived neurotrophic factor (BDNF), and tyrosine receptor kinase B (TrkB) in several nuclei. In rats exposed to a 7 day chronic variate stress paradigm, chronic stress enhanced baseline startle responding induced by handling and exposure to bright lights. Following chronic stress, quantitative transcript assessments of brain regions demonstrated dramatic increases in PACAP and PAC1 receptor, BDNF, and TrkB receptor mRNA expression selectively in the dorsal aspect of the anterolateral bed nucleus of the stria terminalis (dBNST). Related vasoactive intestinal peptide (VIP) and VPAC receptor, and other stress peptide transcript levels were not altered compared to controls. Moreover, acute PACAP38 infusion into the dBNST resulted in a robust dose-dependent anxiogenic response on baseline startle responding that persisted for 7 days. PACAP/PAC1 receptor signaling has established trophic functions and its coordinate effects with chronic stress-induced dBNST BDNF and TrkB transcript expression may underlie the maladaptive BNST remodeling and plasticity associated with anxiety-like behavior. PMID:19181454

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.

Event related desynchronization-modulated functional electrical stimulation system for stroke rehabilitation: a feasibility study.

PubMed

Takahashi, Mitsuru; Takeda, Kotaro; Otaka, Yohei; Osu, Rieko; Hanakawa, Takashi; Gouko, Manabu; Ito, Koji

2012-08-16

We developed an electroencephalogram-based brain computer interface system to modulate functional electrical stimulation (FES) to the affected tibialis anterior muscle in a stroke patient. The intensity of FES current increased in a stepwise manner when the event-related desynchronization (ERD) reflecting motor intent was continuously detected from the primary cortical motor area. We tested the feasibility of the ERD-modulated FES system in comparison with FES without ERD modulation. The stroke patient who presented with severe hemiparesis attempted to perform dorsiflexion of the paralyzed ankle during which FES was applied either with or without ERD modulation. After 20 minutes of training, the range of movement at the ankle joint and the electromyography amplitude of the affected tibialis anterior muscle were significantly increased following the ERD-modulated FES compared with the FES alone. The proposed rehabilitation technique using ERD-modulated FES for stroke patients was feasible. The system holds potentials to improve the limb function and to benefit stroke patients.

AX+/BX- Discrimination Learning in the Fear-Potentiated Startle Paradigm in Monkeys

ERIC Educational Resources Information Center

Winslow, James T.; Noble, Pamela L.; Davis, Michael

2008-01-01

Individuals with anxiety disorders often do not respond to safety signals and hence continue to be afraid and anxious. Consequently, it is important to develop paradigms in animals that can directly study brain systems involved in learning about, and responding to, safety signals. We previously developed a discrimination procedure in rats of the…

A College-Level Foundational Mathematics Course: Evaluation, Challenges, and Future Directions

ERIC Educational Resources Information Center

Maciejewski, Wes

2012-01-01

Recently in Ontario, Canada, the College Math Project brought to light startling data on the achievement of students in Ontario's College of Applied Arts and Technology System related to their performance in first-year mathematics courses: one-third of the students had failed their first-year mathematics course or were at risk of not completing…

Differing Effects of Systemically Administered Rapamycin on Consolidation and Reconsolidation of Context vs. Cued Fear Memories

ERIC Educational Resources Information Center

Glover, Ebony M.; Ressler, Kerry J.; Davis, Michael

2010-01-01

Rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR) kinase, has attracted interest as a possible prophylactic for post-traumatic stress disorder (PTSD)-associated fear memories. We report here that although rapamycin (40 mg/kg, i.p.) disrupted the consolidation and reconsolidation of fear-potentiated startle paradigm to a…

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.

Cannabinoids prevent the differential long-term effects of exposure to severe stress on hippocampal- and amygdala-dependent memory and plasticity.

PubMed

Shoshan, Noa; Segev, Amir; Abush, Hila; Mizrachi Zer-Aviv, Tomer; Akirav, Irit

2017-10-01

Exposure to excessive or uncontrolled stress is a major factor associated with various diseases including posttraumatic stress disorder (PTSD). The consequences of exposure to trauma are affected not only by aspects of the event itself, but also by the frequency and severity of trauma reminders. It was suggested that in PTSD, hippocampal-dependent memory is compromised while amygdala-dependent memory is strengthened. Several lines of evidence support the role of the endocannabinoid (eCB) system as a modulator of the stress response. In this study we aimed to examine cannabinoids modulation of the long-term effects (i.e., 1 month) of exposure to a traumatic event on memory and plasticity in the hippocampus and amygdala. Following exposure to the shock and reminders model of PTSD in an inhibitory avoidance light-dark apparatus rats demonstrated: (i) enhanced fear retrieval and impaired inhibitory extinction (Ext), (ii) no long-term potentiation (LTP) in the CA1, (iii) impaired hippocampal-dependent short-term memory in the object location task, (iv) enhanced LTP in the amygdala, and (v) enhanced amygdala-dependent conditioned taste aversion memory. The cannabinoid CB1/2 receptor agonist WIN55-212,2 (0.5mg/kg, i.p.) and the fatty acid amide hydrolase (FAAH) inhibitor URB597 (0.3mg/kg, i.p.), administered 2 hr after shock exposure prevented these opposing effects on hippocampal- and amygdala-dependent processes. Moreover, the effects of WIN55-212,2 and URB597 on Ext and acoustic startle were prevented by co-administration of a low dose of the CB1 receptor antagonist AM251 (0.5mg/kg, i.p.), suggesting that the preventing effects of both drugs are mediated by CB1 receptors. Exposure to shock and reminders increased CB1 receptor levels in the CA1 and basolateral amygdala 1 month after shock exposure and this increase was also prevented by administering WIN55-212,2 or URB597. Taken together, these findings suggest the involvement of the eCB system, and specifically CB1 receptors, in the opposite effects of severe stress on memory and plasticity in the hippocampus and amygdala. © 2017 Wiley Periodicals, Inc.

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.

Characterizing the Anomalous Cognition-Emotion Interactions in Externalizing

PubMed Central

Baskin-Sommers, Arielle R.; Curtin, John J.; Larson, Christine L.; Stout, Daniel; Kiehl, Kent A.; Newman, Joseph P.

2012-01-01

Externalizing traits are characterized by exaggerated emotional (e.g., frustration, anger) and behavioral (e.g., drug seeking, reactive aggression) reactions to motivationally-significant stimuli. Explanations for this exaggerated reactivity emphasize attention, executive function, and affective processes, but the associations among these processes is rarely investigated. To examine these interactions, we measure fear potentiated startle (FPS; Experiment 1) and neural activation (Experiment 2) in an instructed fear paradigm that manipulates attentional focus, demands on executive functioning, and emotion. In both studies, exaggerated emotional reactivity associated with externalizing was specific to conditions that focused attention on threat information and placed minimal demands on executive functioning. Results suggest that a crucial cognition-emotion interaction affecting externalizing is the over-prioritization and over-allocation of attention to motivationally-significant information, which in turn, may impair executive and affective regulation. PMID:22579718

Pharmacologic Treatment with GABAB Receptor Agonist of Methamphetamine-Induced Cognitive Impairment in Mice

PubMed Central

Mizoguchi, Hiroyuki; Yamada, Kiyofumi

2011-01-01

Methamphetamine (METH) is a highly addictive drug, and addiction to METH has increased to epidemic proportions worldwide. Chronic use of METH causes psychiatric symptoms, such as hallucinations and delusions, and long-term cognitive deficits, which are indistinguishable from paranoid schizophrenia. The GABA receptor system is known to play a significant role in modulating the dopaminergic neuronal system, which is related to behavioral changes induced by drug abuse. However, few studies have investigated the effects of GABA receptor agonists on cognitive deficits induced by METH. In the present review, we show that baclofen, a GABA receptor agonist, is effective in treating METH-induced impairment of object recognition memory and prepulse inhibition (PPI) of the startle reflex, a measure of sensorimotor gating in mice. Acute and repeated treatment with METH induced a significant impairment of PPI. Furthermore, repeated but not acute treatment of METH resulted in a long-lasting deficit of object recognition memory. Baclofen, a GABAB receptor agonist, dose-dependently ameliorated the METH-induced PPI deficits and object recognition memory impairment in mice. On the other hand, THIP, a GABAA receptor agonist, had no effect on METH-induced cognitive deficits. These results suggest that GABAB receptors may constitute a putative new target in treating cognitive deficits in chronic METH users. PMID:21886573

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.

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.

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.

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.

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.

Effects of Intra-Amygdala Infusion of CB1 Receptor Agonists on the Reconsolidation of Fear-Potentiated Startle

ERIC Educational Resources Information Center

Lin, Hui-Ching; Mao, Sheng-Chun; Gean, Po-Wu

2006-01-01

The cannabinoid CB1 receptor has been shown to be critically involved in the extinction of fear memory. Systemic injection of a CB1 receptor antagonist prior to extinction training blocked extinction. Conversely, administration of the cannabinoid uptake inhibitor AM404 facilitated extinction in a dose-dependent manner. Here we show that bilateral…

Testing the effects of Δ9-THC and D-cycloserine on extinction of conditioned fear in humans

PubMed Central

Klumpers, Floris; Denys, Damiaan; Kenemans, J Leon; Grillon, Christian; van der Aart, Jasper; Baas, Johanna MP

2012-01-01

Preclinical evidence implicates several neurotransmitter systems in the extinction of conditioned fear. These results are of great interest, because the reduction of acquired fear associations is critical in therapies for anxiety disorders. We tested whether findings with respect to the N-methyl-D-aspartate (NMDA) and cannabinoid receptor (CB) systems in animals carry over to healthy human subjects. To that end, we administered selected doses of D-cycloserine (partial NMDA receptor agonist, 250 mg), delta-9-tetrahydrocannabinol (THC, CB1 receptor agonist, 10 mg), or placebo prior to the extinction session of a 3-day conditioning protocol. D-cycloserine did not affect within-session extinction, or the retention of extinction in healthy human participants, in contrast with patient data but in line with previous reports in healthy volunteers. During extinction training, Δ9-THC reduced conditioned skin conductance responses, but not fear-potentiated startle. This effect was not retained at the retention test 2 days later, suggesting it was dependent on acute effects of the drug. Our findings implicate that facilitation of the CB1 or NMDA system with the substances used in this study does not affect conditioned fear extinction lastingly in healthy humans. The apparent discrepancy between these findings and the results from (pre-) clinical trials is discussed in terms of room for improvement in these systems in healthy volunteers, and the lack of specificity of THC as a CB1 agonist. PMID:22351380

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.

The nursing hypothesis: an evolutionary account of emotional modulation of the postauricular reflex.

PubMed

Johnson, Gabriella M; Valle-Inclán, Fernando; Geary, David C; Hackley, Steven A

2012-02-01

The postauricular reflex (PAR) is anomalous because it seems to be potentiated during positive emotions and inhibited during negative states, unlike eyeblink and other components of the startle reflex. Two evolutionary explanations based on simian facial emotion expressions were tested. Reflexes were elicited while 47 young adult volunteers made lip pursing or grimacing poses and viewed neutral, intimidating, or appetitive photos. The PAR was enhanced during appetitive slides, but only as subjects carried out the lip-pursing maneuver. These results support the nursing hypothesis, which assumes that infant mammals instinctively retract their pinnae while nursing in order to comfortably position the head. Appetitive emotions prime the ear-retraction musculature, even in higher primates whose postauricular muscles are vestigial. Copyright © 2011 Society for Psychophysiological Research.

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.

Environmental change during postnatal development alters behaviour, cognitions and neurogenesis of mice.

PubMed

Iso, Hiroyuki; Simoda, Shigero; Matsuyama, Tomohiro

2007-04-16

Four groups of male C57BL/6 mice were reared differing combinations of the two environments from 3 to 11 weeks after birth. At 12 and 13 weeks they were assessed by measures of behaviour and learning: open-field activity, auditory startle reflex and prepulse inhibition, water maze learning, and passive avoidance. Another four groups of mice reared under these varying conditions were examined for generation of neurons in hippocampus and cerebral cortex using bromodeoxyuridine (BrdU) at 12 weeks. Enriched (EE) and impoverished (PP) groups were housed in their respective environment for 8 weeks, enriched-impoverished (EP) and impoverished-enriched (PE) mice respectively were reared for 6 weeks in the first-mentioned environment and then for 2 weeks in the second. PP and EP mice showed hyperactivity, greater startle amplitude and significantly slower learning in a water maze than EE or PE animals, and also showed a memory deficit in a probe test, avoidance performance did not differ. Neural generation was greater in the EE and PE than PP and EP groups, especially in the hippocampus. These results suggest that environmental change critically affects behavioural and anatomic brain development, even if brief. In these mice, the effect of unfavourable early experience could be reversed by a later short of favourable experience.

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

Developmental exposure to methimazole increases anxiety behavior in zebrafish.

PubMed

Reider, Masha; Connaughton, Victoria P

2015-10-01

The role of thyroid hormones in vertebrate development has been well documented for several decades. As hypothyroidism during critical periods of development can cause defects to the development of every major organ system, including brain, eye, and general morphology, we hypothesized that hypothyroidism would affect specific behaviors. To assess this, we treated zebrafish with the hypothyroid drug methimazole (MMI) and examined changes in anxiety, shoaling, vision, and locomotion. Following low-dose MMI exposure for the first 10 days of life, a time of rapid and significant development, larvae were removed from treatment and allowed to develop until 1 month of age. Comparisons between treated and controls took place between 10 and 30 days postfertilization to examine times both during and after treatment. Using the novel tank and startle response tests, we found that anxiety behaviors are significantly increased following MMI treatment. These effects persisted for several days following removal from treatment and indicate a prolonged effect of early hypothyroidism. However, permanent MMI effects on anxiety were not observed, as anxiety behaviors of early treated zebrafish recovered to control levels following 10 days out of treatment. In contrast to the strong link between MMI treatment and anxiety, shoaling and visual behaviors were not significantly affected within our experimental parameters. This indicates that disruption of thyroid system functioning early in life can differentially affect behavior by specifically altering anxiety responses without producing indiscriminate changes to overall behavioral development. (c) 2015 APA, all rights reserved).

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.

Time-dependent effects of rapamycin on consolidation of predator stress-induced hyperarousal.

PubMed

Fifield, Kathleen; Hebert, Mark; Williams, Kimberly; Linehan, Victoria; Whiteman, Jesse D; Mac Callum, Phillip; Blundell, Jacqueline

2015-06-01

Previous studies have indicated that rapamycin, a potent inhibitor of the mammalian target of rapamycin (mTOR) pathway, blocks consolidation of shock-induced associative fear memories. Moreover, rapamycin's block of associative fear memories is time-dependent. It is unknown, however, if rapamycin blocks consolidation of predator stress-induced non-associative fear memories. Furthermore, the temporal pattern of mTOR activation following predator stress is unknown. Thus, the goal of the current studies was to determine if rapamycin blocks consolidation of predator stress-induced fear memories and if so, whether rapamycin's effect is time-dependent. Male rats were injected systemically with rapamycin at various time points following predator stress. Predator stress involves an acute, unprotected exposure of a rat to a cat, which causes long-lasting non-associative fear memories manifested as generalized hyperarousal and increased anxiety-like behaviour. We show that rapamycin injected immediately after predator stress blocked consolidation of stress-induced startle. However, rapamycin injected 9, 24 or 48h post predator stress potentiated stress-induced startle. Consistent with shock-induced associative fear memories, we show that mTOR signalling is essential for consolidation of predator stress-induced hyperarousal. However, unlike shock-induced fear memories, a second, persistent, late phase mTOR-dependent process following predator stress actually dampens startle. Consistent with previous findings, our data support the potential role for rapamycin in treatment of stress related disorders such as posttraumatic stress disorder. However, our data suggest timing of rapamycin administration is critical. Copyright © 2015 Elsevier B.V. All rights reserved.

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

Contextual-specificity of short-delay extinction in humans: Renewal of fear-potentiated startle in a virtual environment

PubMed Central

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 by examining the context specificity of short-delay extinction in an ABA renewal procedure using virtual reality environments. A second objective was to examine whether renewal, if any, would be influenced by context conditioning. Subjects underwent differential aversive conditioning in virtual context A, which was immediately followed by extinction in virtual context B. Extinction was followed by tests of renewal in context A and B, with the order counterbalanced across subjects. Results showed that extinction was context dependent. Evidence for renewal was established using fear-potentiated startle as well as skin conductance and fear ratings. In addition, although contextual anxiety was greater in the acquisition context than in the extinction context during renewal, as assessed with startle, context conditioning did not influence the renewal effect. These data do not support the view that extinction conducted shortly after acquisition is context independent. Hence, they do not provide evidence that extinction can lead to erasure of a fear memory established via Pavlovian conditioning. PMID:17412963

Partial Genetic Deletion of Neuregulin 1 Modulates the Effects of Stress on Sensorimotor Gating, Dendritic Morphology, and HPA Axis Activity in Adolescent Mice

PubMed Central

Chohan, Tariq W.; Boucher, Aurelie A.; Spencer, Jarrah R.; Kassem, Mustafa S.; Hamdi, Areeg A.; Karl, Tim; Fok, Sandra Y.; Bennett, Maxwell R.; Arnold, Jonathon C.

2014-01-01

Stress has been linked to the pathogenesis of schizophrenia. Genetic variation in neuregulin 1 (NRG1) increases the risk of developing schizophrenia and may help predict which high-risk individuals will transition to psychosis. NRG1 also modulates sensorimotor gating, a schizophrenia endophenotype. We used an animal model to demonstrate that partial genetic deletion of Nrg1 interacts with stress to promote neurobehavioral deficits of relevance to schizophrenia. Nrg1 heterozygous (HET) mice displayed greater acute stress-induced anxiety-related behavior than wild-type (WT) mice. Repeated stress in adolescence disrupted the normal development of higher prepulse inhibition of startle selectively in Nrg1 HET mice but not in WT mice. Further, repeated stress increased dendritic spine density in pyramidal neurons of the medial prefrontal cortex (mPFC) selectively in Nrg1 HET mice. Partial genetic deletion of Nrg1 also modulated the adaptive response of the hypothalamic-pituitary-adrenal axis to repeated stress, with Nrg1 HET displaying a reduced repeated stress-induced level of plasma corticosterone than WT mice. Our results demonstrate that Nrg1 confers vulnerability to repeated stress-induced sensorimotor gating deficits, dendritic spine growth in the mPFC, and an abberant endocrine response in adolescence. PMID:24442851

Contrasting effect of prepulse signals on performance of Toxoplasma-infected and Toxoplasma-free subjects in an acoustic reaction times test.

