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

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.

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.

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.

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.

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.

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

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.

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.

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.

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

PubMed Central

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

2016-01-01

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

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.

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

PubMed

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

2012-04-01

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

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.

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

PubMed Central

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

2014-01-01

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

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

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

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

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

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.

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.

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.

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

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.

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.

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

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.

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.

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.

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

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.

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.

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.

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.

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

PubMed Central

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

2009-01-01

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

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.

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

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

PubMed

Luck, Camilla C; Lipp, Ottmar V

2017-05-01

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

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

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

PubMed

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

2012-08-01

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

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.

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.

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.

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

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.

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 ...

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.

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

PubMed

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

2018-05-18

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

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

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.

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.

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

PubMed Central

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

2017-01-01

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

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

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.

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.

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

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.

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.

"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.

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

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

PubMed

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

2013-12-01

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

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

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.

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.

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

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.

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

EPA Science Inventory

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

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…

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

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

PubMed Central

Genevsky, Alexander; Gard, David E.

2014-01-01

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

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

PubMed

Genevsky, Alexander; Gard, David E

2012-04-01

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

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.

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.

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

Generalized versus partial reflex seizures: a review.

PubMed

Italiano, Domenico; Ferlazzo, Edoardo; Gasparini, Sara; Spina, Edoardo; Mondello, Stefania; Labate, Angelo; Gambardella, Antonio; Aguglia, Umberto

2014-08-01

In this review we assess our currently available knowledge about reflex seizures with special emphasis on the difference between "generalized" reflex seizures induced by visual stimuli, thinking, praxis and language tasks, and "focal" seizures induced by startle, eating, music, hot water, somatosensory stimuli and orgasm. We discuss in particular evidence from animal, clinical, neurophysiological and neuroimaging studies supporting the concept that "generalized" reflex seizures, usually occurring in the setting of IGE, should be considered as focal seizures with quick secondary generalization. We also review recent advances in genetic and therapeutic approach of reflex seizures. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

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

PubMed

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

2017-05-15

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

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

PubMed

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

2013-11-15

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

Variable Foreperiod Deficits in Parkinson's Disease: Dissociation across Reflexive and Voluntary Behaviors

ERIC Educational Resources Information Center

Jurkowski, A.J.; Stepp, E.; Hackley, S.A.

2005-01-01

The effect of a visual warning signal (1.0-6.5s random foreperiod, FP) on the latency of voluntary (hand-grip) and reflexive (startle-eyeblink) reactions was investigated in Parkinson's disease (PD) patients and in young and aged control subjects. Equivalent FP effects on blink were observed across groups. By contrast, FP effects diverged for…

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

PubMed

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

2016-01-01

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

[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.

Hip proprioceptors preferentially modulate reflexes of the leg in human spinal cord injury

PubMed Central

Onushko, Tanya; Hyngstrom, Allison

2013-01-01

Stretch-sensitive afferent feedback from hip muscles has been shown to trigger long-lasting, multijoint reflex responses in people with chronic spinal cord injury (SCI). These reflexes could have important implications for control of leg movements during functional activities, such as walking. Because the control of leg movement relies on reflex regulation at all joints of the limb, we sought to determine whether stretch of hip muscles modulates reflex activity at the knee and ankle and, conversely, whether knee and ankle stretch afferents affect hip-triggered reflexes. A custom-built servomotor apparatus was used to stretch the hip muscles in nine chronic SCI subjects by oscillating the legs about the hip joint bilaterally from 10° of extension to 40° flexion. To test whether stretch-related feedback from the knee or ankle would be affected by hip movement, patellar tendon percussions and Achilles tendon vibration were delivered when the hip was either extending or flexing. Surface electromyograms (EMGs) and joint torques were recorded from both legs. Patellar tendon percussions and Achilles tendon vibration both elicited reflex responses local to the knee or ankle, respectively, and did not influence reflex responses observed at the hip. Rather, the movement direction of the hip modulated the reflex responses local to the joint. The patellar tendon reflex amplitude was larger when the perturbation was delivered during hip extension compared with hip flexion. The response to Achilles vibration was modulated by hip movement, with an increased tonic component during hip flexion compared with extension. These results demonstrate that hip-mediated sensory signals modulate activity in distal muscles of the leg and appear to play a unique role in modulation of spastic muscle activity throughout the leg in SCI. PMID:23615544

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.

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

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

[Clinical and genetic analysis of hyperekplexia in a Chinese child and literature review].

PubMed

Li, H; Yang, Z X; Xue, J; Qian, P; Liu, X Y

2017-02-02

Objective: To investigate the clinical and genetic features of a Chinese child with hyperekplexia and review the related literature. Method: The clinical and genetic data of one patient with hyperekplexia, who had visited the department of Pediatrics, Peking University First Hospital in July 2012, were analyzed. "Hyperekplexia" "startle disease" "GLRB" were used as key words to search at CNKI, Wanfang and PubMed from the database from creation to August 2016. Result: The one-year-old female patient showed exaggerated startle reflexes and generalized stiffness in response to external sudden, unexpected stimuli at 2 hours after birth, which existed every day. Her younger twin sister died of severe apnea due to a continuous generalized stiffness at the age of 7 months. Physical examination exhibited the positive nose-tapping reflex. There were no obvious abnormalities in laboratory tests, electroencephalogram (EEG) and neuroimaging tests. The patient was revealed to have compound heterozygous mutations in GLRB gene, c. 298-1G>A (or IVS4-1G>A) inherited from the father and c. 347T>C (p. L116P) inherited from the mother. The mutation L116P in GLRB gene was not reported before. During the follow-up until 5 years old, the girl's symptoms of startle reflexes and generalized stiffness were controlled with clonazepam treatment. Her mental development was normal, but she walked very carefully as wide-based gait to avoid of external sudden stimuli. Literature retrieval obtained 8 reports (all in English) with 39 GLRB-related cases. Combined analysis of the data of the 39 foreign cases and our case showed that the onset age of all 40 cases was in neonatal or in utero, and all presented exaggerated startle reflexes and generalized stiffness in response to external stimuli. Other symptoms included neonatal apneas (83%, 20/24), falls (56%, 15/27) and squint (42%, 10/24) etc. EEG (13/13) and brain imaging (90%, 28/31) were normal, or unrelated/nonspecific to hyperekplexia. In the total 17 mutations of GLRB gene found in 28 cases, the most frequent mutations were GLRB gene M177R (9 cases) and IVS5+ 5G>A (5 cases). Most cases (82%, 32/39) had received the treatment of clonazepam. The symptoms of hyperekplexia all could be improved in different degree after treatment, and 84% (32/38) of the cases were completely controlled or only existed exaggerated startle reflexes. The psychomotor development could be normal (13 cases) or retarded (25 cases). Conclusion: The patient presented typical clinical manifestations of hyperekplexia and had a good response to clonazepam. The patient carried GLRB gene mutations found by genetic analysis, and was finally diagnosed with hyperekplexia. The younger twin sister died due to lack of timely diagnosis and treatment, suggesting the significance of early detection and proper treatment for this disease.

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.

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.

Methodological optimization of tinnitus assessment using prepulse inhibition of the acoustic startle reflex.

PubMed

Longenecker, R J; Galazyuk, A V

2012-11-16

Recently prepulse inhibition of the acoustic startle reflex (ASR) became a popular technique for tinnitus assessment in laboratory animals. This method confers a significant advantage over the previously used time-consuming behavioral approaches utilizing basic mechanisms of conditioning. Although this technique has been successfully used to assess tinnitus in different laboratory animals, many of the finer details of this methodology have not been described enough to be replicated, but are critical for tinnitus assessment. Here we provide detail description of key procedures and methodological issues that provide guidance for newcomers with the process of learning to correctly apply gap detection techniques for tinnitus assessment in laboratory animals. The major categories of these issues include: refinement of hardware for best performance, optimization of stimulus parameters, behavioral considerations, and identification of optimal strategies for data analysis. This article is part of a Special Issue entitled: Tinnitus Neuroscience. Copyright © 2012. Published by Elsevier B.V.

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

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 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.

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.

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).

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

Effects of perinatal asphyxia on the neurobehavioral and retinal development of newborn rats.

PubMed

Kiss, Peter; Szogyi, Donat; Reglodi, Dora; Horvath, Gabor; Farkas, Jozsef; Lubics, Andrea; Tamas, Andrea; Atlasz, Tamas; Szabadfi, Krisztina; Babai, Norbert; Gabriel, Robert; Koppan, Miklos

2009-02-19

Perinatal asphyxia during delivery produces long-term deficits and represents a major problem in both neonatal and pediatric care. Several morphological, biochemical and behavioral changes have been described in rats exposed to perinatal asphyxia. The aim of the present study was to evaluate how perinatal asphyxia affects the complex early neurobehavioral development and retinal structure of newborn rats. Asphyxia was induced in ready-to-deliver mothers by removing the pups by cesarian section after 15 min of asphyxia. Somatic and neurobehavioral development was tested daily during the first 3 weeks, and motor coordination tests were performed on postnatal weeks 3-5. After completion of the testing procedure, retinas were removed for histological analysis. We found that in spite of the fast catch-up-growth of asphyctic pups, nearly all examined reflexes were delayed by 1-4 days: negative geotaxis, sensory reflexes, righting reflexes, development of fore- and hindlimb grasp and placing, gait and auditory startle reflexes. Time to perform negative geotaxis, surface righting and gait reflexes was significantly longer during the first few weeks in asphyctic pups. Among the motor coordination tests, a markedly weaker performance was observed in the grid walking and footfault test and in the walk initiation test. Retinal structure showed severe degeneration in the layer of the photoreceptor and bipolar cell bodies. In summary, our present study provided a detailed description of reflex and motor development following perinatal asphyxia, showing that asphyxia led to a marked delay in neurobehavioral development and a severe retinal degeneration.

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

Putative antipsychotics with pronounced agonism at serotonin 5-HT1A and partial agonist activity at dopamine D2 receptors disrupt basal PPI of the startle reflex in rats.

PubMed

Auclair, Agnès L; Galinier, Alexandra; Besnard, Joël; Newman-Tancredi, Adrian; Depoortère, Ronan

2007-07-01

Prepulse inhibition (PPI) of the startle reflex has been extensively studied because it is disrupted in several psychiatric diseases, most notably schizophrenia. In rats, and to a lesser extent, in humans, PPI can be diminished by dopamine (DA) D(2)/D(3) and serotonin 5-HT(1A) receptor agonists. A novel class of potential antipsychotics (SSR181507, bifeprunox, and SLV313) possess partial agonist/antagonist properties at D(2) receptors and various levels of 5-HT(1A) activation. It thus appeared warranted to assess, in Sprague-Dawley rats, the effects of these antipsychotics on basal PPI. SSR181507, sarizotan, and bifeprunox decreased PPI, with a near-complete abolition at 2.5-10 mg/kg; SLV313 had a significant effect at 0.16 mg/kg only. Co-treatment with the 5-HT(1A) receptor antagonist WAY100,635 (0.63 mg/kg) showed that the 5-HT(1A) agonist activity of SSR181507 was responsible for its effect. By contrast, antipsychotics with low affinity and/or efficacy at 5-HT(1A) receptors, such as aripiprazole (another DA D(2)/D(3) and 5-HT(1A) ligand), and established typical and atypical antipsychotics (haloperidol, clozapine, risperidone, olanzapine, quetiapine, and ziprasidone) had no effect on basal PPI (0.01-2.5 to 2.5-40 mg/kg). The present data demonstrate that some putative antipsychotics with pronounced 5-HT(1A) agonist activity, coupled with partial agonist activity at DA D(2) receptors, markedly diminish PPI of the startle reflex in rats. These data raise the issue of the influence of such compounds on sensorimotor gating in humans.

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.

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.

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/.

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.

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

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.

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…

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.

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.

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.

Measuring Anxious Responses to Predictable and Unpredictable Threat in Children and Adolescents

ERIC Educational Resources Information Center

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

2011-01-01

Research has highlighted the need for new methods to assess emotions in children on multiple levels to gain better insight into the complex processes of emotional development. The startle reflex is a unique translational tool that has been used to study physiological processes during fear and anxiety in rodents and in human participants. However,…

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.

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.

Understanding the pathophysiology of reflex epilepsy using simultaneous EEG-fMRI.

PubMed

Sandhya, Manglore; Bharath, Rose Dawn; Panda, Rajanikant; Chandra, S R; Kumar, Naveen; George, Lija; Thamodharan, A; Gupta, Arun Kumar; Satishchandra, P

2014-03-01

Measuring neuro-haemodynamic correlates in the brain of epilepsy patients using EEG-fMRI has opened new avenues in clinical neuroscience, as these are two complementary methods for understanding brain function. In this study, we investigated three patients with drug-resistant reflex epilepsy using EEG-fMRI. Different types of reflex epilepsy such as eating, startle myoclonus, and hot water epilepsy were included in the study. The analysis of EEG-fMRI data was based on the visual identification of interictal epileptiform discharges on scalp EEG. The convolution of onset time and duration of these epilepsy spikes was estimated, and using these condition-specific effects in a general linear model approach, we evaluated activation of fMRI. Patients with startle myoclonus epilepsy experienced epilepsy in response to sudden sound or touch, in association with increased delta and theta activity with a spike-and-slow-wave pattern of interictal epileptiform discharges on EEG and fronto-parietal network activation pattern on SPECT and EEG-fMRI. Eating epilepsy was triggered by sight or smell of food and fronto-temporal discharges were noted on video-EEG (VEEG). Similarly, fronto-temporo-parietal involvement was noted on SPECT and EEG-fMRI. Hot water epilepsy was triggered by contact with hot water either in the bath or by hand immersion, and VEEG showed fronto-parietal involvement. SPECT and EEG fMRI revealed a similar fronto-parietal-occipital involvement. From these results, we conclude that continuous EEG recording can improve the modelling of BOLD changes related to interictal epileptic activity and this can thus be used to understand the neuro-haemodynamic substrates involved in reflex epilepsy.

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.

Excitability of pontine startle processing neurones is regulated by the two-pore-domain K+ channel TASK-3 coupled to 5-HT2C receptors.

PubMed

Weber, Maruschka; Schmitt, Angelika; Wischmeyer, Erhard; Döring, Frank

2008-09-01

The mammalian startle reflex is a fast response to sudden intense sensory stimuli that can be increased by anxiety or decreased by reward. The cellular integration of sensory and modulatory information takes place in giant neurones of the caudal pontine reticular formation (PnC). The startle reflex is known to be enhanced by 5-hydroxytryptamine (5-HT); however, signalling mechanisms that change the excitability of the PnC giant neurones are poorly understood. Possible molecular candidates are two-pore-domain K(+) (K(2)P) channels that generate a variable K(+) background conductance and control neuronal excitability upon activation of G-protein-coupled receptors. We demonstrate by in situ hybridization that the K(2)P channel TASK-3 is substantially expressed in PnC giant neurones. Brain slice recordings revealed a corresponding background K(+) current in these cells that forms about 30% of the outward current at -30 mV. Inactivation of TASK-3 at pH 6.4 and by ruthenium red depolarized the cells by about 7 mV and increased the action potential frequency as well as duration. Specific activation of Galpha(q)-coupled 5-HT(2) receptors with alpha-methyl 5-HT evoked a similar increase of neuronal excitability. Consistently, we measured afferent synaptic inputs from serotonergic raphe neurones and detected 5-HT(2C) receptors in PnC giant neurones by immunohistochemistry. Thus, neuronal excitability of PnC giant neurones in vivo is most likely increased by serotonergic projections via the K(2)P channel TASK-3.

Routine post-weaning handling of rats prevents isolation rearing-induced deficit in prepulse inhibition.

PubMed

Rosa, M L N M; Silva, R C B; Moura-de-Carvalho, F T; Brandão, M L; Guimarães, F S; Del Bel, E A

2005-11-01

Rats reared under isolation conditions from weaning present a number of behavioral changes compared to animals reared under social conditions (group housing). These changes include deficits in prepulse inhibition (PPI) of the startle reflex to a loud sound. PPI refers to the reduction of the magnitude of the startle reflex when a relatively weak stimulus (the prepulse) precedes by an appropriate time interval the intense startle-elicing stimulus (the pulse). PPI is useful for studying sensorimotor integration. The present study evaluated the effect of handling on the impairment of PPI induced by isolation-rearing. Male Wistar rats (N = 11-15/group) were housed in groups (5 per cage and handled three times a week) or isolated (housed individually) since weaning (21 days) for 10 weeks when they reach approximately 150 g. The isolated rats were divided into "minimally handled" animals (handled once a week for cleaning purposes only) or "handled" animals (handled three times a week). This handling consisted of grasping the rat by the tail and moving it to a clean cage (approximately 5 s). A statistically significant reduction (52%) in the PPI test was found only in the isolated group with minimal handling while no difference was seen between grouped animals and isolated handled animals. These results indicate that isolation rearing causes disruption in the PPI at adult age, which serves as an index of attention deficit. This change in the sensory processing of information induced by post-weaning isolation can be prevented by handling during the development of the animal.

Effects of ankle joint position and submaximal muscle contraction intensity on soleus H-reflex modulation in young and older adults.

PubMed

Chen, Yung-Sheng; Zhou, Shi; Cartwright, Colleen

2014-04-01

This study investigated the effects of ankle joint position and submaximal contraction intensity on soleus (SOL) H-reflex modulation. Twenty young (25.1 ± 4.8 years) and 20 older adults (74.2 ± 5.1 years) performed plantar flexions during 10%, 30% and 50% maximal voluntary contractions (MVC) and at ankle positions of neutral (0°), plantar flexion (20°) and dorsiflexion (-20°) in a sitting position. The SOL H-reflex gain in older adults was relatively lower than that in young adults during 10%, 30% and 50% MVC. The SOL H-reflex gain was significantly affected by the intensity of plantar flexion in the respective ankle joint position in both age groups. The latency of H-reflex was prolonged in older adults and was ankle joint dependent in young adults. Young adults demonstrated a shorter duration of the H-reflex response than that of older adults. The results indicated that there were age-related changes in the SOL H-reflex during the ankle plantar flexors activities.

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.

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.

Neural control of rhythmic arm cycling after stroke

PubMed Central

Loadman, Pamela M.; Hundza, Sandra R.

2012-01-01

Disordered reflex activity and alterations in the neural control of walking have been observed after stroke. In addition to impairments in leg movement that affect locomotor ability after stroke, significant impairments are also seen in the arms. Altered neural control in the upper limb can often lead to altered tone and spasticity resulting in impaired coordination and flexion contractures. We sought to address the extent to which the neural control of movement is disordered after stroke by examining the modulation pattern of cutaneous reflexes in arm muscles during arm cycling. Twenty-five stroke participants who were at least 6 mo postinfarction and clinically stable, performed rhythmic arm cycling while cutaneous reflexes were evoked with trains (5 × 1.0-ms pulses at 300 Hz) of constant-current electrical stimulation to the superficial radial (SR) nerve at the wrist. Both the more (MA) and less affected (LA) arms were stimulated in separate trials. Bilateral electromyography (EMG) activity was recorded from muscles acting at the shoulder, elbow, and wrist. Analysis was conducted on averaged reflexes in 12 equidistant phases of the movement cycle. Phase-modulated cutaneous reflexes were present, but altered, in both MA and LA arms after stroke. Notably, the pattern was “blunted” in the MA arm in stroke compared with control participants. Differences between stroke and control were progressively more evident moving from shoulder to wrist. The results suggest that a reduced pattern of cutaneous reflex modulation persists during rhythmic arm movement after stroke. The overall implication of this result is that the putative spinal contributions to rhythmic human arm movement remain accessible after stroke, which has translational implications for rehabilitation. PMID:22572949

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.

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.

H-reflex modulation in the human medial and lateral gastrocnemii during standing and walking

PubMed Central

Makihara, Yukiko; Segal, Richard L.; Wolpaw, Jonathan R.; Thompson, Aiko K.

2011-01-01

Introduction The soleus H-reflex is dynamically modulated during walking. However, modulation of the gastrocnemii H-reflexes has not been studied systematically. Methods The medial and lateral gastrocnemii (MG and LG) and soleus H-reflexes were measured during standing and walking in humans. Results Maximum H-reflex amplitude was significantly smaller in MG (mean 1.1 mV) or LG (1.1 mV) than in soleus (3.3 mV). Despite these size differences, the reflex amplitudes of the three muscles were positively correlated. The MG and LG H-reflexes were phase- and task-dependently modulated in ways similar to the soleus H-reflex. Discussion Although there are anatomical and physiological differences between the soleus and gastrocnemii muscles, the reflexes of the three muscles are similarly modulated during walking and between standing and walking. The findings support the hypothesis that these reflexes are synergistically modulated during walking to facilitate ongoing movement. PMID:22190317

Opioid modulation of reflex versus operant responses following stress in the rat.

PubMed

King, C D; Devine, D P; Vierck, C J; Mauderli, A; Yezierski, R P

2007-06-15

In pre-clinical models intended to evaluate nociceptive processing, acute stress suppresses reflex responses to thermal stimulation, an effect previously described as stress-induced "analgesia." Suggestions that endogenous opioids mediate this effect are based on demonstrations that stress-induced hyporeflexia is enhanced by high dose morphine (>5 mg/kg) and is reversed by naloxone. However, reflexes and pain sensations can be modulated differentially. Therefore, in the present study direct comparisons were made of opioid agonist and antagonist actions, independently and in combination with acute restraint stress in Long Evans rats, on reflex lick-guard (L/G) and operant escape responses to nociceptive thermal stimulation (44.5 degrees C). A high dose of morphine (>8 mg/kg) was required to reduce reflex responding, but a moderate dose of morphine (1 mg/kg) significantly reduced escape responding. The same moderate dose (and also 5 mg/kg) of morphine significantly enhanced reflex responding. Naloxone (3 mg/kg) significantly enhanced escape responding but did not affect L/G responding. Restraint stress significantly suppressed L/G reflexes (hyporeflexia) but enhanced escape responses (hyperalgesia). Stress-induced hyperalgesia was significantly reduced by morphine and enhanced by naloxone. In contrast, stress-induced hyporeflexia was blocked by both naloxone and 1 mg/kg of morphine. Thus, stress-induced hyperalgesia was opposed by endogenous opioid release and by administration of morphine. Stress-induced hyporeflexia was dependent upon endogenous opioid release but was counteracted by a moderate dose of morphine. These data demonstrate a differential modulation of reflex and operant outcome measures by stress and by separate or combined opioid antagonism or administration of morphine.

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.

Role of Autonomic Reflex Arcs in Cardiovascular Responses to Air Pollution Exposure

PubMed Central

Hazari, Mehdi S.; Farraj, Aimen K.

2016-01-01

The body responds to environmental stressors by triggering autonomic reflexes in the pulmonary receptors, baroreceptors, and chemoreceptors to maintain homeostasis. Numerous studies have shown that exposure to various gases and airborne particles can alter the functional outcome of these reflexes, particularly with respect to the cardiovascular system. Modulation of autonomic neural input to the heart and vasculature following direct activation of sensory nerves in the respiratory system, elicitation of oxidative stress and inflammation, or through other mechanisms is one of the primary ways that exposure to air pollution affects normal cardiovascular function. Any homeostatic process that utilizes the autonomic nervous system to regulate organ function might be affected. Thus, air pollution and other inhaled environmental irritants have the potential to alter both local airway function and baro-and chemoreflex responses, which modulate autonomic control of blood pressure and detect concentrations of key gases in the body. While each of these reflex pathways causes distinct responses, the systems are heavily integrated and communicate through overlapping regions of the brainstem to cause global effects. This short review summarizes the function of major pulmonary sensory receptors, baroreceptors, and carotid body chemoreceptors and discusses the impacts of air pollution exposure on these systems. PMID:25123706

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

PubMed

Marable, Brian R; Maurissen, Jacques P J

2004-01-01

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

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.

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

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

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.

Interactions of Stress and Nicotine on Amplitude, Pre-Pulse Inhibition and Habituation of the Acoustic Startle Reflex

DTIC Science & Technology

1992-09-24

Marquez , Armario , & Gelpi, 1988) consistent with a stress response . Restraint stress has been reported to increase the amplitude of sensory...and NE in the brain (Adell , Garcia- Marquez , Armario , & Gelpi , 1988) consistent with a stress response. Restraint stress has been reported t o...and non- reactive strains. Al coholism. Clinical and Experimental Research, ~(2), 170-174. Adell, A., Garcia - Marquez, C., Armario , A. , & Gelpi , E

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.

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

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

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

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.

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

PubMed

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

2017-01-01

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

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

PubMed Central

Marker, Ryan J.; Campeau, Serge

2016-01-01

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

STS-55 Pilot Henricks with baroreflex collar in SL-D2 module onboard OV-102

NASA Image and Video Library

1993-05-06

STS055-233-019 (26 April-6 May 1993) --- Terence T. (Tom) Henricks, STS-55 pilot, wears a special collar for a space adaptation experiment in the science module onboard the Earth-orbiting Space Shuttle Columbia. The Baroreflex (BA) experiment is designed to investigate the theory that light-headedness and a reduction in blood pressures upon standing after landing may arise because the normal reflex system regulating blood pressure behaves differently after having adapted to a microgravity environment. These space-based measurements of the baroreflex will be compared to ground measurements to determine if microgravity affects the reflex.

Emotional Reactivity and Appraisal of Food in Relation to Eating Disorder Cognitions and Behaviours: Evidence to Support the Motivational Conflict Hypothesis.

PubMed

Racine, Sarah E; Hebert, Karen R; Benning, Stephen D

2018-01-01

Eating disorders are associated with both negative and positive emotional reactions towards food. Individual eating disorder symptoms may relate to distinct emotional responses to food, which could necessitate tailored treatments based on symptom presentation. We examined associations between eating disorder symptoms and psychophysiological responses to food versus neutral images in 87 college students [mean (SD) age = 19.70 (2.09); mean (SD) body mass index = 23.25(2.77)]. Reflexive and facial electromyography measures tapping negative emotional reactivity (startle blink reflex) and appraisal (corrugator muscle response) as well as positive emotional reactivity (postauricular reflex) and appraisal (zygomaticus muscle response) were collected. Eating disorder cognitions correlated with more corrugator activity to food versus neutral images, indicating negative appraisals of food. Binge eating was associated with increased postauricular reflex reactivity to food versus neutral images, suggesting enhanced appetitive motivation to food. The combination of cognitive eating disorder symptoms and binge eating may result in motivational conflict towards food. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

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.

Modulation of the masseteric reflex by gastric vagal afferents.

PubMed

Pettorossi, V E

1983-04-01

Several investigations have shown that the vagal nerve can affect the reflex responses of the masticatory muscles acting at level either of trigeminal motoneurons or of the mesencephalic trigeminal nucleus (MTN). The present experiments have been devoted to establish the origin of the vagal afferent fibres involved in modulating the masseteric reflex. In particular, the gastric vagal afferents were taken into consideration and selective stimulations of such fibres were performed in rabbit. Conditioning electrical stimulation of truncus vagalis ventralis (TVV) reduced the excitability of the MTN cells as shown by a decrease of the antidromic response recorded from the semilunar ganglion and elicited by MTN single-shock electrical stimulation. Sympathetic and cardiovascular influences were not involved in these responses. Mechanical stimulation of gastric receptors, by means of gastric distension, clearly diminished the amplitude of twitch tension of masseteric reflex and inhibited the discharge frequency of proprioceptive MTN units. The effect was phasic and depended upon the velocity of distension. Thus the sensory volleys originating from rapid adapting receptors reach the brain stem through vagal afferents and by means of a polysynaptic connection inhibits the masseteric reflex at level of MTN cells.

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.

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

The differential role of motor cortex in the stretch reflex modulation induced by changes in environmental mechanics and verbal instruction

PubMed Central

Shemmell, Jonathan; An, Je Hi; Perreault, Eric J.

2009-01-01

The motor cortex assumes an increasingly important role in higher mammals relative to that in lower mammals. This is true to such an extent that the human motor cortex is deeply involved in reflex regulation and it is common to speak of “transcortical reflex loops”. Such loops appear to add flexibility to the human stretch reflex, once considered to be immutable, allowing it to adapt across a range of functional tasks. However, the purpose of this adaptation remains unclear. A common proposal is that stretch reflexes contribute to the regulation of limb stability; increased reflex sensitivity during tasks performed in unstable environments supports this hypothesis. Alternatively, prior to movement onset, stretch reflexes can assist an imposed stretch, opposite to what would be expected from a stabilizing response. Here we show that stretch reflex modulation in tasks that require changes in limb stability is mediated by motor cortical pathways, and that these differ from pathways contributing to reflex modulation that depends on how the subject is instructed to react to an imposed perturbation. By timing muscle stretches such that the modulated portion of the reflex occurred within a cortical silent period induced by transcranial magnetic stimulation, we abolished the increase in reflex sensitivity observed when individuals stabilized arm posture within a compliant environment. Conversely, reflex modulation caused by altered task instruction was unaffected by cortical silence. These results demonstrate that task-dependent changes in reflex function can be mediated through multiple neural pathways and that these pathways have task specific roles. PMID:19846713

The differential role of motor cortex in stretch reflex modulation induced by changes in environmental mechanics and verbal instruction.