PubMed

Příplatová, Lenka; Sebánková, Blanka; Flegr, Jaroslav

2014-01-01

About 30% of people on Earth have latent toxoplasmosis. Infected subjects do not express any clinical symptoms, however, they carry dormant stages of parasite Toxoplasma for the rest of their life. This form of toxoplasmosis is mostly considered harmless, however, recent studies showed its specific effects on physiology, behaviour and its associations with various diseases, including psychiatric disorders such as schizophrenia. Individuals who suffer from schizophrenia have about 2.7 times higher prevalence of Toxoplasma-seropositivity than controls, which suggests that some traits characteristic of schizophrenic patients, including the sex difference in schizophrenia onset, decrease of grey matter density in specific brain areas and modification of prepulse inhibition of startle reaction could in fact be caused by toxoplasmosis for those patients who are Toxoplasma-seropositive. We measured the effect of prepulse inhibition/facilitation of the startle reaction on reaction times. The students, 170 women and 66 men, were asked to react as quickly as possible to a startling acoustic signal by pressing a computer mouse button. Some of the startling signals were without the prepulse, some were 20 msec. preceded by a short (20 msec.) prepulse signal of lower intensity. Toxoplasma-seropositive subjects had longer reaction times than the controls. Acoustic prepulse shorted the reaction times in all subjects. This effect of prepulse on reaction times was stronger in male subjects and increased with the duration of infection, suggesting that it represented a cumulative effect of latent toxoplasmosis, rather than a fading out after effect of past acute toxoplasmosis. Different sensitivity of Toxoplasma-seropositive and Toxoplasma-seronegative subjects on effect of prepulses on reaction times (the toxoplasmosis-prepulse interaction) suggested, but of course did not prove, that the alternations of prepulse inhibition of startle reaction observed in schizophrenia patients probably joined the list of schizophrenia symptoms that are in fact caused by latent toxoplasmosis.

Cortical and reticular contributions to human precision and power grip.

PubMed

Tazoe, Toshiki; Perez, Monica A

2017-04-15

The corticospinal tract contributes to the control of finger muscles during precision and power grip. We explored the neural mechanisms contributing to changes in corticospinal excitability during these gripping configurations. Motor evoked potentials (MEPs) elicited by cortical, but not by subcortical, stimulation were more suppressed during power grip compared with precision grip and index finger abduction. Intracortical inhibition was more reduced during power grip compared with the other tasks. An acoustic startle cue, a stimulus that engages the reticular system, suppressed MEP size during power grip to a lesser extent than during the other tasks at a cortical level and this positively correlated with changes in intracortical inhibition. Our findings suggest that changes in corticospinal excitability during gross more than fine finger manipulations are largely cortical in origin and that the reticular system contributed, at least in part, to these effects. It is well accepted that the corticospinal tract contributes to the control of finger muscles during precision and power grip in humans but the neural mechanisms involved remain poorly understood. Here, we examined motor evoked potentials elicited by cortical and subcortical stimulation of corticospinal axons (MEPs and CMEPs, respectively) and the activity in intracortical circuits (suppression of voluntary electromyography) and spinal motoneurons (F-waves) in an intrinsic hand muscle during index finger abduction, precision grip and power grip. We found that the size of MEPs, but not CMEPs, was more suppressed during power grip compared with precision grip and index finger abduction, suggesting a cortical origin for these effects. Notably, intracortical inhibition was more reduced during power grip compared with the other tasks. To further examine the origin of changes in intracortical inhibition we assessed the contribution of the reticular system, which projects to cortical neurons, and projects to spinal motoneurons controlling hand muscles. An acoustic startle cue, which engages the reticular system, suppressed MEP size during power grip to a lesser extent than during the other tasks and this positively correlated with changes in intracortical inhibition. A startle cue decreased intracortical inhibition, but not CMEPs, during power grip. F-waves remained unchanged across conditions. Our novel findings show that changes in corticospinal excitability present during power grip compared with fine finger manipulations are largely cortical in origin and suggest that the reticular system contributed, at least in part, to these effects. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Disrupting Jagged1-Notch signaling impairs spatial memory formation in adult mice.

PubMed

Sargin, Derya; Botly, Leigh C P; Higgs, Gemma; Marsolais, Alexander; Frankland, Paul W; Egan, Sean E; Josselyn, Sheena A

2013-07-01

It is well-known that Notch signaling plays a critical role in brain development and growing evidence implicates this signaling pathway in adult synaptic plasticity and memory formation. The Notch1 receptor is activated by two subclasses of ligands, Delta-like (including Dll1 and Dll4) and Jagged (including Jag1 and Jag2). Ligand-induced Notch1 receptor signaling is modulated by a family of Fringe proteins, including Lunatic fringe (Lfng). Although Dll1, Jag1 and Lfng are critical regulators of Notch signaling, their relative contribution to memory formation in the adult brain is unknown. To investigate the roles of these important components of Notch signaling in memory formation, we examined spatial and fear memory formation in adult mice with reduced expression of Dll1, Jag1, Lfng and Dll1 plus Lfng. We also examined motor activity, anxiety-like behavior and sensorimotor gating using the acoustic startle response in these mice. Of the lines of mutant mice tested, we found that only mice with reduced Jag1 expression (mice heterozygous for a null mutation in Jag1, Jag1(+/-)) showed a selective impairment in spatial memory formation. Importantly, all other behavior including open field activity, conditioned fear memory (both context and discrete cue), acoustic startle response and prepulse inhibition, was normal in this line of mice. These results provide the first in vivo evidence that Jag1-Notch signaling is critical for memory formation in the adult brain. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

The effect of intranasal oxytocin treatment on conditioned fear extinction and recall in a healthy human sample.

PubMed

Acheson, Dean; Feifel, David; de Wilde, Sofieke; McKinney, Rebecca; Lohr, James; Risbrough, Victoria

2013-09-01

To improve outcomes for patients undergoing extinction-based therapies (e.g., exposure therapy) for anxiety disorders such as post-traumatic stress disorder (PTSD), there has been interest in identifying pharmaceutical compounds that might facilitate fear extinction learning and recall. Oxytocin (OT) is a mammalian neuropeptide that modulates activation of fear extinction-based neural circuits and fear responses. Little is known, however, about the effects of OT treatment on conditioned fear responding and extinction in humans. The purpose of the present study was to assess the effects of OT in a fear-potentiated startle task of fear conditioning and extinction. A double-blind, placebo-controlled study of 44 healthy human participants was conducted. Participants underwent a conditioned fear acquisition procedure, after which they were randomized to treatment group and delivered OT (24 IU) or placebo via intranasal (IN) spray. Forty-five minutes after treatment, participants underwent extinction training. Twenty-four hours later, subjects were tested for extinction recall. Relative to placebo, the OT group showed increased fear-potentiated startle responding during the earliest stage of extinction training relative to placebo; however, all treatment groups showed the same level of reduced responding by the end of extinction training. Twenty-four hours later, the OT group showed significantly higher recall of extinction relative to placebo. The current study provides preliminary evidence that OT may facilitate fear extinction recall in humans. These results support further study of OT as a potential adjunctive treatment for extinction-based therapies in fear-related disorders.

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

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

DTIC Science & Technology

2010-09-01

physiopathologies of PTSD . The effect of oxytocin on background anxiety in our fear- potentiated startle studies in rats is also reminiscent of the findings... fMRI Study . CNS Neurosci Ther, print copy in press (originally published online 16 April 2010, at http://www3. interscience.wiley.com/journal...specific fear, but are sustained beyond the immediate threat. Oxytocin might be promising as a drug with novel benefits for patients with PTSD . 15

One-trial overshadowing: Evidence for fast specific fear learning in humans.

PubMed

Haesen, Kim; Beckers, Tom; Baeyens, Frank; Vervliet, Bram

2017-03-01

Adaptive defensive actions necessitate a fear learning system that is both fast and specific. Fast learning serves to minimize the number of threat confrontations, while specific learning ensures that the acquired fears are tied to threat-relevant cues only. In Pavlovian fear conditioning, fear acquisition is typically studied via repetitive pairings of a single cue with an aversive experience, which is not optimal for the examination of fast specific fear learning. In this study, we adopted the one-trial overshadowing procedure from basic learning research, in which a combination of two visual cues is presented once and paired with an aversive electrical stimulation. Using on-line shock expectancy ratings, skin conductance reactivity and startle reflex modulation as indices of fear learning, we found evidence of strong fear after a single conditioning trial (fast learning) as well as attenuated fear responding when only half of the trained stimulus combination was presented (specific learning). Moreover, specificity of fear responding tended to correlate with levels of state and trait anxiety. These results suggest that one-trial overshadowing can be used as a model to study fast specific fear learning in humans and individual differences therein. Copyright © 2016 Elsevier Ltd. All rights reserved.

Preclinical evaluation of the antipsychotic potential of the mGlu2-positive allosteric modulator JNJ-40411813

PubMed Central

Lavreysen, Hilde; Langlois, Xavier; Donck, Luc Ver; Nuñez, José María Cid; Pype, Stefan; Lütjens, Robert; Megens, Anton

2015-01-01

JNJ-40411813/ADX71149 (1-butyl-3-chloro-4-(4-phenylpiperidin-1-yl) pyridin-2(1H)-one) is a positive allosteric modulator (PAM) of the mGlu2 receptor, which also displays 5-Hydroxytryptamine (5HT2A) antagonism after administration in rodents due to a rodent-specific metabolite. JNJ-40411813 was compared with the orthosteric mGlu2/3 agonist LY404039 (4-amino-2-thiabicyclo [3.1.0] hexane-4,6-dicarboxylic acid 2,2-dioxide), the selective mGlu2 PAM JNJ-42153605 (3-(cyclopropylmethyl)-7-(4-phenylpiperidin-1-yl)-8-(trifluoromethyl)[1,2,4]triazolo[4,3-a]pyridine) and the 5HT2A antagonist ritanserin in rodent models for antipsychotic activity and potential side effects, attempting to differentiate between the various compounds and mechanisms of action. In mice, JNJ-40411813, JNJ-42153605, and LY404039 inhibited spontaneous locomotion and phencyclidine- and scopolamine-induced but not d-amphetamine-induced hyperlocomotion; the 5HT2A antagonist ritanserin inhibited only spontaneous locomotion and phencyclidine-induced hyperlocomotion. As measured by 2-deoxyglucose uptake, all compounds reversed memantine-induced brain activation in mice. The two mGlu2 PAMs and LY404039, but not ritanserin, inhibited conditioned avoidance behavior in rats. Like ritanserin, the mGlu2 ligands antagonized 2,5-dimethoxy-4-methylamphetamine-induced head twitches in rats. LY404039 but not the mGlu2 PAMs impaired rotarod performance in rats and increased the acoustic startle response in mice. Our results show that although 5HT2A antagonism has effect in some models, mGlu2 receptor activation is sufficient for activity in several animal models of antipsychotic activity. The mGlu2 PAMs mimicked the in vivo pharmacodynamic effects observed with LY404039 except for effects on the rotarod and acoustic startle, suggesting that they produce a primary activity profile similar to that of the mGlu2/3 receptor agonist while they can be differentiated based on their secondary activity profile. The results are discussed in light of clinical data available for some of these molecules, in particular JNJ-40411813. PMID:25692027

Retrieval per se is not sufficient to trigger reconsolidation of human fear memory.

PubMed

Sevenster, Dieuwke; Beckers, Tom; Kindt, Merel

2012-03-01

Ample evidence suggests that consolidated memories, upon their retrieval, enter a labile state, in which they might be susceptible to change. It has been proposed that memory labilization allows for the integration of relevant information in the established memory trace (memory updating). Memory labilization and reconsolidation do not necessarily occur when a memory is being reactivated, but only when there is something to be learned during memory retrieval (prediction error). Thus, updating of a fear memory trace should not occur under retrieval conditions in which the outcome is fully predictable (no prediction error). Here, we addressed this issue, using a human differential fear conditioning procedure, by eliminating the very possibility of reinforcement of the reminder cue. A previously established fear memory (picture-shock pairings) was reactivated with shock-electrodes attached (Propranolol group, n=18) or unattached (Propranolol No-Shock Expectation group, n=19). We additionally tested a placebo-control group with the shock-electrodes attached (Placebo group, n=18). Reconsolidation was not triggered when nothing could be learned during the reminder trial, as noradrenergic blockade did not affect expression of the fear memory 24h later in the Propranolol No-Shock Expectation group. Only when the outcome of the retrieval cue was not fully predictable, propranolol, contrary to placebo, reduced the startle fear response and prevented the return of fear (reinstatement) the following day. In line with previous studies, skin conductance response and shock expectancies were not affected by propranolol. Remarkably, a double dissociation emerged between the emotional (startle response) and more cognitive expression (expectancies, SCR) of the fear memory. Our findings have important implications for reconsolidation blockade as treatment strategy for emotional disorders. First, fear reducing procedures that target the emotional component of fear memory do not necessarily affect the cognitive component and vice versa. Second, mere retrieval of the fear memory is not sufficient to induce its labilization and reconsolidation. Copyright © 2012 Elsevier Inc. All rights reserved.

Boron deprivation alters rat behaviour and brain mineral composition differently when fish oil instead of safflower oil is the diet fat source.

PubMed

Nielsen, Forrest H; Penland, James G

2006-01-01

To determine whether boron deprivation affects rat behaviour and whether behavioural responses to boron deprivation are modified by differing amounts of dietary long-chain omega-3 fatty acids. Female rats were fed diets containing 0.1 mg (9 micromol)/kg boron in a factorial arrangement with dietary variables of supplemental boron at 0 and 3mg (278 micromol)/kg and fat sources of 75 g/kg safflower oil or 65 g/kg fish (menhaden) oil plus 10 g/kg linoleic acid. After 6 weeks, six females per treatment were bred. Dams and pups continued on their respective diets through gestation, lactation and after weaning. Between ages 6 and 20 weeks, behavioural tests were performed on 13-15 male offspring from three dams in each dietary treatment. The rats were euthanized at age 21 weeks for the collection of tissues and blood. At ages 6 and 19 weeks, auditory startle was evaluated with an acoustic startle system and avoidance behaviour was evaluated by using an elevated plus maze. At ages 7 and 20 weeks, spontaneous behaviour activity was evaluated with a photobeam activity system. A brightness discrimination test was performed on the rats between age 15 and 16 weeks. Brain mineral composition was determined by coupled argon plasma atomic emission spectroscopy. Plasma total glutathione was determined by HPLC and total cholesterol and 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) were determined by using commercially available kits. Boron-deficient rats were less active than boron-adequate rats when fed safflower oil based on reduced number, distance and time of horizontal movements, front entries, margin distance and vertical breaks and jumps in the spontaneous activity evaluation. Feeding fish oil instead of safflower oil attenuated the activity response to boron deprivation. In the plus maze evaluation, the behavioural reactivity of the boron-deficient rats fed fish oil was noticeably different than the other three treatments. They made more entries into both open and closed arms and the center area and thus visited more locations. The boron-deficient rats fed fish oil also exhibited the lowest copper and zinc and highest boron concentrations in brain and the highest plasma glutathione concentration. Both boron deprivation and safflower oil increased plasma 8-iso-PGF2alpha. Both dietary boron and long-chain omega-3 fatty acids influence rat behaviour and brain composition and the influence of one these bioactive substances can be altered by changing the intake of the other. Brain mineral and plasma cholesterol, glutathione and 8-iso-PGF2alpha findings suggest that rat behaviour is affected by an interaction between boron and fish oil because both affect oxidative metabolism and act the cellular membrane level.

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.

The Hidden Side of Zero Tolerance Policies: The African American Perspective

PubMed Central

Bell, Charles

2015-01-01

Several papers have documented the disproportionate representation of African Americans in school discipline and incarceration settings as a result of zero tolerance policies. In 2009, a federal study of the Chicago Public School system found African American boys represented 23 percent of the school age population, 44 percent of students who were suspended, and 61 percent of students who were expelled within the 2007 school year. Twenty years after the implementation of the Anti-Drug Abuse Acts of 1986 and 1988, studies show African Americans comprised a startling 74 percent of those incarcerated for drug offenses despite being only 15 percent of America’s drug users. Despite overwhelming evidence that suggests African Americans are adversely affected by zero tolerance policies, African American perceptions of zero tolerance policies remain relatively hidden in the literature. The current review seeks to explore a seemingly bidirectional process that involves how zero tolerance impacts African Americans and how African Americans perceive zero tolerance policies. PMID:25893006

How should the psychological well-being of zoo elephants be objectively investigated?

PubMed

Mason, Georgia J; Veasey, Jake S

2010-01-01

Animal welfare (sometimes termed "well-being") is about feelings - states such as "suffering" or "contentment" that we can infer but cannot measure directly. Welfare indices have been developed from two main sources: studies of suffering humans, and of research animals deliberately subjected to challenges known to affect emotional state. We briefly review the resulting indices here, and discuss how well they are understood for elephants, since objective welfare assessment should play a central role in evidence-based elephant management. We cover behavioral and cognitive responses (approach/avoidance; intention, redirected and displacement activities; vigilance/startle; warning signals; cognitive biases, apathy and depression-like changes; stereotypic behavior); physiological responses (sympathetic responses; corticosteroid output - often assayed non-invasively via urine, feces or even hair; other aspects of HPA function, e.g. adrenal hypertrophy); and the potential negative effects of prolonged stress on reproduction (e.g. reduced gametogenesis; low libido; elevated still-birth rates; poor maternal care) and health (e.g. poor wound-healing; enhanced disease rates; shortened lifespans). The best validated, most used welfare indices for elephants are corticosteroid outputs and stereotypic behavior. Indices suggested as valid, partially validated, and/or validated but not yet applied within zoos include: measures of preference/avoidance; displacement movements; vocal/postural signals of affective (emotional) state; startle/vigilance; apathy; salivary and urinary epinephrine; female acyclity; infant mortality rates; skin/foot infections; cardio-vascular disease; and premature adult death. Potentially useful indices that have not yet attracted any validation work in elephants include: operant responding and place preference tests; intention and vacuum movements; fear/stress pheromone release; cognitive biases; heart rate, pupil dilation and blood pressure; corticosteroid assay from hair, especially tail-hairs (to access endocrine events up to a year ago); adrenal hypertrophy; male infertility; prolactinemia; and immunological changes.