PubMed

Shemmell, Jonathan; An, Je Hi; Perreault, Eric J

2009-10-21

The motor cortex assumes an increasingly important role in higher mammals relative to that in lower mammals. This is true to such an extent that the human motor cortex is deeply involved in reflex regulation and it is common to speak of "transcortical reflex loops." Such loops appear to add flexibility to the human stretch reflex, once considered to be immutable, allowing it to adapt across a range of functional tasks. However, the purpose of this adaptation remains unclear. A common proposal is that stretch reflexes contribute to the regulation of limb stability; increased reflex sensitivity during tasks performed in unstable environments supports this hypothesis. Alternatively, before movement onset, stretch reflexes can assist an imposed stretch, opposite to what would be expected from a stabilizing response. Here we show that stretch reflex modulation in tasks that require changes in limb stability is mediated by motor cortical pathways, and that these differ from pathways contributing to reflex modulation that depend on how the subject is instructed to react to an imposed perturbation. By timing muscle stretches such that the modulated portion of the reflex occurred within a cortical silent period induced by transcranial magnetic stimulation, we abolished the increase in reflex sensitivity observed when individuals stabilized arm posture within a compliant environment. Conversely, reflex modulation caused by altered task instruction was unaffected by cortical silence. These results demonstrate that task-dependent changes in reflex function can be mediated through multiple neural pathways and that these pathways have task-specific roles.

Habituation in acoustic startle reflex: individual differences in personality.

PubMed

Blanch, Angel; Balada, Ferran; Aluja, Anton

2014-03-01

This study analyzed the relationship of individual differences in personality with habituation in the acoustic startle response (ASR). Data from nine trials in ASR to white noise bursts and a personality questionnaire based on the alternative big five personality approach were modelled with a latent growth curve (LCM) including intercept and slope habituation growth factors. There was a negative correlation between the intercept and slope, indicating that individuals with higher initial ASR levels had also a more pronounced and faster decrease in the ASR. Contrary to expectations, Extraversion and Sensation Seeking did not relate with habituation in ASR. Neuroticism and Aggressiveness related asymmetrically with the habituation rate in ASR. Higher levels of Neuroticism were related with faster habituation, whereas higher levels of Aggressiveness were related with slower habituation. Further studies with the LCM should be undertaken to clarify in a greater extent the association of personality with habituation in ASR. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

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.

Specific brainstem and cortico-spinal reflex abnormalities in coexisting essential tremor and Parkinson's disease (ET-PD).

PubMed

Yavuz, D; Gündüz, A; Ertan, S; Apaydın, H; Şifoğlu, A; Kiziltan, G; Kiziltan, M E

2015-05-01

We aimed to analyze functional changes at brainstem and spinal levels in essential tremor (ET), Parkinson's disease (PD) and coexisting essential tremor and Parkinson's disease (ET-PD). Age- and gender-matched patients with tremor (15 ET, 7 ET with resting tremor, 25 ET-PD and 10 PD) and 12 healthy subjects were enrolled in the study. Diagnosis was established according to standardized clinical criteria. Electrophysiological studies included blink reflex (BR), auditory startle reaction (ASR) and long latency reflex (LLR). Blink reflex was normal and similar in all groups. Probability of ASR was significantly lower in ET-PD group whereas it was similar to healthy subjects in ET and PD (P<0.001). LLR was recorded during voluntary activity in all three groups. LLR II was more common in ET, PD and ET-PD groups. LLR III was far more common in the PD group (n=3, 13.6% in ET; n=4, 16.0% in ET-PD and n=7, 46.7% in PD; p=0.037). Despite the integrity of BR pathways, ASR and LLR show distinctive abnormalities in ET-PD. In our opinion, our electrophysiological findings support the hypothesis that ET-PD is a distinct entity. Copyright © 2015 Elsevier Masson SAS. 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

Modulation of spinal inhibitory reflexes depends on the frequency of transcutaneous electrical nerve stimulation in spastic stroke survivors.

PubMed

Koyama, Soichiro; Tanabe, Shigeo; Takeda, Kazuya; Sakurai, Hiroaki; Kanada, Yoshikiyo

2016-03-01

Neurophysiological studies in healthy subjects suggest that increased spinal inhibitory reflexes from the tibialis anterior (TA) muscle to the soleus (SOL) muscle might contribute to decreased spasticity. While 50 Hz is an effective frequency for transcutaneous electrical nerve stimulation (TENS) in healthy subjects, in stroke survivors, the effects of TENS on spinal reflex circuits and its appropriate frequency are not well known. We examined the effects of different frequencies of TENS on spinal inhibitory reflexes from the TA to SOL muscle in stroke survivors. Twenty chronic stroke survivors with ankle plantar flexor spasticity received 50-, 100-, or 200-Hz TENS over the deep peroneal nerve (DPN) of the affected lower limb for 30 min. Before and immediately after TENS, reciprocal Ia inhibition (RI) and presynaptic inhibition of the SOL alpha motor neuron (D1 inhibition) were assessed by adjusting the unconditioned H-reflex amplitude. Furthermore, during TENS, the time courses of spinal excitability and spinal inhibitory reflexes were assessed via the H-reflex, RI, and D1 inhibition. None of the TENS protocols affected mean RI, whereas D1 inhibition improved significantly following 200-Hz TENS. In a time-series comparison during TENS, repeated stimulation did not produce significant changes in the H-reflex, RI, or D1 inhibition regardless of frequency. These results suggest that the frequency-dependent effect of TENS on spinal reflexes only becomes apparent when RI and D1 inhibition are measured by adjusting the amplitude of the unconditioned H-reflex. However, 200-Hz TENS led to plasticity of synaptic transmission from the antagonist to spastic muscles in stroke survivors.

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.

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.

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

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.

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.

Role of ionotropic GABA, glutamate and glycine receptors in the tonic and reflex control of cardiac vagal outflow in the rat

PubMed Central

2010-01-01

Background Cardiac vagal preganglionic neurons (CVPN) are responsible for the tonic, reflex and respiratory modulation of heart rate (HR). Although CVPN receive GABAergic and glutamatergic inputs, likely involved in respiratory and reflex modulation of HR respectively, little else is known regarding the functions controlled by ionotropic inputs. Activation of g-protein coupled receptors (GPCR) alters these inputs, but the functional consequence is largely unknown. The present study aimed to delineate how ionotropic GABAergic, glycinergic and glutamatergic inputs contribute to the tonic and reflex control of HR and in particular determine which receptor subtypes were involved. Furthermore, we wished to establish how activation of the 5-HT1A GPCR affects tonic and reflex control of HR and what ionotropic interactions this might involve. Results Microinjection of the GABAA antagonist picrotoxin into CVPN decreased HR but did not affect baroreflex bradycardia. The glycine antagonist strychnine did not alter HR or baroreflex bradycardia. Combined microinjection of the NMDA antagonist, MK801, and AMPA antagonist, CNQX, into CVPN evoked a small bradycardia and abolished baroreflex bradycardia. MK801 attenuated whereas CNQX abolished baroreceptor bradycardia. Control intravenous injections of the 5-HT1A agonist 8-OH-DPAT evoked a small bradycardia and potentiated baroreflex bradycardia. These effects were still observed following microinjection of picrotoxin but not strychnine into CVPN. Conclusions We conclude that activation of GABAA receptors set the level of HR whereas AMPA to a greater extent than NMDA receptors elicit baroreflex changes in HR. Furthermore, activation of 5-HT1A receptors evokes bradycardia and enhances baroreflex changes in HR due to interactions with glycinergic neurons involving strychnine receptors. This study provides reference for future studies investigating how diseases alter neurochemical inputs to CVPN. PMID:20939929

Central estrogenic pathways protect against the depressant action of acute nicotine on reflex tachycardia in female rats

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

El-Mas, Mahmoud M., E-mail: mahelm@hotmail.com; Fouda, Mohamed A.; El-gowilly, Sahar M.

We have previously shown that acute exposure of male rats to nicotine preferentially attenuates baroreceptor-mediated control of reflex tachycardia in contrast to no effect on reflex bradycardia. Here, we investigated whether female rats are as sensitive as their male counterparts to the baroreflex depressant effect of nicotine and whether this interaction is modulated by estrogen. Baroreflex curves relating reflex chronotropic responses evoked by i.v. doses (1–16 μg/kg) of phenylephrine (PE) or sodium nitroprusside (SNP), were constructed in conscious freely moving proestrus, ovariectomized (OVX), and estrogen (50 μg/kg/day s.c., 5 days)-replaced OVX (OVXE{sub 2}) rats. Slopes of the curves were takenmore » as a measure of baroreflex sensitivity (BRS{sub PE} and BRS{sub SNP}). Nicotine (100 μg/kg i.v.) reduced BRS{sub SNP} in OVX rats but not in proestrus or OVXE{sub 2} rats. The attenuation of reflex tachycardia by nicotine was also evident in diestrus rats, which exhibited plasma estrogen levels similar to those of OVX rats. BRS{sub PE} was not affected by nicotine in all rat preparations. Experiments were then extended to determine whether central estrogenic receptors modulate the nicotine–BRS{sub SNP} interaction. Intracisteral (i.c.) treatment of OVX rats with estrogen sulfate (0.2 μg/rat) abolished the BRS{sub SNP} attenuating effect of i.v. nicotine. This protective effect of estrogen disappeared when OVX rats were pretreated with i.c. ICI 182,780 (50 μg/rat, selective estrogen receptor antagonist). Together, these findings suggest that central neural pools of estrogen receptors underlie the protection offered by E{sub 2} against nicotine-induced baroreceptor dysfunction in female rats. -- Highlights: ► Estrogen protects against the depressant effect of nicotine on reflex tachycardia. ► The baroreflex response and estrogen status affect the nicotine–BRS interaction. ► The protection offered by estrogen is mediated via central estrogen receptors.« less

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

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

The Moro reaction: More than a reflex, a ritualized behavior of nonverbal communication.

PubMed

Rousseau, Pierre V; Matton, Florence; Lecuyer, Renaud; Lahaye, Willy

2017-02-01

To propose a phylogenetic significance to the Moro reflex which remains unexplained since its publication in 1918 because both hands are free at the end of the gesture. Among the 75 videos of healthy term newborns we have filmed in a research project on antenatal education to parenthood, we describe a sequence that clearly showed the successive movements of the Moro reflex and we report the occurrence of this reflex in the videos that were recorded from Time 0 of birth defined as the moment that lies between the birth of the thorax and the pelvis of the infant. The selected sequence showed the following succession of the newborn's actions: quick extension-adduction of both arms, the orientation of the body, head and eyes towards a human person, and full extension-abduction of both arms with spreading of the fingers, crying and a distressed face. There were 13 Moro reflexes between 2 and 14s from Time 0 of birth. We found a significant association between the occurrence of the Moro reflex and the placement of the newborn at birth in supine position on the mother's abdomen (p=0.002). The quick extension-adduction of both arms which started the sequence may be considered as a startle reflex controlled by the neural fear system and the arm extension-adduction which followed as a Moro reflex. The characteristics of all Moro reflexes were those of ritualization: amplitude, duration, stereotype of the gestures. This evolutionary process turns a physiological behavior, grasping in this case, to a non-verbal communicative behavior whose meaning is a request to be picked up in the arms. The gestures associated with the Moro reflex: crying and orientation of the body, head, and eyes towards a human person, are gestures of intention to communicate which support our hypothesis. The neural mechanism of the Moro reaction probably involves both the fear and the separation-distress systems. This paper proposes for the first time a phylogenetic significance to the Moro reflex: a ritualized behavior of nonverbal communication. Professionals should avoid stimulating the newborns' fear system by unnecessarily triggering Moro reflexes. Antenatal education should teach parents to respond to the Moro reflexes of their newborn infant by picking her up in their arms with mother talk. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Relationships between self-reported ankle function and modulation of Hoffmann reflex in patients with chronic ankle instability.

PubMed

Kim, Kyung-Min; Hart, Joseph M; Saliba, Susan A; Hertel, Jay

2016-01-01

To examine relationships between self-reported ankle function and Hoffmann (H) reflex modulation during changes in body positions in patients with chronic ankle instability (CAI). Observational. Laboratory. Thirty-one young adults with CAI (19 males, 12 females) participated. There were two subscales of Foot and Ankle Ability Measure (FAAM) to quantify self-reported ankle function during activities of daily living (ADL) and sports activities. Maximum H-reflexes (H-max) and motor waves (M-max) from soleus and fibularis longus were recorded while participants lied prone and stood in bipedal and unipedal stances. For each muscle, percent change scores in Hmax:Mmax ratios were calculated between each pair of positions: prone-to-bipedal, bipedal-to-unipedal, and prone-to-unipedal, and used as a measure of H-reflex modulation. Pearson correlation coefficients were calculated between FAAM and H-reflex modulation measures. There were significant correlations between: (1) FAAM-ADL and soleus prone-to-unipedal modulation (r = 0.384, p = 0.04), (2) FAAM-Sport and soleus prone-to-unipedal modulation (r = 0.505, p = 0.005), (3) FAAM-Sport and fibular bipedal-to-unipedal modulation (r = 0.377, p = 0.05), and (4) FAAM-Sport and fibular prone-to-unipedal modulation (r = 0.396, p = 0.04). CAI patients presented moderate, positive relationships between self-reported ankle function and H-reflex modulation during changes in body positions. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

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

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.

Changes in Soleus H-Reflex Modulation after Treadmill Training in Children with Cerebral Palsy

ERIC Educational Resources Information Center

Hodapp, Maike; Vry, Julia; Mall, Volker; Faist, Michael

2009-01-01

In healthy children, short latency leg muscle reflexes are profoundly modulated throughout the step cycle in a functionally meaningful way and contribute to the electromyographic (EMG) pattern observed during gait. With maturation of the corticospinal tract, the reflex amplitudes are depressed via supraspinal inhibitory mechanisms. In the soleus…

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

Tonic blood pressure modulates the relationship between baroreceptor cardiac reflex sensitivity and cognitive performance.

PubMed

Del Paso, Gustavo A Reyes; González, M Isabel; Hernández, José Antonio; Duschek, Stefan; Gutiérrez, Nicolás

2009-09-01

This study explored the effects of tonic blood pressure on the association between baroreceptor cardiac reflex sensitivity and cognitive performance. Sixty female participants completed a mental arithmetic task. Baroreceptor reflex sensitivity was assessed using sequence analysis. An interaction was found, indicating that the relationship between baroreceptor reflex sensitivity and cognitive performance is modulated by blood pressure levels. Reflex sensitivity was inversely associated to performance indices in the subgroup of participants with systolic blood pressure above the mean, whereas the association was positive in participants with systolic values below the mean. These results are in accordance with the findings in the field of pain perception and suggest that tonic blood pressure modulates the inhibitory effects of baroreceptor stimulation on high central nervous functions.

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

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.

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.

Origin and function of short-latency inputs to the neural substrates underlying the acoustic startle reflex

PubMed Central

Gómez-Nieto, Ricardo; Horta-Júnior, José de Anchieta C.; Castellano, Orlando; Millian-Morell, Lymarie; Rubio, Maria E.; López, Dolores E.

2014-01-01

The acoustic startle reflex (ASR) is a survival mechanism of alarm, which rapidly alerts the organism to a sudden loud auditory stimulus. In rats, the primary ASR circuit encompasses three serially connected structures: cochlear root neurons (CRNs), neurons in the caudal pontine reticular nucleus (PnC), and motoneurons in the medulla and spinal cord. It is well-established that both CRNs and PnC neurons receive short-latency auditory inputs to mediate the ASR. Here, we investigated the anatomical origin and functional role of these inputs using a multidisciplinary approach that combines morphological, electrophysiological and behavioral techniques. Anterograde tracer injections into the cochlea suggest that CRNs somata and dendrites receive inputs depending, respectively, on their basal or apical cochlear origin. Confocal colocalization experiments demonstrated that these cochlear inputs are immunopositive for the vesicular glutamate transporter 1 (VGLUT1). Using extracellular recordings in vivo followed by subsequent tracer injections, we investigated the response of PnC neurons after contra-, ipsi-, and bilateral acoustic stimulation and identified the source of their auditory afferents. Our results showed that the binaural firing rate of PnC neurons was higher than the monaural, exhibiting higher spike discharges with contralateral than ipsilateral acoustic stimulations. Our histological analysis confirmed the CRNs as the principal source of short-latency acoustic inputs, and indicated that other areas of the cochlear nucleus complex are not likely to innervate PnC. Behaviorally, we observed a strong reduction of ASR amplitude in monaural earplugged rats that corresponds with the binaural summation process shown in our electrophysiological findings. Our study contributes to understand better the role of neuronal mechanisms in auditory alerting behaviors and provides strong evidence that the CRNs-PnC pathway mediates fast neurotransmission and binaural summation of the ASR. PMID:25120419

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).

Reflex reticular myoclonus: relationship to some brainstem pathophysiological mechanisms.

PubMed

Rektor, I; Kadanka, Z; Bednarik, J

1991-04-01

Two patients with reflex reticular myoclonus [RRM] were tested electrophysiologically and pharmacologically. In one of the cases the underlying disease was chronic Lyme borreliosis. In the other, the RRM attacks may have been associated with procarbazine therapy applied for Hodgkin's disease. No cortical lesion could be demonstrated either clinically or electrophysiologically [EEG, averaged EEg preceeding the jerks, SSEP]. An EMG analysis of the jerks revealed the shortest latency in the muscles innervated by the accessory nerve. The latencies became longer in a more rostral muscle [masseter], as well as in a more caudal one, the muscles innervated by the facial nerve were spared. it is presumed that the complete movement pattern of the myoclonus residues in the jerk generating structure. RRM in the described cases differs from the startle by sparing the facial nerve and from the Papio papio baboon non-epileptic myoclonus by the activating effect of physostigmine. A partial therapeutic effect was achieved with a serotonine precursor, but a GABAergic therapy proved to be the most effective.

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.

Modulation of spinal reflexes by sexual films of increasing intensity.

PubMed

Both, Stephanie; Boxtel, Geert; Stekelenburg, Jeroen; Everaerd, Walter; Laan, Ellen

2005-11-01

Sexual arousal can be viewed as an emotional state generating sex-specific autonomic and general somatic motor system responses that prepare for sexual action. In the present study modulation of spinal tendious (T) reflexes by sexual films of varying intensity was investigated. T reflexes were expected to increase as a function of increased film intensity. Through use of a between-subjects design, participants were exposed to three erotic films of low, moderate, and high intensity or to three films of moderate intensity. Self-report and genital data confirmed the induction of increasing versus stable levels of sexual arousal. Exposure to the films of increasing intensity resulted in increasing T reflexes. The results indicate that T reflex modulation is sensitive to varying levels of sexual arousal and may be of use in research on behavioral mechanisms underlying appetitive motivation.

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

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

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

Cocaine affects foraging behaviour and biogenic amine modulated behavioural reflexes in honey bees.

PubMed

Søvik, Eirik; Even, Naïla; Radford, Catherine W; Barron, Andrew B

2014-01-01

In humans and other mammals, drugs of abuse alter the function of biogenic amine pathways in the brain leading to the subjective experience of reward and euphoria. Biogenic amine pathways are involved in reward processing across diverse animal phyla, however whether cocaine acts on these neurochemical pathways to cause similar rewarding behavioural effects in animal phyla other than mammals is unclear. Previously, it has been shown that bees are more likely to dance (a signal of perceived reward) when returning from a sucrose feeder after cocaine treatment. Here we examined more broadly whether cocaine altered reward-related behaviour, and biogenic amine modulated behavioural responses in bees. Bees developed a preference for locations at which they received cocaine, and when foraging at low quality sucrose feeders increase their foraging rate in response to cocaine treatment. Cocaine also increased reflexive proboscis extension to sucrose, and sting extension to electric shock. Both of these simple reflexes are modulated by biogenic amines. This shows that systemic cocaine treatment alters behavioural responses that are modulated by biogenic amines in insects. Since insect reward responses involve both octopamine and dopamine signalling, we conclude that cocaine treatment altered diverse reward-related aspects of behaviour in bees. We discuss the implications of these results for understanding the ecology of cocaine as a plant defence compound. Our findings further validate the honey bee as a model system for understanding the behavioural impacts of cocaine, and potentially other drugs of abuse.

Modulation of the Fibularis Longus Hoffmann Reflex and Postural Instability Associated With Chronic Ankle Instability

PubMed Central

Kim, Kyung-Min; Hart, Joseph M.; Saliba, Susan A.; Hertel, Jay

2016-01-01

Context: Individuals with chronic ankle instability (CAI) present with decreased modulation of the Hoffmann reflex (H-reflex) from a simple to a more challenging task. The neural alteration is associated with impaired postural control, but the relationship has not been investigated in individuals with CAI. Objective: To determine differences in H-reflex modulation and postural control between individuals with or without CAI and to identify if they are correlated in individuals with CAI. Design: Descriptive laboratory study. Setting: Laboratory. Patients or Other Participants: A total of 15 volunteers with CAI (9 males, 6 females; age = 22.6 ± 5.8 years, height = 174.7 ± 8.1 cm, mass = 74.9 ± 12.8 kg) and 15 healthy sex-matched volunteers serving as controls (9 males, 6 females; age = 23.8 ± 5.8 years, height = 171.9 ± 9.9 cm, mass = 68.9 ± 15.5 kg) participated. Intervention(s): Maximum H-reflex (Hmax) and motor wave (Mmax) from the soleus and fibularis longus were recorded while participants lay prone and then stood in unipedal stance. We assessed postural tasks of unipedal stance with participants' eyes closed for 10 seconds using a forceplate. Main Outcome Measure(s): We normalized Hmax to Mmax to obtain Hmax : Mmax ratios for the 2 positions. For each muscle, H-reflex modulation was quantified using the percentage change scores in Hmax : Mmax ratios calculated from prone position to unipedal stance. Center-of-pressure data were used to compute 4 time-to-boundary variables. Separate independent-samples t tests were performed to determine group differences. Pearson product moment correlation coefficients were calculated between the modulation and balance measures in the CAI group. Results: The CAI group presented less H-reflex modulation in the soleus (t26 = −3.77, P = .001) and fibularis longus (t25 = −2.59, P = .02). The mean of the time-to-boundary minima in the anteroposterior direction was lower in the CAI group (t28 = −2.06, P = .048). We observed a correlation (r = 0.578, P = .049) between the fibular longus modulation and mean of time-to-boundary minima in the anteroposterior direction. Conclusions: The strong relationship indicated that, as H-reflex amplitude in unipedal stance was less down modulated, unipedal postural control was more impaired. Given the deficits in H-reflex modulation and postural control in the CAI group, the relationship may provide insights into the neurophysiologic mechanism of postural instability. PMID:27583692

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

Soleus H-reflex gain in humans walking and running under simulated reduced gravity

NASA Technical Reports Server (NTRS)

Ferris, D. P.; Aagaard, P.; Simonsen, E. B.; Farley, C. T.; Dyhre-Poulsen, P.

2001-01-01

The Hoffmann (H-) reflex is an electrical analogue of the monosynaptic stretch reflex, elicited by bypassing the muscle spindle and directly stimulating the afferent nerve. Studying H-reflex modulation provides insight into how the nervous system centrally modulates stretch reflex responses.A common measure of H-reflex gain is the slope of the relationship between H-reflex amplitude and EMG amplitude. To examine soleus H-reflex gain across a range of EMG levels during human locomotion, we used simulated reduced gravity to reduce muscle activity. We hypothesised that H-reflex gain would be independent of gravity level.We recorded EMG from eight subjects walking (1.25 m s-1) and running (3.0 m s-1) at four gravity levels (1.0, 0.75, 0.5 and 0.25 G (Earth gravity)). We normalised the stimulus M-wave and resulting H-reflex to the maximal M-wave amplitude (Mmax) elicited throughout the stride to correct for movement of stimulus and recording electrodes relative to nerve and muscle fibres. Peak soleus EMG amplitude decreased by 30% for walking and for running over the fourfold change in gravity. As hypothesised, slopes of linear regressions fitted to H-reflex versus EMG data were independent of gravity for walking and running (ANOVA, P > 0.8). The slopes were also independent of gait (P > 0.6), contrary to previous studies. Walking had a greater y-intercept (19.9% Mmax) than running (-2.5% Mmax; P < 0.001). At all levels of EMG, walking H-reflex amplitudes were higher than running H-reflex amplitudes by a constant amount. We conclude that the nervous system adjusts H-reflex threshold but not H-reflex gain between walking and running. These findings provide insight into potential neural mechanisms responsible for spinal modulation of the stretch reflex during human locomotion.

Soleus H-reflex gain in humans walking and running under simulated reduced gravity

PubMed Central

Ferris, Daniel P; Aagaard, Per; Simonsen, Erik B; Farley, Claire T; Dyhre-Poulsen, Poul

2001-01-01

The Hoffmann (H-) reflex is an electrical analogue of the monosynaptic stretch reflex, elicited by bypassing the muscle spindle and directly stimulating the afferent nerve. Studying H-reflex modulation provides insight into how the nervous system centrally modulates stretch reflex responses. A common measure of H-reflex gain is the slope of the relationship between H-reflex amplitude and EMG amplitude. To examine soleus H-reflex gain across a range of EMG levels during human locomotion, we used simulated reduced gravity to reduce muscle activity. We hypothesised that H-reflex gain would be independent of gravity level. We recorded EMG from eight subjects walking (1.25 m s−1) and running (3.0 m s−1) at four gravity levels (1.0, 0.75, 0.5 and 0.25 G (Earth gravity)). We normalised the stimulus M-wave and resulting H-reflex to the maximal M-wave amplitude (Mmax) elicited throughout the stride to correct for movement of stimulus and recording electrodes relative to nerve and muscle fibres. Peak soleus EMG amplitude decreased by ≈30% for walking and for running over the fourfold change in gravity. As hypothesised, slopes of linear regressions fitted to H-reflex versus EMG data were independent of gravity for walking and running (ANOVA, P > 0.8). The slopes were also independent of gait (P > 0.6), contrary to previous studies. Walking had a greater y-intercept (19.9%Mmax) than running (-2.5%Mmax; P < 0.001). At all levels of EMG, walking H-reflex amplitudes were higher than running H-reflex amplitudes by a constant amount. We conclude that the nervous system adjusts H-reflex threshold but not H-reflex gain between walking and running. These findings provide insight into potential neural mechanisms responsible for spinal modulation of the stretch reflex during human locomotion. PMID:11136869

Convergence of flexor reflex and corticospinal inputs on tibialis anterior network in humans.

PubMed

Mackey, Ann S; Uttaro, Denise; McDonough, Maureen P; Krivis, Lisa I; Knikou, Maria

2016-01-01

Integration between descending and ascending inputs at supraspinal and spinal levels is a key characteristic of neural control of movement. In this study, we characterized convergence of the flexor reflex and corticospinal inputs on the tibialis anterior (TA) network in healthy human subjects. Specifically, we characterized the modulation profiles of the spinal TA flexor reflex following subthreshold and suprathreshold transcranial magnetic stimulation (TMS). We also characterized the modulation profiles of the TA motor evoked potentials (MEPs) following medial arch foot stimulation at sensory and above reflex threshold. TA flexor reflexes were evoked following stimulation of the medial arch of the foot with a 30 ms pulse train at innocuous intensities. TA MEPs were evoked following TMS of the leg motor cortex area. TMS at 0.7 and at 1.2 MEP resting threshold increased the TA flexor reflex when TMS was delivered 40-100 ms after foot stimulation, and decreased the TA flexor reflex when TMS was delivered 25-110 ms before foot stimulation. Foot stimulation at sensory and above flexor reflex threshold induced a similar time-dependent modulation in resting TA MEPs, that were facilitated when foot stimulation was delivered 40-100 ms before TMS. The flexor reflex and MEPs recorded from the medial hamstring muscle were modulated in a similar manner to that observed for the TA flexor reflex and MEP. Cutaneomuscular afferents from the distal foot can increase the output of the leg motor cortex area. Descending motor volleys that directly or indirectly depolarize flexor motoneurons increase the output of the spinal FRA interneuronal network. The parallel facilitation of flexor MEPs and flexor reflexes is likely cortical in origin. Afferent mediated facilitation of corticospinal excitability can be utilized to strengthen motor cortex output in neurological disorders. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

No evidence hip joint angle modulates intrinsically produced stretch reflex in human hopping.

PubMed

Gibson, W; Campbell, A; Allison, G

2013-09-01

Motor output in activities such as walking and hopping is suggested to be mediated neurally by purported stretch reflex augmentation of muscle output. Reflex EMG activity during these tasks has been frequently investigated in the soleus muscle; with alterations in reflex amplitude being associated with changes in hip joint angle/phase of the gait cycle. Previous work has focussed on reflex activity induced by an artificial perturbation or by induction of H-reflexes. As such, it is currently unknown if stretch reflex activity induced intrinsically (as part of the task) is modulated by changes in hip joint angle. This study investigated whether hip joint angle modulated reflex EMG 'burst' activity during a hopping task performed on a custom-built partially reclined sleigh. Ten subjects participated; EMG and kinematic data (VICON motor capture system) was collected for each hop cycle. Participants completed 5 sets of 30s of self-paced hopping in (1) hip neutral and (2) hip 60° flexion conditions. There was no difference in EMG 'burst' activity or in sagittal plane kinematics (knee/ankle) in the hopping task between the two conditions. The results indicate that during a functional task such as hopping, changes in hip angle do not alter the stretch reflex-like activity associated with landing. Copyright © 2013 Elsevier B.V. All rights reserved.

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.

Fearful imagery in social phobia: generalization, comorbidity, and physiological reactivity.

PubMed

McTeague, Lisa M; Lang, Peter J; Laplante, Marie-Claude; Cuthbert, Bruce N; Strauss, Cyd C; Bradley, Margaret M

2009-03-01

Social phobia has been characterized as a disorder of exaggerated fear of social threat and heightened sensitivity to imagery of social failure. To assess the physiological basis of this description, social phobia patients (n=75) and demographically matched control participants (n=75) imagined neutral and fearful events while acoustic startle probes were occasionally presented and eye-blink responses (orbicularis occuli) recorded. Changes in heart rate, skin conductance level, and facial expressivity were also indexed. In addition to comparing control participants and social phobia patients, the influences of diagnostic subtype (circumscribed, generalized), comorbid depression, and chronicity were assessed. Patients exceeded control participants in startle reflex and autonomic responding during imagery of social threat, whereas the groups evinced commensurate reactivity to contents depicting commonly shared fears (survival threat). Individuals with circumscribed performance phobia were similar to control participants, with the exception of more robust reactions to idiographic, performance fear imagery. In contrast, generalized phobic patients were characterized by longer disorder chronicity and demonstrated heightened sensitivity to a broader range of fear contents. Those with generalized phobia plus comorbid depression showed attenuation of fear-potentiated startle and reported the most protracted social anxiety. Subtypes of social phobia can be objectively distinguished in patterns of physiological reactivity. Furthermore, subtypes vary systematically in chronicity and defensive engagement with the shortest disorder duration (circumscribed phobia) associated with the most robust and focal physiological reactivity, followed by broader defensive sensitivity in more chronic generalized phobia, and finally attenuation of the formerly exaggerated fear potentiation in the comorbidly depressed, the most chronic form.

Fearful imagery in social phobia: Generalization, comorbidity, and physiological reactivity

PubMed Central

McTeague, Lisa M.; Lang, Peter J.; Laplante, Marie-Claude; Cuthbert, Bruce N.; Strauss, Cyd C.; Bradley, Margaret M.

2009-01-01

Background Social phobia has been characterized as a disorder of exaggerated fear of social threat and heightened sensitivity to imagery of social failure. Methods To assess the physiological basis of this description, social phobia patients (n=75) and demographically-matched controls (n=75) imagined neutral and fearful events while acoustic startle probes were occasionally presented and eye-blink responses (orbicularis occuli) recorded. Changes in heart rate, skin conductance level, and facial expressivity were also indexed. In addition to comparing controls and social phobia patients, the influences of diagnostic subtype (circumscribed, generalized), comorbid depression, and chronicity were assessed. Results Patients exceeded controls in startle reflex and autonomic responding during imagery of social threat whereas the groups evinced commensurate reactivity to contents depicting commonly shared fears (survival threat). Individuals with circumscribed performance phobia were similar to controls, with the exception of more robust reactions to idiographic, performance fear imagery. In contrast, generalized phobic patients were characterized by longer disorder chronicity and demonstrated heightened sensitivity to a broader range of fear contents. Those with generalized phobia plus comorbid depression showed attenuation of fear-potentiated startle and reported the most protracted social anxiety. Conclusions Subtypes of social phobia can be objectively distinguished in patterns of physiological reactivity. Furthermore, subtypes vary systematically in chronicity and defensive engagement with the shortest disorder duration (circumscribed phobia) associated with the most robust and focal physiological reactivity, followed by broader defensive sensitivity in more chronic generalized phobia, and finally attenuation of the formerly exaggerated fear potentiation in the comorbidly depressed—the most chronic form. PMID:18996510

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

PubMed

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

2012-09-15

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

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

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.

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.

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

RDoC, DSM, and the reflex physiology of fear: A bio-dimensional analysis of the anxiety disorders spectrum

PubMed Central

Lang, Peter J.; McTeague, Lisa M.; Bradley, Margaret M.

2015-01-01

Evidence is presented supporting a dimension of defensive reactivity that varies across the anxiety disorder spectrum and is defined by physiological responses during threat-imagery challenges that covary with objective measures of psychopathology. Previous imagery studies of anxiety disorders are reviewed, highlighting that, regardless of contemporary diagnostic convention, reliable psychophysiological patterns emerge for patients diagnosed with circumscribed fear compared to those diagnosed with pervasive anxious-misery disorders. Based on the heuristic outlined by the Research Domain Criteria (RDoC) initiative, an exploratory transdiagnostic analysis is presented, based on a sample of 425 treatment-seeking patients from across the spectrum of DSM-IV anxiety diagnoses. Using a composite index of startle reflex and heart rate reactivity during idiographic-fear imagery for each patient, a defensive dimension was defined by ranking patients from most defensively reactive to least reactive and then creating five groups of equivalent size (quintile; N = 85). Subsequent analyses showed significant, parallel trends of diminishing reactivity in both electrodermal and facial EMG reactions across this defensive dimension. Negative affectivity, defined by questionnaire, and extent of functional interference, however, showed consistent, inverse trends with defensive reactivity -- as reports of distress increased, defensive reactivity was increasingly attenuated. Notably, representatives of each principal diagnosis appeared in each quintile, underscoring the reality of pronounced within-diagnosis heterogeneity in defensive reactivity. In concluding, we describe our new RDoC research project, focusing on the assessment of brain circuit function as it determines hypo/hyper reactivity to challenge—somatic and autonomic—and may relate to patients’ stress history and genetic inheritance. PMID:26877123

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

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.

Nociception-specific blink reflex: pharmacology in healthy volunteers.

PubMed

Marin, J C A; Gantenbein, A R; Paemeleire, K; Kaube, H; Goadsby, P J

2015-01-01

The physiology and pharmacology of activation or perception of activation of pain-coding trigeminovascular afferents in humans is fundamental to understanding the biology of headache and developing new treatments. The blink reflex was elicited using a concentric electrode and recorded in four separate sessions, at baseline and two minutes after administration of ramped doses of diazepam (final dose 0.07 mg/kg), fentanyl (final dose 1.11 μg/kg), ketamine (final dose 0.084 mg/kg) and 0.9 % saline solution. The AUC (area under the curve, μV*ms) and the latency (ms) of the ipsi- and contralateral R2 component of the blink reflex were calculated by PC-based offline analysis. Immediately after each block of blink reflex recordings certain psychometric parameters were assessed. There was an effect due to DRUG on the ipsilateral (F 3,60 = 7.3, P < 0.001) AUC as well as on the contralateral (F 3,60 = 6.02, P < 0.001) AUC across the study. A significant decrement in comparison to placebo was observed only for diazepam, affecting the ipsilateral AUC. The scores of alertness, calmness, contentedness, reaction time and precision were not affected by the DRUG across the sessions. Previous studies suggest central, rather than peripheral changes in nociceptive trigeminal transmission in migraine. This study demonstrates a robust effect of benzodiazepine receptor modulation of the nociception specific blink reflex (nBR) without any μ-opiate or glutamate NMDA receptor component. The nociception specific blink reflex offers a reproducible, quantifiable method of assessment of trigeminal nociceptive system in humans that can be used to dissect pharmacology relevant to primary headache disorders.

Neural Control of the Immune System

ERIC Educational Resources Information Center

Sundman, Eva; Olofsson, Peder S.

2014-01-01

Neural reflexes support homeostasis by modulating the function of organ systems. Recent advances in neuroscience and immunology have revealed that neural reflexes also regulate the immune system. Activation of the vagus nerve modulates leukocyte cytokine production and alleviates experimental shock and autoimmune disease, and recent data have…

Stance control is not affected by paresis and reflex hyperexcitability: the case of spastic patients

PubMed Central

Nardone, A; Galante, M; Lucas, B; Schieppati, M

2001-01-01

OBJECTIVES—Spastic patients were studied to understand whether stance unsteadiness is associated with changes in the control of voluntary force, muscle tone, or reflex excitability, rather than to abnormal posture connected to the motor deficit itself.
METHODS—Twenty four normal subjects, 12 patients affected by amyotrophic lateral sclerosis (ALS), seven by spastic paraparesis, and 14 by hemiparesis were studied. All patients featured various degrees of spasticity and paresis but were free from clinically evident sensory deficits. Body sway during quiet upright stance was assessed through a stabilometric platform under both eyes open (EO) and eyes closed (EC) conditions. The sudden rotation of a supporting platform, in a toe up and toe down direction respectively, evoked short (SLR) and medium latency (MLR) reflex responses to stretch of the soleus or the tibialis anterior (TA) muscle.
RESULTS—No relation was found between clinical findings (tone, muscle strength, tendon reflexes, plantar response, and duration of disease) and body sway. On average, all patient groups exhibited a forward shift of the centre of foot pressure (CFP) with respect to normal subjects; in addition, paraparetic and to a much larger extent hemiparetic patients showed a lateral shift of CFP. Body sway area was significantly increased only in the hemiparetic patients. No relation was found between position of the CFP and sway within any patient group. Soleus SLR was increased in all patients with respect to normal subjects. TA SLR was often seen in both patients with ALS and paraparetic patients, but only rarely in normal subjects and hemiparetic patients. However, no relation was found between amplitude of soleus or TA SLRs and stabilometric variables. The frequency and size of soleus MLR and TA MLR were decreased in all patients. These responses were decreased in size and not modulated by background EMG in the affected leg of hemiparetic patients, suggesting a disturbed control of spinal reflexes fed by spindle group II afferent fibres.
CONCLUSIONS—It is proposed that body posture, paresis, or monosynaptic reflex hyperexcitability do not affect the control of equilibrium during quiet upright stance. In hemiparetic patients, the decreased amplitude of MLRs might be the main cause of the large postural instability. The results are congruent with the hypothesis of a role for group II afferent input in the reflex control of equilibrium.

 PMID:11309458

Ultrasonic vocalizations, predictability and sensorimotor gating in the rat.

PubMed

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

2013-09-15

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

Effects of postural and voluntary muscle contraction on modulation of the soleus H reflex by transcranial magnetic stimulation.

PubMed

Guzmán-López, Jessica; Selvi, Aikaterini; Solà-Valls, Núria; Casanova-Molla, Jordi; Valls-Solé, Josep

2015-12-01

Modulation of spinal reflexes depends largely on the integrity of the corticospinal tract. A useful method to document the influence of descending tracts on reflexes is to examine the effects of transcranial magnetic stimulation (TMS) on the soleus H reflex elicited by posterior tibial nerve electrical stimuli (PTS). In 12 healthy volunteers, we investigated how postural or voluntary muscle contraction modified such descending modulation. We first characterized the effects of TMS at 95 % of motor threshold for leg responses on the H reflex elicited by a preceding PTS at inter-stimuli intervals (ISIs) between 0 and 120 ms at rest and, then, during voluntary plantar flexion (pf), dorsal flexion (df), and standing still (ss). During pf, there was an increase in the facilitation of the H reflex at ISIs 0-20 ms. During df, there were no effects of TMS on the H reflex. During ss, there was inhibition at ISIs 40-60 ms. Our observations suggest that muscle contraction prevails over the baseline effects of TMS on the soleus H reflex. While contraction of the antagonist (df) suppressed most of the effects, contraction of the agonist had different effects depending on the type of activity (pf or ss). The characterization of the interaction between descending corticospinal volleys and segmental peripheral inputs provides useful information on motor control for physiological research and further understanding of the effects of spinal cord lesions.

Volitional control of reflex cough

PubMed Central

Bolser, Donald C.; Davenport, Paul W.

2012-01-01

Multiple studies suggest a role for the cerebral cortex in the generation of reflex cough in awake humans. Reflex cough is preceded by detection of an urge to cough; strokes specifically within the cerebral cortex can affect parameters of reflex cough, and reflex cough can be voluntarily suppressed. However, it is not known to what extent healthy, awake humans can volitionally modulate the cough reflex, aside from suppression. The aims of this study were to determine whether conscious humans can volitionally modify their reflexive cough and, if so, to determine what parameters of the cough waveform and corresponding muscle activity can be modified. Twenty adults (18–40 yr, 4 men) volunteered for study participation and gave verbal and written informed consent. Participants were seated and outfitted with a facemask and pneumotacograph, and two surface EMG electrodes were positioned over expiratory muscles. Capsaicin (200 μM) was delivered via dosimeter and one-way (inspiratory) valve attached to a side port between the facemask and pneumotachograph. Cough airflow and surface EMG activity were recorded across tasks including 1) baseline, 2) small cough (cough smaller or softer than normal), 3) long cough (cough longer or louder than normal), and 4) not cough (alternative behavior). All participants coughed in response to 200 μM capsaicin and were able to modify the cough. Variables exhibiting changes include those related to the peak airflow during the expiratory phase. Results demonstrate that it is possible to volitionally modify cough motor output characteristics. PMID:22492938

OPERANT CONDITIONING OF A SPINAL REFLEX CAN IMPROVE LOCOMOTION AFTER SPINAL CORD INJURY IN HUMANS

PubMed Central

Thompson, Aiko K.; Pomerantz, Ferne; Wolpaw, Jonathan R.

2013-01-01

Operant conditioning protocols can modify the activity of specific spinal cord pathways and can thereby affect behaviors that use these pathways. To explore the therapeutic application of these protocols, we studied the impact of down-conditioning the soleus H-reflex in people with impaired locomotion caused by chronic incomplete spinal cord injury. After a baseline period in which soleus H-reflex size was measured and locomotion was assessed, subjects completed either 30 H-reflex down-conditioning sessions (DC subjects) or 30 sessions in which the H-reflex was simply measured (Unconditioned (UC) subjects), and locomotion was reassessed. Over the 30 sessions, the soleus H-reflex decreased in two-thirds of the DC subjects (a success rate similar to that in normal subjects) and remained smaller several months later. In these subjects, locomotion became faster and more symmetrical, and the modulation of EMG activity across the step-cycle increased bilaterally. Furthermore, beginning about halfway through the conditioning sessions, all of these subjects commented spontaneously that they were walking faster and farther in their daily lives, and several noted less clonus, easier stepping, and/or other improvements. The H-reflex did not decrease in the other DC subjects or in any of the UC subjects; and their locomotion did not improve. These results suggest that reflex conditioning protocols can enhance recovery of function after incomplete spinal cord injuries and possibly in other disorders as well. Because they are able to target specific spinal pathways, these protocols could be designed to address each individual’s particular deficits, and might thereby complement other rehabilitation methods. PMID:23392666

Sequential modulation of cardiac autonomic control induced by cardiopulmonary and arterial baroreflex mechanisms

NASA Technical Reports Server (NTRS)

Furlan, R.; Jacob, G.; Palazzolo, L.; Rimoldi, A.; Diedrich, A.; Harris, P. A.; Porta, A.; Malliani, A.; Mosqueda-Garcia, R.; Robertson, D.

2001-01-01

BACKGROUND: Nonhypotensive lower body negative pressure (LBNP) induces a reflex increase in forearm vascular resistance and muscle sympathetic neural discharge without affecting mean heart rate. We tested the hypothesis that a reflex change of the autonomic modulation of heartbeat might arise during low intensity LBNP without changes of mean heart rate. METHODS AND RESULTS: Ten healthy volunteers underwent plasma catecholamine evaluation and a continuous recording of ECG, finger blood pressure, respiratory activity, and central venous pressure (CVP) during increasing levels of LBNP up to -40 mm Hg. Spectrum and cross-spectrum analyses assessed the changes in the spontaneous variability of R-R interval, respiration, systolic arterial pressure (SAP), and CVP and in the gain (alpha(LF)) of arterial baroreflex control of heart rate. Baroreceptor sensitivity was also evaluated by the SAP/R-R spontaneous sequences technique. LBNP began decreasing significantly: CVP at -10, R-R interval at -20, SAP at -40, and the indexes alpha(LF) and baroreceptor sensitivity at -30 and -20 mm Hg, compared with baseline conditions. Plasma norepinephrine increased significantly at -20 mm Hg. The normalized low-frequency component of R-R variability (LF(R-R)) progressively increased and was significantly higher than in the control condition at -15 mm Hg. CONCLUSIONS: Nonhypotensive LBNP elicits a reflex increase of cardiac sympathetic modulation, as evaluated by LF(R-R), which precedes the changes in the hemodynamics and in the indexes of arterial baroreflex control.

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.

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.

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.

Functional organization of primate translational vestibulo-ocular reflexes and effects of unilateral labyrinthectomy

NASA Technical Reports Server (NTRS)

Angelaki, D. E.; McHenry, M. Q.; Newlands, S. D.; Dickman, J. D.

1999-01-01

Translational vestibulo-ocular reflexes (trVORs) are characterized by distinct spatio-temporal properties and sensitivities that are proportional to the inverse of viewing distance. Anodal (inhibitory) labyrinthine stimulation (100 microA, < 2 s) during motion decreased the high-pass filtered dynamics, as well as horizontal trVOR sensitivity and its dependence on viewing distance. Cathodal (excitatory) currents had opposite effects. Translational VORs were also affected after unilateral labyrinthectomy. Animals lost their ability to modulate trVOR sensitivity as a function of viewing distance acutely after the lesion. These deficits partially recovered over time, albeit a significant reduction in trVOR sensitivity as a function of viewing distance remained in compensated animals. During fore-aft motion, the effects of unilateral labyrinthectomy were more dramatic. Both acute and compensated animals permanently lost their ability to modulate fore-aft trVOR responses as a function of target eccentricity. These results suggest that (1) the dynamics and viewing distance-dependent properties of the trVORs are very sensitive to changes in the resting firing rate of vestibular afferents and, consequently, vestibular nuclei neurons; (2) the most irregularly firing primary otolith afferents that are most sensitive to labyrinthine electrical stimulation might contribute to reflex dynamics and sensitivity; (3) inputs from both labyrinths are necessary for the generation of the translational VORs.

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.

Effect of pinching-evoked pain on jaw-stretch reflexes and exteroceptive suppression periods in healthy subjects.

PubMed

Biasiotta, A; Peddireddy, A; Wang, K; Romaniello, A; Frati, A; Svensson, P; Arendt-Nielsen, L

2007-10-01

To investigate the influence of conditioning cutaneous nociceptive inputs by a new "pinch" model on the jaw-stretch reflex and the exteroceptive suppression periods (ES1 and ES2) in jaw muscles. The jaw-stretch reflex was evoked with the use of a custom-made muscle stretcher and electrical stimuli were used to evoke an early and late exteroceptive suppression period (ES1 and ES2) in the jaw-closing muscles. Electromyographic (EMG) activity was recorded bilaterally from the masseter and temporalis muscles. These brainstem reflexes were recorded in 19 healthy men (28.8+/-1.1 years) during three different conditions: one painful clip applied to the earlobe; one painful clip applied to the nostril, and four painful clips applied simultaneously to the earlobe, nostril, eyebrow, and lower lip. Pain intensity induced by the application of the clips was scored continuously by the subjects on a 100mm visual analogue scale (VAS). The highest VAS pain scores were evoked by placement of four clips (79+/-0.5mm). There was no significant modulation of the jaw-stretch reflex (ANOVAs: P=0.929), the ES1 (P=0.298) or ES2 (P=0.082) in any of the three painful conditions. Intense and tonic cutaneous pain could be elicited by this new "pinch" pain model; however, there was no significant modulation on either excitatory or inhibitory brainstem reflex responses. The novel observation that high-intensity pinch stimuli applied to the craniofacial region fail to modulate two different brainstem reflexes is in contrast to other experimental pain studies documented facilitation of the jaw-stretch reflexes or inhibition of exteroceptive suppression periods. The clinical implication of the present findings is that only some craniofacial pain conditions could be expected to show perturbation of the brainstem reflex responses.

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.

Impact of aerobic exercise intensity on craving and reactivity to smoking cues.

PubMed

Janse Van Rensburg, Kate; Elibero, Andrea; Kilpatrick, Marcus; Drobes, David J

2013-06-01

Aerobic exercise can acutely reduce cigarette cravings during periods of nicotine deprivation. The primary aim of this study was to assess the differential effects of light and vigorous intensity aerobic exercise on cigarette cravings, subjective and physiological reactivity to smoking cues, and affect after overnight nicotine deprivation. A secondary aim was to examine cortisol change as a mediator of the effects of exercise on smoking motivation. 162 (55 female, 107 male) overnight nicotine-deprived smokers were randomized to one of three exercise conditions: light intensity, vigorous intensity, or a passive control condition. After each condition, participants engaged in a standardized cue reactivity assessment. Self-reported urges to smoke, affect, and salivary cortisol were assessed at baseline (i.e., before each condition), immediately after each condition, and after the cue reactivity assessment. Light and vigorous exercise significantly decreased urges to smoke and increased positive affect, relative to the control condition. In addition, those in the vigorous exercise condition demonstrated suppressed appetitive reactivity to smoking cues, as indexed by the startle eyeblink reflex. Although exercise intensity was associated with expected changes in cortisol concentration, these effects were not related to changes in craving or cue reactivity. Both light and vigorous exercise can reduce general cravings to smoke, whereas vigorous exercise appears especially well-suited for reducing appetitive reactions to cues that may precede smoking. Results did not support exercise-induced cortisol release as a mechanism for these effects. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Toward a Neural Chronometry for the Aesthetic Experience of Music

PubMed Central

Brattico, Elvira; Bogert, Brigitte; Jacobsen, Thomas

2013-01-01

Music is often studied as a cognitive domain alongside language. The emotional aspects of music have also been shown to be important, but views on their nature diverge. For instance, the specific emotions that music induces and how they relate to emotional expression are still under debate. Here we propose a mental and neural chronometry of the aesthetic experience of music initiated and mediated by external and internal contexts such as intentionality, background mood, attention, and expertise. The initial stages necessary for an aesthetic experience of music are feature analysis, integration across modalities, and cognitive processing on the basis of long-term knowledge. These stages are common to individuals belonging to the same musical culture. The initial emotional reactions to music include the startle reflex, core “liking,” and arousal. Subsequently, discrete emotions are perceived and induced. Presumably somatomotor processes synchronizing the body with the music also come into play here. The subsequent stages, in which cognitive, affective, and decisional processes intermingle, require controlled cross-modal neural processes to result in aesthetic emotions, aesthetic judgments, and conscious liking. These latter aesthetic stages often require attention, intentionality, and expertise for their full actualization. PMID:23641223

The Spleen: A Hub Connecting Nervous and Immune Systems in Cardiovascular and Metabolic Diseases

PubMed Central

Lori, Andrea; Perrotta, Marialuisa; Lembo, Giuseppe; Carnevale, Daniela

2017-01-01

Metabolic disorders have been identified as major health problems affecting a large portion of the world population. In addition, obesity and insulin resistance are principal risk factors for the development of cardiovascular diseases. Altered immune responses are common features of both hypertension and obesity and, moreover, the involvement of the nervous system in the modulation of immune system is gaining even more attention in both pathophysiological contexts. For these reasons, during the last decades, researches focused their efforts on the comprehension of the molecular mechanisms connecting immune system to cardiovascular and metabolic diseases. On the other hand, it has been reported that in these pathological conditions, central neural pathways modulate the activity of the peripheral nervous system, which is strongly involved in onset and progression of the disease. It is interesting to notice that neural reflex can also participate in the modulation of immune functions. In this scenario, the spleen becomes the crucial hub allowing the interaction of different systems differently involved in metabolic and cardiovascular diseases. Here, we summarize the major findings that dissect the role of the immune system in disorders related to metabolic and cardiovascular dysfunctions, and how this could also be influenced by neural reflexes. PMID:28590409

Follow My Eyes: The Gaze of Politicians Reflexively Captures the Gaze of Ingroup Voters

PubMed Central

Liuzza, Marco Tullio; Cazzato, Valentina; Vecchione, Michele; Crostella, Filippo; Caprara, Gian Vittorio; Aglioti, Salvatore Maria

2011-01-01

Studies in human and non-human primates indicate that basic socio-cognitive operations are inherently linked to the power of gaze in capturing reflexively the attention of an observer. Although monkey studies indicate that the automatic tendency to follow the gaze of a conspecific is modulated by the leader-follower social status, evidence for such effects in humans is meager. Here, we used a gaze following paradigm where the directional gaze of right- or left-wing Italian political characters could influence the oculomotor behavior of ingroup or outgroup voters. We show that the gaze of Berlusconi, the right-wing leader currently dominating the Italian political landscape, potentiates and inhibits gaze following behavior in ingroup and outgroup voters, respectively. Importantly, the higher the perceived similarity in personality traits between voters and Berlusconi, the stronger the gaze interference effect. Thus, higher-order social variables such as political leadership and affiliation prepotently affect reflexive shifts of attention. PMID:21957479

Ocular Reflex Phase During Off-Vertical Axis Rotation In Humans Is Modified By Head-On-Trunk Position

NASA Technical Reports Server (NTRS)

Wood, Scott; Clement, Gilles; Denise, Pierre; Reschke, Millard

2005-01-01

Constant velocity Off-Vertical Axis Rotation (OVAR) imposes a continuously varying orientation of the head and body relative to gravity. The ensuing ocular reflexes include modulation of both horizontal and torsional eye velocity as a function of the varying linear acceleration along the lateral plane. The purpose of this study was to examine whether the modulation of these ocular reflexes would be modified by different head-on-trunk positions. Ten human subjects were rotated in darkness about their longitudinal axis 20 deg off-vertical at constant rates of 45 and 180 deg/s, corresponding to 0.125 and 0.5 Hz. Binocular responses were obtained with video-oculography with the head and trunk aligned, and then with the head turned relative to the trunk 40 deg to the right or left of center. Sinusoidal curve fits were used to derive amplitude, phase and bias velocity of the eye movements across multiple cycles for each head-on-trunk position. Consistent with previous studies, the modulation of torsional eye movements was greater at 0.125 Hz while the modulation of horizontal eye movements was greater at 0.5 Hz. Neither amplitude nor bias velocities were significantly altered by head-on-trunk position. The phases of both torsional and horizontal ocular reflexes, on the other hand, shifted towards alignment with the head. These results are consistent with the modulation of torsional and horizontal ocular reflexes during OVAR being primarily mediated by the otoliths in response to the sinusoidally varying linear acceleration along the interaural head axis.

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).

Increased excitability of spinal pain reflexes and altered frequency-dependent modulation in the dopamine D3-receptor knockout mouse.

PubMed

Keeler, Benjamin E; Baran, Christine A; Brewer, Kori L; Clemens, Stefan

2012-12-01

Frequency-dependent modulation and dopamine (DA) receptors strongly modulate neural circuits in the spinal cord. Of the five known DA receptor subtypes, the D3 receptor has the highest affinity to DA, and D3-mediated actions are mainly inhibitory. Using an animal model of spinal sensorimotor dysfunction, the D3 receptor knockout mouse (D3KO), we investigated the physiological consequences of D3 receptor dysfunction on pain-associated signaling pathways in the spinal cord, the initial integration site for the processing of pain signaling. In the D3KO spinal cord, inhibitory actions of DA on the proprioceptive monosynaptic stretch reflex are converted from depression to facilitation, but its effects on longer-latency and pain-associated reflex responses and the effects of FM have not been studied. Using behavioral approaches in vivo, we found that D3KO animals exhibit reduced paw withdrawal latencies to thermal pain stimulation (Hargreaves' test) over wild type (WT) controls. Electrophysiological and pharmacological approaches in the isolated spinal cord in vitro showed that constant current stimulation of dorsal roots at a pain-associated frequency was associated with a significant reduction in the frequency-dependent modulation of longer-latency reflex (LLRs) responses but not monosynaptic stretch reflexes (MSRs) in D3KO. Application of the D1 and D2 receptor agonists and the voltage-gated calcium-channel ligand, pregabalin, but not DA, was able to restore the frequency-dependent modulation of the LLR in D3KO to WT levels. Thus we demonstrate that nociception-associated LLRs and proprioceptive MSRs are differentially modulated by frequency, dopaminergics and the Ca(2+) channel ligand, pregabalin. Our data suggest a role for the DA D3 receptor in pain modulation and identify the D3KO as a possible model for increased nociception. Copyright © 2012 Elsevier Inc. All rights reserved.

Roller massage decreases spinal excitability to the soleus.

PubMed

Young, James D; Spence, Alyssa-Joy; Behm, David G

2018-04-01

Roller massage (RM) interventions have shown acute increases in range of motion (ROM) and pain pressure threshold (PPT). It is unclear whether the RM-induced increases can be attributed to changes in neural or muscle responses. The purpose of this study was to evaluate the effect of altered afferent input via application of RM on spinal excitability, as measured with the Hoffmann (H-) reflex. A randomized within-subjects design was used. Three 30-s bouts of RM were implemented on a rested, nonexercised, injury-free muscle with 30 s of rest between bouts. The researcher applied RM to the plantar flexors at three intensities of pain: high, moderate, and sham. Measures included normalized M-wave and H-reflex peak-to-peak amplitudes before, during, and up to 3 min postintervention. M-wave and H-reflex measures were highly reliable. RM resulted in significant decreases in soleus H-reflex amplitudes. High-intensity, moderate-intensity, and sham conditions decreased soleus H-reflex amplitudes by 58%, 43%, and 19%, respectively. H-reflexes induced with high-intensity rolling discomfort or pain were significantly lower than moderate and sham conditions. The effects were transient in nature, with an immediate return to baseline following RM. This is the first evidence of RM-induced modulation of spinal excitability. The intensity-dependent response observed indicates that rolling pressure or pain perception may play a role in modulation of the inhibition. Roller massage-induced neural modulation of spinal excitability may explain previously reported increases in ROM and PPT. NEW & NOTEWORTHY Recent evidence indicates that the benefits of foam rolling and roller massage are primarily accrued through neural mechanisms. The present study attempts to determine the neuromuscular response to roller massage interventions. We provide strong evidence of roller massage-induced neural modulation of spinal excitability to the soleus. It is plausible that reflex inhibition may explain subsequent increases in pain pressure threshold.

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

Reflexive Pedagogy for Reading across the Curriculum: The University of KwaZulu-Natal Faculty of Education Experience

ERIC Educational Resources Information Center

Mgqwashu, Emmanuel Mfanafuthi

2011-01-01

This article is a qualitative evaluation of the role of reflexive pedagogy; a pedagogic approach used in a first year, academic literacy compulsory module for all first year Bachelor of Education (B. Ed) students offered by the School of Language, Literacies, Media and Drama Education at the University of KwaZulu-Natal. The module is called…

The effect of operant-conditioning balance training on the down-regulation of spinal H-reflexes in a spastic patient.