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.

Methylphenidate and emotional-motivational processing in attention-deficit/hyperactivity disorder.

PubMed

Conzelmann, Annette; Woidich, Eva; Mucha, Ronald F; Weyers, Peter; Müller, Mathias; Lesch, Klaus-Peter; Jacob, Christian P; Pauli, Paul

2016-08-01

In line with the assumption that emotional-motivational deficits are one core dysfunction in ADHD, in one of our previous studies we observed a reduced reactivity towards pleasant pictures in adult ADHD patients as compared to controls. This was indicated by a lack of attenuation of the startle reflex specifically during pleasant pictures in ADHD patients. The first choice medical agents in ADHD, methylphenidate (MPH), is discussed to normalize these dysfunctions. However, experimental evidence in the sense of double-blind placebo-controlled study designs is lacking. Therefore, we investigated 61 adult ADHD patients twice, one time with placebo and one time with MPH with the same experimental design as in our study previously and assessed emotion processing during the presentation of pleasant, neutral and unpleasant pictures. We obtained startle reflex data as well as valence and arousal ratings in association with the pictures. As previously shown, ADHD patients showed a diminished startle attenuation during pleasant pictures while startle potentiation during unpleasant pictures was normal. Valence and arousal ratings unsuspiciously increased with increasing pleasantness and arousal of the pictures, respectively. There were no significant influences of MPH. The study replicates that ADHD patients show a reduced reactivity towards pleasant stimuli. MPH did not normalize this dysfunction. Possibly, MPH only influences emotions during more complex behavioural tasks that involve executive functions in adults with ADHD. Our results emphasize the importance for the use of double-blind placebo-controlled designs in psychopharmacological research.

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.

Harm avoidance in adolescents modulates late positive potentials during affective picture processing.

PubMed

Zhang, Wenhai; Lu, Jiamei; Ni, Ziyin; Liu, Xia; Wang, Dahua; Shen, Jiliang

2013-08-01

Research in adults has shown that individual differences in harm avoidance (HA) modulate electrophysiological responses to affective stimuli. To determine whether HA in adolescents modulates affective information processing, we collected event-related potentials from 70 adolescents while they viewed 90 pictures from the Chinese affective picture system. Multiple regressions revealed that HA negatively predicted late positive potential (LPP) for positive pictures and positively predicted for negative pictures; however, HA did not correlate with LPP for neutral pictures. The results suggest that at the late evaluative stage, high-HA adolescents display attentional bias to negative pictures while low-HA adolescents display attentional bias to negative pictures. Moreover, these dissociable attentional patterns imply that individual differences in adolescents' HA modulate the late selective attention mechanism of affective information. Copyright © 2013. Published by Elsevier Ltd.

Design of Measure and Control System for Precision Pesticide Deploying Dynamic Simulating Device

NASA Astrophysics Data System (ADS)

Liang, Yong; Liu, Pingzeng; Wang, Lu; Liu, Jiping; Wang, Lang; Han, Lei; Yang, Xinxin

A measure and control system for precision deploying pesticide simulating equipment is designed in order to study pesticide deployment technology. The system can simulate every state of practical pesticide deployment, and carry through precise, simultaneous measure to every factor affecting pesticide deployment effects. The hardware and software incorporates a structural design of modularization. The system is divided into many different function modules of hardware and software, and exploder corresponding modules. The modules’ interfaces are uniformly defined, which is convenient for module connection, enhancement of system’s universality, explodes efficiency and systemic reliability, and make the program’s characteristics easily extended and easy maintained. Some relevant hardware and software modules can be adapted to other measures and control systems easily. The paper introduces the design of special numeric control system, the main module of information acquisition system and the speed acquisition module in order to explain the design process of the module.

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

Models and mechanisms of anxiety: evidence from startle studies

PubMed Central

Grillon, Christian

2009-01-01

Rationale Preclinical data indicates that threat stimuli elicit two classes of defensive behaviors, those that are associated with imminent danger and are characterized by avoidance or fight (fear), and those that are associated with temporally uncertain danger and are characterized by sustained apprehension and hypervigilance (anxiety). Objective To 1) review evidence for a distinction between fear and anxiety in animal and human experimental models using the startle reflex as an operational measure of aversive states, 2) describe experimental models of anxiety, as opposed to fear, in humans, 3) examine the relevance of these models to clinical anxiety. Results The distinction between phasic fear to imminent threat and sustained anxiety to temporally uncertain danger is suggested by psychopharmacological and behavioral evidence from ethological studies and can be traced back to distinct neuroanatomical systems, the amygdala and the bed nucleus of the stria terminalis. Experimental models of anxiety, not fear, are relevant to non-phobic anxiety disorders. Conclusions Progress in our understanding of normal and abnormal anxiety is critically dependent on our ability to model sustained aversive states to temporally uncertain threat. PMID:18058089

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.

Medial prefrontal cortex serotonergic and GABAergic mechanisms modulate the expression of contextual fear: intratelencephalic pathways and differential involvement of cortical subregions.

PubMed

Almada, R C; Coimbra, N C; Brandão, M L

2015-01-22

Several lines of evidence indicate that the dorsal hippocampus (dH) and medial prefrontal cortex (mPFC) regulate contextual fear conditioning. The prelimbic (PrL), infralimbic (IL) and the anterior cingulate cortex (ACC) subregions of the mPFC likely play distinct roles in the expression of fear. Moreover, studies have highlighted the role of serotonin (5-hydroxytryptamine, 5-HT)- and γ-aminobutyric acid (GABA)-mediated mechanisms in the modulation of innate fear in the mPFC. The present study characterized dH-mPFC pathways and investigated the role of serotonergic and GABAergic mechanisms of the PrL, IL and ACC-area 1 (Cg1) in the elaboration of contextual fear conditioning using fear-potentiated startle (FPS) and freezing behavior in Rattus norvegicus. The results of neurotracing with microinjections of biotinylated dextran amine into the dH revealed a neural link of the dH with the PrL and ACC. Intra-PrL injections of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) and the GABAA receptor-selective agonist muscimol reduced contextual FPS and freezing responses. Intra-Cg1 injections of muscimol but not 8-OH-DPAT decreased FPS and freezing responses. However, neither intra-IL injections of a 5-HT1A agonist nor of a GABAA agonist affected these defensive responses. Labeled neuronal fibers from the dH reached the superficial layers of the PrL cortex and spread to the inner layers of PrL and Cg1 cortices, supporting the pharmacological findings. The present results confirmed the involvement of PrL and Cg1 in the expression of FPS and freezing responses to aversive conditions. In addition, PrL serotoninergic mechanisms play a key role in contextual fear conditioning. This study suggests that PrL, IL and Cg1 distinctively contribute to the modulation of contextual fear conditioning. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

GLAST Deficiency in Mice Exacerbates Gap Detection Deficits in a Model of Salicylate-Induced Tinnitus.

PubMed

Yu, Hong; Vikhe Patil, Kim; Han, Chul; Fabella, Brian; Canlon, Barbara; Someya, Shinichi; Cederroth, Christopher R

2016-01-01

Gap detection or gap pre-pulse inhibition of the acoustic startle (GPIAS) has been successfully used in rat and guinea pig models of tinnitus, yet this system has been proven to have low efficacy in CBA mice, with low basal GPIAS and subtle tinnitus-like effects. Here, we tested five mouse strains (CBA, BalbC, CD-1, C57BL/6 and 129sv) for pre-pulse inhibition (PPI) and gap detection with varying interstimulus intervals (ISI) and found that mice from a CBA genetic background had the poorest capacities of suppressing the startle response in the presence of a pre-pulse or a gap. CD-1 mice displayed variable responses throughout all ISI. Interestingly, C57BL/6, 129sv and BalbC showed efficient suppression with either pre-pulses or gaps with shorter ISI. The glutamate aspartate transporter (GLAST) is expressed in support cells from the cochlea and buffers the excess of glutamate. We hypothesized that loss of GLAST function could sensitize the ear to tinnitus-inducing agents, such as salicylate. Using shorter ISI to obtain a greater dynamic range to assess tinnitus-like effects, we found that disruption of gap detection by salicylate was exacerbated across various intensities of a 32-kHz narrow band noise gap carrier in GLAST knockout (KO) mice when compared to their wild-type (WT) littermates. Auditory brainstem responses (ABR) and distortion-product otoacoustic emission (DPOAE) were performed to evaluate the effects on hearing functions. Salicylate caused greater auditory threshold shifts (near 15 dB) in GLAST KO mice than in WT mice across all tested frequencies, despite similarly reduced DPOAE. Despite these changes, inhibition using broad-band gap carriers and 32 kHz pre-pulses were not affected. Our study suggests that GLAST deficiency could become a useful experimental model to decipher the mechanisms underlying drug-induced tinnitus. Future studies addressing the neurological correlates of tinnitus in this model could provide additional insights into the mechanisms of tinnitus.

New definitions of 6 clinical signs of perceptual disorder in children with cerebral palsy: an observational study through reliability measures.

PubMed

Ferrari, A; Sghedoni, A; Alboresi, S; Pedroni, E; Lombardi, F

2014-12-01

Recently authors have begun to emphasize the non-motor aspects of Cerebral Palsy and their influence on motor control and recovery prognosis. Much has been written about single clinical signs (i.e., startle reaction) but so far no definitions of the six perceptual signs presented in this study have appeared in literature. This study defines 6 signs (startle reaction, upper limbs in startle position, frequent eye blinking, posture freezing, averted eye gaze, grimacing) suggestive of perceptual disorders in children with cerebral palsy and measures agreement on sign recognition among independent observers and consistency of opinions over time. Observational study with both cross-sectional and prospective components. Fifty-six videos presented to observers in random order. Videos were taken from 19 children with a bilateral form of cerebral palsy referred to the Children Rehabilitation Unit in Reggio Emilia. Thirty-five rehabilitation professionals from all over Italy: 9 doctors and 26 physiotherapists. Measure of agreement among 35 independent observers was compiled from a sample of 56 videos. Interobserver reliability was determined using the K index of Fleiss and reliability intra-observer was calculated by the Spearman correlation index between ranks (rho - ρ). Percentage of agreement between observers and Gold Standard was used as criterion validity. Interobserver reliability was moderate for startle reaction, upper limb in startle position, adverted eye gaze and eye-blinking and fair for posture freezing and grimacing. Intraobserver reliability remained consistent over time. Criterion validity revealed very high agreement between independent observer evaluation and gold standard. Semiotics of perceptual disorders can be used as a specific and sensitive instrument in order to identify a new class of patients within existing heterogeneous clinical types of bilateral cerebral palsy forms and could help clinicians in identifying functional prognosis. To provide clinicians with a definition of 6 clinical signs found in children with cerebral palsy in routine rehabilitation settings. Future research should explore the link between these signs and motor prognosis (i.e., time to independent walking).

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

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.

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

Cognitive mechanisms of diazepam administration: a healthy volunteer model of emotional processing.

PubMed

Pringle, A; Warren, M; Gottwald, J; Cowen, P J; Harmer, C J

2016-06-01

Benzodiazepine drugs continue to be prescribed relatively frequently for anxiety disorders, especially where other treatments have failed or when rapid alleviation of anxiety is imperative. The neuropsychological mechanism by which these drugs act to relieve symptoms, however, remains underspecified. Cognitive accounts of anxiety disorders emphasise hypervigilance for threat in the maintenance of the disorders. The current study examined the effects of 7- or 8-day administration of diazepam in healthy participants (n = 36) on a well-validated battery of tasks measuring emotional processing, including measures of vigilance for threat and physiological responses to threat. Compared to placebo, diazepam reduced vigilant-avoidant patterns of emotional attention (p < 0.01) and reduced general startle responses (p < .05). Diazepam administration had limited effects on emotional processing, enhancing the response to positive vs negative words in the emotional categorisation task (p < .05), modulating emotional memory in terms of false accuracy (p < .05) and slowing the recognition of all facial expressions of emotion (p = .01). These results have implications for our understanding of the cognitive mechanisms of benzodiazepine treatment. The data reported here suggests that diazepam modulates emotional attention, an effect which may be involved in its therapeutic actions in anxiety.

The interplay of attention and emotion: top-down attention modulates amygdala activation in psychopathy.

PubMed

Larson, Christine L; Baskin-Sommers, Arielle R; Stout, Daniel M; Balderston, Nicholas L; Curtin, John J; Schultz, Douglas H; Kiehl, Kent A; Newman, Joseph P

2013-12-01

Psychopathic behavior has long been attributed to a fundamental deficit in fear that arises from impaired amygdala function. Growing evidence has demonstrated that fear-potentiated startle (FPS) and other psychopathy-related deficits are moderated by focus of attention, but to date, no work on adult psychopathy has examined attentional modulation of the amygdala or concomitant recruitment of relevant attention-related circuitry. Consistent with previous FPS findings, here we report that psychopathy-related differences in amygdala activation appear and disappear as a function of goal-directed attention. Specifically, decreased amygdala activity was observed in psychopathic offenders only when attention was engaged in an alternative goal-relevant task prior to presenting threat-relevant information. Under this condition, psychopaths also exhibited greater activation in selective-attention regions of the lateral prefrontal cortex (LPFC) than did nonpsychopaths, and this increased LPFC activation mediated psychopathy's association with decreased amygdala activation. In contrast, when explicitly attending to threat, amygdala activation did not differ in psychopaths and nonpsychopaths. This pattern of amygdala activation highlights the potential role of LPFC in mediating the failure of psychopathic individuals to process fear and other important information when it is peripheral to the primary focus of goal-directed attention.

The Interplay of Attention and Emotion: Top-down Attention Modulates Amygdala Activation in Psychopathy

PubMed Central

Larson, Christine L.; Baskin-Sommers, Arielle R.; Stout, Daniel M.; Balderston, Nicholas L.; Curtin, John J.; Schultz, Douglas H.; Kiehl, Kent A.; Newman, Joseph P.

2013-01-01

Psychopathic behavior has long been attributed to a fundamental deficit in fear that arises from impaired amygdala function. Growing evidence demonstrates that fear potentiated startle (FPS) and other psychopathy-related deficits are moderated by focus of attention but, to date, no work on adult psychopathy has examined attentional modulation of the amygdala, or concomitant recruitment of relevant attention-related circuitry. Consistent with previous FPS findings, here we report that psychopathy-related differences in amygdala activation appear and disappear as a function of goal-directed attention. Specifically, decreased amygdala activity was observed in psychopathic offenders only when attention was engaged in an alternative goal-relevant task prior to presenting threat-relevant information. Under this condition, psychopaths also exhibited greater activation in selective attention regions of the lateral prefrontal cortex (LPFC) than non-psychopaths, and this increased LPFC activation mediated psychopathy’s association with decreased amygdala activation. In contrast, when explicitly attending to threat, amygdala activation in psychopaths did not differ from non-psychopaths. This pattern of amygdala activation highlights the potential role of LPFC in mediating the failure of psychopathic individuals to process fear and other important information when it is peripheral to the primary focus of goal-directed attention. PMID:23712665

Stress modulation of cognitive and affective processes

PubMed Central

CAMPEAU, SERGE; LIBERZON, ISRAEL; MORILAK, DAVID; RESSLER, KERRY

2012-01-01

This review summarizes the major discussion points of a symposium on stress modulation of cognitive and affective processes, which was held during the 2010 workshop on the neurobiology of stress (Boulder, CO, USA). The four discussants addressed a number of specific cognitive and affective factors that are modulated by exposure to acute or repeated stress. Dr David Morilak discussed the effects of various repeated stress situations on cognitive flexibility, as assessed with a rodent model of attentional set-shifting task, and how performance on slightly different aspects of this test is modulated by different prefrontal regions through monoaminergic neurotransmission. Dr Serge Campeau summarized the findings of several studies exploring a number of factors and brain regions that regulate habituation of various autonomic and neuroendocrine responses to repeated audiogenic stress exposures. Dr Kerry Ressler discussed a body of work exploring the modulation and extinction of fear memories in rodents and humans, especially focusing on the role of key neurotransmitter systems including excitatory amino acids and brain-derived neurotrophic factor. Dr Israel Liberzon presented recent results on human decision-making processes in response to exogenous glucocorticoid hormone administration. Overall, these discussions are casting a wider framework on the cognitive/affective processes that are distinctly regulated by the experience of stress and some of the brain regions and neurotransmitter systems associated with these effects. PMID:21790481

Web-based Traffic Noise Control Support System for Sustainable Transportation

NASA Astrophysics Data System (ADS)

Fan, Lisa; Dai, Liming; Li, Anson

Traffic noise is considered as one of the major pollutions that will affect our communities in the future. This paper presents a framework of web-based traffic noise control support system (WTNCSS) for a sustainable transportation. WTNCSS is to provide the decision makers, engineers and publics a platform to efficiently access the information, and effectively making decisions related to traffic control. The system is based on a Service Oriented Architecture (SOA) which takes the advantages of the convenience of World Wide Web system with the data format of XML. The whole system is divided into different modules such as the prediction module, ontology-based expert module and dynamic online survey module. Each module of the system provides a distinct information service to the decision support center through the HTTP protocol.

Evolution of brains and behavior for optimal foraging: A tale of two predators

PubMed Central

Catania, Kenneth C.

2012-01-01

Star-nosed moles and tentacled snakes have exceptional mechanosensory systems that illustrate a number of general features of nervous system organization and evolution. Star-nosed moles use the star for active touch—rapidly scanning the environment with the nasal rays. The star has the densest concentration of mechanoreceptors described for any mammal, with a central tactile fovea magnified in anatomically visible neocortical modules. The somatosensory system parallels visual system organization, illustrating general features of high-resolution sensory representations. Star-nosed moles are the fastest mammalian foragers, able to identify and eat small prey in 120 ms. Optimal foraging theory suggests that the star evolved for profitably exploiting small invertebrates in a competitive wetland environment. The tentacled snake’s facial appendages are superficially similar to the mole’s nasal rays, but they have a very different function. These snakes are fully aquatic and use tentacles for passive detection of nearby fish. Trigeminal afferents respond to water movements and project tentacle information to the tectum in alignment with vision, illustrating a general theme for the integration of different sensory modalities. Tentacled snakes act as rare enemies, taking advantage of fish C-start escape responses by startling fish toward their strike—often aiming for the future location of escaping fish. By turning fish escapes to their advantage, snakes increase strike success and reduce handling time with head-first captures. The latter may, in turn, prevent snakes from becoming prey when feeding. Findings in these two unusual predators emphasize the importance of a multidisciplinary approach for understanding the evolution of brains and behavior. PMID:22723352

Glycine receptor modulating antibody predicting treatable stiff-person spectrum disorders.

PubMed

Hinson, Shannon R; Lopez-Chiriboga, A Sebastian; Bower, James H; Matsumoto, Joseph Y; Hassan, Anhar; Basal, Eati; Lennon, Vanda A; Pittock, Sean J; McKeon, Andrew

2018-03-01

Glycine receptor alpha-1 subunit (GlyRα1)-immunoglobulin G (IgG) is diagnostic of stiff-person syndrome (SPS) spectrum but has been reported detectable in other neurologic diseases for which significance is less certain. To assess GlyRα1-IgGs as biomarkers of SPS spectrum among patients and controls, specimens were tested using cell-based assays (binding [4°C] and modulating [antigen endocytosing, 37°C]). Medical records of seropositive patients were reviewed. GlyRα1-IgG (binding antibody) was detected in 21 of 247 patients with suspected SPS spectrum (8.5%) and in 8 of 190 healthy subject sera (4%) but not CSF. Among 21 seropositive patients, 20 had confirmed SPS spectrum clinically, but 1 was later determined to have a functional neurologic disorder. Sera from 9 patients with SPS spectrum , but not 7 controls, nor the functional patient, caused GlyRα1 modulation (100% specificity). SPS spectrum phenotypes included progressive encephalomyelitis with rigidity and myoclonus (PERM) (8), classic SPS (5), stiff limb (5), stiff trunk (1), and isolated exaggerated startle (hyperekplexia, 1). Neuropsychiatric symptoms present in 12 patients (60%) were anxiety (11), depression (6), and delirium (3). Anxiety was particularly severe in 3 patients with PERM. Objective improvements in SPS neurologic symptoms were recorded in 16 of 18 patients who received first-line immunotherapy (89%, 9/10 treated with corticosteroids, 8/10 treated with IVIg, 3/4 treated with plasma exchange, and 1 treated with rituximab). Treatment-sparing maintenance strategies were successful in 4 of 7 patients (rituximab [2/3], azathioprine [1/1], and mycophenolate [1/3]). GlyRα1-modulating antibody improves diagnostic specificity for immunologically treatable SPS spectrum disorders. This study provides Class IV evidence that GlyRα1-modulating antibody accurately identifies patients with treatable SPS spectrum disorders.

Niche metabolism in parasitic protozoa

PubMed Central

Ginger, Michael L

2005-01-01

Complete or partial genome sequences have recently become available for several medically and evolutionarily important parasitic protozoa. Through the application of bioinformatics complete metabolic repertoires for these parasites can be predicted. For experimentally intractable parasites insight provided by metabolic maps generated in silico has been startling. At its more extreme end, such bioinformatics reckoning facilitated the discovery in some parasites of mitochondria remodelled beyond previous recognition, and the identification of a non-photosynthetic chloroplast relic in malarial parasites. However, for experimentally tractable parasites, mapping of the general metabolic terrain is only a first step in understanding how the parasite modulates its streamlined, yet still often puzzlingly complex, metabolism in order to complete life cycles within host, vector, or environment. This review provides a comparative overview and discussion of metabolic strategies used by several different parasitic protozoa in order to subvert and survive host defences, and illustrates how genomic data contribute to the elucidation of parasite metabolism. PMID:16553311

Water System Adaptation To Hydrological Changes: Module 3, Consequences of Prolonged Drought on Urban Water System Resilience: Case Study from Las Vegas, Nevada, USA

EPA Science Inventory

This course focuses on water system adaptation to short-term and long-term climate and hydrologic stressors that affect water availability, water quality, security, and resilience. The course is organized into 15 sequential modules. The lectures will be augmented by weekly assign...

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

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.

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.

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.

Herbal medicine IMOD suppresses LPS-induced production of proinflammatory cytokines in human dendritic cells

PubMed Central

Mirzaee, Saeedeh; Drewniak, Agata; Sarrami-Forooshani, Ramin; Kaptein, Tanja M.; Gharibdoost, Farhad; Geijtenbeek, Teunis B. H.

2015-01-01

Traditional medicines that stimulate or modulate the immune system can be used as innovative approaches to treat immunological diseases. The herbal medicine IMOD has been shown to strongly modulate immune responses in several animal studies as well as in clinical trials. However, little is known about the mechanisms of IMOD to modulate immunity. Here we have investigated whether IMOD modulates the immunological function of human dendritic cells (DCs). IMOD alone did not induce DC maturation nor production of cytokines. Notably, IMOD decreased the production of pro-inflammatory cytokines IL-6, IL-12 p70, and TNFα by LPS-activated DCs at both mRNA and protein levels in a dose dependent manner. In contrast, treatment with IMOD did not affect LPS induced-production of the anti-inflammatory cytokine IL-10. Furthermore, IMOD inhibited T cell activation/proliferation by LPS-treated DCs and skewed T-cells responses toward the T helper type 2 polarization. These data strongly indicate that IMOD has a potent immunomodulatory ability that affects TLR signaling and thereby modulates DC function. Insight into the immunomodulatory effect of herbal medicine IMOD may provide innovative strategies to affect the immune system and to help combat various diseases. PMID:25870561

T/R Multi-Chip MMIC Modules for 150 GHz

NASA Technical Reports Server (NTRS)

Samoska, Lorene A.; Pukala, David M.; Soria, Mary M.; Sadowy, Gregory A.

2009-01-01

Modules containing multiple monolithic microwave integrated-circuit (MMIC) chips have been built as prototypes of transmitting/receiving (T/R) modules for millimeter-wavelength radar systems, including phased-array radar systems to be used for diverse purposes that could include guidance and avoidance of hazards for landing spacecraft, imaging systems for detecting hidden weapons, and hazard-avoidance systems for automobiles. Whereas prior landing radar systems have operated at frequencies around 35 GHz, the integrated circuits in this module operate in a frequency band centered at about 150 GHz. The higher frequency (and, hence, shorter wavelength), is expected to make it possible to obtain finer spatial resolution while also using smaller antennas and thereby reducing the sizes and masses of the affected systems.

Ocean warming has a greater effect than acidification on the early life history development and swimming performance of a large circumglobal pelagic fish.

PubMed

Watson, Sue-Ann; Allan, Bridie J M; McQueen, David E; Nicol, Simon; Parsons, Darren M; Pether, Stephen M J; Pope, Stephen; Setiawan, Alvin N; Smith, Neville; Wilson, Carly; Munday, Philip L

2018-05-22

Ocean warming and acidification are serious threats to marine life; however, their individual and combined effects on large pelagic and predatory fishes are poorly understood. We determined the effects of projected future temperature and carbon dioxide (CO 2 ) levels on survival, growth, morphological development and swimming performance on the early life stages of a large circumglobal pelagic fish, the yellowtail kingfish Seriola lalandi. Eggs, larvae and juveniles were reared in cross-factored treatments of temperature (21 and 25°C) and pCO 2 (500 and 985 μatm) from fertilisation to 25 days post hatching (dph). Temperature had the greatest effect on survival, growth and development. Survivorship was lower, but growth and morphological development were faster at 25°C, with surviving fish larger and more developed at 1, 11 and 21 dph. Elevated pCO 2 affected size at 1 dph, but not at 11 or 21 dph, and did not affect survival or morphological development. Elevated temperature and pCO 2 had opposing effects on swimming performance at 21 dph. Critical swimming speed (U crit ) was increased by elevated temperature but reduced by elevated pCO 2 . Additionally, elevated temperature increased the proportion of individuals that responded to a startle stimulus, reduced latency to respond and increased maximum escape speed, potentially due to the more advanced developmental stage of juveniles at 25°C. By contrast, elevated pCO 2 reduced the distance moved and average speed in response to a startle stimulus. Our results show that higher temperature is likely to be the primary driver of global change impacts on kingfish early life history; however, elevated pCO 2 could affect critical aspects of swimming performance in this pelagic species. Our findings will help parameterise and structure fisheries population dynamics models and improve projections of impacts to large pelagic fishes under climate change scenarios to better inform adaptation and mitigation responses. © 2018 John Wiley & Sons Ltd.

Distinct responses to predictable and unpredictable threat in anxiety pathologies: effect of panic attack.

PubMed

Grillon, Christian; O'Connell, Katherine; Lieberman, Lynne; Alvarez, Gabriella; Geraci, Marilla; Pine, Daniel S; Ernst, Monique

2017-10-01

Delineating specific clinical phenotypes of anxiety disorders is a crucial step toward better classification and understanding of these conditions. The present study sought to identify differential aversive responses to predictable and unpredictable threat of shock in healthy comparisons and in non-medicated anxiety patients with and without a history of panic attacks (PAs). 143 adults (72 healthy controls; 71 patients with generalized anxiety disorder (GAD) or/and social anxiety disorder (SAD), 24 with and 47 without PAs) were exposed to three conditions: 1) predictable shocks signaled by a cue, 2) unpredictable shocks, and 3) no shock. Startle magnitude was used to assess aversive responses. Across disorders, a PA history was specifically associated with hypersensitivity to unpredictable threat. By disorder, SAD was associated with hypersensitivity to predictable threat, whereas GAD was associated with exaggerated baseline startle. These results identified three physiological patterns. The first is hypersensitivity to unpredictable threat in individuals with PAs. The second is hypersensitivity to predictable threat, which characterizes SAD. The third is enhanced baseline startle in GAD, which may reflect propensity for self-generated anxious thoughts in the absence of imminent danger. These results inform current thinking by linking specific clinical features to particular physiology profiles.

Context conditioning and behavioral avoidance in a virtual reality environment: effect of predictability.

PubMed

Grillon, Christian; Baas, Johanna M P; Cornwell, Brian; Johnson, Linda

2006-10-01

Sustained anxiety can be modeled using context conditioning, which can be studied in a virtual reality environment. Unpredictable stressors increase context conditioning in animals. This study examined context conditioning to predictable and unpredictable shocks in humans using behavioral avoidance, potentiated startle, and subjective reports of anxiety. Subjects were guided through three virtual rooms (no-shock, predictable, unpredictable contexts). Eight-sec duration colored lights served as conditioned stimuli (CS). During acquisition, no shock was administered in the no-shock context. Shocks were paired with the CS in the predictable context and were administered randomly in the unpredictable context. No shock was administered during extinction. Startle stimuli were delivered during CS and between CS to assess cued and context conditioning, respectively. To assess avoidance, subjects freely navigated into two of the three contexts to retrieve money. Startle between CS was potentiated in the unpredictable context compared to the two other contexts. Following acquisition, subjects showed a strong preference for the no-shock context and avoidance of the unpredictable context. Consistent with animal data, context conditioning is increased by unpredictability. These data support virtual reality as a tool to extend research on physiological and behavioral signs of fear and anxiety in humans.

Three cases of Creutzfeldt-Jakob disease with prion protein gene codon180 mutation presenting with pathological laughing and crying.

PubMed

Iwasaki, Yasushi

2012-08-15

Although there are no reports of pathological laughing and crying being observed in patients with Creutzfeldt-Jakob disease (CJD), the author experienced three patients with CJD with prion protein gene codon180 mutation (V180I CJD) who showed this characteristic clinical finding. This finding was observed from the early disease stage in all 3 patients and continued for several months. Startle reaction was also remarkable in all patients, although myoclonus was generally mild. The dissociation between the startle reaction and myoclonus was suspected to be another feature of V180I CJD. The pathological laughing and crying co-occured with the startle reaction and stopped right before the onset of akinetic mutism, and the degree of both symptoms was almost parallel during this period. On the basis of MRI and autopsy findings, pathological laughing and crying was suspected of being induced by the widespread cerebral cortical involvement that is characteristic of V180I CJD. From the present observations, the author speculated that pathological laughing and crying may be a comparatively frequent observation in V180I CJD patients. Copyright © 2012 Elsevier B.V. All rights reserved.

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.

The effects of control field detuning on the modulation instability in a three-level quantum well system

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

Borgohain, Nitu, E-mail: nituborgohain.ism@gmail.com; Konar, S.

The paper presents a theoretical study of the modulation instability of a continuous or quasi-continuous optical probe in a three level quantum well system under electromagnetically induced transparency. The modulation instability is affected by the control field detuning, as well as even-order dispersion and by the strength of Kerr (third-order) and quintic (fifth-order) nonlinearities. The fourth-order dispersion reduces the bandwidth over which modulation instability occurs, whereas the quintic nonlinearity saturates the growth of the modulation instability. Detuning the control field from resonance can significantly reduce the growth of the modulation instability at both low and high power levels. At lowmore » powers, the system becomes stable against modulation instability for small detuning of the control field and at high powers modulation instability disappears for larger detuning.« less

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.

Lessons unlearned in Japan before 2011: Effects of the 2004 Indian Ocean tsunami on a nuclear plant in India

NASA Astrophysics Data System (ADS)

Sugimoto, M.

2015-12-01

The 2004 Indian Ocean tsunami killed around 220,000 people and startled the world. North of Chennai (Madras), the Indian plant nearly affected by tsunami in 2004. The local residents really did not get any warning in India. "On December 26, the Madras Atomic Power Station looked like a desolate place with no power, no phones, no water, no security arrangement and no hindrance whatsoever for outsiders to enter any part of the plant," said S.P. Udaykumar of SACCER. Nuclear issues hide behind such big tsunami damaged. Few media reported outside India. As for US, San Francisco Chronicle reported scientists had to rethink about nuclear power plants by the 2004 tsunami in 11th July 2005. Few tsunami scientsts did not pay attention to nucler power plants nearly affected by tsunami in US. On the other hand, US government noticed the Indian plant nearly affected in 2004. US Goverment supported nucler disaster management in several countries. As for Japan, Japanese goverment mainly concentrated reconstrucation in affected areas and tsunami early warning system. I worked in Japanese embassy in Jakarta Indonesia at that time. I did not receive the information about the Indian plant nearly affected by tsunami and US supported nucler safety to the other coutries. The 2011 Tohoku earthquake and tsunami damaged society and nuclear power stations. The Fukushima Dai-ichi Nuclear Power Plant (FDNPP) accident resulted in the largest release of radioactive material since the 1986 Chernobyl accident. Why did not Japanese tsunami scientists learn from warning signs from the nuclear plant in India by the 2004 Indian Ocean tsunami to the 2011 Fukushima accident? I would like to clarify the reason few tsunami scientist notice this point in my presentation.

Advanced Transport Operating System (ATOPS) control display unit software description

NASA Technical Reports Server (NTRS)

Slominski, Christopher J.; Parks, Mark A.; Debure, Kelly R.; Heaphy, William J.

1992-01-01

The software created for the Control Display Units (CDUs), used for the Advanced Transport Operating Systems (ATOPS) project, on the Transport Systems Research Vehicle (TSRV) is described. Module descriptions are presented in a standardized format which contains module purpose, calling sequence, a detailed description, and global references. The global reference section includes subroutines, functions, and common variables referenced by a particular module. The CDUs, one for the pilot and one for the copilot, are used for flight management purposes. Operations performed with the CDU affects the aircraft's guidance, navigation, and display software.

Partial genetic deletion of neuregulin 1 modulates the effects of stress on sensorimotor gating, dendritic morphology, and HPA axis activity in adolescent mice.

PubMed

Chohan, Tariq W; Boucher, Aurelie A; Spencer, Jarrah R; Kassem, Mustafa S; Hamdi, Areeg A; Karl, Tim; Fok, Sandra Y; Bennett, Maxwell R; Arnold, Jonathon C

2014-11-01

Stress has been linked to the pathogenesis of schizophrenia. Genetic variation in neuregulin 1 (NRG1) increases the risk of developing schizophrenia and may help predict which high-risk individuals will transition to psychosis. NRG1 also modulates sensorimotor gating, a schizophrenia endophenotype. We used an animal model to demonstrate that partial genetic deletion of Nrg1 interacts with stress to promote neurobehavioral deficits of relevance to schizophrenia. Nrg1 heterozygous (HET) mice displayed greater acute stress-induced anxiety-related behavior than wild-type (WT) mice. Repeated stress in adolescence disrupted the normal development of higher prepulse inhibition of startle selectively in Nrg1 HET mice but not in WT mice. Further, repeated stress increased dendritic spine density in pyramidal neurons of the medial prefrontal cortex (mPFC) selectively in Nrg1 HET mice. Partial genetic deletion of Nrg1 also modulated the adaptive response of the hypothalamic-pituitary-adrenal axis to repeated stress, with Nrg1 HET displaying a reduced repeated stress-induced level of plasma corticosterone than WT mice. Our results demonstrate that Nrg1 confers vulnerability to repeated stress-induced sensorimotor gating deficits, dendritic spine growth in the mPFC, and an abberant endocrine response in adolescence. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Water System Adaptation to Hydrological Changes: Module 2, Stormwater Management and Sewer Performance under Intense Storms: Case Study from Lawrence, Massachusetts, U.S.A.