PubMed

Hoseini, Najmeh; Koceja, David M; Riley, Zachary A

2011-10-24

Spasticity in chronic hemiparetic stroke patients has primarily been treated pharmacologically. However, there is increasing evidence that physical rehabilitation can help manage hyper-excitability of reflexes (hyperreflexia), which is a primary contributor to spasticity. In the present study, one chronic hemiparetic stroke patient operantly conditioned the soleus H-reflex while training on a balance board for two weeks. The results showed a minimal decrease in the Hmax-Mmax ratio for both the affected and unaffected limb, indicating that the H-reflex was not significantly altered with training. Alternatively, paired-reflex depression (PRD), a measure of history-dependent changes in reflex excitability, could be conditioned. This was evident by the rightward shift and decreased slope of reflex excitability in the affected limb. The non-affected limb decreased as well, although the non-affected limb was very sensitive to PRD initially, whereas the affected limb was not. Based on these results, it was concluded that PRD is a better index of hyperreflexia, and this measurement could be more informative of synapse function than simple H-reflexes. This study presents a novel and non-pharmacological means of managing spasticity that warrants further investigation with the potential of being translated to the clinic. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Both Predator and Prey

PubMed Central

Löw, Andreas; Lang, Peter J.; Smith, J. Carson; Bradley, Margaret M.

2013-01-01

This research examined the psychophysiology of emotional arousal anticipatory to potentially aversive and highly pleasant outcomes. Human brain reactions (event-related potentials) and body reactions (heart rate, skin conductance, the probe startle reflex) were assessed along motivational gradients determined by apparent distance from sites of potential punishment or reward. A predator-prey survival context was simulated using cues that signaled possible money rewards or possible losses; the cues appeared to loom progressively closer to the viewer, until a final step when a rapid key response could ensure reward or avoid a punishing loss. The observed anticipatory response patterns of heightened vigilance and physiological mobilization are consistent with the view that the physiology of emotion is founded on action dispositions that evolved in mammals to facilitate survival by dealing with threats or capturing life-sustaining rewards. PMID:18947351

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.

Exposure to Bisphenol A Exacerbates Migraine-Like Behaviors in a Multibehavior Model of Rat Migraine

PubMed Central

Berman, Nancy E. J.

2014-01-01

Migraine is a common and debilitating neurological disorder suffered worldwide. Women experience this condition 3 times more frequently than men, with estrogen strongly implicated to play a role. Bisphenol A (BPA), a highly prevalent xenoestrogen, is known to have estrogenic activity and may have an effect in migraine onset, intensity, and duration through estrogen receptor signaling. It was hypothesized that BPA exposure exacerbates migraine symptoms through estrogen signaling and downstream activation of nociception related pathways. Utilizing a multibehavior model of migraine in ovariectomized female rats, changes in locomotion, light and sound sensitivity, grooming, and acoustic startle were examined. Furthermore, changes in the expression of genes related to estrogen (ERα, GPR30), and nociception (extracellular signal regulated kinase, ERK, sodium gated channel, Nav1.8, and fatty acid amide hydrolase, FAAH) were studied following behavioral experiments. The following results were obtained: BPA treatment significantly exacerbated migraine-like behaviors in rats. Rats exposed to BPA demonstrated decreased locomotion, exacerbated light and sound aversion, altered grooming habits, and enhanced startle reflexes. Furthermore, BPA exposure increased mRNA expression of estrogen receptors, total ERK mRNA and ERK activation, as well as Nav1.8, and FAAH mRNA, indicative of altered estrogen signaling and altered nociception. These results show that BPA, an environmentally pervasive xenoestrogen, exacerbates migraine-like behavior in a rat model and alters expression of estrogen and nociception-related genes. PMID:24189132

Effects of administration of sodium glutamate during the neonatal period on behavior and blood corticosterone levels in male mice.

PubMed

Kuznetsova, E G; Amstislavskaya, T G; Bulygina, V V; Il'nitskaya, S I; Tibeikina, M A; Skrinskaya, Yu A

2007-10-01

Treatment of male DBA/2 mice with sodium glutamate (4 mg/g) on postnatal days 1, 3, 5, 7, and 9 induced reductions in the numbers of square crossings, vertical rearings, excursions to the center, and the time spent in the center in adulthood, as compared with a group of males given physiological saline at the same times. These measures showed no change as compared with intact animals. In the light-dark test, the time spent by mice in the light sector was greater after administration of sodium glutamate than after administration of physiological saline but did not differ from that in intact animals. In the acoustic startle reflex test, sodium glutamate decreased startle amplitude but had no effect on the magnitude of prestimulus inhibition. Sexual motivation in males decreased after sodium glutamate, physiological saline producing a tendency to decreased sexual motivation. Neonatal administration of sodium glutamate increased basal blood corticosterone in adult males by a factor of 4, while physiological saline had no effect on this measure. These results lead to the conclusion that neonatal administration of sodium glutamate decreases motor and investigative activity, anxiety, and sexual motivation in adult male mice and increases basal corticosterone. Physiological saline increased all these parameters apart from sexual motivation, though this was not associated with changes in basal corticosterone.

Elevated Responding to Safe Conditions as a Specific Risk Factor for Anxiety Versus Depressive Disorders: Evidence From a Longitudinal Investigation

PubMed Central

Craske, Michelle G.; Wolitzky–Taylor, Kate B.; Mineka, Susan; Zinbarg, Richard; Waters, Allison M.; Vrshek–Schallhorn, Suzanne; Epstein, Alyssa; Naliboff, Bruce; Ornitz, Edward

2013-01-01

The current study evaluated the degree to which startle reflexes (SRs) in safe conditions versus danger conditions were predictive of the onset of anxiety disorders. Specificity of these effects to anxiety disorders was evaluated in comparison to unipolar depressive disorders and with consideration of level of neuroticism. A startle paradigm was administered at baseline to 132 nondisordered adolescents as part of a longitudinal study examining risk factors for emotional disorders. Participants underwent a repetition of eight safe-danger sequences and were told that delivery of an aversive stimulus leading to a muscle contraction of the arm would occur only in the late part of danger conditions. One aversive stimulus occurred midway in the safe-danger sequences. Participants were assessed for the onset of anxiety and unipolar depressive disorders annually over the next 3 to 4 years. Larger SR magnitude during safe conditions following delivery of the aversive stimulus predicted the subsequent first onset of anxiety disorders. Moreover, prediction of the onset of anxiety disorders remained significant above and beyond the effects of comorbid unipolar depression, neuroticism, and subjective ratings of intensity of the aversive stimulus. In sum, elevated responding to safe conditions following an aversive stimulus appears to be a specific, prospective risk factor for the first onset of anxiety disorders. PMID:21988452

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

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

PubMed

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

2018-01-15

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

Lead exposure and fear-potentiated startle in the VA Normative Aging Study: a pilot study of a novel physiological approach to investigating neurotoxicant effects.

PubMed

Grashow, Rachel; Miller, Mark W; McKinney, Ann; Nie, Linda H; Sparrow, David; Hu, Howard; Weisskopf, Marc G

2013-01-01

Physiologically-based indicators of neural plasticity in humans could provide mechanistic insights into toxicant actions on learning in the brain, and perhaps prove more objective and sensitive measures of such effects than other methods. We explored the association between lead exposure and classical conditioning of the acoustic startle reflex (ASR)-a simple form of associative learning in the brain-in a population of elderly men. Fifty-one men from the VA Normative Aging Study with cumulative bone lead exposure measurements made with K-X-Ray-Fluorescence participated in a fear-conditioning protocol. The mean age of the men was 75.5years (standard deviation [sd]=5.9) and mean patella lead concentration was 22.7μg/g bone (sd=15.9). Baseline ASR eyeblink response decreased with age, but was not associated with subsequent conditioning. Among 37 men with valid responses at the end of the protocol, higher patella lead was associated with decreased awareness of the conditioning contingency (declarative learning; adjusted odds ratio [OR] per 20μg/g patella lead=0.91, 95% confidence interval [CI]: 0.84, 0.99, p=0.03). Eyeblink conditioning (non-declarative learning) was 0.44sd less (95% CI: -0.91, 0.02; p=0.06) per 20μg/g patella lead after adjustment. Each result was stronger when correcting for the interval between lead measurement and startle testing (awareness: OR=0.88, 95% CI: 0.78, 0.99, p=0.04; conditioning: -0.79sd less, 95% CI: -1.56, 0.03, p=0.04). This initial exploration suggests that lead exposure interferes with specific neural mechanisms of learning and offers the possibility that the ASR may provide a new approach to physiologically explore the effects of neurotoxicant exposures on neural mechanisms of learning in humans with a paradigm that is directly comparable to animal models. Copyright © 2013 Elsevier Inc. All rights reserved.

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.

Pathological anxiety and function/dysfunction in the brain's fear/defense circuitry.

PubMed

Lang, Peter J; McTeague, Lisa M; Bradley, Margaret M

2014-01-01

Research from the University of Florida Center for the Study of Emotion and Attention aims to develop neurobiological measures that objectively discriminate among symptom patterns in patients with anxiety disorders. From this perspective, anxiety and mood pathologies are considered to be brain disorders, resulting from dysfunction and maladaptive plasticity in the neural circuits that determine fearful/defensive and appetitive/reward behavior (Insel et al., 2010). We review recent studies indicating that an enhanced probe startle reflex during the processing of fear memory cues (mediated by cortico-limbic circuitry and thus indicative of plastic brain changes), varies systematically in strength over a spectrum-wide dimension of anxiety pathology-across and within diagnoses-extending from strong focal fear reactions to a consistently blunted reaction in patients with more generalized anxiety and comorbid mood disorders. Preliminary studies with functional magnetic resonance imaging (fMRI) encourage the hypothesis that fear/defense circuit dysfunction covaries with this same dimension of psychopathology. Plans are described for an extended study of the brain's motivation circuitry in anxiety spectrum patients, with the aim of defining the specifics of circuit dysfunction in severe disorders. A sub-project explores the use of real-time fMRI feedback in circuit analysis and as a modality to up-regulate circuit function in the context of blunted affect.

Blast-Induced Tinnitus and Elevated Central Auditory and Limbic Activity in Rats: A Manganese-Enhanced MRI and Behavioral Study.

PubMed

Ouyang, Jessica; Pace, Edward; Lepczyk, Laura; Kaufman, Michael; Zhang, Jessica; Perrine, Shane A; Zhang, Jinsheng

2017-07-07

Blast-induced tinitus is the number one service-connected disability that currently affects military personnel and veterans. To elucidate its underlying mechanisms, we subjected 13 Sprague Dawley adult rats to unilateral 14 psi blast exposure to induce tinnitus and measured auditory and limbic brain activity using manganese-enhanced MRI (MEMRI). Tinnitus was evaluated with a gap detection acoustic startle reflex paradigm, while hearing status was assessed with prepulse inhibition (PPI) and auditory brainstem responses (ABRs). Both anxiety and cognitive functioning were assessed using elevated plus maze and Morris water maze, respectively. Five weeks after blast exposure, 8 of the 13 blasted rats exhibited chronic tinnitus. While acoustic PPI remained intact and ABR thresholds recovered, the ABR wave P1-N1 amplitude reduction persisted in all blast-exposed rats. No differences in spatial cognition were observed, but blasted rats as a whole exhibited increased anxiety. MEMRI data revealed a bilateral increase in activity along the auditory pathway and in certain limbic regions of rats with tinnitus compared to age-matched controls. Taken together, our data suggest that while blast-induced tinnitus may play a role in auditory and limbic hyperactivity, the non-auditory effects of blast and potential traumatic brain injury may also exert an effect.

Effects of the beta-blocker propranolol on cued and contextual fear conditioning in humans.

PubMed

Grillon, Christian; Cordova, Jeremy; Morgan, Charles Andrew; Charney, Dennis S; Davis, Michael

2004-09-01

Beta-adrenergic receptors are involved in the consolidation of emotional memories. Yet, a number of studies using Pavlovian cued fear conditioning have been unable to demonstrate an effect of beta-adrenergic blockade on acquisition or retention of fear conditioning. Evidence for the involvement of beta-adrenergic receptors in emotional memories comes mostly from studies using fear inhibitory avoidance in rodents. It is possible that fear inhibitory avoidance is more akin to contextual conditioning than to cued fear conditioning, suggesting that context conditioning may be disrupted by beta-adrenergic blockade. This study investigated the effects of the beta-adrenergic blocker propranolol on cued and contextual fear conditioning in humans. Subjects were given either placebo (n=15) or 40 mg propranolol (n=15) prior to differential cued conditioning. A week later, they were tested for retention of context and cued fear conditioning using physiological (startle reflex and electrodermal activity) and subjective measures of emotional arousal. The results were consistent with the hypothesis. The skin conductance level (SCL) and the subjective measure of arousal suggested reduced emotional arousal upon returning to the conditioning context in the propranolol group, compared to the placebo group. The acquisition and retention of cued fear conditioning were not affected by propranolol. These results suggest that beta-adrenergic receptors are involved in contextual fear conditioning.

Increased whole-body auditory startle reflex and autonomic reactivity in children with anxiety disorders

PubMed Central

Bakker, Mirte J.; Tijssen, Marina A.J.; van der Meer, Johan N.; Koelman, Johannes H.T.M.; Boer, Frits

2009-01-01

Background Young patients with anxiety disorders are thought to have a hypersensitive fear system, including alterations of the early sensorimotor processing of threatening information. However, there is equivocal support in auditory blink response studies for an enlarged auditory startle reflex (ASR) in such patients. We sought to investigate the ASR measured over multiple muscles (whole-body) in children and adolescents with anxiety disorders. Methods Between August and December 2006, we assessed ASRs (elicited by 8 consecutive tones of 104 dB, interstimulus interval of about 2 min) in 25 patients and 25 matched controls using a case–control design and in 9 nonaffected siblings. We recorded the electromyographic activity of 6 muscles and the sympathetic skin response. We investigated response occurrence (probability %) and response magnitude (area under the curve in μV × ms) of the combined response of 6 muscles and of the single blink response. Results In patients (17 girls, mean age 12 years; 13 social phobia, 9 generalized anxiety, 3 other), the combined response probability (p = 0.027) of all muscles, the combined area under the curve of all muscles (p = 0.011) and the sympathetic skin response (p = 0.006) were enlarged compared with matched controls. The response probability (p = 0.48) and area under the curve (p = 0.07) of the blink response were normal in patients compared with controls. The ASR pattern was normal with normal latencies in patients compared with controls. In nonaffected siblings, the sympathetic skin response (p = 0.038), but not the combined response probability of all muscles (p = 0.15), was enlarged compared with controls. Limitations Limitations are the sample size and restricted comparison to the psychophysiological ASR paradigm. Conclusion The results point toward a hypersensitive central nervous system (fear system), including early sensorimotor processing alterations and autonomic hyperreactivity. The multiple muscle (whole-body) ASR is suggested to be a better tool to detect ASR abnormalities in patients with anxiety disorders than the blink response alone. Abnormalities in ASR serve as a candidate endophenotype of anxiety disorders. PMID:19568483

Periodic modulation of repetitively elicited monosynaptic reflexes of the human lumbosacral spinal cord

PubMed Central

Danner, Simon M.; Freundl, Brigitta; Binder, Heinrich; Mayr, Winfried; Rattay, Frank; Minassian, Karen

2015-01-01

In individuals with motor-complete spinal cord injury, epidural stimulation of the lumbosacral spinal cord at 2 Hz evokes unmodulated reflexes in the lower limbs, while stimulation at 22–60 Hz can generate rhythmic burstlike activity. Here we elaborated on an output pattern emerging at transitional stimulation frequencies with consecutively elicited reflexes alternating between large and small. We analyzed responses concomitantly elicited in thigh and leg muscle groups bilaterally by epidural stimulation in eight motor-complete spinal cord-injured individuals. Periodic amplitude modulation of at least 20 successive responses occurred in 31.4% of all available data sets with stimulation frequency set at 5–26 Hz, with highest prevalence at 16 Hz. It could be evoked in a single muscle group only but was more strongly expressed and consistent when occurring in pairs of antagonists or in the same muscle group bilaterally. Latencies and waveforms of the modulated reflexes corresponded to those of the unmodulated, monosynaptic responses to 2-Hz stimulation. We suggest that the cyclical changes of reflex excitability resulted from the interaction of facilitatory and inhibitory mechanisms emerging after specific delays and with distinct durations, including postactivation depression, recurrent inhibition and facilitation, as well as reafferent feedback activation. The emergence of large responses within the patterns at a rate of 5.5/s or 8/s may further suggest the entrainment of spinal mechanisms as involved in clonus. The study demonstrates that the human lumbosacral spinal cord can organize a simple form of rhythmicity through the repetitive activation of spinal reflex circuits. PMID:25904708

Cannabinoid-induced effects on the nociceptive system: a neurophysiological study in patients with secondary progressive multiple sclerosis.

PubMed

Conte, Antonella; Bettolo, Chiara Marini; Onesti, Emanuela; Frasca, Vittorio; Iacovelli, Elisa; Gilio, Francesca; Giacomelli, Elena; Gabriele, Maria; Aragona, Massimiliano; Tomassini, Valentina; Pantano, Patrizia; Pozzilli, Carlo; Inghilleri, Maurizio

2009-05-01

Although clinical studies show that cannabinoids improve central pain in patients with multiple sclerosis (MS) neurophysiological studies are lacking to investigate whether they also suppress these patients' electrophysiological responses to noxious stimulation. The flexion reflex (FR) in humans is a widely used technique for assessing the pain threshold and for studying spinal and supraspinal pain pathways and the neurotransmitter system involved in pain control. In a randomized, double-blind, placebo-controlled, cross-over study we investigated cannabinoid-induced changes in RIII reflex variables (threshold, latency and area) in a group of 18 patients with secondary progressive MS. To investigate whether cannabinoids act indirectly on the nociceptive reflex by modulating lower motoneuron excitability we also evaluated the H-reflex size after tibial nerve stimulation and calculated the H wave/M wave (H/M) ratio. Of the 18 patients recruited and randomized 17 completed the study. After patients used a commercial delta-9-tetrahydrocannabinol (THC) and cannabidiol mixture as an oromucosal spray the RIII reflex threshold increased and RIII reflex area decreased. The visual analogue scale score for pain also decreased, though not significantly. Conversely, the H/M ratio measured before patients received cannabinoids remained unchanged after therapy. In conclusion, the cannabinoid-induced changes in the RIII reflex threshold and area in patients with MS provide objective neurophysiological evidence that cannabinoids modulate the nociceptive system in patients with MS.

Three-dimensional organization of otolith-ocular reflexes in rhesus monkeys. I. Linear acceleration responses during off-vertical axis rotation

NASA Technical Reports Server (NTRS)

Angelaki, D. E.; Hess, B. J.

1996-01-01

1. The dynamic properties of otolith-ocular reflexes elicited by sinusoidal linear acceleration along the three cardinal head axes were studied during off-vertical axis rotations in rhesus monkeys. As the head rotates in space at constant velocity about an off-vertical axis, otolith-ocular reflexes are elicited in response to the sinusoidally varying linear acceleration (gravity) components along the interaural, nasooccipital, or vertical head axis. Because the frequency of these sinusoidal stimuli is proportional to the velocity of rotation, rotation at low and moderately fast speeds allows the study of the mid-and low-frequency dynamics of these otolith-ocular reflexes. 2. Animals were rotated in complete darkness in the yaw, pitch, and roll planes at velocities ranging between 7.4 and 184 degrees/s. Accordingly, otolith-ocular reflexes (manifested as sinusoidal modulations in eye position and/or slow-phase eye velocity) were quantitatively studied for stimulus frequencies ranging between 0.02 and 0.51 Hz. During yaw and roll rotation, torsional, vertical, and horizontal slow-phase eye velocity was sinusoidally modulated as a function of head position. The amplitudes of these responses were symmetric for rotations in opposite directions. In contrast, mainly vertical slow-phase eye velocity was modulated during pitch rotation. This modulation was asymmetric for rotations in opposite direction. 3. Each of these response components in a given rotation plane could be associated with an otolith-ocular response vector whose sensitivity, temporal phase, and spatial orientation were estimated on the basis of the amplitude and phase of sinusoidal modulations during both directions of rotation. Based on this analysis, which was performed either for slow-phase eye velocity alone or for total eye excursion (including both slow and fast eye movements), two distinct response patterns were observed: 1) response vectors with pronounced dynamics and spatial/temporal properties that could be characterized as the low-frequency range of "translational" otolith-ocular reflexes; and 2) response vectors associated with an eye position modulation in phase with head position ("tilt" otolith-ocular reflexes). 4. The responses associated with two otolith-ocular vectors with pronounced dynamics consisted of horizontal eye movements evoked as a function of gravity along the interaural axis and vertical eye movements elicited as a function of gravity along the vertical head axis. Both responses were characterized by a slow-phase eye velocity sensitivity that increased three- to five-fold and large phase changes of approximately 100-180 degrees between 0.02 and 0.51 Hz. These dynamic properties could suggest nontraditional temporal processing in utriculoocular and sacculoocular pathways, possibly involving spatiotemporal otolith-ocular interactions. 5. The two otolith-ocular vectors associated with eye position responses in phase with head position (tilt otolith-ocular reflexes) consisted of torsional eye movements in response to gravity along the interaural axis, and vertical eye movements in response to gravity along the nasooccipital head axis. These otolith-ocular responses did not result from an otolithic effect on slow eye movements alone. Particularly at high frequencies (i.e., high speed rotations), saccades were responsible for most of the modulation of torsional and vertical eye position, which was relatively large (on average +/- 8-10 degrees/g) and remained independent of frequency. Such reflex dynamics can be simulated by a direct coupling of primary otolith afferent inputs to the oculomotor plant. (ABSTRACT TRUNCATED).

A modular telerobotic task execution system

NASA Technical Reports Server (NTRS)

Backes, Paul G.; Tso, Kam S.; Hayati, Samad; Lee, Thomas S.

1990-01-01

A telerobot task execution system is proposed to provide a general parametrizable task execution capability. The system includes communication with the calling system, e.g., a task planning system, and single- and dual-arm sensor-based task execution with monitoring and reflexing. A specific task is described by specifying the parameters to various available task execution modules including trajectory generation, compliance control, teleoperation, monitoring, and sensor fusion. Reflex action is achieved by finding the corresponding reflex action in a reflex table when an execution event has been detected with a monitor.

Involvement of ERK phosphorylation in brainstem neurons in modulation of swallowing reflex in rats

PubMed Central

Tsujimura, Takanori; Kondo, Masahiro; Kitagawa, Junichi; Tsuboi, Yoshiyuki; Saito, Kimiko; Tohara, Haruka; Ueda, Koichiro; Sessle, Barry J; Iwata, Koichi

2009-01-01

In order to evaluate the neuronal mechanisms underlying functional abnormalities of swallowing in orofacial pain patients, this study investigated the effects of noxious orofacial stimulation on the swallowing reflex, phosphorylated extracellular signal-regulated kinase (pERK) and γ-aminobutyric acid (GABA) immunohistochemical features in brainstem neurons, and also analysed the effects of brainstem lesioning and of microinjection of GABA receptor agonist or antagonist into the nucleus tractus solitarii (NTS) on the swallowing reflex in anaesthetized rats. The swallowing reflex elicited by topical administration of distilled water to the pharyngolaryngeal region was inhibited after capsaicin injection into the facial (whisker pad) skin or lingual muscle. The capsaicin-induced inhibitory effect on the swallowing reflex was itself depressed after the intrathecal administration of MAPK kinase (MEK) inhibitor. No change in the capsaicin-induced inhibitory effect was observed after trigeminal spinal subnucleus caudalis lesioning, but the inhibitory effect was diminished by paratrigeminal nucleus (Pa5) lesioning. Many pERK-like immunoreactive neurons in the NTS showed GABA immunoreactivity. The local microinjection of the GABAA receptor agonist muscimol into the NTS produced a significant reduction in swallowing reflex, and the capsaicin-induced depression of the swallowing reflex was abolished by microinjection of the GABAA receptor antagonist bicuculline into the NTS. The present findings suggest that facial skin–NTS, lingual muscle–NTS and lingual muscle–Pa5–NTS pathways are involved in the modulation of swallowing reflex by facial and lingual pain, respectively, and that the activation of GABAergic NTS neurons is involved in the inhibition of the swallowing reflex following noxious stimulation of facial and intraoral structures. PMID:19124539

Electroacupuncture modulation of reflex hypertension in rats: role of cholecystokinin octapeptide

PubMed Central

Tjen-A-Looi, Stephanie C.; Guo, Zhi-Ling; Longhurst, John C.

2013-01-01

Acupuncture or electroacupuncture (EA) potentially offers a nonpharmacological approach to reduce high blood pressure (BP). However, ∼70% of the patients and animal subjects respond to EA, while 30% do not. EA acts, in part, through an opioid mechanism in the rostral ventrolateral medulla (rVLM) to inhibit sympathoexcitatory reflexes induced by gastric distention. CCK-8 opposes the action of opioids during analgesia. Therefore, we hypothesized that CCK-8 in the rVLM antagonizes EA modulation of sympathoexcitatory cardiovascular reflex responses. Male rats anesthetized with ketamine and α-chloralose subjected to repeated gastric distension every 10 min were examined for their responsiveness to EA (2 Hz, 0.5 ms, 1–4 mA) at P5-P6 acupoints overlying median nerve. Repeated gastric distension every 10 min evoked consistent sympathoexcitatory responses. EA at P5-P6 modulated gastric distension-induced responses. Microinjection of CCK-8 in the rVLM reversed the EA effect in seven responders. The CCK1 receptor antagonist devazepide microinjected into the rVLM converted six nonresponders to responders by lowering the reflex response from 21 ± 2.2 to 10 ± 2.9 mmHg (first vs. second application of EA). The EA modulatory action in rats converted to responders with devazepide was reversed with rVLM microinjection of naloxone (n = 6). Microinjection of devazepide in the absence of a second application of EA did not influence the primary pressor reflexes of nonresponders. These data suggest that CCK-8 antagonizes EA modulation of sympathoexcitatory cardiovascular responses through an opioid mechanism and that inhibition of CCK-8 can convert animals that initially are unresponsive to EA to become responsive. PMID:23785073

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.

"Madam, Are You One of Them?" "Reflexivities of Discomfort" in Researching an "Illicit" Subject

ERIC Educational Resources Information Center

Namatende-Sakwa, Lydia

2018-01-01

Informed largely by Affect theory (2004), this paper takes up "reflexivities of discomfort" to reflexively engage with my affective struggles as a Christian, heterosexual, mother, educator, undertaking a study on homosexuality, which is a thorny issue in Uganda. It a methodological prologue, reflecting my thoughts and struggles before I…

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

Specific modulation of corticospinal and spinal excitabilities during maximal voluntary isometric, shortening and lengthening contractions in synergist muscles

PubMed Central

Duclay, Julien; Pasquet, Benjamin; Martin, Alain; Duchateau, Jacques

2011-01-01

Abstract This study was designed to investigate the cortical and spinal mechanisms involved in the modulations of neural activation during lengthening compared with isometric and shortening maximal voluntary contractions (MVCs). Two muscles susceptible to different neural adjustments at the spinal level, the soleus (SOL) and medial gastrocnemius (MG), were compared. Twelve healthy males participated in at least two experimental sessions designed to assess corticospinal and spinal excitabilities. We compared the modulation of motor evoked potentials (MEPs) in response to transcranial magnetic stimulation and Hoffmann reflexes (H-reflexes) during isometric and anisometric MVCs. The H-reflex and MEP responses, recorded during lengthening and shortening MVCs, were compared with those obtained during isometric MVCs. The results indicate that the maximal amplitude of both MEP and H-reflex in the SOL were smaller (P < 0.01) during lengthening MVCs compared with isometric and shortening MVCs but similar (P > 0.05) in MG for all three muscle contraction types. The silent period that follows maximal MEPs was reduced (P < 0.01) during lengthening MVCs in the SOL but not the MG. Similar observations were obtained regardless of the initial length of the MG muscle. Collectively, the current results indicate that the relative contribution of both cortical and spinal mechanisms to the modulation of neural activation differs during lengthening MVCs and between two synergist muscles. The comparison of SOL and MG responses further suggests that the specific modulation of the corticospinal excitability during lengthening MVCs depends mainly on pre- and postsynaptic inhibitory mechanisms acting at the spinal level. PMID:21502288

From Spontaneous Motor Activity to Coordinated Behaviour: A Developmental Model

PubMed Central

Marques, Hugo Gravato; Bharadwaj, Arjun; Iida, Fumiya

2014-01-01

In mammals, the developmental path that links the primary behaviours observed during foetal stages to the full fledged behaviours observed in adults is still beyond our understanding. Often theories of motor control try to deal with the process of incremental learning in an abstract and modular way without establishing any correspondence with the mammalian developmental stages. In this paper, we propose a computational model that links three distinct behaviours which appear at three different stages of development. In order of appearance, these behaviours are: spontaneous motor activity (SMA), reflexes, and coordinated behaviours, such as locomotion. The goal of our model is to address in silico four hypotheses that are currently hard to verify in vivo: First, the hypothesis that spinal reflex circuits can be self-organized from the sensor and motor activity induced by SMA. Second, the hypothesis that supraspinal systems can modulate reflex circuits to achieve coordinated behaviour. Third, the hypothesis that, since SMA is observed in an organism throughout its entire lifetime, it provides a mechanism suitable to maintain the reflex circuits aligned with the musculoskeletal system, and thus adapt to changes in body morphology. And fourth, the hypothesis that by changing the modulation of the reflex circuits over time, one can switch between different coordinated behaviours. Our model is tested in a simulated musculoskeletal leg actuated by six muscles arranged in a number of different ways. Hopping is used as a case study of coordinated behaviour. Our results show that reflex circuits can be self-organized from SMA, and that, once these circuits are in place, they can be modulated to achieve coordinated behaviour. In addition, our results show that our model can naturally adapt to different morphological changes and perform behavioural transitions. PMID:25057775

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.

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 ...

The parallel programming of voluntary and reflexive saccades.