EPA Science Inventory

This course focuses on water system adaptation to short-term and long-term climate and hydrologic stressors that affect water availability, water quality, security, and resilience. The course is organized into 15 sequential modules. The lectures will be augmented by weekly assign...

Water System Adaptations To Hydrological Changes: Module 4, Water Quality Response to Land-use and Precipitation Changes : Case Study of Ohio River Valley, USA

EPA Science Inventory

This course focuses on water system adaptation to short-term and long-term climate and hydrologic stressors that affect water availability, water quality, security, and resilience. The course is organized into 15 sequential modules. The lectures will be augmented by weekly assign...

Identification of Unstable Network Modules Reveals Disease Modules Associated with the Progression of Alzheimer’s Disease

PubMed Central

Kikuchi, Masataka; Ogishima, Soichi; Miyamoto, Tadashi; Miyashita, Akinori; Kuwano, Ryozo; Nakaya, Jun; Tanaka, Hiroshi

2013-01-01

Alzheimer’s disease (AD), the most common cause of dementia, is associated with aging, and it leads to neuron death. Deposits of amyloid β and aberrantly phosphorylated tau protein are known as pathological hallmarks of AD, but the underlying mechanisms have not yet been revealed. A high-throughput gene expression analysis previously showed that differentially expressed genes accompanying the progression of AD were more down-regulated than up-regulated in the later stages of AD. This suggested that the molecular networks and their constituent modules collapsed along with AD progression. In this study, by using gene expression profiles and protein interaction networks (PINs), we identified the PINs expressed in three brain regions: the entorhinal cortex (EC), hippocampus (HIP) and superior frontal gyrus (SFG). Dividing the expressed PINs into modules, we examined the stability of the modules with AD progression and with normal aging. We found that in the AD modules, the constituent proteins, interactions and cellular functions were not maintained between consecutive stages through all brain regions. Interestingly, the modules were collapsed with AD progression, specifically in the EC region. By identifying the modules that were affected by AD pathology, we found the transcriptional regulation-associated modules that interact with the proteasome-associated module via UCHL5 hub protein, which is a deubiquitinating enzyme. Considering PINs as a system made of network modules, we found that the modules relevant to the transcriptional regulation are disrupted in the EC region, which affects the ubiquitin-proteasome system. PMID:24348898

Targeting Glia with N-Acetylcysteine Modulates Brain Glutamate and Behaviors Relevant to Neurodevelopmental Disorders in C57BL/6J Mice

PubMed Central

Durieux, Alice M. S.; Fernandes, Cathy; Murphy, Declan; Labouesse, Marie Anais; Giovanoli, Sandra; Meyer, Urs; Li, Qi; So, Po-Wah; McAlonan, Grainne

2015-01-01

An imbalance between excitatory (E) glutamate and inhibitory (I) GABA transmission may underlie neurodevelopmental conditions such as autism spectrum disorder (ASD) and schizophrenia. This may be direct, through alterations in synaptic genes, but there is increasing evidence for the importance of indirect modulation of E/I balance through glial mechanisms. Here, we used C57BL/6J mice to test the hypothesis that striatal glutamate levels can be shifted by N-acetylcysteine (NAC), which acts at the cystine-glutamate antiporter of glial cells. Striatal glutamate was quantified in vivo using proton magnetic resonance spectroscopy. The effect of NAC on behaviors relevant to ASD was examined in a separate cohort. NAC induced a time-dependent decrease in striatal glutamate, which recapitulated findings of lower striatal glutamate reported in ASD. NAC-treated animals were significantly less active and more anxious in the open field test; and NAC-treated females had significantly impaired prepulse inhibition of startle response. This at least partly mimics greater anxiety and impaired sensorimotor gating reported in neurodevelopmental disorders. Thus glial mechanisms regulate glutamate acutely and have functional consequences even in adulthood. Glial cells may be a potential drug target for the development of new therapies for neurodevelopmental disorders across the life-span. PMID:26696857

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.

Perinatal exposure to the selective serotonin reuptake inhibitor citalopram alters spatial learning and memory, anxiety, depression, and startle in Sprague-Dawley rats.

PubMed

Sprowles, Jenna L N; Hufgard, Jillian R; Gutierrez, Arnold; Bailey, Rebecca A; Jablonski, Sarah A; Williams, Michael T; Vorhees, Charles V

2016-11-01

Selective serotonin reuptake inhibitors (SSRIs) block the serotonin (5-HT) reuptake transporter (SERT) and increase synaptic 5-HT. 5-HT is also important in brain development; hence when SSRIs are taken during pregnancy there exists the potential for these drugs to affect CNS ontogeny. Prenatal SSRI exposure has been associated with an increased prevalence of autism spectrum disorder (ASD), and peripheral 5-HT is elevated in some ASD patients. Perinatal SSRI exposure in rodents has been associated with increased depression and anxiety-like behavior, decreased sociability, and impaired learning in the offspring, behaviors often seen in ASD. The present study investigated whether perinatal exposure to citalopram causes persistent neurobehavioral effects. Gravid Sprague-Dawley rats were assigned to two groups and subcutaneously injected twice per day with citalopram (10mg/kg; Cit) or saline (Sal) 6h apart on embryonic day (E)6-21, and then drug was given directly to the pups after delivery from postnatal day (P)1-20. Starting on P60, one male/female from each litter was tested in the Cincinnati water maze (CWM) and open-field before and after MK-801. A second pair from each litter was tested in the Morris water maze (MWM) and open-field before and after (+)-amphetamine. A third pair was tested as follows: elevated zero-maze, open-field, marble burying, prepulse inhibition of acoustic startle, social preference, and forced swim. Cit-exposed rats were impaired in the MWM during acquisition and probe, but not during reversal, shift, or cued trials. Cit-exposed rats also showed increased marble burying, decreased time in the center of the open-field, decreased latency to immobility in forced swim, and increased acoustic startle across prepulse intensities with no effects on CWM. The results are consistent with citalopram inducing several ASD-like effects. The findings add to concerns about use of SSRIs during pregnancy. Further research on different classes of antidepressants, dose-effect relationships, timing of exposure periods, and mechanisms for these effects are needed. It is also important to balance the effects described here against the effects of the disorders for which the drugs are given. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.

Impact of environmental hazards on internal soiling within concentrator photovoltaic (CPV) modules

NASA Astrophysics Data System (ADS)

Ellis, Sara

2014-09-01

Environmental conditions have a significant impact on internal soiling of a CPV system, which affects overall system performance and efficiency. The International Electrotechnical Commission (IEC) 62108, Section 10, standard includes accelerated testing such as temperature cycling, damp heat, and humidity freeze to assess a CPV module's ability to withstand environmental hazards that can compromise the typical 25-year lifetime. This paper discusses the IEC 60529 ingress protection (IP) test protocols and how they can be used to evaluate the performance of CPV modules to block water and particulate contaminants. Studies with GORE® Protective Vents installed in a CPV module and subjected to environmental hazard testing have shown increased reliability of the module over the lifetime of the system by protecting the seals from pressure differentials and keeping out contaminants.

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.

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.

A cardiorespiratory classifier of voluntary and involuntary electrodermal activity

PubMed Central

2010-01-01

Background Electrodermal reactions (EDRs) can be attributed to many origins, including spontaneous fluctuations of electrodermal activity (EDA) and stimuli such as deep inspirations, voluntary mental activity and startling events. In fields that use EDA as a measure of psychophysiological state, the fact that EDRs may be elicited from many different stimuli is often ignored. This study attempts to classify observed EDRs as voluntary (i.e., generated from intentional respiratory or mental activity) or involuntary (i.e., generated from startling events or spontaneous electrodermal fluctuations). Methods Eight able-bodied participants were subjected to conditions that would cause a change in EDA: music imagery, startling noises, and deep inspirations. A user-centered cardiorespiratory classifier consisting of 1) an EDR detector, 2) a respiratory filter and 3) a cardiorespiratory filter was developed to automatically detect a participant's EDRs and to classify the origin of their stimulation as voluntary or involuntary. Results Detected EDRs were classified with a positive predictive value of 78%, a negative predictive value of 81% and an overall accuracy of 78%. Without the classifier, EDRs could only be correctly attributed as voluntary or involuntary with an accuracy of 50%. Conclusions The proposed classifier may enable investigators to form more accurate interpretations of electrodermal activity as a measure of an individual's psychophysiological state. PMID:20184746

Electrophysiological responses to threat in youth with and without Posttraumatic Stress Disorder.

PubMed

Grasso, Damion J; Simons, Robert F

2012-04-01

The current study was designed to examine event-related brain potentials and autonomic responses to pictures indicating threat, relative to non-threat, and acoustic startle reflexes in traumatized youth diagnosed with PTSD, relative to non-exposed children, before and after receiving psychotherapy. Children in the control group were individually yoked and demographically matched to the PTSD group. Both groups displayed enhanced late positive potentials and more prolonged heart rate deceleration to pictures indicating threat, relative to non-threat, and larger skin conductance responses to pictures indicating threat, relative to non-threat, at time one. At time two, controls appeared to habituate, as reflected by an overall attenuated skin conductance response, whereas the PTSD group showed little change. Across time points the PTSD group exhibited greater acoustic startle reflexes than the control group. Psychotherapy and symptom reduction was not associated with electrophysiology. Drawing from the adult literature, this study was an attempt to address the scarcity of research examining electrophysiological irregularities in childhood PTSD. The overall results suggest that children and adolescents allocate more attention to threat-related stimuli regardless of PTSD status, and exaggerated startle and a possible failure to habituate skin conductance responses to threat-related stimuli in youth with versus without PTSD. Copyright © 2012 Elsevier B.V. All rights reserved.

An integrated telemedicine platform for the assessment of affective physiological states

PubMed Central

Katsis, Christos D; Ganiatsas, George; Fotiadis, Dimitrios I

2006-01-01

AUBADE is an integrated platform built for the affective assessment of individuals. The system performs evaluation of the emotional state by classifying vectors of features extracted from: facial Electromyogram, Respiration, Electrodermal Activity and Electrocardiogram. The AUBADE system consists of: (a) a multisensorial wearable, (b) a data acquisition and wireless communication module, (c) a feature extraction module, (d) a 3D facial animation module which is used for the projection of the obtained data through a generic 3D face model; whereas the end-user will be able to view the facial expression of the subject in real time, (e) an intelligent emotion recognition module, and (f) the AUBADE databases where the acquired signals along with the subject's animation videos are saved. The system is designed to be applied to human subjects operating under extreme stress conditions, in particular car racing drivers, and also to patients suffering from neurological and psychological disorders. AUBADE's classification accuracy into five predefined emotional classes (high stress, low stress, disappointment, euphoria and neutral face) is 86.0%. The pilot system applications and components are being tested and evaluated on Maserati's car. racing drivers. PMID:16879757

Brain and Serum Androsterone Is Elevated in Response to Stress in Rats with Mild Traumatic Brain Injury

PubMed Central

Servatius, Richard J.; Marx, Christine E.; Sinha, Swamini; Avcu, Pelin; Kilts, Jason D.; Naylor, Jennifer C.; Pang, Kevin C. H.

2016-01-01

Exposure to lateral fluid percussion (LFP) injury consistent with mild traumatic brain injury (mTBI) persistently attenuates acoustic startle responses (ASRs) in rats. Here, we examined whether the experience of head trauma affects stress reactivity. Male Sprague-Dawley rats were matched for ASRs and randomly assigned to receive mTBI through LFP or experience a sham surgery (SHAM). ASRs were measured post injury days (PIDs) 1, 3, 7, 14, 21, and 28. To assess neurosteroids, rats received a single 2.0 mA, 0.5 s foot shock on PID 34 (S34), PID 35 (S35), on both days (2S), or the experimental context (CON). Levels of the neurosteroids pregnenolone (PREG), allopregnanolone (ALLO), and androsterone (ANDRO) were determined for the prefrontal cortex, hippocampus, and cerebellum. For 2S rats, repeated blood samples were obtained at 15, 30, and 60 min post-stressor for determination of corticosterone (CORT) levels after stress or context on PID 34. Similar to earlier work, ASRs were severely attenuated in mTBI rats without remission for 28 days after injury. No differences were observed between mTBI and SHAM rats in basal CORT, peak CORT levels or its recovery. In serum and brain, ANDRO levels were the most stress-sensitive. Stress-induced ANDRO elevations were greater than those in mTBI rats. As a positive allosteric modulator of gamma-aminobutyric acid (GABAA) receptors, increased brain ANDRO levels are expected to be anxiolytic. The impact of brain ANDRO elevations in the aftermath of mTBI on coping warrants further elaboration. PMID:27616978

On enhancing energy harvesting performance of the photovoltaic modules using an automatic cooling system and assessing its economic benefits of mitigating greenhouse effects on the environment

NASA Astrophysics Data System (ADS)

Wang, Jen-Cheng; Liao, Min-Sheng; Lee, Yeun-Chung; Liu, Cheng-Yue; Kuo, Kun-Chang; Chou, Cheng-Ying; Huang, Chen-Kang; Jiang, Joe-Air

2018-02-01

The performance of photovoltaic (PV) modules under outdoor operation is greatly affected by their location and environmental conditions. The temperature of a PV module gradually increases as it is exposed to solar irradiation, resulting in degradation of its electrical characteristics and power generation efficiency. This study adopts wireless sensor network (WSN) technology to develop an automatic water-cooling system for PV modules in order to improve their PV power generation efficiency. A temperature estimation method is developed to quickly and accurately estimate the PV module temperatures based on weather data provided from the WSN monitoring system. Further, an estimation method is also proposed for evaluation of the electrical characteristics and output power of the PV modules, which is performed remotely via a control platform. The automatic WSN-based water-cooling mechanism is designed to avoid the PV module temperature from reaching saturation. Equipping each PV module with the WSN-based cooling system, the ambient conditions are monitored automatically so that the temperature of the PV module is controlled by sprinkling water on the panel surface. The field-test experiment results show an increase in the energy harvested by the PV modules of approximately 17.75% when using the proposed WSN-based cooling system.

RCRA, superfund and EPCRA hotline training module. Introduction to: RCRA state programs updated June 1996

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

NONE

1996-06-01

The module outlines the requirements and procedures for a state to become authorized to manage and oversee its own RCRA program. It also describes how the state authorization system can affect the applicability of certain rules. When one has completed the module they will be familiar with the state authorization process for hazardous waste management programs.

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

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

A model of Occupational Safety and Health Management System (OSHMS) for promoting and controlling health and safety in textile industry.

PubMed

Manimaran, S; Rajalakshmi, R; Bhagyalakshmi, K

2015-01-01

The development of Occupational Safety and Health Management System in textile industry will rejuvenate the workers and energize the economy as a whole. In India, especially in Tamil Nadu, approximately 1371 textile business is running with the help of 38,461 workers under Ginning, Spinning, Weaving, Garment and Dyeing sectors. Textile industry of contributes to the growth of Indian economy but it fails to foster education and health as key components of human development and help new democracies. The present work attempts to measure and develop OSHMS which reduce the hazards and risk involved in textile industry. Among all other industries textile industry is affected by enormous hazards and risk because of negligence by management and Government. It is evident that managements are not abiding by law when an accident has occurred. Managements are easily deceiving workers and least bothered about the Quality of Work Life (QWL). A detailed analysis of factors promoting safety and health to the workers has been done by performing confirmatory factor analysis, evaluating Risk Priority Number and the framework of OHMS has been conceptualized using Structural Equation Model. The data have been collected using questionnaire and interview method. The study finds occupation health for worker in Textile industry is affected not only by safety measure but also by technology and management. The work shows that difficulty in identifying the cause and effect of hazards, the influence of management in controlling and promoting OSHMS under various dimensions. One startling fact is existence of very low and insignificance correlation between health factors and outcome.

GLAST Deficiency in Mice Exacerbates Gap Detection Deficits in a Model of Salicylate-Induced Tinnitus

PubMed Central

Yu, Hong; Vikhe Patil, Kim; Han, Chul; Fabella, Brian; Canlon, Barbara; Someya, Shinichi; Cederroth, Christopher R.

2016-01-01

Gap detection or gap pre-pulse inhibition of the acoustic startle (GPIAS) has been successfully used in rat and guinea pig models of tinnitus, yet this system has been proven to have low efficacy in CBA mice, with low basal GPIAS and subtle tinnitus-like effects. Here, we tested five mouse strains (CBA, BalbC, CD-1, C57BL/6 and 129sv) for pre-pulse inhibition (PPI) and gap detection with varying interstimulus intervals (ISI) and found that mice from a CBA genetic background had the poorest capacities of suppressing the startle response in the presence of a pre-pulse or a gap. CD-1 mice displayed variable responses throughout all ISI. Interestingly, C57BL/6, 129sv and BalbC showed efficient suppression with either pre-pulses or gaps with shorter ISI. The glutamate aspartate transporter (GLAST) is expressed in support cells from the cochlea and buffers the excess of glutamate. We hypothesized that loss of GLAST function could sensitize the ear to tinnitus-inducing agents, such as salicylate. Using shorter ISI to obtain a greater dynamic range to assess tinnitus-like effects, we found that disruption of gap detection by salicylate was exacerbated across various intensities of a 32-kHz narrow band noise gap carrier in GLAST knockout (KO) mice when compared to their wild-type (WT) littermates. Auditory brainstem responses (ABR) and distortion-product otoacoustic emission (DPOAE) were performed to evaluate the effects on hearing functions. Salicylate caused greater auditory threshold shifts (near 15 dB) in GLAST KO mice than in WT mice across all tested frequencies, despite similarly reduced DPOAE. Despite these changes, inhibition using broad-band gap carriers and 32 kHz pre-pulses were not affected. Our study suggests that GLAST deficiency could become a useful experimental model to decipher the mechanisms underlying drug-induced tinnitus. Future studies addressing the neurological correlates of tinnitus in this model could provide additional insights into the mechanisms of tinnitus. PMID:27582696

Anticipation of smoking sufficiently dampens stress reactivity in nicotine-deprived smokers.

PubMed

Bradford, Daniel E; Curtin, John J; Piper, Megan E

2015-02-01

Most smokers attempting to quit will relapse, even when using evidence-based cessation treatment. This illustrates the need for better understanding of the relapse process to thereby improve cessation treatments. Although the impact of stress sensitivity on relapse is clear, little research has precisely examined stress reactivity in addicted individuals. Further, most research on relapse focuses on affect surrounding self-administration, and does not address potentially important preconsumption processes such as anticipation of use. We examined the effects of anticipation and actual smoking on stress reactivity in 34 deprived smokers withdrawn for 24 hr and 37 nondeprived smokers, with 37 nonsmoker controls. Using a cued shock stressor task, we measured stress reactivity via startle potentiation and self-reported anxiety. After completing the task once, smokers anticipated smoking a cigarette resting in front of them while they completed the task a second time. Smokers then smoked before completing the task a third and final time. Nonsmokers anticipated and drank water as a control. Anticipation of smoking significantly attenuated both startle potentiation and self-reported anxiety to shock cues for deprived smokers relative to nondeprived smokers. Smokers' stress reactivity was not reduced by smoking beyond the prior effect of anticipation. These results suggest that anticipation, rather than actual drug consumption, may drive the primary reinforcing effect of reduced stress reactivity in smoking. Future research is needed to understand this effect of anticipation on drug use and to determine whether anticipation would make an effective intervention target for addiction and other psychopathology that exhibits increased stress sensitivity. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Anticipation of Smoking Sufficiently Dampens Stress Reactivity in Nicotine Deprived Smokers

PubMed Central

Bradford, Daniel E.; Curtin, John J.; Piper, Megan E.

2014-01-01

Most smokers attempting to quit will relapse, even when using evidence-based cessation treatment. This illustrates the need for better understanding of the relapse process to thereby improve cessation treatments. While the impact of stress sensitivity on relapse is clear, little research has precisely examined stress reactivity in addicted individuals. Further, most research on relapse focuses on affect surrounding self-administration, and doesn't address potentially important pre-consumption processes such as anticipation of use. We examined the effects of anticipation and actual smoking on stress reactivity in 34 deprived smokers withdrawn for 24 hours and 37 non-deprived smokers, with 37 non-smoker controls. Using a cued shock stressor task, we measured stress reactivity via startle potentiation and self-reported anxiety. After completing the task once, smokers anticipated smoking a cigarette resting in front of them while they completed the task a second time. Smokers then smoked before completing the task a third and final time. Non-smokers anticipated and drank water as a control. Anticipation of smoking significantly attenuated both startle potentiation and self-reported anxiety to shock cues for deprived smokers relative to non-deprived smokers. Smokers' stress reactivity was not reduced by smoking beyond the prior effect of anticipation. These results suggest that anticipation, rather than actual drug consumption, may drive the primary reinforcing effect of reduced stress reactivity in smoking. Future research is needed to understand this effect of anticipation on drug use and determine whether anticipation would make an effective intervention target for addiction and other psychopathology which exhibits increased stress sensitivity. PMID:25688439

Effects of memantine on hippocampal long-term potentiation, gamma activity, and sensorimotor gating in freely moving rats.

PubMed

Ma, Jingyi; Mufti, Asfandyar; Stan Leung, L

2015-09-01

Memantine, an uncompetitive N-methyl-D-aspartate receptor antagonist, is used for treatment of patients with Alzheimer's disease. The mechanisms of memantine in relieving cognitive and behavioral symptoms are unclear, and this study attempts to elucidate its action on network and synaptic functions of the hippocampus. The effects of memantine on electrographic activity and hippocampal long-term potentiation (LTP) were investigated in freely moving rats. Basal dendritic excitation on hippocampal CA1 pyramidal cells showed a robust LTP after theta-frequency primed bursts, and the LTP was higher after 5-10 mg/kg intraperitoneal (ip) memantine pretreatment, as compared with saline pretreatment. Injection of scopolamine (5 mg/kg ip) before memantine failed to block the LTP-enhancing effect of memantine. Memantine as compared with saline pretreatment did not affect the LTP after an afterdischarge induced by high-frequency (200-Hz) train stimulation. Memantine (5 or 10 mg/kg ip) significantly enhanced gamma oscillations in the hippocampal local field potentials of 40-100 Hz during walking and awake immobility. Memantine at 10 mg/kg ip, but not at 5 mg/kg ip, increased prepulse inhibition of the acoustic startle response, while both 5 and 10 mg/kg ip memantine enhanced the acoustic startle response as compared with saline-injected rats. These electrophysiological and behavioral effects of memantine are unique among N-methyl-D-aspartate receptor antagonists but are consistent with memantine's effects in improving cognitive and sensorimotor functions of Alzheimer's patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Decoupled Modulation Control

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

Wang, Shaobu; Huang, Renke; Huang, Zhenyu

The objective of this research work is to develop decoupled modulation control methods for damping inter-area oscillations with low frequencies, so the damping control can be more effective and easier to design with less interference among different oscillation modes in the power system. A signal-decoupling algorithm was developed that can enable separation of multiple oscillation frequency contents and extraction of a “pure” oscillation frequency mode that are fed into Power System Stabilizers (PSSs) as the modulation input signals. As a result, instead of introducing interferences between different oscillation modes from the traditional approaches, the output of the new PSS modulationmore » control signal mainly affects only one oscillation mode of interest. The new decoupled modulation damping control algorithm has been successfully developed and tested on the standard IEEE 4-machine 2-area test system and a minniWECC system. The results are compared against traditional modulation controls, which demonstrates the validity and effectiveness of the newly-developed decoupled modulation damping control algorithm.« less

Benzodiazepine-induced anxiolysis and reduction of conditioned fear are mediated by distinct GABAA receptor subtypes in mice

PubMed Central

Smith, Kiersten S.; Engin, Elif; Meloni, Edward G.; Rudolph, Uwe

2012-01-01

GABAA receptor modulating drugs such as benzodiazepines (BZs) have been used to treat anxiety disorders for over five decades. In order to determine whether the same or different GABAA receptor subtypes are necessary for the anxiolytic-like action of BZs in unconditioned anxiety and conditioned fear models, we investigated the role of different GABAA receptor subtypes by challenging wild type, α1(H101R), α2(H101R) and α3(H126R) mice bred on the C57BL/6J background with diazepam or chlordiazepoxide in the elevated plus maze and the fear-potentiated startle paradigms. Both drugs significantly increased open arm exploration in the elevated plus maze in wild type, α1(H101R) and α3(H126R), but this effect was abolished in α2(H101R) mice; these were expected results based on previous published results. In contrast, while administration of diazepam and chlordiazepoxide significantly attenuated fear-potentiated startle (FPS) in wild type mice and α3(H126R) mice, the fear-reducing effects of these drugs were absent in both α1(H101R) and α2(H101R) point mutants, indicating that both α1- and α2-containing GABAA receptors are necessary for BZs to exert their effects on conditioned fear responses.. Our findings illustrate both an overlap and a divergence between the GABAA receptor subtype requirements for the impact of BZs, specifically that both α1- and α2-containing GABAA receptors are necessary for BZs to reduce conditioned fear whereas only α2-containing GABAA receptors are needed for BZ-induced anxiolysis in unconditioned tests of anxiety. This raises the possibility that GABAergic pharmacological interventions for specific anxiety disorders can be differentially tailored. PMID:22465203

A systematic review and meta-analysis of cognitive bias to food stimuli in people with disordered eating behaviour.

PubMed

Brooks, Samantha; Prince, Alexis; Stahl, Daniel; Campbell, Iain C; Treasure, Janet

2011-02-01

Maladaptive cognitions about food, weight and shape bias attention, memory and judgment and may be linked to disordered eating behaviour. This paper reviews information processing of food stimuli (words, pictures) in people with eating disorders (ED). PubMed, Ovid, ScienceDirect, PsychInfo, Web of Science, Cochrane Library and Google Scholar were searched to December 2009. 63 studies measured attention, memory and judgment bias towards food stimuli in women with ED. Stroop tasks had sufficient sample size for a meta-analyses and effects ranged from small to medium. Other studies of attention bias had variable effects (e.g. the Dot-Probe task, distracter tasks and Startle Eyeblink Modulation). A meta-analysis of memory bias studies in ED and RE yielded insignificant effect. Effect sizes for judgment bias ranged from negligible to large. People with ED have greater attentional bias to food stimuli than healthy controls (HC). Evidence for a memory and judgment bias in ED is limited. Copyright © 2010 Elsevier Ltd. All rights reserved.

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

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

STS-70 Discovery launch startling the birds

NASA Technical Reports Server (NTRS)

1995-01-01

Startled birds scatter as the stillness of a summer morning is broken by a giant's roar. The Space Shuttle Discovery thundered into space from launch Pad 39-B at 9:41:55:078 a.m. EDT. STS-70 is the 70th Shuttle flight overall, the 21st for Discovery (OV- 103), and the fourth Shuttle flight in 1995. On board for the nearly eight-day mission are a crew of five: Commander Terence 'Tom' Hendricks; Pilot Kevin R. Kregel; and Mission Specialists Nancy Jane Currie, Donald A. Thomas and Mary Ellen Weber. The crew's primary objective is to deploy the Tracking and Data Relay Satellite-G (TDRS-G), which will join a constellation of other TDRS spacecraft already on orbit.

STS-70 Discovery launch startled birds at ignition

NASA Technical Reports Server (NTRS)

1995-01-01

Startled birds scatter as the stillness of a summer morning is broken by a giant's roar. The Space Shuttle Discovery thundered into space from launch Pad 39-B at 9:41:55:078 a.m. EDT. STS-70 is the 70th Shuttle flight overall, the 21st for Discovery (OV- 103), and the fourth Shuttle flight in 1995. On board for the nearly eight-day mission are a crew of five: Commander Terence 'Tom' Hendricks; Pilot Kevin R. Kregel; and Mission Specialists Nancy Jane Currie, Donald A. Thomas and Mary Ellen Weber. The crew's primary objective is to deploy the Tracking and Data Relay Satellite-G (TDRS-G), which will join a constellation of other TDRS spacecraft already on orbit.

Anthropogenic noise compromises the anti-predator behaviour of the European seabass, Dicentrarchus labrax (L.).

PubMed

Spiga, Ilaria; Aldred, Nicholas; Caldwell, Gary S

2017-09-15

Anthropogenic noise is a significant pollutant of the world's oceans, affecting behavioural and physiological traits in a range of species, including anti-predator behaviours. Using the open field test, we investigated the effects of recordings of piling and drilling noise on the anti-predator behaviour of captive juvenile European seabass in response to a visual stimulus (a predatory mimic). The impulsive nature of piling noise triggered a reflexive startle response, which contrasted the behaviour elicited by the continuous drilling noise. When presented with the predatory mimic, fish exposed to both piling and drilling noise explored the experimental arena more extensively than control fish exposed to ambient noise. Fish under drilling and piling conditions also exhibited reduced predator inspection behaviour. Piling and drilling noise induced stress as measured by ventilation rate. This study provides further evidence that the behaviour and physiology of European seabass is significantly affected by exposure to elevated noise levels. Copyright © 2017. Published by Elsevier Ltd.

Joy without demands: Hospital clowns in the world of ailing children

PubMed Central

Linge, Lotta

2011-01-01

The aim of the present study was to achieve, using an affect theory approach (Tomkins, 1962; 1963; 1991), a deeper theoretical understanding of the psychological significance of hospital clowns' work in caring for ailing children viewed from a care-giver perspective. The methodological approach was qualitative and based on 20 interviews with healthcare staff: 3 men and 17 women. The result showed how the staff emphasized a psychological quality of care alongside the physical quality of care. The hospital clowns' “unexpected possibility” provided a safe area for recovery, for both the children and the staff. The theoretical interpretation showed the presence of the affects surprise/startle, interest/excitement, and enjoyment/joy as well as specifically how “joy without demands” often had a lingering effect in the form of vitality. Joy without demands is discussed in relation to psychological theory with emphasis on: a confirmation of the body's possibilities, a magical attachment, a chance to transcend boundaries, and a non-demanding situation. PMID:21394247

A gut feeling: Microbiome-brain-immune interactions modulate social and affective behaviors.

PubMed

Sylvia, Kristyn E; Demas, Gregory E

2018-03-01

The expression of a wide range of social and affective behaviors, including aggression and investigation, as well as anxiety- and depressive-like behaviors, involves interactions among many different physiological systems, including the neuroendocrine and immune systems. Recent work suggests that the gut microbiome may also play a critical role in modulating behavior and likely functions as an important integrator across physiological systems. Microbes within the gut may communicate with the brain via both neural and humoral pathways, providing numerous avenues of research in the area of the gut-brain axis. We are now just beginning to understand the intricate relationships among the brain, microbiome, and immune system and how they work in concert to influence behavior. The effects of different forms of experience (e.g., changes in diet, immune challenge, and psychological stress) on the brain, gut microbiome, and the immune system have often been studied independently. Though because these systems do not work in isolation, it is essential to shift our focus to the connections among them as we move forward in our investigations of the gut-brain axis, the shaping of behavioral phenotypes, and the possible clinical implications of these interactions. This review summarizes the recent progress the field has made in understanding the important role the gut microbiome plays in the modulation of social and affective behaviors, as well as some of the intricate mechanisms by which the microbiome may be communicating with the brain and immune system. Copyright © 2018 Elsevier Inc. All rights reserved.

Corollary discharge inhibition of wind-sensitive cercal giant interneurons in the singing field cricket

PubMed Central

Hedwig, Berthold

2014-01-01

Crickets carry wind-sensitive mechanoreceptors on their cerci, which, in response to the airflow produced by approaching predators, triggers escape reactions via ascending giant interneurons (GIs). Males also activate their cercal system by air currents generated due to the wing movements underlying sound production. Singing males still respond to external wind stimulation, but are not startled by the self-generated airflow. To investigate how the nervous system discriminates sensory responses to self-generated and external airflow, we intracellularly recorded wind-sensitive afferents and ventral GIs of the cercal escape pathway in fictively singing crickets, a situation lacking any self-stimulation. GI spiking was reduced whenever cercal wind stimulation coincided with singing motor activity. The axonal terminals of cercal afferents showed no indication of presynaptic inhibition during singing. In two ventral GIs, however, a corollary discharge inhibition occurred strictly in phase with the singing motor pattern. Paired intracellular recordings revealed that this inhibition was not mediated by the activity of the previously identified corollary discharge interneuron (CDI) that rhythmically inhibits the auditory pathway during singing. Cercal wind stimulation, however, reduced the spike activity of this CDI by postsynaptic inhibition. Our study reveals how precisely timed corollary discharge inhibition of ventral GIs can prevent self-generated airflow from triggering inadvertent escape responses in singing crickets. The results indicate that the responsiveness of the auditory and wind-sensitive pathway is modulated by distinct CDIs in singing crickets and that the corollary discharge inhibition in the auditory pathway can be attenuated by cercal wind stimulation. PMID:25318763

Fear processing and social networking in the absence of a functional amygdala.

PubMed

Becker, Benjamin; Mihov, Yoan; Scheele, Dirk; Kendrick, Keith M; Feinstein, Justin S; Matusch, Andreas; Aydin, Merve; Reich, Harald; Urbach, Horst; Oros-Peusquens, Ana-Maria; Shah, Nadim J; Kunz, Wolfram S; Schlaepfer, Thomas E; Zilles, Karl; Maier, Wolfgang; Hurlemann, René

2012-07-01

The human amygdala plays a crucial role in processing social signals, such as face expressions, particularly fearful ones, and facilitates responses to them in face-sensitive cortical regions. This contributes to social competence and individual amygdala size correlates with that of social networks. While rare patients with focal bilateral amygdala lesion typically show impaired recognition of fearful faces, this deficit is variable, and an intriguing possibility is that other brain regions can compensate to support fear and social signal processing. To investigate the brain's functional compensation of selective bilateral amygdala damage, we performed a series of behavioral, psychophysiological, and functional magnetic resonance imaging experiments in two adult female monozygotic twins (patient 1 and patient 2) with equivalent, extensive bilateral amygdala pathology as a sequela of lipoid proteinosis due to Urbach-Wiethe disease. Patient 1, but not patient 2, showed preserved recognition of fearful faces, intact modulation of acoustic startle responses by fear-eliciting scenes, and a normal-sized social network. Functional magnetic resonance imaging revealed that patient 1 showed potentiated responses to fearful faces in her left premotor cortex face area and bilaterally in the inferior parietal lobule. The premotor cortex face area and inferior parietal lobule are both implicated in the cortical mirror-neuron system, which mediates learning of observed actions and may thereby promote both imitation and empathy. Taken together, our findings suggest that despite the pre-eminent role of the amygdala in processing social information, the cortical mirror-neuron system may sometimes adaptively compensate for its pathology. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Nonlinear optical effects of opening a gap in graphene

NASA Astrophysics Data System (ADS)

Carvalho, David N.; Biancalana, Fabio; Marini, Andrea

2018-05-01

Graphene possesses remarkable electronic, optical, and mechanical properties that have taken the research of two-dimensional relativistic condensed matter systems to prolific levels. However, the understanding of how its nonlinear optical properties are affected by relativisticlike effects has been broadly uncharted. It has been recently shown that highly nontrivial currents can be generated in free-standing samples, notably leading to the generation of even harmonics. Since graphene monolayers are centrosymmetric media, for which such harmonic generation at normal incidence is deemed inaccessible, this light-driven phenomenon is both startling and promising. More realistically, graphene samples are often deposited on a dielectric substrate, leading to additional intricate interactions. Here, we present a treatment to study this instance by gapping the spectrum and we show this leads to the appearance of a Berry phase in the carrier dynamics. We analyze the role of such a phase in the generated nonlinear current and conclude that it suppresses odd-harmonic generation. The pump energy can be tuned to the energy gap to yield interference among odd harmonics mediated by interband transitions, allowing even harmonics to be generated. Our results and general methodology pave the way for understanding the role of gap opening in the nonlinear optics of two-dimensional lattices.