PubMed

Walker, Robin; McSorley, Eugene

2006-06-01

A novel two-step paradigm was used to investigate the parallel programming of consecutive, stimulus-elicited ('reflexive') and endogenous ('voluntary') saccades. The mean latency of voluntary saccades, made following the first reflexive saccades in two-step conditions, was significantly reduced compared to that of voluntary saccades made in the single-step control trials. The latency of the first reflexive saccades was modulated by the requirement to make a second saccade: first saccade latency increased when a second voluntary saccade was required in the opposite direction to the first saccade, and decreased when a second saccade was required in the same direction as the first reflexive saccade. A second experiment confirmed the basic effect and also showed that a second reflexive saccade may be programmed in parallel with a first voluntary saccade. The results support the view that voluntary and reflexive saccades can be programmed in parallel on a common motor map.

Effect of a single dose of levodopa on sexual response in men and women.

PubMed

Both, Stephanie; Everaerd, Walter; Laan, Ellen; Gooren, Louis

2005-01-01

From animal research, there is ample evidence for a facilitating effect of dopamine on sexual behavior. In humans, little experimental research has been conducted on the inter-relation between dopamine and sexual response, even less so in women than in men. We investigated the effect of levodopa (100 mg) on sexual response in men and women following a double-blind, placebo-controlled crossover design. Genital and subjective sexual responses were measured as well as somatic motor system activity by means of Achilles tendon (T) reflex modulation. Genital and subjective sexual arousal were not affected by levodopa. However, the drug increased T reflex magnitude in response to sexual stimulation in men, but not in women. These results support the view that dopamine is involved in the energetic aspects of appetitive sexual behavior in men. The observed gender difference in the effect of levodopa is discussed in the perspective of possible dopamine-steroid interaction.

The medial olivocochlear reflex in children during active listening.

PubMed

Smith, Spencer B; Cone, Barbara

2015-08-01

To determine if active listening modulates the strength of the medial olivocochlear (MOC) reflex in children. Click-evoked otoacoustic emissions (CEOAEs) were recorded from the right ear in quiet and in four test conditions: one with contralateral broadband noise (BBN) only, and three with active listening tasks wherein attention was directed to speech embedded in contralateral BBN. Fifteen typically-developing children (ranging in age from 8 to14 years) with normal hearing. CEOAE levels were reduced in every condition with contralateral acoustic stimulus (CAS) when compared to preceding quiet conditions. There was an additional systematic decrease in CEOAE level with increased listening task difficulty, although this effect was very small. These CEOAE level differences were most apparent in the 8-18 ms region after click onset. Active listening may change the strength of the MOC reflex in children, although the effects reported here are very subtle. Further studies are needed to verify that task difficulty modulates the activity of the MOC reflex in children.

The medial olivocochlear reflex in children during active listening

PubMed Central

Smith, Spencer B.; Cone, Barbara

2015-01-01

Objective To determine if active listening modulates the strength of the medial olivocochlear (MOC) reflex in children. Design Click-evoked otoacoustic emissions (CEOAEs) were recorded from the right ear in quiet and in four test conditions: one with contralateral broadband noise (BBN) only, and three with active listening tasks wherein attention was directed to speech embedded in contralateral BBN. Study sample Fifteen typically-developing children (ranging in age from 8 to 14 years) with normal hearing. Results CEOAE levels were reduced in every condition with contralateral acoustic stimulus (CAS) when compared to preceding quiet conditions. There was an additional systematic decrease in CEOAE level with increased listening task difficulty, although this effect was very small. These CEOAE level differences were most apparent in the 8–18 ms region after click onset. Conclusions Active listening may change the strength of the MOC reflex in children, although the effects reported here are very subtle. Further studies are needed to verify that task difficulty modulates the activity of the MOC reflex in children. PMID:25735203

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.

Soleus and lateral gastrocnemius H-reflexes during standing with unstable footwear.

PubMed

Friesenbichler, Bernd; Lepers, Romuald; Maffiuletti, Nicola A

2015-05-01

Unstable footwear has been shown to increase lower extremity muscle activity, but the reflex response to perturbations induced by this intervention is unknown. Twenty healthy subjects stood in stable and unstable footwear conditions (presented randomly) while H-reflex amplitude and background muscle activity were measured in the soleus and lateral gastrocnemius (LG) muscles. Wearing unstable footwear resulted in larger H-reflexes (normalized to the maximal M-wave) for the LG (+12%; P = 0.025), but not for the soleus (+4%; P > 0.05). Background activity of both muscles was significantly higher in the unstable condition. The H-reflex facilitation observed with unstable footwear was unexpected, as challenging postural conditions usually result in reflex depression. Increased muscle activity, decreased presynaptic inhibition, and/or more forward postural position may have (over-)compensated the expected reflex depression. Differences between LG and soleus H-reflex modulation may be due to diverging motor unit recruitment thresholds. © 2015 Wiley Periodicals, Inc.

Modification of medullary respiratory-related discharge patterns by behaviors and states of arousal.

PubMed

Chang, F C

1992-02-07

The modulatory influences of behaviors and states of arousal on bulbar respiratory-related unit (RRU) discharge patterns were studied in an unanesthetized, freely behaving guinea pig respiratory model system. When fully instrumented, this model system permits concurrent monitoring and recording of (i) single units from either Bötzinger complex or nucleus para-ambiguus; (ii) electrocorticogram; and, (iii) diaphragmatic EMG. In addition to being used in surveys of RRU discharge patterns in freely behaving states, the model system also offered a unique opportunity in investigating the effects of pentobarbital on RRU discharge patterns before, throughout the course of, and during recovery from anesthesia. In anesthetized preparations, a particular RRU discharge pattern (such as tonic, incrementing or decrementing) typically displayed little, if any notable variation. The most striking development following pentobarbital was a state of progressive bradypnea attributable to a significantly augmented RRU cycle duration, burst duration and an increase in the RRU spike frequencies during anesthesia. In freely behaving states, medullary RRU activities rarely adhered to a fixed, immutable discharge pattern. More specifically, the temporal organization (such as burst duration, cycle duration, and the extent of modulation of within-burst spike frequencies) of RRU discharge patterns regularly showed complex and striking variations, not only with states of arousal (sleep/wakefulness, anesthesia) but also with discrete alterations in electrocorticogram (ECoG) activities and a multitude of on-going behavioral repertoires such as volitional movement, postural modification, phonation, mastication, deglutition, sniffing/exploratory behavior, alerting/startle reflexes. Only during sleep, and on occasions when the animal assumed a motionless, resting posture, could burst patterns of relatively invariable periodicity and uniform temporal attributes be observed. RRU activities during sniffing reflex is worthy of further note in that, based on power spectrum analyses of concurrently recorded ECoG activities, this particular discharge pattern was clearly associated with the activation of a 6-10 Hz theta rhythm. These findings indicated that bulbar RRU activity patterns are subject to change by not only behaviors and sleep/wakefulness cycles, but also a variety of modulatory influences and feedback/feedforward biases from other central and peripheral physiological control mechanisms.

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.

Neural control of locomotion and training-induced plasticity after spinal and cerebral lesions.

PubMed

Knikou, Maria

2010-10-01

Standing and walking require a plethora of sensorimotor interactions that occur throughout the nervous system. Sensory afferent feedback plays a crucial role in the rhythmical muscle activation pattern, as it affects through spinal reflex circuits the spinal neuronal networks responsible for inducing and maintaining rhythmicity, drives short-term and long-term re-organization of the brain and spinal cord circuits, and contributes to recovery of walking after locomotor training. Therefore, spinal circuits integrating sensory signals are adjustable networks with learning capabilities. In this review, I will synthesize the mechanisms underlying phase-dependent modulation of spinal reflexes in healthy humans as well as those with spinal or cerebral lesions along with findings on afferent regulation of spinal reflexes and central pattern generator in reduced animal preparations. Recovery of walking after locomotor training has been documented in numerous studies but the re-organization of spinal interneuronal and cortical circuits need to be further explored at cellular and physiological levels. For maximizing sensorimotor recovery in people with spinal or cerebral lesions, a multidisciplinary approach (rehabilitation, pharmacology, and electrical stimulation) delivered during various sensorimotor constraints is needed. Copyright 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Limb segment vibration modulates spinal reflex excitability and muscle mRNA expression after spinal cord injury

PubMed Central

Chang, Shuo-Hsiu; Tseng, Shih-Chiao; McHenry, Colleen L.; Littmann, Andrew E.; Suneja, Manish; Shields, Richard K.

2012-01-01

Objective We investigated the effect of various doses of vertical oscillation (vibration) on soleus H-reflex amplitude and post-activation depression in individuals with and without SCI. We also explored the acute effect of short-term limb vibration on skeletal muscle mRNA expression of genes associated with spinal plasticity. Methods Six healthy adults and five chronic complete SCI subjects received vibratory stimulation of their tibia over three different gravitational accelerations (0.3g, 0.6g, and 1.2g) at a fixed frequency (30 Hz). Soleus H-reflexes were measured before, during, and after vibration. Two additional chronic complete SCI subjects had soleus muscle biopsies 3 h following a single bout of vibration. Results H-reflex amplitude was depressed over 83% in both groups during vibration. This vibratory-induced inhibition lasted over 2 min in the control group, but not in the SCI group. Post-activation depression was modulated during the long-lasting vibratory inhibition. A single bout of mechanical oscillation altered mRNA expression from selected genes associated with synaptic plasticity. Conclusions Vibration of the lower leg inhibits the H-reflex amplitude, influences post-activation depression, and alters skeletal muscle mRNA expression of genes associated with synaptic plasticity. Significance Limb segment vibration may offer a long term method to reduce spinal reflex excitability after SCI. PMID:21963319

Plasticity of the human otolith-ocular reflex

NASA Technical Reports Server (NTRS)

Wall, C. 3rd; Smith, T. R.; Furman, J. M.

1992-01-01

The eye movement response to earth vertical axis rotation in the dark, a semicircular canal stimulus, can be altered by prior exposure to combined visual-vestibular stimuli. Such plasticity of the vestibulo-ocular reflex has not been described for earth horizontal axis rotation, a dynamic otolith stimulus. Twenty normal human subjects underwent one of two types of adaptation paradigms designed either to attenuate or enhance the gain of the semicircular canal-ocular reflex prior to undergoing otolith-ocular reflex testing with horizontal axis rotation. The adaptation paradigm paired a 0.2 Hz sinusoidal rotation about a vertical axis with a 0.2 Hz optokinetic stripe pattern that was deliberately mismatched in peak velocity. Pre- and post-adaptation horizontal axis rotations were at 60 degrees/s in the dark and produced a modulation in the slow component velocity of nystagmus having a frequency of 0.17 Hz due to putative stimulation of the otolith organs. Results showed that the magnitude of this modulation component response was altered in a manner similar to the alteration in semicircular canal-ocular responses. These results suggest that physiologic alteration of the vestibulo-ocular reflex using deliberately mismatched visual and semicircular canal stimuli induces changes in both canal-ocular and otolith-ocular responses. We postulate, therefore, that central nervous system pathways responsible for controlling the gains of canal-ocular and otolith-ocular reflexes are shared.

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.

Task- and time-dependent modulation of Ia presynaptic inhibition during fatiguing contractions performed by humans

PubMed Central

Maerz, Adam H.; Gould, Jeffrey R.; Enoka, Roger M.

2011-01-01

Presynaptic modulation of Ia afferents converging onto the motor neuron pool of the extensor carpi radialis (ECR) was compared during contractions (20% of maximal force) sustained to failure as subjects controlled either the angular position of the wrist while supporting an inertial load (position task) or exerted an equivalent force against a rigid restraint (force task). Test Hoffmann (H) reflexes were evoked in the ECR by stimulating the radial nerve above the elbow. Conditioned H reflexes were obtained by stimulating either the median nerve above the elbow or at the wrist (palmar branch) to assess presynaptic inhibition of homonymous (D1 inhibition) and heteronymous Ia afferents (heteronymous Ia facilitation), respectively. The position task was briefer than the force task (P = 0.001), although the maximal voluntary force and electromyograph for ECR declined similarly at failure for both tasks. Changes in the amplitude of the conditioned H reflex were positively correlated between the two conditioning methods (P = 0.02) and differed between the two tasks (P < 0.05). The amplitude of the conditioned H reflex during the position task first increased (129 ± 20.5% of the initial value, P < 0.001) before returning to its initial value (P = 0.22), whereas it increased progressively during the force task to reach 122 ± 17.4% of the initial value at failure (P < 0.001). Moreover, changes in conditioned H reflexes were associated with the time to task failure and force fluctuations. The results suggest a task- and time-dependent modulation of presynaptic inhibition of Ia afferents during fatiguing contractions. PMID:21543747

Affective associative learning modifies the sensory perception of nociceptive stimuli without participant's awareness.

PubMed

Wunsch, Annabel; Philippot, Pierre; Plaghki, Léon

2003-03-01

The present experiment examined the possibility to change the sensory and/or the affective perception of thermal stimuli by an emotional associative learning procedure known to operate without participants' awareness (evaluative conditioning). In a mixed design, an aversive conditioning procedure was compared between subjects to an appetitive conditioning procedure. Both groups were also compared within-subject to a control condition (neutral conditioning). The aversive conditioning was induced by associating non-painful and painful thermal stimuli - delivered on the right forearm - with unpleasant slides. The appetitive conditioning consisted in an association between thermal stimuli - also delivered on the right forearm - and pleasant slides. The control condition consisted in an association between thermal stimuli - delivered for all participants on the left forearm - and neutral slides. The effects of the conditioning procedures on the sensory and affective dimensions were evaluated with visual analogue scale (VAS)-intensity and VAS-unpleasantness. Startle reflex was used as a physiological index of emotional valence disposition. Results confirmed that no participants were aware of the conditioning procedure. After unpleasant slides (aversive conditioning), non-painful and painful thermal stimuli were judged more intense and more unpleasant than when preceded by neutral slides (control condition) or pleasant slides (appetitive conditioning). Despite a strong correlation between the intensity and the unpleasantness scales, effects were weaker for the affective scale and, became statistically non-significant when VAS-intensity was used as covariate. This experiment shows that it is possible to modify the perception of intensity of thermal stimuli by a non-conscious learning procedure based on the transfer of the valence of the unconditioned stimuli (pleasant or unpleasant slides) towards the conditioned stimuli (non-painful and painful thermal stimuli). These results plead for a conception of pain as a conscious output of complex informational processes all of which are not accessible to participants' awareness. Mechanisms by which affective input may influence sensory experience and clinical implications of the present study are discussed.

Noise and stress: a comprehensive approach.

PubMed Central

Westman, J C; Walters, J R

1981-01-01

The fundamental purposes of hearing are to alert and to warn. As a result sound directly evokes emotions and actions. The processing of sound by the brain is outlined to provide a biological and psychological basis for understanding the way in which sound can become a human stressor. The auditory orienting response, startle reflex and defensive response translate sound stimuli into action and sometimes into stress induced bodily changes through "fight or flight" neural mechanisms. The literature on the health and mental health effects of noise then is reviewed in the context of an integrated model that offers a holistic approach to noise research and public policy formulation. The thesis of this paper is that research upon, and efforts to prevent or minimize the harmful effects of noise have suffered from the lack of a full appreciation of the ways in which humans process and react to sound. PMID:7333243

On the Modeling of Electrical Effects Experienced by Space Explorers During Extra Vehicular Activities: Intracorporal Currents, Resistances, and Electric Fields

NASA Technical Reports Server (NTRS)

Cela, Carlos J.; Loizos, Kyle; Lazzi, Gianluca; Hamilton, Douglas; Lee, Raphael C.

2011-01-01

Recent research has shown that space explorers engaged in Extra Vehicular Activities (EVAs) may be exposed, under certain conditions, to undesired electrical currents. This work focuses on determining whether these undesired induced electrical currents could be responsible for involuntary neuromuscular activity in the subjects, possibly caused by either large diameter peripheral nerve activation or reflex activity from cutaneous afferent stimulation. An efficient multiresolution variant of the admittance method along with a millimeter-resolution model of a male human body were used to calculate induced electric fields, resistance between contact electrodes used to simulate the potential exposure condition, and currents induced in the human body model. Results show that, under realistic exposure conditions using a 15V source, current density magnitudes and total current injected are well above previously reported startle reaction thresholds. This indicates that, under the considered conditions, the subjects could experience involuntary motor response.

Altering length and velocity feedback during a neuro-musculoskeletal simulation of normal gait contributes to hemiparetic gait characteristics.

PubMed

Jansen, Karen; De Groote, Friedl; Aerts, Wouter; De Schutter, Joris; Duysens, Jacques; Jonkers, Ilse

2014-04-30

Spasticity is an important complication after stroke, especially in the anti-gravity muscles, i.e. lower limb extensors. However the contribution of hyperexcitable muscle spindle reflex loops to gait impairments after stroke is often disputed. In this study a neuro-musculoskeletal model was developed to investigate the contribution of an increased length and velocity feedback and altered reflex modulation patterns to hemiparetic gait deficits. A musculoskeletal model was extended with a muscle spindle model providing real-time length and velocity feedback of gastrocnemius, soleus, vasti and rectus femoris during a forward dynamic simulation (neural control model). By using a healthy subject's base muscle excitations, in combination with increased feedback gains and altered reflex modulation patterns, the effect on kinematics was simulated. A foot-ground contact model was added to account for the interaction effect between the changed kinematics and the ground. The qualitative effect i.e. the directional effect and the specific gait phases where the effect is present, on the joint kinematics was then compared with hemiparetic gait deviations reported in the literature. Our results show that increased feedback in combination with altered reflex modulation patterns of soleus, vasti and rectus femoris muscle can contribute to excessive ankle plantarflexion/inadequate dorsiflexion, knee hyperextension/inadequate flexion and increased hip extension/inadequate flexion during dedicated gait cycle phases. Increased feedback of gastrocnemius can also contribute to excessive plantarflexion/inadequate dorsiflexion, however in combination with excessive knee and hip flexion. Increased length/velocity feedback can therefore contribute to two types of gait deviations, which are both in accordance with previously reported gait deviations in hemiparetic patients. Furthermore altered modulation patterns, in particular the reduced suppression of the muscle spindle feedback during swing, can contribute largely to an increased plantarflexion and knee extension during the swing phase and consequently to hampered toe clearance. Our results support the idea that hyperexcitability of length and velocity feedback pathways, especially in combination with altered reflex modulation patterns, can contribute to deviations in hemiparetic gait. Surprisingly, our results showed only subtle temporal differences between length and velocity feedback. Therefore, we cannot attribute the effects seen in kinematics to one specific type of feedback.

Gain modulation of the middle latency cutaneous reflex in patients with chronic joint instability after ankle sprain.

PubMed

Futatsubashi, Genki; Sasada, Shusaku; Tazoe, Toshiki; Komiyama, Tomoyoshi

2013-07-01

To investigate the neural alteration of reflex pathways arising from cutaneous afferents in patients with chronic ankle instability. Cutaneous reflexes were elicited by applying non-noxious electrical stimulation to the sural nerve of subjects with chronic ankle instability (n=17) and control subjects (n=17) while sitting. Electromyographic (EMG) signals were recorded from each ankle and thigh muscle. The middle latency response (MLR; latency: 70-120 ms) component was analyzed. In the peroneus longus (PL) and vastus lateralis (VL) muscles, linear regression analyses between the magnitude of the inhibitory MLR and background EMG activity showed that, compared to the uninjured side and the control subjects, the gain of the suppressive MLR was increased in the injured side. This was also confirmed by the pooled data for both groups. The degree of MLR alteration was significantly correlated to that of chronic ankle instability in the PL. The excitability of middle latency cutaneous reflexes in the PL and VL is modulated in subjects with chronic ankle instability. Cutaneous reflexes may be potential tools to investigate the pathological state of the neural system that controls the lower limbs in subjects with chronic ankle instability. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

N-aryl piperazine metabotropic glutamate receptor 5 positive allosteric modulators possess efficacy in preclinical models of NMDA hypofunction and cognitive enhancement.

PubMed

Gregory, K J; Herman, E J; Ramsey, A J; Hammond, A S; Byun, N E; Stauffer, S R; Manka, J T; Jadhav, S; Bridges, T M; Weaver, C D; Niswender, C M; Steckler, T; Drinkenburg, W H; Ahnaou, A; Lavreysen, H; Macdonald, G J; Bartolomé, J M; Mackie, C; Hrupka, B J; Caron, M G; Daigle, T L; Lindsley, C W; Conn, P J; Jones, C K

2013-11-01

Impaired transmission through glutamatergic circuits has been postulated to play a role in the underlying pathophysiology of schizophrenia. Furthermore, inhibition of the N-methyl-d-aspartate (NMDA) subtype of ionotropic glutamate receptors (NMDAR) induces a syndrome that recapitulates many of the symptoms observed in patients with schizophrenia. Selective activation of metabotropic glutamate receptor subtype 5 (mGlu5) may provide a novel therapeutic approach for treatment of symptoms associated with schizophrenia through facilitation of transmission through central glutamatergic circuits. Here, we describe the characterization of two novel N-aryl piperazine mGlu5 positive allosteric modulators (PAMs): 2-(4-(2-(benzyloxy)acetyl)piperazin-1-yl)benzonitrile (VU0364289) and 1-(4-(2,4-difluorophenyl)piperazin-1-yl)-2-((4-fluorobenzyl)oxy)ethanone (DPFE). VU0364289 and DPFE induced robust leftward shifts in the glutamate concentration-response curves for Ca(2+) mobilization and extracellular signal-regulated kinases 1 and 2 phosphorylation. Both PAMs displayed micromolar affinity for the common mGlu5 allosteric binding site and high selectivity for mGlu5. VU0364289 and DPFE possessed suitable pharmacokinetic properties for dosing in vivo and produced robust dose-related effects in reversing amphetamine-induced hyperlocomotion, a preclinical model predictive of antipsychotic-like activity. In addition, DPFE enhanced acquisition of contextual fear conditioning in rats and reversed behavioral deficits in a mouse model of NMDAR hypofunction. In contrast, DPFE had no effect on reversing apomorphine-induced disruptions of prepulse inhibition of the acoustic startle reflex. These mGlu5 PAMs also increased monoamine levels in the prefrontal cortex, enhanced performance in a hippocampal-mediated memory task, and elicited changes in electroencephalogram dynamics commensurate with procognitive effects. Collectively, these data support and extend the role for the development of novel mGlu5 PAMs for the treatment of psychosis and cognitive deficits observed in individuals with schizophrenia.

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

The effects of sertraline administration from adolescence to adulthood on physiological and emotional development in prenatally stressed rats of both sexes

PubMed Central

Pereira-Figueiredo, Inês; Sancho, Consuelo; Carro, Juan; Castellano, Orlando; López, Dolores E.

2014-01-01

Sertraline (SERT) is a clinically effective Selective Serotonin Reuptake Inhibitor (SSRI) known to increase and stabilize serotonin levels. This neurotransmitter plays an important role in adolescent brain development in both rodents and humans, and its dysregulation has been correlated with deficits in behavior and emotional regulation. Since prenatal stress may disturb serotoninergic homeostasis, the aim of this study was to examine the long-lasting effects of exposure to SERT throughout adolescence on behavioral and physiological developmental parameters in prenatally stressed Wistar rats. SERT was administered (5 mg/kg/day p.o.) from the age of 1–3 months to half of the progeny, of both sexes, of gestating dams stressed by use of a restraint (PS) or not stressed. Our data reveal that long-term SERT treatment slightly reduced weight gain in both sexes, but reversed the developmental disturbed “catch-up” growth found in PS females. Neither prenatal stress nor SERT treatment induced remarkable alterations in behavior and had no effects on mean startle reflex values. However, a sex-dependent effects of PS was found: in males the PS paradigm slightly increased anxiety-like behavior in the open field, while in females, it impaired startle habituation. In both cases, SERT treatment reversed the phenomena. Additionally, the PS animals exhibited a disturbed leukocyte profile in both sexes, which was reversed by SERT. The present findings are evidence that continuous SERT administration from adolescence through adulthood is safe in rodents and lessens the impact of prenatal stress in rats. PMID:25147514

Neurotoxic lesions of the dorsal and ventral hippocampus impair acquisition and expression of trace-conditioned fear-potentiated startle in rats.

PubMed

Trivedi, Mehul A; Coover, Gary D

2006-04-03

Pavlovian delay conditioning, in which a conditioned stimulus (CS) and unconditioned stimulus (US) co-terminate, is thought to reflect non-declarative memory. In contrast, trace conditioning, in which the CS and US are temporally separate, is thought to reflect declarative memory. Hippocampal lesions impair acquisition and expression of trace conditioning measured by the conditioned freezing and eyeblink responses, while having little effect on the acquisition of delay conditioning. Recent evidence suggests that lesions of the ventral hippocampus (VH) impair conditioned fear under conditions in which dorsal hippocampal (DH) lesions have little effect. In the present study, we examined the time-course of fear expression after delay and trace conditioning using the fear-potentiated startle (FPS) reflex, and the effects of pre- and post-training lesions to the VH and DH on trace-conditioned FPS. We found that both delay- and trace-conditioned rats displayed significant FPS near the end of the CS relative to the unpaired control group. In contrast, trace-conditioned rats displayed significant FPS throughout the duration of the trace interval, whereas FPS decayed rapidly to baseline after CS offset in delay-conditioned rats. In experiment 2, both DH and VH lesions were found to significantly reduce the overall magnitude of FPS compared to the control group, however, no differences were found between the DH and VH groups. These findings support a role for both the DH and VH in trace fear conditioning, and suggest that the greater effect of VH lesions on conditioned fear might be specific to certain measures of fear.

Learned control over spinal nociception in patients with chronic back pain.

PubMed

Krafft, S; Göhmann, H-D; Sommer, J; Straube, A; Ruscheweyh, R

2017-10-01

Descending pain inhibition suppresses spinal nociception, reducing nociceptive input to the brain. It is modulated by cognitive and emotional processes. In subjects with chronic pain, it is impaired, possibly contributing to pain persistence. A previously developed feedback method trains subjects to activate their descending inhibition. Participants are trained to use cognitive-emotional strategies to reduce their spinal nociception, as quantified by the nociceptive flexor reflex (RIII reflex), under visual feedback about their RIII reflex size. The aim of the present study was to test whether also subjects with chronic back pain can achieve a modulation of their descending pain inhibition under RIII feedback. In total, 33 subjects with chronic back pain received either true (n = 18) or sham RIII feedback (n = 15), 15 healthy control subjects received true RIII feedback. All three groups achieved significant RIII suppression, largest in controls (to 76 ± 26% of baseline), intermediate in chronic back pain subjects receiving true feedback (to 82 ± 13%) and smallest in chronic back pain subjects receiving sham feedback (to 89 ± 14%, all p < 0.05). However, only chronic pain subjects receiving true feedback significantly improved their descending inhibition over the feedback training, quantified by the conditioned pain modulation effect (test pain reduction of baseline before training: to 98 ± 26%, after: to 80 ± 21%, p < 0.01). Our results show that subjects with chronic back pain can achieve a reduction of their spinal nociception and improve their descending pain inhibition under RIII feedback training. Subjects with chronic back pain can learn to control their spinal nociception, quantified by the RIII reflex, when they receive feedback about the RIII reflex. © 2017 European Pain Federation - EFIC®.

Factors Affecting the Occurrence of Spinal Reflexes in Brain Dead Cases.

PubMed

Hosseini, Mahsa Sadat; Ghorbani, Fariba; Ghobadi, Omid; Najafizadeh, Katayoun

2015-08-01

Brain death is defined as the permanent absence of all cortical and brain stem reflexes. A wide range of spontaneous or reflex movements that are considered medullary reflexes are observed in heart beating cases that appear brain dead, which may create uncertainty about the diagnosis of brain death and cause delays in deceased-donor organ donation process. We determined the frequency and type of medullary reflexes and factors affecting their occurrence in brain dead cases. During 1 year, 122 cases who fulfilled the criteria for brain death were admitted to the special intensive care unit for organ procurement of Masih Daneshvari Hospital. Presence of spinal reflexes was evaluated by trained coordinators and was recorded in a form in addition to other information including demographic characteristics, cause of brain death, time from detection of brain death, history of craniotomy, vital signs, serum electrolyte levels, and parameters of arterial blood gas determination. Most cases (63%) included in this study were male, and mean age was 33 ± 15 y. There was > 1 spinal reflex observed in 40 cases (33%). The most frequent reflex was plantar response (17%) following by myoclonus (10%), triple flexion reflex (9%), pronator extension reflex (8%), and undulating toe reflex (7%). Mean systolic blood pressure was significantly higher in cases who exhibited medullary reflexes than other cases (126 ± 19 mm Hg vs 116 ± 17 mm Hg; P = .007). Spinal reflexes occur frequently in brain dead cases, especially when they become hemodynamically stable after treatment in the organ procurement unit. Observing these movements by caregivers and family members has a negative effect on obtaining family consent and organ donation. Increasing awareness about spinal reflexes is necessary to avoid suspicion about the brain death diagnosis and delays in organ donation.

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.

Could the Use of Acoustic Reflexes Prior to Administering Distortion Product Otoacoustic Emissions (DPOAEs) Affect the Results of DPOAEs?

PubMed

Garrette, Rachel; Jones, Alisha L; Wilson, Martha W

2018-05-15

The purpose of this study is to investigate whether acoustic reflex threshold testing before administration of distortion product otoacoustic emissions can affect the results of the distortion product otoacoustic emissions testing using an automated protocol. Fifteen young adults with normal hearing ranging in age from 19 to 25 years participated in the study. All participants had clear external ear canals and normal Jerger Type A tympanograms and had passed a hearing screening. Testing was performed using the Interacoustics Titan acoustic reflex threshold and distortion product otoacoustic emissions protocol. Participants underwent baseline distortion product otoacoustic emissions. A paired-samples t test was conducted for both the right and left ears to assess within-group differences between baseline distortion product otoacoustic emissions and repeated distortion product otoacoustic emissions measures. No significant differences were found in distortion product otoacoustic emission measures following administration of acoustic reflexes. The use of a protocol when using an automated system that includes both acoustic reflexes and distortion product otoacoustic emissions is important. Overall, presentation of acoustic reflexes prior to measuring distortion product otoacoustic emission did not affect distortion product otoacoustic emission results; therefore, test sequence can be modified as needed.