Association Study of CHRNA7 Promoter Variants with Sensory and Sensorimotor Gating in Schizophrenia Patients and Healthy Controls: A Danish Case-Control Study.

PubMed

Bertelsen, Birgitte; Oranje, Bob; Melchior, Linea; Fagerlund, Birgitte; Werge, Thomas M; Mikkelsen, Jens D; Tümer, Zeynep; Glenthøj, Birte Y

2015-12-01

Schizophrenia is a severe psychiatric disorder with a core component of impaired cognitive function still remaining as one of the greatest challenges in the pharmacological treatment of the disorder. The CHRNA7 gene, encoding the subunit of the human α7 nicotinic acetylcholine receptor (α7nAChR), is suggested as a susceptibility factor for schizophrenia. CHRNA7 has also been genetically linked to the P50 auditory evoked potential deficit, a candidate endophenotype of schizophrenia, but not to prepulse inhibition of the startle reflex (PPI). In this study, 95 antipsychotic-naïve schizophrenic patients and 450 unaffected controls were screened for CHRNA7 promoter variants to investigate the association with schizophrenia, P50 suppression and PPI. We found that the promoter variant -194C (rs28531779) was significantly associated with schizophrenia, but did not find any association of this variant with P50 suppression or PPI. In addition, individuals with CHRNA7 promoter variants had elevated startle magnitude in pulse-alone trials compared to individuals without a variant. The present findings provide further support for a role of the α7nAChR in schizophrenia and show a genetic link between CHRNA7 and startle magnitude, indicating that cholinergic neurotransmission involving the α7nAChR could be involved in sensory registration processes.

Cystic Fibrosis and the Nervous System.

PubMed

Reznikov, Leah R

2017-05-01

Cystic fibrosis (CF) is a life-shortening autosomal recessive disorder caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is an anion channel that conducts bicarbonate and chloride across cell membranes. Although defective anion transport across epithelial cells is accepted as the basic defect in CF, many of the features observed in people with CF and organs affected by CF are modulated by the nervous system. This is of interest because CFTR expression has been reported in both the peripheral and central nervous systems, and it is well known that the transport of anions, such as chloride, greatly modulates neuronal excitability. Thus it is predicted that in CF, lack of CFTR in the nervous system affects neuronal function. Consistent with this prediction, several nervous system abnormalities and nervous system disorders have been described in people with CF and in animal models of CF. The goal of this special feature article is to highlight the expression and function of CFTR in the nervous system. Special emphasis is placed on nervous system abnormalities described in people with CF and in animal models of CF. Finally, features of CF that may be modulated by or attributed to faulty nervous system function are discussed. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

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 ...

The issue of FM to AM conversion on the National Ignition Facility

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

Browning, D F; Rothenberg, J E; Wilcox, R B

1998-08-13

The National Ignition Facility (NIF) baseline configuration for inertial confinement fusion requires phase modulation for two purposes. First, ~ 1Å of frequency modulation (FM) bandwidth at low modulation frequency is required to suppress buildup of Stimulated Brioullin Scattering (SBS) in the large aperture laser optics. Also ~ 3 Å or more bandwidth at high modulation frequency is required for smoothing of the speckle pattern illuminating the target by the smoothing by spectral dispersion method (SSD). Ideally, imposition of bandwidth by pure phase modulation does not affect the beam intensity. However, as a result of a large number of effects, themore » FM converts to amplitude modulation (AM). In general this adversely affects the laser performance, e.g. by reducing the margin against damage to the optics. In particular, very large conversion of FM to AM has been observed in the NIF all-fiber master oscillator and distribution systems. The various mechanisms leading to AM are analyzed and approaches to minimizing their effects are discussed.« less

A quantitative method for photovoltaic encapsulation system optimization

NASA Technical Reports Server (NTRS)

Garcia, A., III; Minning, C. P.; Cuddihy, E. F.

1981-01-01

It is pointed out that the design of encapsulation systems for flat plate photovoltaic modules requires the fulfillment of conflicting design requirements. An investigation was conducted with the objective to find an approach which will make it possible to determine a system with optimum characteristics. The results of the thermal, optical, structural, and electrical isolation analyses performed in the investigation indicate the major factors in the design of terrestrial photovoltaic modules. For defect-free materials, minimum encapsulation thicknesses are determined primarily by structural considerations. Cell temperature is not strongly affected by encapsulant thickness or thermal conductivity. The emissivity of module surfaces exerts a significant influence on cell temperature. Encapsulants should be elastomeric, and ribs are required on substrate modules. Aluminum is unsuitable as a substrate material. Antireflection coating is required on cell surfaces.

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.

Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain.

PubMed

Levin, Raquel; Peres, Fernanda F; Almeida, Valéria; Calzavara, Mariana B; Zuardi, Antonio W; Hallak, Jaime E C; Crippa, José Alexandre S; Abílio, Vanessa C

2014-01-01

Clinical and neurobiological findings suggest that the cannabinoids and the endocannabinoid system may be implicated in the pathophysiology and treatment of schizophrenia. We described that the spontaneously hypertensive rats (SHR) strain presents a schizophrenia behavioral phenotype that is specifically attenuated by antipsychotic drugs, and potentiated by proschizophrenia manipulations. Based on these findings, we have suggested this strain as an animal model of schizophrenia. The aim of this study was to evaluate the effects of cannabinoid drugs on the deficit of prepulse inhibition (PPI) of startle, the main paradigm used to study sensorimotor gating impairment related to schizophrenia, presented by the SHR strain. The following drugs were used: (1) WIN55212,2 (cannabinoid agonist), (2) rimonabant (CB1 antagonist), (3) AM404 (anandamide uptake inhibitor), and (4) cannabidiol (CBD; indirect CB1/CB2 receptor antagonist, among other effects). Wistar rats (WRs) and SHRs were treated with vehicle (VEH) or different doses of WIN55212 (0.3, 1, or 3 mg/kg), rimonabant (0.75, 1.5, or 3 mg/kg), AM404 (1, 5, or 10 mg/kg), or CBD (15, 30, or 60 mg/kg). VEH-treated SHRs showed a decreased PPI when compared to WRs. This PPI deficit was reversed by 1 mg/kg WIN and 30 mg/kg CBD. Conversely, 0.75 mg/kg rimonabant decreased PPI in SHR strain, whereas AM404 did not modify it. Our results reinforce the role of the endocannabinoid system in the sensorimotor gating impairment related to schizophrenia, and point to cannabinoid drugs as potential therapeutic strategies.

Dopaminergic regulation of sleep and cataplexy in a murine model of narcolepsy.

PubMed

Burgess, Christian R; Tse, Gavin; Gillis, Lauren; Peever, John H

2010-10-01

To determine if the dopaminergic system modulates cataplexy, sleep attacks and sleep-wake behavior in narcoleptic mice. Hypocretin/orexin knockout (i.e., narcoleptic) and wild-type mice were administered amphetamine and specific dopamine receptor modulators to determine their effects on sleep, cataplexy and sleep attacks. Hypocretin knockout (n = 17) and wild-type mice (n = 21). Cataplexy, sleep attacks and sleep-wake behavior were identified using electroencephalogram, electromyogram and videography. These behaviors were monitored for 4 hours after an i.p. injection of saline, amphetamine and specific dopamine receptor modulators (D1- and D2-like receptor modulators). Amphetamine (2 mg/kg), which increases brain dopamine levels, decreased sleep attacks and cataplexy by 61% and 67%, suggesting that dopamine transmission modulates such behaviors. Dopamine receptor modulation also had powerful effects on sleep attacks and cataplexy. Activation (SKF 38393; 20 mg/kg) and blockade (SCH 23390; 1 mg/kg) of D1-like receptors decreased and increased sleep attacks by 77% and 88%, without affecting cataplexy. Pharmacological activation of D2-like receptors (quinpirole; 0.5 mg/kg) increased cataplectic attacks by 172% and blockade of these receptors (eticlopride; 1 mg/kg) potently suppressed them by 97%. Manipulation of D2-like receptors did not affect sleep attacks. We show that the dopaminergic system plays a role in regulating both cataplexy and sleep attacks in narcoleptic mice. We found that cataplexy is modulated by a D2-like receptor mechanism, whereas dopamine modulates sleep attacks by a D1-like receptor mechanism. These results support a role for the dopamine system in regulating sleep attacks and cataplexy in a murine model of narcolepsy.

Noninvasive treatment alternative for intractable startle epilepsy

PubMed Central

Klinkenberg, Sylvia; Ubbink, Sander; Vles, Johannes; de Louw, Anton; van Hall, Mariette Debeij; Scheijen, Dyon; Brokx, Jan

2014-01-01

We describe a treatment alternative for intractable, startle-provoked, epileptic seizures in four children aged between 8 and 14. Three of the four children had symptomatic localization-related epilepsy. They all suffered from intractable epilepsy precipitated by sudden sounds. The fact that seizures tended to occur with high frequency – more than one seizure a day – had a clear impact on daily life. Clinical seizure pattern demonstrated asymmetric tonic posturing in all four children. Three children experienced several seizure types including focal seizure onset. All children had focal neurological signs or learning disabilities or a combination of both. Our noninvasive treatment method using psychoeducational counseling and sound generators was applied in four children, resulting in a seizure frequency reduction of ≥ 50% in two of them. PMID:25667869

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

Tsalafoutas, Ioannis A.; Varsamidis, Athanasios; Thalassinou, Stella

Purpose: To investigate the utility of the nested polymethylacrylate (PMMA) phantom (which is available in many CT facilities for CTDI measurements), as a tool for the presentation and comparison of the ways that two different CT automatic exposure control (AEC) systems respond to a phantom when various scan parameters and AEC protocols are modified.Methods: By offsetting the two phantom's components (the head phantom and the body ring) half-way along their longitudinal axis, a phantom with three sections of different x-ray attenuation was created. Scan projection radiographs (SPRs) and helical scans of the three-section phantom were performed on a Toshiba Aquilionmore » 64 and a Philips Brilliance 64 CT scanners, with different scan parameter selections [scan direction, pitch factor, slice thickness, and reconstruction interval (ST/RI), AEC protocol, and tube potential used for the SPRs]. The dose length product (DLP) values of each scan were recorded and the tube current (mA) values of the reconstructed CT images were plotted against the respective Z-axis positions on the phantom. Furthermore, measurements of the noise levels at the center of each phantom section were performed to assess the impact of mA modulation on image quality.Results: The mA modulation patterns of the two CT scanners were very dissimilar. The mA variations were more pronounced for Aquilion 64, where changes in any of the aforementioned scan parameters affected both the mA modulations curves and DLP values. However, the noise levels were affected only by changes in pitch, ST/RI, and AEC protocol selections. For Brilliance 64, changes in pitch affected the mA modulation curves but not the DLP values, whereas only AEC protocol and SPR tube potential selection variations affected both the mA modulation curves and DLP values. The noise levels increased for smaller ST/RI, larger weight category AEC protocol, and larger SPR tube potential selection.Conclusions: The nested PMMA dosimetry phantom can be effectively utilized for the comprehension of CT AEC systems performance and the way that different scan conditions affect the mA modulation patterns, DLP values, and image noise. However, in depth analysis of the reasons why these two systems exhibited such different behaviors in response to the same phantom requires further investigation which is beyond the scope of this study.« less

Emotional reactivity to threat modulates activity in mentalizing network during aggression.

PubMed

Beyer, Frederike; Münte, Thomas F; Erdmann, Christian; Krämer, Ulrike M

2014-10-01

Aggression is a common response to provocation, albeit with considerable interindividual differences. In this fMRI study, we investigated emotional reactivity to threat as possible link between provocation and aggression, as well as the neural correlates of this relationship. We hypothesized that emotional reactivity, measured as fear potentiation (FP) of the startle response, would be negatively associated with aggressive behavior and would modulate neural activity during an aggressive interaction. In 30 healthy female participants, FP was measured as the difference between blink amplitudes while watching threatening vs neutral pictures. Participants subsequently engaged in a variant of the Taylor Aggression Paradigm (TAP), while being scanned. During the TAP, participants selected a punishment level for either a highly provoking or a nonprovoking opponent. There was no difference in aggressive behavior between participants high and low in FP. However, we found a negative correlation between FP and the neural provocation effect in several regions of a network previously associated with mentalizing including the medial prefrontal cortex, precuneus and the temporo-parietal junction. Independently of the FP variability, aggressive behavior correlated with the provocation effect on activity in the caudate nucleus. Our results indicate that during a provocative confrontation, high emotional reactivity to threat suppresses recruitment of the mentalizing network. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

"Hey, Bernie," I Said, "What's New?"

ERIC Educational Resources Information Center

Otto, Wayne

1994-01-01

Discusses a startlingly current 1953 article called "Recent Trends in the Teaching of Reading" by Virgil Herrick, and a 1992 book by James Moffett called "Harmonic Learning: Keynoting School Reform." (SR)

Field Trials of the Multi-Source Approach for Resistivity and Induced Polarization Data Acquisition

NASA Astrophysics Data System (ADS)

LaBrecque, D. J.; Morelli, G.; Fischanger, F.; Lamoureux, P.; Brigham, R.

2013-12-01

Implementing systems of distributed receivers and transmitters for resistivity and induced polarization data is an almost inevitable result of the availability of wireless data communication modules and GPS modules offering precise timing and instrument locations. Such systems have a number of advantages; for example, they can be deployed around obstacles such as rivers, canyons, or mountains which would be difficult with traditional 'hard-wired' systems. However, deploying a system of identical, small, battery powered, transceivers, each capable of injecting a known current and measuring the induced potential has an additional and less obvious advantage in that multiple units can inject current simultaneously. The original purpose for using multiple simultaneous current sources (multi-source) was to increase signal levels. In traditional systems, to double the received signal you inject twice the current which requires you to apply twice the voltage and thus four times the power. Alternatively, one approach to increasing signal levels for large-scale surveys collected using small, battery powered transceivers is it to allow multiple units to transmit in parallel. In theory, using four 400 watt transmitters on separate, parallel dipoles yields roughly the same signal as a single 6400 watt transmitter. Furthermore, implementing the multi-source approach creates the opportunity to apply more complex current flow patterns than simple, parallel dipoles. For a perfect, noise-free system, multi-sources adds no new information to a data set that contains a comprehensive set of data collected using single sources. However, for realistic, noisy systems, it appears that multi-source data can substantially impact survey results. In preliminary model studies, the multi-source data produced such startling improvements in subsurface images that even the authors questioned their veracity. Between December of 2012 and July of 2013, we completed multi-source surveys at five sites with depths of exploration ranging from 150 to 450 m. The sites included shallow geothermal sites near Reno Nevada, Pomarance Italy, and Volterra Italy; a mineral exploration site near Timmins Quebec; and a landslide investigation near Vajont Dam in northern Italy. These sites provided a series of challenges in survey design and deployment including some extremely difficult terrain and a broad range of background resistivity and induced values. Despite these challenges, comparison of multi-source results to resistivity and induced polarization data collection with more traditional methods support the thesis that the multi-source approach is capable of providing substantial improvements in both depth of penetration and resolution over conventional approaches.

Land Application of Wastes: An Educational Program. Waste Characteristics - Module 5, Objectives, and Script.

ERIC Educational Resources Information Center

Clarkson, W. W.; And Others

This module introduces the physical, biological, and chemical constituents of wastewaters and sludges which are of concern in land treatment systems. The characteristics of typical municipal wastewater are tabulated for strong, medium, and weak sewages. Some of the factors affecting pollutant concentrations are listed. Flow, distribution and…

Transient Delivery of Adenosine as a Novel Therapy to Prevent Epileptogenesis

DTIC Science & Technology

2013-08-01

rats characterized by the development of SRS triggered by systemic kainic acid–induced (KA-induced) status epilepticus (SE) (Figure 3A). Using...to modulate DNA methylation status , have not been studied to date. Based on ADO’s role as an obligatory end product of DNA methylation, we...1E). Together, these findings show that modulating ADO tone either directly or via modulation of ADK expression can affect DNA methylation status in

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 Association of Schizophrenia Risk -Amino Acid Oxidase Polymorphisms With Sensorimotor Gating, Working Memory and Personality in Healthy Males

PubMed Central

Roussos, Panos; Giakoumaki, Stella G; Adamaki, Eva; Anastasios, Georgakopoulos; Nikos, Robakis K; Bitsios, Panos

2011-01-01

There is evidence supporting a role for the -amino acid oxidase (DAO) locus in schizophrenia. This study aimed to determine the relationship of five single-nucleotide polymorphisms (SNPs) within the DAO gene identified as promising schizophrenia risk genes (rs4623951, rs2111902, rs3918346, rs3741775, and rs3825251) to acoustic startle, prepulse inhibition (PPI), working memory, and personality dimensions. A highly homogeneous study entry cohort (n=530) of healthy, young male army conscripts (n=703) originating from the Greek LOGOS project (Learning On Genetics Of Schizophrenia Spectrum) underwent PPI of the acoustic startle reflex, working memory, and personality assessment. The QTPHASE from the UNPHASED package was used for the association analysis of each SNP or haplotype data, with p-values corrected for multiple testing by running 10 000 permutations of the data. The rs4623951_T-rs3741775_G and rs4623951_T-rs2111902_T diplotypes were associated with reduced PPI and worse performance in working memory tasks and a personality pattern characterized by attenuated anxiety. Median stratification analysis of the risk diplotype group (ie, those individuals homozygous for the T and G alleles (TG+)) showed reduced PPI and working memory performance only in TG+ individuals with high trait anxiety. The rs4623951_T allele, which is the DAO polymorphism most strongly associated with schizophrenia, might tag a haplotype that affects PPI, cognition, and personality traits in general population. Our findings suggest an influence of the gene in the neural substrate mediating sensorimotor gating and working memory, especially when combined with high anxiety and further validate DAO as a candidate gene for schizophrenia and spectrum disorders. PMID:21471957

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

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.

Omega-3 prevents behavior response and brain oxidative damage in the ketamine model of schizophrenia.