Vibration parameters affecting vibration-induced reflex muscle activity.

PubMed

Cidem, Muharrem; Karacan, Ilhan; Cakar, Halil Ibrahim; Cidem, Mehmet; Sebik, Oguz; Yilmaz, Gizem; Turker, Kemal Sitki; Karamehmetoglu, Safak Sahir

2017-03-01

To determine vibration parameters affecting the amplitude of the reflex activity of soleus muscle during low-amplitude whole-body vibration (WBV). This study was conducted on 19 participants. Vibration frequencies of 25, 30, 35, 40, 45, and 50 Hz were used. Surface electromyography, collision force between vibration platform and participant's heel measured using a force sensor, and acceleration measured using an accelerometer fixed to the vibration platform were simultaneously recorded. The collision force was the main independent predictor of electromyographic amplitude. The essential parameter of vibration affecting the amplitude of the reflex muscle activity is the collision force.

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

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.

The pupil as a measure of emotional arousal and autonomic activation

PubMed Central

Bradley, Margaret M.; Miccoli, Laura; Escrig, Miguel A.; Lang, Peter J.

2013-01-01

Pupil diameter was monitored during picture viewing to assess effects of hedonic valence and emotional arousal on pupillary responses. Autonomic activity (heart rate and skin conductance) was concurrently measured to determine whether pupillary changes are mediated by parasympathetic or sympathetic activation. Following an initial light reflex, pupillary changes were larger when viewing emotionally arousing pictures, regardless of whether these were pleasant or unpleasant. Pupillary changes during picture viewing covaried with skin conductance change, supporting the interpretation that sympathetic nervous systemactivity modulates these changes in the context of affective picture viewing. Taken together, the data provide strong support for the hypothesis that the pupil’s response during affective picture viewing reflects emotional arousal associated with increased sympathetic activity. PMID:18282202

Neural reflex pathways in intestinal inflammation: hypotheses to viable therapy.

PubMed

Willemze, Rose A; Luyer, Misha D; Buurman, Wim A; de Jonge, Wouter J

2015-06-01

Studies in neuroscience and immunology have clarified much of the anatomical and cellular basis for bidirectional interactions between the nervous and immune systems. As with other organs, intestinal immune responses and the development of immunity seems to be modulated by neural reflexes. Sympathetic immune modulation and reflexes are well described, and in the past decade the parasympathetic efferent vagus nerve has been added to this immune-regulation network. This system, designated 'the inflammatory reflex', comprises an afferent arm that senses inflammation and an efferent arm that inhibits innate immune responses. Intervention in this system as an innovative principle is currently being tested in pioneering trials of vagus nerve stimulation using implantable devices to treat IBD. Patients benefit from this treatment, but some of the working mechanisms remain to be established, for instance, treatment is effective despite the vagus nerve not always directly innervating the inflamed tissue. In this Review, we will focus on the direct neuronal regulatory mechanisms of immunity in the intestine, taking into account current advances regarding the innervation of the spleen and lymphoid organs, with a focus on the potential for treatment in IBD and other gastrointestinal pathologies.

Functional evidence for the inflammatory reflex in teleosts: A novel α7 nicotinic acetylcholine receptor modulates the macrophage response to dsRNA.

PubMed

Torrealba, Débora; Balasch, Joan Carles; Criado, Manuel; Tort, Lluís; Mackenzie, Simon; Roher, Nerea

2018-07-01

The inflammatory reflex modulates the innate immune system, keeping in check the detrimental consequences of overstimulation. A key player controlling the inflammatory reflex is the alpha 7 acetylcholine receptor (α7nAChR). This receptor is one of the signalling molecules regulating cytokine expression in macrophages. In this study, we characterize a novel teleost α7nAChR. Protein sequence analysis shows a high degree of conservation with mammalian orthologs and trout α7nAChR has all the features and essential amino acids to form a fully functional receptor. We demonstrate that trout macrophages can bind α-bungarotoxin (α-BTX), a competitive antagonist for α7nAChRs. Moreover, nicotine stimulation produces a decrease in pro-inflammatory cytokine expression after stimulation with poly(I:C). These results suggest the presence of a functional α7nAChR in the macrophage plasma membrane. Further, in vivo injection of poly(I:C) induced an increase in serum ACh levels in rainbow trout. Our results manifest for the first time the functional conservation of the inflammatory reflex in teleosts. Copyright © 2018 Elsevier Ltd. All rights reserved.

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.

Reliability of the Achilles tendon tap reflex evoked during stance using a pendulum hammer.

PubMed

Mildren, Robyn L; Zaback, Martin; Adkin, Allan L; Frank, James S; Bent, Leah R

2016-01-01

The tendon tap reflex (T-reflex) is often evoked in relaxed muscles to assess spinal reflex circuitry. Factors contributing to reflex excitability are modulated to accommodate specific postural demands. Thus, there is a need to be able to assess this reflex in a state where spinal reflex circuitry is engaged in maintaining posture. The aim of this study was to determine whether a pendulum hammer could provide controlled stimuli to the Achilles tendon and evoke reliable muscle responses during normal stance. A second aim was to establish appropriate stimulus parameters for experimental use. Fifteen healthy young adults stood on a forceplate while taps were applied to the Achilles tendon under conditions in which postural sway was constrained (by providing centre of pressure feedback) or unconstrained (no feedback) from an invariant release angle (50°). Twelve participants repeated this testing approximately six months later. Within one experimental session, tap force and T-reflex amplitude were found to be reliable regardless of whether postural sway was constrained (tap force ICC=0.982; T-reflex ICC=0.979) or unconstrained (tap force ICC=0.968; T-reflex ICC=0.964). T-reflex amplitude was also reliable between experimental sessions (constrained ICC=0.894; unconstrained ICC=0.890). When a T-reflex recruitment curve was constructed, optimal mid-range responses were observed using a 50° release angle. These results demonstrate that reliable Achilles T-reflexes can be evoked in standing participants without the need to constrain posture. The pendulum hammer provides a simple method to allow researchers and clinicians to gather information about reflex circuitry in a state where it is involved in postural control. Copyright © 2015 Elsevier B.V. All rights reserved.

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

Response of soleus Ia afferents to vibration in the presence of the tonic vibration reflex in the decerebrate cat.

PubMed

Clark, F J; Matthews, P B; Muir, R B

1981-02-01

1. Micro-electrode recordings were made from single Ia afferents in the intact nerve to the soleus muscle in the decerebrate cat while the muscle was developing a tonic vibration reflex. This was done in order to test how effectively the afferents were excited by the vibration, and to see if any insecurity in driving might be related to tremor.2. When the amplitude of vibration was 50 mum, and the tonic vibration reflex was reasonably well developed (> 1 N of active tension) all but one of forty-four Ia afferents were driven 1:1 by the vibration. Most were still driven by 30 mum vibration. The vibration, consisting of a train of discrete pulses at 150 Hz, was applied longitudinally in combination with a stretch of 1 mm to make the muscle taut.3. If the reflex was poorly developed (active tension < 1 N) the driving was on average less secure. However, fourteen of eighteen afferents then studied were still driven 1:1 by 50 mum vibration. The lower level of excitation by vibration was thought to be due to a deficiency of spontaneous fusimotor activity, because stroking the cat's tail or other similar gentle manipulation led each of the three misbehaving afferents so tested to be driven securely by 50 mum vibration; at the same time the reflex tension increased.4. Additional, indirect evidence favouring widespread security of Ia driving by 50 mum vibration in the presence of the reflex was obtained by modulating the amplitude of the 150 Hz vibration with a 7-10 Hz square wave and detecting any tension fluctuations at that frequency by spectral analysis. Small degrees of modulation (e.g. < 10%) produced little if any effect, although larger depths of modulation had a powerful action.5. When the amplitude of vibration was reduced to permit insecure driving but still to elicit a reflex response, the fluctuations in Ia firing pattern were unlike those previously seen in the de-efferented muscle. Spectral analysis showed that these firing fluctuations bore a general similarity to the tremor in the same preparation, but measurement of coherence demonstrated that the tremor and Ia firing were not well related. This was probably because individual Ia afferents were primarily influenced by local factors, and provides further evidence against the tremor of this preparation being attributable to the action of the stretch reflex.

Response of soleus Ia afferents to vibration in the presence of the tonic vibration reflex in the decerebrate cat

PubMed Central

Clark, F. J.; Matthews, P. B. C.; Muir, R. B.

1981-01-01

1. Micro-electrode recordings were made from single Ia afferents in the intact nerve to the soleus muscle in the decerebrate cat while the muscle was developing a tonic vibration reflex. This was done in order to test how effectively the afferents were excited by the vibration, and to see if any insecurity in driving might be related to tremor. 2. When the amplitude of vibration was 50 μm, and the tonic vibration reflex was reasonably well developed (> 1 N of active tension) all but one of forty-four Ia afferents were driven 1:1 by the vibration. Most were still driven by 30 μm vibration. The vibration, consisting of a train of discrete pulses at 150 Hz, was applied longitudinally in combination with a stretch of 1 mm to make the muscle taut. 3. If the reflex was poorly developed (active tension < 1 N) the driving was on average less secure. However, fourteen of eighteen afferents then studied were still driven 1:1 by 50 μm vibration. The lower level of excitation by vibration was thought to be due to a deficiency of spontaneous fusimotor activity, because stroking the cat's tail or other similar gentle manipulation led each of the three misbehaving afferents so tested to be driven securely by 50 μm vibration; at the same time the reflex tension increased. 4. Additional, indirect evidence favouring widespread security of Ia driving by 50 μm vibration in the presence of the reflex was obtained by modulating the amplitude of the 150 Hz vibration with a 7-10 Hz square wave and detecting any tension fluctuations at that frequency by spectral analysis. Small degrees of modulation (e.g. < 10%) produced little if any effect, although larger depths of modulation had a powerful action. 5. When the amplitude of vibration was reduced to permit insecure driving but still to elicit a reflex response, the fluctuations in Ia firing pattern were unlike those previously seen in the de-efferented muscle. Spectral analysis showed that these firing fluctuations bore a general similarity to the tremor in the same preparation, but measurement of coherence demonstrated that the tremor and Ia firing were not well related. This was probably because individual Ia afferents were primarily influenced by local factors, and provides further evidence against the tremor of this preparation being attributable to the action of the stretch reflex. PMID:7264987

Golden tapetal reflex in male patients with X-linked retinitis pigmentosa. Case report and practical implications.

PubMed

van Osch, L; van Schooneveld, M; Bleekerwagemakers, E M

1990-12-01

The golden tapetal reflex in the ocular fundus is considered pathognomonic of the carrier state in some families with X-linked retinitis pigmentosa (XRP). Reports concerning affected males with this characteristic reflex are scarce. A six-year-old boy with XRP having a tapetal reflex is described. Recently the tapetal reflex has drawn attention in linkage studies. XRP is probably genetically heterogeneous and has at least two genetic forms. The finding of a tapetal reflex in one or more female carriers in a family with XRP may be helpful in differentiating between these two genetic forms.

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

Vergence-mediated modulation of the human horizontal vestibulo-ocular reflex is eliminated by a partial peripheral gentamicin lesion.

PubMed

Migliaccio, Americo A; Minor, Lloyd B; Carey, John P

2004-11-01

The angular vestibulo-ocular reflex normally has an increased response during vergence on a near target. Surgical unilateral vestibular deafferentation reduces the horizontal vestibulo-ocular reflex (VOR) in response to far target viewing and eliminates this vergence effect. Intratympanic gentamicin treatment reduces VOR gain during far viewing, but the reduction is less severe than that after unilateral vestibular deafferentation. We sought to determine how gentamicin would affect vergence-mediated modulation of the VOR. The VOR in response to passive head impulses in the horizontal plane while viewing a far (124 cm) or near (15 cm) target was evaluated in 11 subjects following intratympanic gentamicin treatment. Three of these subjects had also been tested immediately prior to receiving gentamicin. The impulses were low amplitude (approximately 20 degrees ), high velocity (approximately 150 degrees /s), high acceleration (approximately 3,000 degrees /s2) horizontal head rotations administered manually by the investigator. Binocular eye and head velocity were recorded using the scleral search coil technique. The VOR gain was defined as eye velocity divided by inverted head velocity. Prior to intratympanic gentamicin, the VOR gain during rotations to either side was symmetric and showed the same vergence-mediated increase. Following gentamicin, head impulses towards the untreated side yielded VOR gains of 0.91+/-0.12 while viewing a far target and 1.27+/-0.22 while viewing a near target, an increase of 33%. Head impulses towards the treated side produced a hypometric VOR with no increase between far and near viewing. The average latency of the VOR was 7.6+/-2.5 ms towards the untreated side for either near or far viewing and 20.7+/-13.1 ms towards the treated side for either near or far viewing. Our findings show that a peripheral lesion caused by gentamicin does not ablate the VOR but does eliminate a component of the vestibular signal that is necessary for vergence-mediated modulation of the VOR. Gentamicin has preferential toxicity for the hair cells in the central zone of the crista, where irregular afferents predominate. Our findings are consistent with the hypothesis that irregular afferents provide the necessary signal for vergence-mediated modulation of the VOR.

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...

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

Measuring attention using the Posner cuing paradigm: the role of across and within trial target probabilities

PubMed Central

Hayward, Dana A.; Ristic, Jelena

2013-01-01

Numerous studies conducted within the recent decades have utilized the Posner cuing paradigm for eliciting, measuring, and theoretically characterizing attentional orienting. However, the data from recent studies suggest that the Posner cuing task might not provide an unambiguous measure of attention, as reflexive spatial orienting has been found to interact with extraneous processes engaged by the task's typical structure, i.e., the probability of target presence across trials, which affects tonic alertness, and the probability of target presence within trials, which affects voluntary temporal preparation. To understand the contribution of each of these two processes to the measurement of attentional orienting we assessed their individual and combined effects on reflexive attention elicited by a spatially nonpredictive peripheral cue. Our results revealed that the magnitude of spatial orienting was modulated by joint changes in the global probability of target presence across trials and the local probability of target presence within trials, while the time course of spatial orienting was susceptible to changes in the probability of target presence across trials. These data thus raise important questions about the choice of task parameters within the Posner cuing paradigm and their role in both the measurement and theoretical attributions of the observed attentional effects. PMID:23730280

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

The control of male sexual responses.

PubMed

Courtois, Frédérique; Carrier, Serge; Charvier, Kathleen; Guertin, Pierre A; Journel, Nicolas Morel

2013-01-01

Male sexual responses are reflexes mediated by the spinal cord and modulated by neural circuitries involving both the peripheral and central nervous system. While the brain interact with the reflexes to allow perception of sexual sensations and to exert excitatory or inhibitory influences, penile reflexes can occur despite complete transections of the spinal cord, as demonstrated by the reviewed animal studies on spinalization and human studies on spinal cord injury. Neurophysiological and neuropharmacological substrates of the male sexual responses will be discussed in this review, starting with the spinal mediation of erection and its underlying mechanism with nitric oxide (NO), followed by the description of the ejaculation process, its neural mediation and its coordination by the spinal generator of ejaculation (SGE), followed by the occurrence of climax as a multisegmental sympathetic reflex discharge. Brain modulation of these reflexes will be discussed through neurophysiological evidence involving structures such as the medial preoptic area of hypothalamus (MPOA), the paraventricular nucleus (PVN), the periaqueductal gray (PAG), and the nucleus para-gigantocellularis (nPGI), and through neuropharmacological evidence involving neurotransmitters such as serotonin (5-HT), dopamine and oxytocin. The pharmacological developments based on these mechanisms to treat male sexual dysfunctions will complete this review, including phosphodiesterase (PDE-5) inhibitors and intracavernous injections (ICI) for the treatment of erectile dysfunctions (ED), selective serotonin reuptake inhibitor (SSRI) for the treatment of premature ejaculation, and cholinesterase inhibitors as well as alpha adrenergic drugs for the treatment of anejaculation and retrograde ejaculation. Evidence from spinal cord injured studies will be highlighted upon each step.

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.

"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…

Inhalation toxicology of diesel fuel obscurant aerosol in Sprague-Dawley rats. Final report, Phase 3, subchronic exposures

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

Lock, S.; Dalbey, W.; Schmoyer, R.

1984-12-01

Inhalation exposures were performed twice per week, for 13 weeks, to determine whether there was any potential toxicity to rats of comparatively low concentrations of a condensation aerosol from diesel fuel. Changes in breathing frequency and the response of animals to a loud sharp sound (startle response) were measured in selected animals prior to the start of the exposures, at various time points during the thirteen week exposure period, and at monthly intervals during the recovery period. Assays were performed on selected animals at the end of the exposure period, and again after the two month recovery period. Endpoints includedmore » pulmonary function tests, numbers of alveolar free cells, clinical chemistry, hematology, organ weights and histopathology. No mortalities were recorded during the exposure or recovery periods. Slight toxicity occurred at these low aerosol concentrations with the loss in body weight of all treated animals during the exposure period. During the exposure period there were also some slight changes in startle reflex, however, these were apparently acute effects, and there appeared to be no permanent CNS involvement as measured by this endpoint. Immediately post-exposure, the numbers of lavaged alveolar macrophages were slightly elevated in all aerosol exposed animals. Pulmonary function tests, pulmonary gas exchange and dynamic lung tests were all apparently unaffected by these low diesel fuel aerosol exposures. Changes in tissue weights in aerosol exposed animals were minor and the few histopathological lesions were randomly scattered amongst all groups included in this study and were more attributable to the age of the animals than any specific treatment group. No significant cumulative toxicity may be attributed to these diesel fuel aerosol exposures. 14 references, 1 figure, 42 tables.« less

Role of dopamine receptors in the ventral tegmental area in conditioned fear.

PubMed

de Oliveira, Amanda Ribeiro; Reimer, Adriano Edgar; Brandão, Marcus Lira

2009-05-16

The increased startle reflex in the presence of a stimulus that has been previously paired with footshock has been termed fear-potentiated startle (FPS) and is considered a reliable index of anxiety. Some studies have suggested an association between stressful situations and alterations in dopaminergic (DA) transmission. Many studies converge on the hypothesis that the mesocorticolimbic pathway, originating from DA neurons in the ventral tegmental area (VTA), is particularly sensitive to fear-arousing stimuli. The present study explored the involvement of VTA DA receptors in the acquisition and expression of conditioned fear to a light conditioned stimulus (CS). We evaluated the effects of intra-VTA administration of SKF 38393 (D(1) agonist), SCH 23390 (D(1) antagonist), quinpirole (D(2) agonist), and sulpiride (D(2) antagonist) on FPS. All drugs were administered bilaterally into the VTA (1.0 microg/0.2 microl/site). Locomotor activity/exploration and motor coordination were evaluated in the open-field and rotarod tests. None of the drugs produced significant effects on FPS when injected before conditioning, indicating that VTA DA receptors are not involved in the acquisition of conditioned fear to a light-CS. In contrast, when injected before the test session, quinpirole significantly reduced FPS, whereas the other drugs had no effect. Quinpirole's ability to decrease FPS may be the result of an action on VTA D(2) presynaptic autoreceptors that decrease dopamine levels in terminal fields of the mesocorticolimbic pathway. Altogether, the present results suggest the importance of VTA DA neurons in the fear-activating effects of Pavlovian conditioning. In addition to demonstrating the importance of dopaminergic mechanisms in the motivational consequences of footshock, the present findings also indicate that these neural circuits are mainly involved in the expression, rather than acquisition, of conditioned fear.

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.

Assessing fear and anxiety in humans using the threat of predictable and unpredictable aversive events (the NPU-threat test)

PubMed Central

Schmitz, Anja; Grillon, Christian

2012-01-01

The threat of predictable and unpredictable aversive events was developed to assess short-duration (fear) and long-duration (anxiety) aversive states in humans. A typical experiment consists of three conditions: a safe condition (neutral (N)), during which participants are safe from aversive stimuli, and two threat conditions—one in which aversive events are administered predictably (P) (i.e., signaled by a threat cue), and one in which aversive stimuli are administered unpredictably (U). During the so-called NPU -threat test, ongoing change in aversive states is measured with the startle reflex. The NPU -threat test has been validated in pharmacological and clinical studies and can be implemented in children and adults. Similar procedures have been applied in animal models, making the NPU -threat test an ideal tool for translational research. The procedure is relatively short (35 min), simple to implement and generates consistent results with large effect sizes. PMID:22362158

Comparison of neuromuscular abnormalities between upper and lower extremities in hemiparetic stroke.

PubMed

Mirbagheri, M M; AliBiglou, L; Thajchayapong, M; Lilaonitkul, T; Rymer, W Z

2006-01-01

We studied the neuromuscular mechanical properties of the elbow and ankle joints in chronic, hemiparetic stroke patients and healthy subjects. System identification techniques were used to characterize the mechanical abnormalities of these joints and to identify the contribution of intrinsic and reflex stiffness to these abnormalities. Modulation of intrinsic and reflex stiffness with the joint angle was studied by applying PRBS perturbations to the joint at different joint angles. The experiments were performed for both spastic (stroke) and contralateral (control) sides of stroke patients and one side of healthy (normal) subjects. We found reflex stiffness gain (GR) was significantly larger in the stroke than the control side for both elbow and ankle joints. GR was also strongly position dependent in both joints. However, the modulation of GR with position was slightly different in two joints. GR was also larger in the control than the normal joints but the differences were significant only for the ankle joint. Intrinsic stiffness gain (K) was also significantly larger in the stroke than the control joint at elbow extended positions and at ankle dorsiflexed positions. Modulation of K with the ankle angle was similar for stroke, control and normal groups. In contrast, the position dependency of the elbow was different. K was larger in the control than normal ankle whereas it was lower in the control than normal elbow. However, the differences were not significant for any joint. The findings demonstrate that both reflex and intrinsic stiffness gain increase abnormally in both upper and lower extremities. However, the major contribution of intrinsic and reflex stiffness to the abnormalities is at the end of ROM and at the middle ROM, respectively. The results also demonstrate that the neuromuscular properties of the contralateral limb are not normal suggesting that it may not be used as a suitable control at least for the ankle study.

Contribution of cerebellar intracortical inhibition to Purkinje cell response during vestibulo-ocular reflex of alert rabbits.

PubMed Central

Miyashita, Y; Nagao, S

1984-01-01

Ionophoretic application of bicuculline, an antagonist of gamma-aminobutyric acid (GABA), was used to examine the contribution of intracortical inhibition to vestibular responses of Purkinje cells in the cerebellar flocculus of alert rabbits. Purkinje cells were sampled extracellularly (with triple-barrelled micropipettes) from the floccular area where electrical stimulation through the micro-electrode evoked abduction of the ipsilateral eye, indicating its close functional relationship to the horizontal vestibulo-ocular reflex. These cells exhibited frequency modulation of simple spike discharges in-phase or out-phase with sinusoidal head rotation (0.5 cycles/s, 5 degrees peak-to-peak) in the horizontal plane. Bicuculline was ejected ionophoretically through one barrel with a 20-60 nA current. The pharmacological effectiveness of the ejected bicuculline was confirmed for each Purkinje cell by its blocking action upon the depressant action of GABA applied ionophoretically through another barrel. Bicuculline usually shifted the simple spike modulation in the in-phase direction: it reduced the amplitude of out-phase modulation in three cells, converted out-phase modulation to the in-phase type in four cells, and increased in-phase modulation in five cells. In three other cells, however, bicuculline shifted the modulation in the out-phase direction. Because bicuculline application usually increased the resting discharge level of a Purkinje cell, ionophoretic application of DL-homocysteate was used in ten Purkinje cells to control for the effect of a generalized increase in excitability. In contrast to bicuculline, DL-homocysteate generally induced a slight increase of the simple spike modulation regardless of the phase relationship. Since frequency modulation of the simple spike discharges of flocculus Purkinje cells is presumed to contribute to the control of vestibulo-ocular reflexes, these results point to an important functional role of intracortical post-synaptic inhibition in the cerebellar cortex. PMID:6611408

Underwater Noise and the Conservation of Divers’ Hearing: A Review. Volume 1

DTIC Science & Technology

1989-10-01

reflex attenuation, since the tensor tympani is unaffected and since Bell ’ palsy may affect the VIIIth (auditory) nerve as well as the VIlth (facial...studied acoustic reflexes in patients with acute facial nerve paralysis (Bell’s palsy ). These patients had absent stapedius reflexes on the side of the...voluntary middle ear muscle activation. 24 Bell’s palsy cases; attenuation estimated by shift in reflex amplitude- intensity functions (contralateral), re

THE REELIN RECEPTORS VLDLR AND ApoER2 REGULATE SENSORIMOTOR GATING IN MICE

PubMed Central

Barr, Alasdair M.; Fish, Kenneth N.; Markou, Athina

2007-01-01

Summary Postmortem brain loss of reelin is noted in schizophrenia patients. Accordingly, heterozygous reeler mutant mice have been proposed as a putative model of this disorder. Little is known, however, about the involvement of the two receptors for reelin, Very-Low-Density Lipoprotein Receptor (VLDLR) and Apolipoprotein E Receptor 2 (ApoER2), on pre-cognitive processes of relevance to deficits seen in schizophrenia. Thus, we evaluated sensorimotor gating in mutant mice heterozygous or homozygous for the two reelin receptors. Mutant mice lacking one of these reelin receptors were tested for prepulse inhibition (PPI) of the acoustic startle reflex prior to and following puberty, and on a crossmodal PPI task, involving the presentation of acoustic and tactile stimuli. Furthermore, because schizophrenia patients show increased sensitivity to N-methyl-D-aspartate (NMDA) receptor blockade, we assessed the sensitivity of these mice to the PPI-disruptive effects of the NMDA receptor antagonist phencyclidine. The results demonstrated that acoustic PPI did not differ between mutant and wildtype mice. However, VLDLR homozygous mice displayed significant deficits in crossmodal PPI, while ApoER2 heterozygous and homozygous mice displayed significantly increased crossmodal PPI. Both ApoER2 and VLDLR heterozygous and homozygous mice exhibited greater sensitivity to the PPI-disruptive effects of phencyclidine than wildtype mice. These results indicate that partial or complete loss of either one of the reelin receptors results in a complex pattern of alterations in PPI function that include alterations in crossmodal, but not acoustic, PPI and increased sensitivity to NMDA receptor blockade. Thus, reelin receptor function appears to be critically involved in crossmodal PPI and the modulation of the PPI response by NMDA receptors. These findings have relevance to a range of neuropsychiatric disorders that involve sensorimotor gating deficits, including schizophrenia.. PMID:17261317

Effects of patterned peripheral nerve stimulation on soleus spinal motor neuron excitability

PubMed Central

Dileone, Michele; Campolo, Michela; Carrasco-Lopez, Carmen; Moitinho-Ferreira, Fabricia; Gallego-Izquierdo, Tomas; Siebner, Hartwig R.; Valls-Solé, Josep; Aguilar, Juan

2018-01-01

Spinal plasticity is thought to contribute to sensorimotor recovery of limb function in several neurological disorders and can be experimentally induced in animals and humans using different stimulation protocols. In healthy individuals, electrical continuous Theta Burst Stimulation (TBS) of the median nerve has been shown to change spinal motoneuron excitability in the cervical spinal cord as indexed by a change in mean H-reflex amplitude in the flexor carpi radialis muscle. It is unknown whether continuous TBS of a peripheral nerve can also shift motoneuron excitability in the lower limb. In 26 healthy subjects, we examined the effects of electrical TBS given to the tibial nerve in the popliteal fossa on the excitability of lumbar spinal motoneurons as measured by H-reflex amplitude of the soleus muscle evoked by tibial nerve stimulation. Continuous TBS was given at 110% of H-reflex threshold intensity and compared to non-patterned regular electrical stimulation at 15 Hz. To disclose any pain-induced effects, we also tested the effects of TBS at individual sensory threshold. Moreover, in a subgroup of subjects we evaluated paired-pulse inhibition of H-reflex. Continuous TBS at 110% of H-reflex threshold intensity induced a short-term reduction of H-reflex amplitude. The other stimulation conditions produced no after effects. Paired-pulse H-reflex inhibition was not modulated by continuous TBS or non-patterned repetitive stimulation at 15 Hz. An effect of pain on the results obtained was discarded, since non-patterned 15 Hz stimulation at 110% HT led to pain scores similar to those induced by EcTBS at 110% HT, but was not able to induce any modulation of the H reflex amplitude. Together, the results provide first time evidence that peripheral continuous TBS induces a short-lasting change in the excitability of spinal motoneurons in lower limb circuitries. Future studies need to investigate how the TBS protocol can be optimized to produce a larger and longer effect on spinal cord physiology and whether this might be a useful intervention in patients with excessive excitability of the spinal motorneurons. PMID:29451889

Influence of urothelial or suburothelial cholinergic receptors on bladder reflexes in chronic spinal cord injured cats.

PubMed

Ungerer, Timothy D; Kim, Kyoungeun A; Daugherty, Stephanie L; Roppolo, James R; Tai, Changfeng; de Groat, William C

2016-11-01

The effects of intravesical administration of a muscarinic receptor agonist (oxotremorine-M, OXO-M) and antagonist (atropine methyl nitrate, AMN) and of a nicotinic receptor agonist (nicotine) and antagonist (hexamethonium, C 6 ) on reflex bladder activity were investigated in conscious female chronic spinal cord injured (SCI) cats using cystometry. OXO-M (50μM) decreased bladder capacity (BC) for triggering micturition contractions, increased maximal micturition pressure (MMP), increased frequency and area under the curve of pre-micturition contractions (PMC-AUC). Nicotine (250μM) decreased BC, increased MMP, but did not alter PMC-AUC. The effects of OXO-M on BC and PMC-AUC were suppressed by intravesical administration of AMN (50-100μM), and the effects of nicotine were blocked by hexamethonium (1mM). Antagonists infused intravesically alone did not alter reflex bladder activity. However, AMN (0.2mg/kg, subcutaneously) decreased PMC-AUC. 8-OH-DPAT (0.5mg/kg, s.c.), a 5-HT 1A receptor agonist, suppressed the OXO-M-induced decrease in BC but not the enhancement of PMC-AUC. These results indicate that activation of cholinergic receptors located near the lumenal surface of the bladder modulates two types of reflex bladder activity (i.e., micturition and pre-micturition contractions). The effects may be mediated by activation of receptors on suburothelial afferent nerves or receptors on urothelial cells which release transmitters that can in turn alter afferent excitability. The selective action of nicotine on BC, while OXO-M affects both BC and PMC-AUC, suggests that micturition reflexes and PMCs are activated by different populations of afferent nerves. The selective suppression of the OXO-M effect on BC by 8-OH-DPAT without altering the effect on PMCs supports this hypothesis. The failure of intravesical administration of either AMN or hexamethonium alone to alter bladder activity indicates that cholinergic receptors located near the lumenal surface do not tonically regulate bladder reflex mechanisms in the SCI cat. Copyright © 2016 Elsevier Inc. All rights reserved.

Repeated cycles of electrical stimulation decrease vasoconstriction and axon-reflex vasodilation to noradrenaline in the human forearm

PubMed Central

Drummond, Peter D

2007-01-01

What is already known about this subject Repeated cycles of electrical stimulation inhibit cutaneous vasoconstriction to noradrenaline, but the mechanism is unknown. Investigating this is important because peripheral electrical stimulation is useful for pain modulation and appears to assist cutaneous wound healing. What this study adds Intermittent, brief electrical stimulation of the forearm over a 10-day period inhibited vasoconstriction and axon-reflex vasodilation to noradrenaline, but did not affect vasoconstriction to vasopressin or axon-reflex vasodilation to histamine. Thus, electrical stimulation may evoke a specific reduction in responsiveness to noradrenaline. Aim To investigate whether desensitization to the vasomotor effects of noradrenaline is a specific effect of electrical stimulation. Methods Three sites on the forearm of 10 healthy volunteers were stimulated with 0.2 mA direct current for 2 min twice daily for 10 days. Noradrenaline and histamine were then displaced from ring-shaped iontophoresis chambers into two of the pretreated sites and two untreated sites on the contralateral forearm. Axon-reflex vasodilation was measured from the centre of the ring described by the iontophoresis chamber with a laser Doppler flowmeter. One or two days later, noradrenaline and vasopressin were introduced into pretreated and untreated sites by iontophoresis, and vasoconstriction at sites of administration was measured in the heated forearm. Results The pretreatment blocked vasoconstriction to noradrenaline [median increase in flow 1%, interquartile range (IR) −41 to 52%; median decrease at the untreated site 53%, IR. −70 to −10%; P < 0.05], but did not block vasoconstriction to vasopressin (median decrease 42% at the untreated site and 45% at the pretreated site). Axon-reflex vasodilation to noradrenaline was diminished at the pretreated site (median increase in flow 33%, IR 2–321%; untreated site 247%, IR 31–1087%; P < 0.05). However, axon-reflex vasodilation to histamine did not differ significantly between the pretreated site (median increase 1085%) and the untreated site (median increase 1345%). Conclusions The conditioning pretreatment appears to evoke a specific decrease in responsiveness to noradrenaline. Repeated cycles of electrical stimulation may downregulate neural and vascular responses to noradrenaline by repetitively activating cutaneous sympathetic nerve fibres. PMID:17441931

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.

Cardiorespiratory interactions in neural circulatory control in humans.

PubMed

Shamsuzzaman, A S; Somers, V K

2001-06-01

The reflex mechanisms and interactions described in this overview provide some explanation for the range of neural circulatory responses evident during changes in breathing. The effects described represent the integrated responses to activation of several reflex mechanisms, including peripheral and central chemoreflexes, arterial baroreflexes, pulmonary stretch receptors, and ventricular mechanoreceptors. These interactions occur on a dynamic basis and the transfer characteristics of any single interaction are, in all likelihood, also highly dynamic. Nevertheless, it is only by attempting to understand individual reflexes and their modulating influences that a more thorough understanding of the responses to complex phenomena such as hyperventilation, apnea, and obstructive sleep apnea can be better understood.

Genetics of reflex seizures and epilepsies in humans and animals.

PubMed

Italiano, Domenico; Striano, Pasquale; Russo, Emilio; Leo, Antonio; Spina, Edoardo; Zara, Federico; Striano, Salvatore; Gambardella, Antonio; Labate, Angelo; Gasparini, Sara; Lamberti, Marco; De Sarro, Giovambattista; Aguglia, Umberto; Ferlazzo, Edoardo

2016-03-01

Reflex seizures are epileptic events triggered by specific motor, sensory or cognitive stimulation. This comprehensive narrative review focuses on the role of genetic determinants in humans and animal models of reflex seizures and epilepsies. References were mainly identified through MEDLINE searches until August 2015 and backtracking of references in pertinent studies. Autosomal dominant inheritance with reduced penetrance was proven in several families with photosensitivity. Molecular genetic studies on EEG photoparoxysmal response identified putative loci on chromosomes 6, 7, 13 and 16 that seem to correlate with peculiar seizure phenotype. No specific mutation has been found in Papio papio baboon, although a genetic etiology is likely. Mutation in synaptic vesicle glycoprotein 2A was found in another animal model of photosensitivity (Fayoumi chickens). Autosomal dominant inheritance with incomplete penetrance overlapping with a genetic background for IGE was proposed for some families with primary reading epilepsy. Musicogenic seizures usually occur in patients with focal symptomatic or cryptogenic epilepsies, but they have been reported in rare genetic epilepsies such as Dravet syndrome. A single LGI1 mutation has been described in a girl with seizures evoked by auditory stimuli. Interestingly, heterozygous knockout (Lgi1(+/-)) mice show susceptibility to sound-triggered seizures. Moreover, in Frings and Black Swiss mice, the spontaneous mutations of MASS1 and JAMS1 genes, respectively, have been linked to audiogenic seizures. Eating seizures usually occur in symptomatic epilepsies but evidences for a genetic susceptibility were mainly provided by family report from Sri Lanka. Eating seizures were also reported in rare patients with MECP2 duplication or mutation. Hot water seizures are genetically heterogeneous but two loci at chromosomes 4 and 10 were identified in families with likely autosomal dominant inheritance. Startle-induced seizures usually occur in patients with symptomatic epilepsies but have also been reported in the setting chromosomal disorders or genetically inherited lysosomal storage diseases. The genetic background of reflex seizures and epilepsies is heterogeneous and mostly unknown with no major gene identified in humans. The benefits offered by next-generation sequencing technologies should be merged with increasing information on animal models that represent an useful tool to study the mechanism underlying epileptogenesis. Finally, we expect that genetic studies will lead to a better understanding of the multiple factors involved in the pathophysiology of reflex seizures, and eventually to develop preventive strategies focused on seizure control and therapy optimization. Copyright © 2016 Elsevier B.V. All rights reserved.

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

DOT National Transportation Integrated Search

1988-08-01

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

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.

Does diurnal variation in cough reflex testing exist in healthy young adults?

PubMed

Perry, Sarah; Huckabee, Maggie-Lee

2017-05-01

The aim of this study was to investigate whether diurnal variation in cough reflex sensitivity exists in healthy young adults when a tidal-breathing method is used. Fifty-three participants (19-37 years) underwent cough reflex testing on two occasions: once in the morning (between 9 am - midday) and once in the afternoon (between 2-5 pm). The order of testing was counter-balanced. Within each assessment, participants inhaled successively higher citric acid concentrations via a facemask, with saline solution randomly interspersed to control for a placebo response. The lowest concentration that elicited a reflexive cough response was recorded. Morning cough thresholds (mean=0.6mol/L) were not different from afternoon cough thresholds (mean=0.6mol/L), p=0.16, T=101, r=-0.14. We found no evidence of diurnal variability in cough reflex testing. There was, however, an order effect irrespective of time of day, confirming that healthy participants are able to volitionally modulate their cough response. Copyright © 2017 Elsevier B.V. All rights reserved.

Locomotor impact of beneficial or nonbeneficial H-reflex conditioning after spinal cord injury

PubMed Central

Chen, Yi; Chen, Lu; Liu, Rongliang; Wang, Yu; Wolpaw, Jonathan R.

2013-01-01

When new motor learning changes neurons and synapses in the spinal cord, it may affect previously learned behaviors that depend on the same spinal neurons and synapses. To explore these effects, we used operant conditioning to strengthen or weaken the right soleus H-reflex pathway in rats in which a right spinal cord contusion had impaired locomotion. When up-conditioning increased the H-reflex, locomotion improved. Steps became longer, and step-cycle asymmetry (i.e., limping) disappeared. In contrast, when down-conditioning decreased the H-reflex, locomotion did not worsen. Steps did not become shorter, and asymmetry did not increase. Electromyographic and kinematic analyses explained how H-reflex increase improved locomotion and why H-reflex decrease did not further impair it. Although the impact of up-conditioning or down-conditioning on the H-reflex pathway was still present during locomotion, only up-conditioning affected the soleus locomotor burst. Additionally, compensatory plasticity apparently prevented the weaker H-reflex pathway caused by down-conditioning from weakening the locomotor burst and further impairing locomotion. The results support the hypothesis that the state of the spinal cord is a “negotiated equilibrium” that serves all the behaviors that depend on it. When new learning changes the spinal cord, old behaviors undergo concurrent relearning that preserves or improves their key features. Thus, if an old behavior has been impaired by trauma or disease, spinal reflex conditioning, by changing a specific pathway and triggering a new negotiation, may enable recovery beyond that achieved simply by practicing the old behavior. Spinal reflex conditioning protocols might complement other neurorehabilitation methods and enhance recovery. PMID:24371288

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

Effects of cathodal trans-spinal direct current stimulation on lower urinary tract function in normal and spinal cord injury mice with overactive bladder

NASA Astrophysics Data System (ADS)

Ahmed, Zaghloul

2017-10-01

Objective. Lower urinary tract (LUT) dysfunction is a monumental problem affecting quality of life following neurotrauma, such as spinal cord injury (SCI). Proper function of the bladder and its associated structures depends on coordinated activity of the neuronal circuitry in the spinal cord and brain. Disconnection between the spinal and brain centers controlling the LUT causes fundamental changes in the mechanisms involved in the micturition and storage reflexes. We investigated the effects of cathodal trans-spinal direct current stimulation (c-tsDCS) of the lumbosacral spine on bladder and external urinary sphincter (EUS) functions. Approach. We used cystometry and electromyography (EMG), in mice with and without SCI. Main results. c-tsDCS caused initiation of the micturition reflex in urethane-anesthetized normal mice with depressed micturition reflexes. This effect was associated with normalized EUS-EMG activity. Moreover, in urethane-anesthetized normal mice with expressed micturition reflexes, c-tsDCS increased the firing frequency, amplitude, and duration of EUS-EMG activity. These effects were associated with increased maximum intravesical pressure (P max) and intercontraction interval (ICI). In conscious normal animals, c-tsDCS caused significant increases in P max, ICI, threshold pressure (P thres), baseline pressure (P base), and number and amplitude of non-voiding contractions (NVCnumb and P im, respectively). In conscious mice with severe contusive SCI and overactive bladder, c-tsDCS increased P max, ICI, and P thres, but decreased P base, NVCnumb, and P im. c-tsDCS reduced the detrusor-overactivity/cystometry ratio, which is a measure of bladder overactivity associated with renal deterioration. Significance. These results indicate that c-tsDCS induces robust modulation of the lumbosacral spinal-cord circuitry that controls the LUT.

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

Modulation of H-Reflex Depression with Paired-Pulse Stimulation in Healthy Active Humans.

PubMed

Oza, Preeti D; Dudley-Javoroski, Shauna; Shields, Richard K

2017-01-01

Depression of the Hoffman reflex (H-reflex) is used to examine spinal control mechanisms during exercise, fatigue, and vibration and in response to training. H-reflex depression protocols frequently use trains of stimuli; this is time-consuming and prevents instantaneous assessment of motor neuronal excitability. The purpose of this study was to determine if paired-pulse H-reflex depression is reproducible and whether paired-pulse stimulation adequately estimates the depression induced by the more traditional ten-pulse train. H-reflexes were elicited via ten-pulse trains at 0.1, 0.2, 1, 2, and 5 Hz in ten neurologically intact individuals on two separate days. We measured the depression elicited by the second pulse (H2) and the mean depression elicited by pulses 2-10 (Hmean). H2 was consistent at all frequencies on both days ( r 2 = 0.97, p < 0.05, and ICC (3,1) = 0.81). H2 did not differ from Hmean ( p > 0.05). The results indicate that paired-pulse H-reflex depression has high between-day reliability and yields depression estimates that are comparable to those obtained via ten-pulse trains. Paired-pulse H-reflex depression may be especially useful for studies that require rapid assessment of motor neuronal excitability, such as during exercise, fatigue, and vibration, or to establish recovery curves following inhibition.

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.

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.

Restoring walking after spinal cord injury: operant conditioning of spinal reflexes can help.

PubMed

Thompson, Aiko K; Wolpaw, Jonathan R

2015-04-01

People with incomplete spinal cord injury (SCI) frequently suffer motor disabilities due to spasticity and poor muscle control, even after conventional therapy. Abnormal spinal reflex activity often contributes to these problems. Operant conditioning of spinal reflexes, which can target plasticity to specific reflex pathways, can enhance recovery. In rats in which a right lateral column lesion had weakened right stance and produced an asymmetrical gait, up-conditioning of the right soleus H-reflex, which increased muscle spindle afferent excitation of soleus, strengthened right stance and eliminated the asymmetry. In people with hyperreflexia due to incomplete SCI, down-conditioning of the soleus H-reflex improved walking speed and symmetry. Furthermore, modulation of electromyographic activity during walking improved bilaterally, indicating that a protocol that targets plasticity to a specific pathway can trigger widespread plasticity that improves recovery far beyond that attributable to the change in the targeted pathway. These improvements were apparent to people in their daily lives. They reported walking faster and farther, and noted less spasticity and better balance. Operant conditioning protocols could be developed to modify other spinal reflexes or corticospinal connections; and could be combined with other therapies to enhance recovery in people with SCI or other neuromuscular disorders. © The Author(s) 2014.

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 peripersonal space: the blink reflex evoked by hand stimulation is increased when the hand is near the face.

PubMed

Sambo, C F; Liang, M; Cruccu, G; Iannetti, G D

2012-02-01

Electrical stimulation of the median nerve at the wrist may elicit a blink reflex [hand blink reflex (HBR)] mediated by a neural circuit at brain stem level. As, in a Sherringtonian sense, the blink reflex is a defensive response, in a series of experiments we tested, in healthy volunteers, whether and how the HBR is modulated by the proximity of the stimulated hand to the face. Electromyographic activity was recorded from the orbicularis oculi, bilaterally. We observed that the HBR is enhanced when the stimulated hand is inside the peripersonal space of the face, compared with when it is outside, irrespective of whether the proximity of the hand to the face is manipulated by changing the position of the arm (experiment 1) or by rotating the head while keeping the arm position constant (experiment 3). Experiment 2 showed that such HBR enhancement has similar magnitude when the participants have their eyes closed. Experiments 4 and 5 showed, respectively, that the blink reflex elicited by the electrical stimulation of the supraorbital nerve, as well as the N20 wave of the somatosensory evoked potentials elicited by the median nerve stimulation, are entirely unaffected by hand position. Taken together, our results provide compelling evidence that the brain stem circuits mediating the HBR in humans undergo tonic and selective top-down modulation from higher order cortical areas responsible for encoding the location of somatosensory stimuli in external space coordinates. These findings support the existence of a "defensive" peripersonal space, representing a safety margin advantageous for survival.

Dopamine is produced in the rat spinal cord and regulates micturition reflex after spinal cord injury

PubMed Central

Hou, Shaoping; Carson, David M.; Wu, Di; Klaw, Michelle C.; Houlé, John D.; Tom, Veronica J.

2016-01-01

Dopamine (DA) neurons in the mammalian central nervous system are thought to be restricted to the brain. DA-mediated regulation of urinary activity is considered to occur through an interaction between midbrain DA neurons and the pontine micturition center. Here we show that DA is produced in the rat spinal cord and modulates the bladder reflex. We observed numerous tyrosine hydroxylase (TH)+ neurons in the autonomic nuclei and superficial dorsal horn in L6–S3 spinal segments. These neurons are dopamine-β-hydroxylase (DBH)− and some contain detectable dopamine decarboxylase (DDC), suggesting their capacity to produce DA. Interestingly, following a complete thoracic spinal cord injury (SCI) to interrupt supraspinal projections, more TH+ neurons emerged in the lumbosacral spinal cord, coincident with a sustained, low level of DA expression there and a partially recovered micturition reflex. Non-selective blockade of spinal DA receptors reduced bladder activity whereas activation of spinal D2-like receptors increased bladder activity and facilitated voiding. Additionally, depletion of lumbosacral TH+ neurons with 6-hydroxydopamine (6-OHDA) decreased bladder non-voiding contractions and voiding efficiency. Furthermore, injecting the transsynaptic neuronal tracer pseudorabies virus (PRV) into the bladder detrusor labeled TH+ cells in the lumbosacral cord, confirming their involvement in spinal micturition reflex circuits. These results illustrate that DA is synthesized in the rat spinal cord; plasticity of lumbosacral TH+ neurons following SCI may contribute to DA expression and modulate the spinal bladder reflex. Thus, spinally-derived DA and receptors could be a novel therapeutic target to improve micturition recovery after SCI. PMID:26655672

Dopamine is produced in the rat spinal cord and regulates micturition reflex after spinal cord injury.

PubMed

Hou, Shaoping; Carson, David M; Wu, Di; Klaw, Michelle C; Houlé, John D; Tom, Veronica J

2016-11-01

Dopamine (DA) neurons in the mammalian central nervous system are thought to be restricted to the brain. DA-mediated regulation of urinary activity is considered to occur through an interaction between midbrain DA neurons and the pontine micturition center. Here we show that DA is produced in the rat spinal cord and modulates the bladder reflex. We observed numerous tyrosine hydroxylase (TH) + neurons in the autonomic nuclei and superficial dorsal horn in L6-S3 spinal segments. These neurons are dopamine-β-hydroxylase (DBH) - and some contain detectable dopamine decarboxylase (DDC), suggesting their capacity to produce DA. Interestingly, following a complete thoracic spinal cord injury (SCI) to interrupt supraspinal projections, more TH + neurons emerged in the lumbosacral spinal cord, coincident with a sustained, low level of DA expression there and a partially recovered micturition reflex. Non-selective blockade of spinal DA receptors reduced bladder activity whereas activation of spinal D 2 -like receptors increased bladder activity and facilitated voiding. Additionally, depletion of lumbosacral TH + neurons with 6-hydroxydopamine (6-OHDA) decreased bladder non-voiding contractions and voiding efficiency. Furthermore, injecting the transsynaptic neuronal tracer pseudorabies virus (PRV) into the bladder detrusor labeled TH + cells in the lumbosacral cord, confirming their involvement in spinal micturition reflex circuits. These results illustrate that DA is synthesized in the rat spinal cord; plasticity of lumbosacral TH + neurons following SCI may contribute to DA expression and modulate the spinal bladder reflex. Thus, spinally-derived DA and receptors could be a novel therapeutic target to improve micturition recovery after SCI. Published by Elsevier Inc.

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

Health Instruction Packages: Consumer--Child Care.

ERIC Educational Resources Information Center

Wojcik, Bonnie; And Others

Text, illustrations, and exercises are utilized in these four learning modules to instruct parents and nursing students in topics related to child care and development. The first module, "Growth and Development: Let's Test Your Baby's Reflexes" by Bonnie Wojcik, describes the behavioral signs that are indicative of eight normal primitive…

Endogenous inhibition of pain and spinal nociception in women with premenstrual dysphoric disorder

PubMed Central

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

2016-01-01

Purpose Premenstrual dysphoric disorder (PMDD) is characterized by severe affective and physical symptoms, such as increased pain, during the late-luteal phase of the menstrual cycle. The mechanisms underlying hyperalgesia in women with PMDD have yet to be identified, and supraspinal pain modulation has yet to be examined in this population. The present study assessed endogenous pain inhibitory processing by examining conditioned pain modulation (CPM, a painful conditioning stimulus inhibiting pain evoked by a test stimulus at a distal body site) of pain and the nociceptive flexion reflex (NFR, a spinally-mediated withdrawal reflex) during the mid-follicular, ovulatory, and late-luteal phases of the menstrual cycle. Methods Participants were regularly-cycling women (14 without PMDD; 14 with PMDD). CPM was assessed by delivering electrocutaneous test stimuli to the sural nerve before, during, and after a painful conditioning ischemia task. Participants rated their pain to electrocutaneous stimuli, and NFR magnitudes were measured. A linear mixed model analysis was used to assess the influence of group and menstrual phase on CPM. Results Compared with controls, women with PMDD experienced greater pain during the late-luteal phase and enhanced spinal nociception during the ovulation phase, both of which were independent of CPM. Both groups showed CPM inhibition of pain that did not differ by menstrual phase. Only women with PMDD evidenced CPM inhibition of NFR. Conclusion Endogenous modulation of pain and spinal nociception is not disrupted in women with PMDD. Additionally, greater NFR magnitudes during ovulation in PMDD may be due to tonically-engaged descending mechanisms that facilitate spinal nociception, leading to enhanced pain during the premenstrual phase. PMID:26929663

Serotonin Affects Movement Gain Control in the Spinal Cord

PubMed Central

Glaser, Joshua I.; Deng, Linna; Thompson, Christopher K.; Stevenson, Ian H.; Wang, Qining; Hornby, Thomas George; Heckman, Charles J.; Kording, Konrad P.

2014-01-01

A fundamental challenge for the nervous system is to encode signals spanning many orders of magnitude with neurons of limited bandwidth. To meet this challenge, perceptual systems use gain control. However, whether the motor system uses an analogous mechanism is essentially unknown. Neuromodulators, such as serotonin, are prime candidates for gain control signals during force production. Serotonergic neurons project diffusely to motor pools, and, therefore, force production by one muscle should change the gain of others. Here we present behavioral and pharmaceutical evidence that serotonin modulates the input–output gain of motoneurons in humans. By selectively changing the efficacy of serotonin with drugs, we systematically modulated the amplitude of spinal reflexes. More importantly, force production in different limbs interacts systematically, as predicted by a spinal gain control mechanism. Psychophysics and pharmacology suggest that the motor system adopts gain control mechanisms, and serotonin is a primary driver for their implementation in force production. PMID:25232107

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.

Differential pathologies resulting from sound exposure: Tinnitus vs hearing loss

NASA Astrophysics Data System (ADS)

Longenecker, Ryan James

The first step in identifying the mechanism(s) responsible for tinnitus development would be to discover a neural correlate that is differentially expressed in tinnitus-positive compared to tinnitus negative animals. Previous research has identified several neural correlates of tinnitus in animals that have tested positive for tinnitus. However it is unknown whether all or some of these correlates are linked to tinnitus or if they are a byproduct of hearing loss, a common outcome of tinnitus induction. Abnormally high spontaneous activity has frequently been linked to tinnitus. However, while some studies demonstrate that hyperactivity positively correlates with behavioral evidence of tinnitus, others show that when all animals develop hyperactivity to sound exposure, not all exposed animals show evidence of tinnitus. My working hypothesis is that certain aspects of hyperactivity are linked to tinnitus while other aspects are linked to hearing loss. The first specific aim utilized the gap induced prepulse inhibition of the acoustic startle reflex (GIPAS) to monitor the development of tinnitus in CBA/CaJ mice during one year following sound exposure. Immediately after sound exposure, GIPAS testing revealed widespread gap detection deficits across all frequencies, which was likely due to temporary threshold shifts. However, three months after sound exposure these deficits were limited to a narrow frequency band and were consistently detected up to one year after exposure. This suggests the development of chronic tinnitus is a long lasting and highly dynamic process. The second specific aim assessed hearing loss in sound exposed mice using several techniques. Acoustic brainstem responses recorded initially after sound exposure reveal large magnitude deficits in all exposed mice. However, at the three month period, thresholds return to control levels in all mice suggesting that ABRs are not a reliable tool for assessing permanent hearing loss. Input/output functions of the acoustic startle reflex show that after sound exposure the magnitude of startle responses decrease in most mice, to varying degrees. Lastly, PPI audiometry was able to detect specific behavioral threshold deficits for each mouse after sound exposure. These deficits persist past initial threshold shifts and are able to detect frequency specific permanent threshold shifts. The third specific aim examined hyperactivity and increased bursting activity in the inferior colliculus after sound exposure in relation to tinnitus and hearing loss. Spontaneous firing rates were increased in all mice after sound exposure regardless of behavioral evidence of tinnitus. However, abnormal increased bursting activity was not found in the animals identified with tinnitus but was exhibited in a mouse with broad-band severe threshold deficits. CBA/CaJ mice are a good model for both tinnitus development and noise-induced hearing loss studies. Hyperactivity which was evident in all exposed animals does not seem to be well correlated with behavioral evidence of tinnitus but more likely to be a general result of acoustic over exposure. Data from one animal strongly suggest that wide-spread severe threshold deficits are linked to an elevation of bursting activity predominantly ipsilateral to the side of sound exposure. This result is intriguing and should be followed up in further studies. Data obtained in this study provide new insights into underlying neural pathologies following sound exposure and have possible clinical applications for development of effective treatments and diagnostic tools for tinnitus and hearing loss.

Abnormal reflex activation of hamstring muscles in dogs with cranial cruciate ligament rupture.

PubMed

Hayes, Graham M; Granger, Nicolas; Langley-Hobbs, Sorrel J; Jeffery, Nick D

2013-06-01

The mechanisms underlying cranial cruciate ligament rupture (CCLR) in dogs are poorly understood. In this study hamstring muscle reflexes in response to cranial tibial translation were analysed to determine whether these active stabilisers of the stifle joint are differently activated in dogs with CCLR compared to control dogs. In a prospective clinical study reflex muscle activity from the lateral and medial hamstring muscles (biceps femoris and semimembranosus) was recorded using surface electrodes in control dogs (n=21) and dogs with CCLR (n=22). These electromyographic recordings were analysed using an algorithm previously validated in humans. The hamstring reflex was reliably and reproducibly recorded in normal dogs. Both a short latency response (SLR, 17.6±2.1ms) and a medium latency response (MLR, 37.7±2.7ms) could be identified. In dogs with unilateral CCLR, the SLR and MLR were not significantly different between the affected and the unaffected limbs, but the MLR latency of both affected and unaffected limbs in CCLR dogs were significantly prolonged compared to controls. In conclusion, the hamstring reflex can be recorded in dogs and the MLR is prolonged in dogs with CCLR. Since both affected and unaffected limbs exhibit prolonged MLR, it is possible that abnormal hamstring reflex activation is a mechanism by which progressive CCL damage may occur. The methodology allows for further investigation of the relationship between neuromuscular imbalance and CCLR or limitations in functional recovery following surgical intervention. Copyright © 2012 Elsevier Ltd. All rights reserved.

Role of TRPV1 in acupuncture modulation of reflex excitatory cardiovascular responses.

PubMed

Guo, Zhi-Ling; Fu, Liang-Wu; Su, Hou-Fen; Tjen-A-Looi, Stephanie C; Longhurst, John C

2018-05-01

We have shown that acupuncture, including manual and electroacupuncture (MA and EA), at the P5-6 acupoints stimulates afferent fibers in the median nerve (MN) to modulate sympathoexcitatory cardiovascular reflexes through central regulation of autonomic function. However, the mechanisms underlying acupuncture activation of these sensory afferent nerves and their cell bodies in the dorsal root ganglia (DRG) are unclear. Transient receptor potential vanilloid type 1 (TRPV1) is present in sensory nerve fibers distributed in the general region of acupoints like ST36 and BL 40 located in the hindlimb. However, the contribution of TRPV1 to activation of sensory nerves by acupuncture, leading to modulation of pressor responses, has not been studied. We hypothesized that TRPV1 participates in acupuncture's activation of sensory afferents and their associated cell bodies in the DRG to modulate pressor reflexes. Local injection of iodoresiniferatoxin (Iodo-RTX; a selective TRPV1 antagonist), but not 5% DMSO (vehicle), into the P6 acupoint on the forelimb reversed the MA's inhibition of pressor reflexes induced by gastric distension (GD). Conversely, inhibition of GD-induced sympathoexcitatory responses by EA at P5-6 was unchanged after administration of Iodo-RTX into P5-6. Single-unit activity of Group III or IV bimodal afferents sensitive to both mechanical and capsaicin stimuli responded to MA stimulation at P6. MA-evoked activity was attenuated significantly ( P < 0.05) by local administration of Iodo-RTX ( n = 12) but not by 5% DMSO ( n = 12) into the region of the P6 acupoint in rats. Administration of Iodo-RTX into P5-6 did not reduce bimodal afferent activity evoked by EA stimulation ( n = 8). Finally, MA at P6 and EA at P5-6 induced phosphorylation of extracellular signal-regulated kinases (ERK; an intracellular signaling messenger involved in cellular excitation) in DRG neurons located at C 7-8 spinal levels receiving MN inputs. After TRPV1 was knocked down in the DRG at these spinal levels with intrathecal injection of TRPV1-siRNA, expression of phosphorylated ERK in the DRG neuron was reduced in MA-treated, but not EA-treated animals. These data suggest that TRPV1 in Group III and IV bimodal sensory afferent nerves contributes to acupuncture inhibition of reflex increases in blood pressure and specifically plays an important role during MA but not EA.