PubMed

Zugno, A I; Chipindo, H L; Volpato, A M; Budni, J; Steckert, A V; de Oliveira, M B; Heylmann, A S; da Rosa Silveira, F; Mastella, G A; Maravai, S G; Wessler, P G; Binatti, A R; Panizzutti, B; Schuck, P F; Quevedo, J; Gama, C S

2014-02-14

Supplementation with omega-3 has been identified as an adjunctive alternative for the treatment of psychiatric disorders, in order to minimize symptoms. Considering the lack of understanding concerning the pathophysiology of schizophrenia, the present study hypothesized that omega 3 prevents the onset of symptoms similar to schizophrenia in young Wistar rats submitted to ketamine treatment. Moreover, the role of oxidative stress in this model was assessed. Omega-3 (0.8g/kg) or vehicle was given by orogastric gavage once daily. Both treatments were performed during 21days, starting at the 30th day of life in young rats. After 14days of treatment with omega-3 or vehicle, a concomitant treatment with saline or ketamine (25mg/kg ip daily) was started and maintained until the last day of the experiment. We evaluated the pre-pulse inhibition of the startle reflex, activity of antioxidant systems and damage to proteins and lipids. Our results demonstrate that supplementation of omega-3 prevented: decreased inhibition of startle reflex, damage to lipids in the hippocampus and striatum and damage to proteins in the prefrontal cortex. Furthermore, these changes are associated with decreased GPx in brain tissues evaluated. Together, our results suggest the prophylactic role of omega-3 against the outcome of symptoms associated with schizophrenia. Copyright © 2014. Published by Elsevier Ltd.

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

Setting apart the affected: the use of behavioral criteria in animal models of post traumatic stress disorder.

PubMed

Cohen, Hagit; Zohar, Joseph; Matar, Michael A; Zeev, Kaplan; Loewenthal, Uri; Richter-Levin, Gal

2004-11-01

Post-traumatic stress disorder (PTSD) affects about 20-30% of exposed individuals. Clinical studies of PTSD generally employ stringent criteria for inclusion in study populations, and yet in animal studies the data collection and analysis are generally expressed as a function of exposed vs nonexposed populations, regardless of individual variation in response. Prior data support an approach to animal models analogous to inclusion criteria in clinical studies. This series of studies sought to assess prevalence rates of maladaptive vs adaptive responses determined according to a more stringent approach to the concept of inclusion/exclusion criteria (cutoff behavioral criteria-CBC), consisting of two successive behavioral tests (elevated plus maze and acoustic startle response tests). The rats were exposed to stressors in two different paradigms; exposure to a predator and underwater trauma. The prevalence rates of maladaptive responses to stress in these two distinct models dropped over time from 90% in the acute phase to 25% enduring/maladaptive response at 7 days, to remain constant over 30 days. As setting the affected individuals apart from the unaffected approximates clinical studies, it might also help to clarify some of the pending issues in PTSD research.

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.

Informing Rodent Behavior in Space: Gene Expression and Hyper-Emotionality Following Prenatal Stress

NASA Technical Reports Server (NTRS)

Moyer, E. L.; Talyansky, Y.; Baer, L. A.; Ronca, A. E.

2017-01-01

As space exploration pushes our boundaries further away from Earth and for longer durations, we will inevitably require the use of multi-generational studies to continue our expansion. Space is a stressful environment not only due to the deleterious effect of spaceflight on physiology, but also due to confinement, limited social interactions, inherently dangerous circumstances, and many other stresses of an unknown environment. Stress can alter the brain chemistry, and these alterations can affect behavior at all stages of development, but it is especially pronounced during the perinatal period and can have longstanding effects, even into adulthood, which manifest through augmented brain function and psychopathology. This study investigated the nexus of brain chemistry and brain function by observing behavior of adult rats whose mothers were exposed to unpredictable variable prenatal stress (UVPS) while they were in the womb. The UVPS consisted of strobe light, tube restraint, and white noise, and was administered at unpredictable times of the day and also varied in length, both of which were measures taken to prevent habituation to the stressor. The offspring rats were then allowed to reach adulthood and at 90 days were subjected to a series of behavioral tests including novel object, startle response, and an unknown intruder to quantify the adult rats stress response and anxiety. Here we report these results of the behavioral analysis and correlate adult behavioral measures with the expression of genes involved in the hypothalamic-pituitary-adrenal axis, which modulates the animals stress response. We hypothesized that hyper-expression of genes involved in the HPA axis would correlate with the observed anxiety-like behaviors associated with early stress.

Red Plankton in the Arabian Sea

NASA Image and Video Library

2004-10-02

In the Arabian Sea, sunlight and nutrients has fueled a startling occurrence of colorful phytoplankton and bacterial assemblages, which is captured in these natural color images from NASA Terra spacecraft October 2, 2004.

Web Based Rapid Mapping of Disaster Areas using Satellite Images, Web Processing Service, Web Mapping Service, Frequency Based Change Detection Algorithm and J-iView

NASA Astrophysics Data System (ADS)

Bandibas, J. C.; Takarada, S.

2013-12-01

Timely identification of areas affected by natural disasters is very important for a successful rescue and effective emergency relief efforts. This research focuses on the development of a cost effective and efficient system of identifying areas affected by natural disasters, and the efficient distribution of the information. The developed system is composed of 3 modules which are the Web Processing Service (WPS), Web Map Service (WMS) and the user interface provided by J-iView (fig. 1). WPS is an online system that provides computation, storage and data access services. In this study, the WPS module provides online access of the software implementing the developed frequency based change detection algorithm for the identification of areas affected by natural disasters. It also sends requests to WMS servers to get the remotely sensed data to be used in the computation. WMS is a standard protocol that provides a simple HTTP interface for requesting geo-registered map images from one or more geospatial databases. In this research, the WMS component provides remote access of the satellite images which are used as inputs for land cover change detection. The user interface in this system is provided by J-iView, which is an online mapping system developed at the Geological Survey of Japan (GSJ). The 3 modules are seamlessly integrated into a single package using J-iView, which could rapidly generate a map of disaster areas that is instantaneously viewable online. The developed system was tested using ASTER images covering the areas damaged by the March 11, 2011 tsunami in northeastern Japan. The developed system efficiently generated a map showing areas devastated by the tsunami. Based on the initial results of the study, the developed system proved to be a useful tool for emergency workers to quickly identify areas affected by natural disasters.

Proteomics tools reveal startlingly high amounts of oxytocin in plasma and serum

NASA Astrophysics Data System (ADS)

Brandtzaeg, Ole Kristian; Johnsen, Elin; Roberg-Larsen, Hanne; Seip, Knut Fredrik; Maclean, Evan L.; Gesquiere, Laurence R.; Leknes, Siri; Lundanes, Elsa; Wilson, Steven Ray

2016-08-01

The neuropeptide oxytocin (OT) is associated with a plethora of social behaviors, and is a key topic at the intersection of psychology and biology. However, tools for measuring OT are still not fully developed. We describe a robust nano liquid chromatography-mass spectrometry (nanoLC-MS) platform for measuring the total amount of OT in human plasma/serum. OT binds strongly to plasma proteins, but a reduction/alkylation (R/A) procedure breaks this bond, enabling ample detection of total OT. The method (R/A + robust nanoLC-MS) was used to determine total OT plasma/serum levels to startlingly high concentrations (high pg/mL-ng/mL). Similar results were obtained when combining R/A and ELISA. Compared to measuring free OT, measuring total OT can have advantages in e.g. biomarker studies.

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.

Gentle vs. aversive handling of pregnant ewes: II. Physiology and behavior of the lambs.

PubMed

Coulon, M; Hild, S; Schroeer, A; Janczak, A M; Zanella, A J

2011-07-06

We compared the effects of aversive and gentle handling in late pregnant ewes on fearfulness, heart rate variability and spatial learning in lambs. Twenty-four Norwegian-Dala ewes were studied. Ewes were subjected to gentle (i.e. soft talking and calm behavior) or aversive handling (i.e. swift movements and shouting) for 10 min twice a day during the last five weeks of pregnancy. Lambs from aversively (AVS) or gently (GEN) treated ewes were tested at 4 weeks of age. Lamb behavior was recorded during a) a human approach test, composed of 4 min of isolation and 4 min of exposure to an unfamiliar human, b) an umbrella startle test followed by 5-min recording, and c) two repetitions of a maze test. In addition, heart rate variability was recorded telemetrically before and after the human and startle tests. The baseline heart rate variability measures suggested a lower influence of vagal stimulation in AVS lambs. In the human approach test, AVS lambs vocalized and explored the environment less, and were slower to approach the human. They also tended to have higher flight distances during the startle test than the GEN lambs. The prenatal treatment had no significant effect in the maze test. In conclusion, we showed that aversive handling of pregnant ewes increased fearfulness and reduced vagal tone in their progeny compared to GEN lambs. These effects can have consequences for how lambs cope with rearing conditions. Copyright © 2011 Elsevier Inc. All rights reserved.

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

Recurrent Moderate Hypoglycemia Suppresses Brain-Derived Neurotrophic Factor Expression in the Prefrontal Cortex and Impairs Sensorimotor Gating in the Post-Hypoglycemia Period in Young Rats

PubMed Central

Rao, Raghavendra; Ennis, Kathleen; Mitchell, Eugena P.; Tran, Phu V.; Gewirtz, Jonathan C.

2016-01-01

Recurrent hypoglycemia is common in infants and children. In developing rat models, recurrent moderate hypoglycemia leads to neuronal injury in the medial prefrontal cortex. To understand the effects beyond neuronal injury, three-week-old male rats were subjected to five episodes of moderate hypoglycemia (blood glucose concentration, approximately 30 mg/dl for 90 min) once daily from postnatal day 24 to 28. Neuronal injury was determined using Fluoro-jade B histochemistry on postnatal day 29. The effects on brain-derived neurotrophic factor (BDNF) and its cognate receptor, tyrosine kinase B (TrkB) expression, which is critical for prefrontal cortex development, were determined on postnatal day 29 and at adulthood. The effects on prefrontal cortex-mediated function were determined by assessing prepulse inhibition of the acoustic startle reflex on postnatal day 29 and two weeks later, and by testing for fear-potentiated startle at adulthood. Recurrent hypoglycemia led to neuronal injury confined primarily to the medial prefrontal cortex. BDNF and TrkB expression in the prefrontal cortex was suppressed on postnatal day 29 and was accompanied by lower prepulse inhibition, suggesting impaired sensorimotor gating. Following the cessation of recurrent hypoglycemia, prepulse inhibition had recovered at two weeks. BDNF/TrkB expression in the prefrontal cortex had normalized and fear-potentiated startle was intact at adulthood. Recurrent moderate hypoglycemia during development has significant adverse effects on the prefrontal cortex in the post-hypoglycemia period. PMID:26820887

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

Biosphere Lost: Rethinking the Study of Global Environmental Systems

NASA Astrophysics Data System (ADS)

Foley, J. A.

2008-12-01

It is fair to say that our planet's most precious resource is land. Land is the source of the vast majority of our food and freshwater, nearly all of our fiber and raw materials, and many other important goods and services. It is also our home. But our relationship to the land has been dramatically changing over the history of our species, mainly through the invention and evolution of agriculture. Today, with the emergence of modern agricultural practices, coupled with the population growth and technological developments of recent centuries, we have transformed a staggering amount of the Earth's surface into highly managed landscapes. Even more startling: the widespread use of irrigation and chemical fertilizers has fundamentally altered the flows of water and nutrients across large regions of the globe. These modifications to the land have driven fundamental changes to the ecology of our planet. Even the effects of future climate change may not have such a major, transformative effect on the environment and on human society as human land use practices. However, despite the importance of land use in the global environment, we still know relatively little about how it affects ecological systems across local, regional and global scales. Here I will discuss new approaches to the study of a human-dominated biosphere. This work requires new, interdisciplinary research to help us understand the changing relationships between human actions and Earth's complex ecological systems. It also requires integrating this latest science into real-world decision- making and public policy, with the ultimate goal of managing our planet's ecological systems sustainably into the future.

DTMF-based pH-COP system

NASA Astrophysics Data System (ADS)

Shakila, Mohammed Fabin; Miriyala Premnath, Pravesh

2011-12-01

Short span notifications or acknowledgment of events plays a major criterion in our world. Henceforth this module can be rigged up with any system in order to control the activity and acknowledge the user at any preconfigured parameter. Approximated that toxic chemicals are mixed every 14.7 seconds Over 2 million Aquatic Creatures are affected every year. About 65% of reported water pollution resulted from Tanneries and Chemical factories. The pH-COP bestows the solution for these catastrophic events. This module being robust can be attached to any system viz. Voltage monitor, Security system, Fluid level/ pressure controller, pH sensor cum controller, etc. The pH-COP primarily comprises of a microcontroller and a DTMF transceiver. This control systems which is efficient enough to be interfaced with the TELE-ALERT MODULE or the pH-COP.

Optical phase aberration generation using a Liquid Crystal Spatial Light Modulator

NASA Astrophysics Data System (ADS)

Wilcox, Christopher C.

In this dissertation, a Liquid Crystal Spatial Light Modulator is used to simulate optical aberrations in an optical system. Any optical aberration can be simulated through the use of software developed for this project. A new method of simulating atmospheric turbulence is also presented. The Earth's atmosphere is a large, non-linear, non-homogeneous medium that is constantly flowing in a random fashion that affects light as it propagates through it. The Kolmogorov model for atmospheric turbulence is a description of the nature of the wavefront perturbations introduced by the atmosphere and it is one of the most accepted models. It is supported by a variety of experimental measurements and research and is quite widely used in simulations for atmospheric imaging. This model provides a statistical description of how random fluctuations in humidity and temperature affect the refractive index of the atmosphere for imaging through atmospheric turbulence. These refractive index fluctuations in turn affect the propagation of light through the atmosphere. An adaptive optical system can be developed to correct these wavefront perturbations for an optical system. However, prior to deployment, an adaptive optical system requires calibration and full characterization in the laboratory. Creating realistic atmospheric simulations is often expensive and computationally intensive using common techniques. To combat some of these issues often the temporal properties in the simulation are neglected. This dissertation outlines a new method developed for generating atmospheric turbulence and a testbed that simulates its aberrations far more inexpensively and with greater fidelity using a Liquid Crystal Spatial Light Modulator. This system allows the simulation of atmospheric seeing conditions ranging from very poor to very good and different algorithms may be easily employed on the device for comparison. These simulations can be dynamically generated and modified very quickly and easily. Using a Liquid Crystal Spatial Light Modulator to induce aberrations in an imaging system is not limited to simulating atmospheric turbulence. Any turbulence model can be used either statically or dynamically for multiple applications.

Automatic response activation in sequential affective priming: an ERP study

PubMed Central

Leuthold, Hartmut; Rothermund, Klaus; Schweinberger, Stefan R.

2012-01-01

Affective priming effects denote faster responses when two successively presented affective stimuli match in valence than when they mismatch. Two mechanisms have been proposed for their explanation: (i) Priming of affective information within a semantic network or distributed memory system (semantic priming). (ii) Automatic activation of the evaluative response through the affective prime (response priming). In this experiment, we sought more direct evidence for prime-induced response activations with measurement of the lateralized readiness potential (LRP). Onset of the stimulus-locked LRP was earlier in affectively congruent trials than in incongruent trials. In addition, priming modulated the LRP-amplitude of slow responses, indicating greater activation of the incorrect response hand in affectively incongruent trials. Onset of the response-locked LRP and peak latency of the P300 component were not modulated by priming but the amplitude of the N400 component was. In combination, these results suggest that both, semantic priming and response priming constitute affective priming effects in the evaluative categorization task. PMID:21642351

Evaluation of monograph selection in a health sciences library.

PubMed Central

Fenske, R E

1994-01-01

This article reports on an evaluation of recent monograph selections in a small academic health sciences library. Actual use of each new book was determined from date-due slips. Data were analyzed by broad subject, discipline, and number of uses. The startling result was that more than 60% of recent selections had been used little or not at all. To determine factors affecting use, the author examined aggregate data, used intuition, and assessed the raw data in more detail. Recommendations made to management were approved and implemented. The study bolstered confidence that it is possible to select materials with the highest potential for use and to depend on remote access for other needed works. It is suggested that other health sciences libraries undertake such studies and question the need to strive for comprehensive collections. PMID:7920335

Gain and power optimization of the wireless optical system with multilevel modulation.

PubMed

Liu, Xian

2008-06-01

When used in an outdoor environment to expedite networking access, the performance of wireless optical communication systems is affected by transmitter sway. In the design of such systems, much attention has been paid to developing power-efficient schemes. However, the bandwidth efficiency is also an important issue. One of the most natural approaches to promote bandwidth efficiency is to use multilevel modulation. This leads to multilevel pulse amplitude modulation in the context of intensity modulation and direct detection. We develop a model based on the four-level pulse amplitude modulation. We show that the model can be formulated as an optimization problem in terms of the transmitter power, bit error probability, transmitter gain, and receiver gain. The technical challenges raised by modeling and solving the problem include the analytical and numerical treatments for the improper integrals of the Gaussian functions coupled with the erfc function. The results demonstrate that, at the optimal points, the power penalty paid to the doubled bandwidth efficiency is around 3 dB.

Using PVFORM, a systems performance model, to determine optimum mounting configurations for flat-plate photovoltaic modules

NASA Astrophysics Data System (ADS)

Menicucci, D. F.

The performance of a photovoltaic (PV) system is affected by the particular mounting configuration selected. But the optimal configuration for various potential designs is unknown because too few PV systems have been fielded. Sandia National Laboratories (SNLA) is currently conducting a controlled field experiment in which four of the most commonly used module mounting configurations are being compared. The data from the experiment are used to verify the accuracy of PVFORM, a new PV performance model. The model is then used to simulate the performance of PV modules mounted in different configurations in eight sites throughtout the U.S. The module mounting configurations, the experimental methods used, the specialized statistical techniques used in the analysis and the final results of the effort are described. The module mounting configurations are rank ordered at each site according to their energy production performane and each is briefly discussed in terms of its advantages or disadvantages in various applications.