Ouabain Modulates Zymosan-Induced Peritonitis in Mice

PubMed Central

Leite, Jacqueline Alves; Alves, Anne Kaliery De Abreu; Galvão, José Guilherme Marques; Teixeira, Mariana Pires; Rumjanek, Vivian Mary; Rodrigues-Mascarenhas, Sandra

2015-01-01

Ouabain, a potent inhibitor of the Na+, K+-ATPase, was identified as an endogenous substance. Recently, ouabain was shown to affect various immunological processes. We have previously demonstrated the ability of ouabain to modulate inflammation, but little is known about the mechanisms involved. Thus, the aim of the present work is to evaluate the immune modulatory role of ouabain on zymosan-induced peritonitis in mice. Our results show that ouabain decreased plasma exudation (33%). After induction of inflammation, OUA treatment led to a 46% reduction in the total number of cells, as a reflex of a decrease of polymorphonuclear leukocytes, which does not appear to be due to cell death. Furthermore, OUA decreased TNF-α (57%) and IL-1β (58%) levels, without interfering with IL-6 and IL-10. Also, in vitro experiments show that ouabain did not affect endocytic capacity. Moreover, electrophoretic mobility shift assay (EMSA) shows that zymosan treatment increased (85%) NF-κB binding activity and that ouabain reduced (30%) NF-κB binding activity induced by zymosan. Therefore, our data suggest that ouabain modulated acute inflammatory response, reducing the number of cells and cytokines levels in the peritoneal cavity, as well as NFκB activation, suggesting a new mode of action of this substance. PMID:26078492

Bodily ownership modulation in defensive responses: physiological evidence in brain-damaged patients with pathological embodiment of other's body parts.

PubMed

Fossataro, C; Gindri, P; Mezzanato, T; Pia, L; Garbarini, F

2016-06-13

Do conscious beliefs about the body affect defensive mechanisms within the body? To answer this question we took advantage from a monothematic delusion of bodily ownership, in which brain-damaged patients misidentify alien limbs as their own. We investigated whether the delusional belief that an alien hand is their own hand modulates a subcortical defensive response, such as the hand-blink reflex. The blink, dramatically increases when the threated hand is inside the defensive peripersonal-space of the face. In our between-subjects design, including patients and controls, the threat was brought near the face either by the own hand or by another person's hand. Our results show an ownership-dependent modulation of the defensive response. In controls, as well as in the patients' intact-side, the response enhancement is significantly greater when the threat was brought near the face by the own than by the alien hand. Crucially, in the patients' affected-side (where the pathological embodiment occurs), the alien (embodied) hand elicited a response enhancement comparable to that found when the threat is brought near the face by the real hand. These findings suggest the existence of a mutual interaction between our conscious beliefs about the body and the physiological mechanisms within the body.

The modulation of visceral functions by somatic afferent activity.

PubMed

Sato, A; Schmidt, R F

1987-01-01

We began by briefly reviewing the historical background of neurophysiological studies of the somato-autonomic reflexes and then discussed recent studies on somatic-visceral reflexes in combination with autonomic efferent nerve activity and effector organ responses. Most of the studies that have advanced our knowledge in this area have been carried out on anesthetized animals, thus eliminating emotional factors. We would like to emphasize again that the functions of many, or perhaps all visceral organs can be modulated by somato-sympathetic or somato-parasympathetic reflex activity induced by a appropriate somatic afferent stimulation in anesthetized animals. As mentioned previously, some autonomic nervous outflow, e.g. the adrenal sympathetic nerve activity, is involved in the control of hormonal secretion. John F. Fulton wrote in his famous textbook "Physiology of the Nervous System" (1949) that the posterior pituitary neurosecretion system (i.e. for oxytocin and vasopressin) could be considered a part of the parasympathetic nervous system. In the study of body homeostasis and environmental adaptation it would seem very important to further analyze the contribution of somatic afferent input to the autonomic nervous and hormonal regulation of visceral organ activity. Also, some immunological functions have been found to be influenced by autonomic nerves or hormones (e.g. adrenal cortical hormone and catecholamines). Finally, we must take into account, as we have briefly discussed, that visceral functions can be modulated by somatic afferent input via various degrees of integration of autonomic nerves, hormones, and immunological processes. We trust that such research will be expanded to higher species of mammals, and that ultimately this knowledge of somato-visceral reflexes obtained in the physiological laboratory will become clinically useful in influencing visceral functions.

GABAA- and glycine-mediated inhibitory modulation of the cough reflex in the caudal nucleus tractus solitarii of the rabbit.

PubMed

Cinelli, Elenia; Iovino, Ludovica; Bongianni, Fulvia; Pantaleo, Tito; Mutolo, Donatella

2016-09-01

Cough-related sensory inputs from rapidly adapting receptors (RARs) and C fibers are processed by second-order neurons mainly located in the caudal nucleus tractus solitarii (NTS). Both GABAA and glycine receptors have been proven to be involved in the inhibitory control of second-order cells receiving RAR projections. We investigated the role of these receptors within the caudal NTS in the modulation of the cough reflex induced by either mechanical or chemical stimulation of the tracheobronchial tree in pentobarbital sodium-anesthetized, spontaneously breathing rabbits. Bilateral microinjections (30-50 nl) of the receptor antagonists bicuculline and strychnine as well as of the receptor agonists muscimol and glycine were performed. Bicuculline (0.1 mM) and strychnine (1 mM) caused decreases in peak abdominal activity and marked increases in respiratory frequency due to decreases in both inspiratory time (Ti) and expiratory time (Te), without concomitant changes in arterial blood pressure. Noticeably, these microinjections induced potentiation of the cough reflex consisting of increases in the cough number associated with decreases either in cough-related Ti after bicuculline or in both cough-related Ti and Te after strychnine. The effects caused by muscimol (0.1 mM) and glycine (10 mM) were in the opposite direction to those produced by the corresponding antagonists. The results show that both GABAA and glycine receptors within the caudal NTS mediate a potent inhibitory modulation of the pattern of breathing and cough reflex responses. They strongly suggest that disinhibition is one important mechanism underlying cough regulation and possibly provide new hints for novel effective antitussive strategies. Copyright © 2016 the American Physiological Society.

Tutoring and Mentoring: An A.R.C. Model for Future Teachers: Affective, Reflexive and Cognitive Orientation to Self-Regulated Learning

ERIC Educational Resources Information Center

Remy, Philippe

2015-01-01

With a specific focus on tutoring among future teachers this article proposes a model of self-regulated learning. The focus on different mechanisms inherent to the tutoring relationship will consider Affective impacts or motivation, Reflexive or metacognitive and Cognitive resolutions. The ARC combination proposes that personal skills will be…

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.

The contribution of a central pattern generator in a reflex-based neuromuscular model

PubMed Central

Dzeladini, Florin; van den Kieboom, Jesse; Ijspeert, Auke

2014-01-01

Although the concept of central pattern generators (CPGs) controlling locomotion in vertebrates is widely accepted, the presence of specialized CPGs in human locomotion is still a matter of debate. An interesting numerical model developed in the 90s’ demonstrated the important role CPGs could play in human locomotion, both in terms of stability against perturbations, and in terms of speed control. Recently, a reflex-based neuro-musculo-skeletal model has been proposed, showing a level of stability to perturbations similar to the previous model, without any CPG components. Although exhibiting striking similarities with human gaits, the lack of CPG makes the control of speed/step length in the model difficult. In this paper, we hypothesize that a CPG component will offer a meaningful way of controlling the locomotion speed. After introducing the CPG component in the reflex model, and taking advantage of the resulting properties, a simple model for gait modulation is presented. The results highlight the advantages of a CPG as feedforward component in terms of gait modulation. PMID:25018712

[Effects of morphine on pupillary light reflex in monkeys].

PubMed

Meng, Zhi-Qiang; Zhang, Yu-Hua; Chen, Nan-Hui; Miao, Ying-Da; Hu, Xin-Tian; Ma, Yuan-Ye

2010-06-01

The pupil size of both human and other animals can be affected by light. Many kinds of psychiatrical and psychological disorders, such as drug abuse, associate with abnormal properties of pupillary light reflex. Thus, the properties of pupillary light reflex could serve as an indicator for drug abuse detection. However, the effect of drug abuse on pupillary light reflex is till unclear. To assess the effects of addictive drugs on pupillary light reflex quantificationally, in the present study, we examined the effects of morphine on pupil diameter and pupillary light reflex in rhesus monkeys. By measuring the pupil diameter at different timing points before and after the administration of morphine, we found that morphine administration reduced the diameter of pupil and decreased the constriction rate. Our present results provide an experimental support for applying the properties of pupillary light reflex as a reference in addicts' detection.

Motor unit firing and its relation to tremor in the tonic vibration reflex of the decerebrate cat.

PubMed

Clark, F J; Matthews, P B; Muir, R B

1981-01-01

1. The discharge of single motor units has been recorded from the soleus muscle of the decerebrate cat during the tonic vibration reflex elicited isometrically, to further understanding of the tremor that is seen in the reflex contraction. The reflex was elicited by pulses of vibration of 50 micrometers amplitude at 150 Hz, and up to four units were studied concurrently. 2. Individual units fired rather regularly and at a low frequency (range 4-14 Hz). The rate of firing of any unit normally fell within the frequency band of the tremor recorded at the same time. On comparing different preparations a higher frequency of tremor was associated with a higher frequency of motor firing. 3. The responses of pairs of motor units recorded concurrently during repeated production of the reflex were compared by cross-correlation analysis; over 1000 spikes from each train were normally used for this. The major of the cross-correlograms were flat with no overt sign of any synchronization between the units other than that due to the vibration. 4. Clear indications of correlated motor unit firing could be produced deliberately by modulating the amplitude of vibration at a frequency comparable to that of the normal tremor and thereby introducing a rhythmic component into the tonic vibration reflex. 5. About 20% of the cross-correlograms obtained during normal tremor showed varying amounts of an irregular 'waviness' suggesting a possible correlation between the times of firing of a pair of units. But such waves never developed steadily throughout the period of analysis, in contrast to the comparable waves produced on modulating the vibration. Similar waves were seen on cross-correlating a motor unit with an electronic oscillator, confirming that their occurrence does not necessarily demonstrate the existence of active neural interactions. 6. It is concluded that there is no strong and widespread neural synchronizing mechanism active during the tonic vibration reflex, although the possibility of some weak neural interactions has not been excluded. The findings favour the idea that the tremor in this preparation is simply the inevitable result of motor units discharging asynchronously, but at closely similar subtetanic frequencies.

Orthodontic treatment-induced temporal alteration of jaw-opening reflex excitability.

PubMed

Sasaki, Au; Hasegawa, Naoya; Adachi, Kazunori; Sakagami, Hiroshi; Suda, Naoto

2017-10-01

The impairment of orofacial motor function during orthodontic treatment needs to be addressed, because most orthodontic patients experience pain and motor excitability would be affected by pain. In the present study, the temporal alteration of the jaw-opening reflex excitability was investigated to determine if orthodontic treatment affects orofacial motor function. The excitability of jaw-opening reflex evoked by electrical stimulation on the gingiva and recorded bilaterally in the anterior digastric muscles was evaluated at 1 (D1), 3 (D3), and 7 days (D7) after orthodontic force application to the teeth of right side; morphological features (e.g., osteoclast genesis and tooth movement) were also evaluated. To clarify the underlying mechanism of orthodontic treatment-induced alteration of orofacial motor excitability, analgesics were administrated for 1 day. At D1 and D3, orthodontic treatment significantly decreased the threshold for inducing the jaw-opening reflex but significantly increased the threshold at D7. Other parameters of the jaw-opening reflex were also evaluated (e.g., latency, duration and area under the curve of anterior digastric muscles activity), and only the latency of the D1 group was significantly different from that of the other groups. Temporal alteration of the jaw-opening reflex excitability was significantly correlated with changes in morphological features. Aspirin (300 mg·kg -1 ·day -1 ) significantly increased the threshold for inducing the jaw-opening reflex, whereas a lower dose (75-150 mg·kg -1 ·day -1 ) of aspirin or acetaminophen (300 mg·kg -1 ·day -1 ) failed to alter the jaw-opening reflex excitability. These results suggest that an increase of the jaw-opening reflex excitability can be induced acutely by orthodontic treatment, possibly through the cyclooxygenase activation. NEW & NOTEWORTHY It is well known that motor function is affected by pain, but the effect of orthodontic treatment-related pain on the trigeminal motor excitability has not been fully understood. We found that, during orthodontic treatment, trigeminal motor excitability is acutely increased and then decreased in a week. Because alteration of trigeminal motor function can be evaluated quantitatively by jaw-opening reflex excitability, the present animal model may be useful to search for alternative approaches to attenuate orthodontic pain. Copyright © 2017 the American Physiological Society.

Estimation of Time-Varying, Intrinsic and Reflex Dynamic Joint Stiffness during Movement. Application to the Ankle Joint

PubMed Central

Guarín, Diego L.; Kearney, Robert E.

2017-01-01

Dynamic joint stiffness determines the relation between joint position and torque, and plays a vital role in the control of posture and movement. Dynamic joint stiffness can be quantified during quasi-stationary conditions using disturbance experiments, where small position perturbations are applied to the joint and the torque response is recorded. Dynamic joint stiffness is composed of intrinsic and reflex mechanisms that act and change together, so that nonlinear, mathematical models and specialized system identification techniques are necessary to estimate their relative contributions to overall joint stiffness. Quasi-stationary experiments have demonstrated that dynamic joint stiffness is heavily modulated by joint position and voluntary torque. Consequently, during movement, when joint position and torque change rapidly, dynamic joint stiffness will be Time-Varying (TV). This paper introduces a new method to quantify the TV intrinsic and reflex components of dynamic joint stiffness during movement. The algorithm combines ensemble and deterministic approaches for estimation of TV systems; and uses a TV, parallel-cascade, nonlinear system identification technique to separate overall dynamic joint stiffness into intrinsic and reflex components from position and torque records. Simulation studies of a stiffness model, whose parameters varied with time as is expected during walking, demonstrated that the new algorithm accurately tracked the changes in dynamic joint stiffness using as little as 40 gait cycles. The method was also used to estimate the intrinsic and reflex dynamic ankle stiffness from an experiment with a healthy subject during which ankle movements were imposed while the subject maintained a constant muscle contraction. The method identified TV stiffness model parameters that predicted the measured torque very well, accounting for more than 95% of its variance. Moreover, both intrinsic and reflex dynamic stiffness were heavily modulated through the movement in a manner that could not be predicted from quasi-stationary experiments. The new method provides the tool needed to explore the role of dynamic stiffness in the control of movement. PMID:28649196

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.

Brainstem mechanisms underlying the cough reflex and its regulation.

PubMed

Mutolo, Donatella

2017-09-01

Cough is a very important airway protective reflex. Cough-related inputs are conveyed to the caudal nucleus tractus solitarii (cNTS) that projects to the brainstem respiratory network. The latter is reconfigured to generate the cough motor pattern. A high degree of modulation is exerted on second-order neurons and the brainstem respiratory network by sensory inputs and higher brain areas. Two medullary structures proved to have key functions in cough production and to be strategic sites of action for centrally active drugs: the cNTS and the caudal ventral respiratory group (cVRG). Drugs microinjected into these medullary structures caused downregulation or upregulation of the cough reflex. The results suggest that inhibition and disinhibition are prominent regulatory mechanisms of this reflex and that both the cNTS and the cVRG are essential in the generation of the entire cough motor pattern. Studies on the basic neural mechanisms subserving the cough reflex may provide hints for novel therapeutic approaches. Different proposals for further investigations are advanced. Copyright © 2017 Elsevier B.V. All rights reserved.

Reflex cardioventilatory responses to hypoxia in the flathead gray mullet (Mugil cephalus) and their behavioral modulation by perceived threat of predation and water turbidity.

PubMed

Shingles, A; McKenzie, D J; Claireaux, G; Domenici, P

2005-01-01

In hypoxia, gray mullet surface to ventilate well-oxygenated water in contact with air, an adaptive response known as aquatic surface respiration (ASR). Reflex control of ASR and its behavioral modulation by perceived threat of aerial predation and turbid water were studied on mullet in a partly sheltered aquarium with free surface access. Injections of sodium cyanide (NaCN) into either the bloodstream (internal) or ventilatory water stream (external) revealed that ASR, hypoxic bradycardia, and branchial hyperventilation were stimulated by chemoreceptors sensitive to both systemic and water O2 levels. Sight of a model avian predator elicited bradycardia and hypoventilation, a fear response that inhibited reflex hyperventilation following external NaCN. The time lag to initiation of ASR following NaCN increased, but response intensity (number of events, time at the surface) was unchanged. Mullet, however, modified their behavior to surface under shelter or near the aquarium edges. Turbid water abolished the fear response and effects of the predator on gill ventilation and timing of ASR following external NaCN, presumably because of reduced visibility. However, in turbidity, mullet consistently performed ASR under shelter or near the aquarium edges. These adaptive modulations of ASR behavior would allow mullet to retain advantages of the chemoreflex when threatened by avian predators or when unable to perceive potential threats in turbidity.

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.

Age-related influence of vision and proprioception on Ia presynaptic inhibition in soleus muscle during upright stance

PubMed Central

Baudry, Stéphane; Duchateau, Jacques

2012-01-01

This study investigated the modulation of Ia afferent input in young and elderly adults during quiet upright stance in normal and modified visual and proprioceptive conditions. The surface EMG of leg muscles, recruitment curve of the soleus (SOL) Hoffmann (H) reflex and presynaptic inhibition of Ia afferents from SOL, assessed with the D1 inhibition and single motor unit methods, were recorded when young and elderly adults stood with eyes open or closed on two surfaces (rigid vs. foam) placed over a force platform. The results showed that elderly adults had a longer path length for the centre of pressure and larger antero-posterior body sway across balance conditions (P < 0.05). Muscle EMG activities were greater in elderly compared with young adults (P < 0.05), whereas the Hmax expressed as a percentage of the Hmax was lower (P = 0.048) in elderly (38 ± 16%) than young adults (58 ± 16%). The conditioned H reflex/test H reflex ratio (D1 inhibition method) increased with eye closure and when standing on foam (P < 0.05), with greater increases for elderly adults (P = 0.019). These changes were accompanied by a reduced peak motor unit discharge probability when standing on rigid and foam surfaces (P ≤ 0.001), with a greater effect for elderly adults (P = 0.026). Based on these latter results, the increased conditioned H reflex/test H reflex ratio in similar sensory conditions is likely to reflect occlusion at the level of presynaptic inhibitory interneurones. Together, these findings indicate that elderly adults exhibit greater modulation of Ia presynaptic inhibition than young adults with variation in the sensory conditions during upright standing. PMID:22946095

The role of capsaicin-sensitive muscle afferents in fatigue-induced modulation of the monosynaptic reflex in the rat.

PubMed

Pettorossi, V E; Della Torre, G; Bortolami, R; Brunetti, O

1999-03-01

1. The role of group III and IV afferent fibres of the lateral gastrocnemious muscle (LG) in modulating the homonymous monosynaptic reflex was investigated during muscle fatigue in spinalized rats. 2. Muscle fatigue was induced by a series of increasing tetanic electrical stimuli (85 Hz, 600 ms) delivered to the LG muscle nerve. Series consisted of increasing train numbers from 1 to 60. 3. Potentials from the spinal cord LG motor pool and from the ventral root were recorded in response to proprioceptive afferent stimulation and analysed before and during tetanic muscle activations. Both the pre- and postsynaptic waves showed an initial enhancement and, after a '12-train' series, an increasing inhibition. 4. The enhancement of the responses to muscle fatiguing stimulation disappeared after L3-L6 dorsal root section, while a partial reflex inhibition was still present. Conversely, after section of the corresponding ventral root, there was only a reduction in the inhibitory effect. 5. The monosynaptic reflex was also studied in animals in which a large number of group III and IV muscle afferents were eliminated by injecting capsaicin (10 mM) into the LG muscle. As a result of capsaicin treatment, the fatigue-induced inhibition of the pre- and postsynaptic waves disappeared, while the response enhancement remained. 6. We concluded that the monosynaptic reflex inhibition, but not the enhancement, was mediated by those group III and IV muscle afferents that are sensitive to the toxic action of capsaicin. The afferents that are responsible for the response enhancement enter the spinal cord through the dorsal root, while those responsible for the inhibition enter the spinal cord through both the ventral and dorsal roots.

The role of capsaicin-sensitive muscle afferents in fatigue-induced modulation of the monosynaptic reflex in the rat

PubMed Central

Pettorossi, V E; Torre, G Della; Bortolami, R; Brunetti, O

1999-01-01

The role of group III and IV afferent fibres of the lateral gastrocnemious muscle (LG) in modulating the homonymous monosynaptic reflex was investigated during muscle fatigue in spinalized rats. Muscle fatigue was induced by a series of increasing tetanic electrical stimuli (85 Hz, 600 ms) delivered to the LG muscle nerve. Series consisted of increasing train numbers from 1 to 60. Potentials from the spinal cord LG motor pool and from the ventral root were recorded in response to proprioceptive afferent stimulation and analysed before and during tetanic muscle activations. Both the pre- and postsynaptic waves showed an initial enhancement and, after a ‘12-train’ series, an increasing inhibition. The enhancement of the responses to muscle fatiguing stimulation disappeared after L3-L6 dorsal root section, while a partial reflex inhibition was still present. Conversely, after section of the corresponding ventral root, there was only a reduction in the inhibitory effect. The monosynaptic reflex was also studied in animals in which a large number of group III and IV muscle afferents were eliminated by injecting capsaicin (10 mM) into the LG muscle. As a result of capsaicin treatment, the fatigue-induced inhibition of the pre- and postsynaptic waves disappeared, while the response enhancement remained. We concluded that the monosynaptic reflex inhibition, but not the enhancement, was mediated by those group III and IV muscle afferents that are sensitive to the toxic action of capsaicin. The afferents that are responsible for the response enhancement enter the spinal cord through the dorsal root, while those responsible for the inhibition enter the spinal cord through both the ventral and dorsal roots. PMID:10050025

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

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.

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.

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.

Endomorphins potentiate acid-sensing ion channel currents and enhance the lactic acid-mediated increase in arterial blood pressure: effects amplified in hindlimb ischaemia.

PubMed

Farrag, Mohamed; Drobish, Julie K; Puhl, Henry L; Kim, Joyce S; Herold, Paul B; Kaufman, Marc P; Ruiz-Velasco, Victor

2017-12-01

Chronic limb ischaemia, characterized by inflammatory mediator release and a low extracellular pH, leads to acid-sensing ion channel (ASIC) activation and reflexively increases mean arterial pressure; endomorphin release is also increased under inflammatory conditions. We examined the modulation of ASIC currents by endomorphins in sensory neurons from rats with freely perfused and ligated femoral arteries: peripheral artery disease (PAD) model. Endomorphins potentiated sustained ASIC currents in both groups of dorsal root ganglion neurons, independent of mu opioid receptor stimulation or G protein activation. Intra-arterial administration of lactic acid (to simulate exercising muscle and evoke a pressor reflex), endomorphin-2 and naloxone resulted in a significantly greater pressor response than lactic acid alone, while administration of APETx2 inhibited endomorphin's enhancing effect in both groups. These results suggest a novel role for endomorphins in modulating ASIC function to effect lactic acid-mediated reflex increase in arterial pressure in patients with PAD. Chronic muscle ischaemia leads to accumulation of lactic acid and other inflammatory mediators with a subsequent drop in interstitial pH. Acid-sensing ion channels (ASICs), expressed in thin muscle afferents, sense the decrease in pH and evoke a pressor reflex known to increase mean arterial pressure. The naturally occurring endomorphins are also released by primary afferents under ischaemic conditions. We examined whether high affinity mu opioid receptor (MOR) agonists, endomorphin-1 (E-1) and -2 (E-2), modulate ASIC currents and the lactic acid-mediated pressor reflex. In rat dorsal root ganglion (DRG) neurons, exposure to E-2 in acidic solutions significantly potentiated ASIC currents when compared to acidic solutions alone. The potentiation was significantly greater in DRG neurons isolated from rats whose femoral arteries were ligated for 72 h. Sustained ASIC current potentiation was also observed in neurons pretreated with pertussis toxin, an uncoupler of G proteins and MOR. The endomorphin-mediated potentiation was a result of a leftward shift of the activation curve to higher pH values and a slight shift of the inactivation curve to lower pH values. Intra-arterial co-administration of lactic acid and E-2 led to a significantly greater pressor reflex than lactic acid alone in the presence of naloxone. Finally, E-2 effects were inhibited by pretreatment with the ASIC3 blocker APETx2 and enhanced by pretreatment with the ASIC1a blocker psalmotoxin-1. These findings have uncovered a novel role of endomorphins by which the opioids can enhance the lactic acid-mediated reflex increase in arterial pressure that is MOR stimulation-independent and APETx2-sensitive. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

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.

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.

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.

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

The application of conditioning paradigms in the measurement of pain

PubMed Central

Li, Jun-Xu

2013-01-01

Pain is a private experience that involves both sensory and emotional components. Animal studies of pain can only be inferred by their responses, and therefore the measurement of reflexive responses dominate the pain literature for nearly a century. It has been argued that although reflexive responses are important to unveil the sensory nature of pain in organisms, pain affect is equally important but largely ignored in pain studies primarily due to the lack of validated animal models. One strategy to begin to understand pain affect is to use conditioning principles to indirectly reveal the affective condition of pain. This review critically analyzed several procedures that are thought to measure affective learning of pain. The procedures regarding the current knowledge, the applications, and their advantages and disadvantages in pain research are discussed. It is proposed that these procedures should be combined with traditional reflex-based pain measurements in future studies of pain, which could greatly benefit both the understanding of neural underpinnings of pain and preclinical assessment of novel analgesics. PMID:23500202

An Intelligent Computerized Stretch Reflex Measurement System For Clinical And Investigative Neurology

NASA Astrophysics Data System (ADS)

Flanagan, P. M.; Chutkow, J. G.; Riggs, M. T.; Cristiano, V. D.

1987-05-01

We describe the design of a reliable, user-friendly preprototype system for quantifying the tendon stretch reflexes in humans and large mammals. A hand-held, instrumented reflex gun, the impactor of which contains a single force sensor, interfaces with a computer. The resulting test system can deliver sequences of reproducible stimuli at graded intensities and adjustable durations to a muscle's tendon ("tendon taps"), measure the impacting force of each tap, and record the subsequent reflex muscle contraction from the same tendon -- all automatically. The parameters of the reflex muscle contraction include latency; mechanical threshold; and peak time, peak magnitude, and settling time. The results of clinical tests presented in this paper illustrate the system's potential usefulness in detecting neurologic dysfunction affecting the tendon stretch reflexes, in documenting the course of neurologic illnesses and their response to therapy, and in clinical and laboratory neurologic research.

EFFECTS OF PRENATAL EXPOSURE TO SODIUM ARSENITE ON MOTOR AND FOOD-MOTIVATED BEHAVIORS FROM BIRTH TO ADULTHOOD IN C57BL6/J MICE

PubMed Central

Markowski, Vincent P.; Reeve, Elizabeth A.; Onos, Kristen; Assadollahzadeh, Mina; McKay, Naomi

2012-01-01

Consumption of arsenic-contaminated drinking water is associated with numerous cancers and dermal and vascular diseases. Arsenic is also a potent nervous system toxicant and epidemiological studies indicate that intellectual functions in children are compromised following early developmental exposure. This study was designed to examine the effects of arsenic on a broad range of age-specific behaviors including basic sensory-motor responses in neonates, locomotor activity and grip strength in juveniles, and operant measures of learning and attention in adults. Pregnant C57BL6/J mice consumed drinking water containing 0, 8, 25, or 80 ppm sodium arsenite from the fourth day of gestation until birth. Arsenic produced a range of behavioral impairments in male and female offspring at each of the test ages. The most striking effects of arsenic were on the development of gait and other motor responses including acoustic startle, righting reflexes, and forelimb grip. These results suggest that developmental arsenic exposure can produce other behavioral impairments in children in addition to cognitive impairment. PMID:22266078

Paradox lost. The latah problem revisited.

PubMed

Kenny, M G

1983-03-01

This paper examines the validity of Dr. R. C. Simons' resolution (Simons, R. C. The resolution of the latah paradox. J. Nerv. Ment. Dis., 168: 195-206, 1980) of the so-called latah paradox. Latah, a Malay condition precipitated by sudden fright and involving compulsive obscenity and mimesis, was found to be closely related to local cultural values; yet a paradox seems to arise from the fact that analogous conditions are reported from unrelated cultures. Simons accounts for this by proposing that latah and its kindred states are based on the universal human startle reflex and that latah is merely a culture-specific exploitation of a neurophysiological potential shared by humans and other animals. It is here argued that the evidence does not support such a view and that latah-like conditions are best considered in terms of their local meaning within their societies of origin; ethnographic material from Siberia is examined as a case in point. It is concluded that the "latah paradox" is illusory and that biomedical approaches to the question have seriously misread the nature of the phenomenon and potentially distort clinical practice in relation to it.

Automated Operant Conditioning in the Mouse Home Cage.

PubMed

Francis, Nikolas A; Kanold, Patrick O

2017-01-01

Recent advances in neuroimaging and genetics have made mice an advantageous animal model for studying the neurophysiology of sensation, cognition, and locomotion. A key benefit of mice is that they provide a large population of test subjects for behavioral screening. Reflex-based assays of hearing in mice, such as the widely used acoustic startle response, are less accurate than operant conditioning in measuring auditory processing. To date, however, there are few cost-effective options for scalable operant conditioning systems. Here, we describe a new system for automated operant conditioning, the Psibox. It is assembled from low cost parts, designed to fit within typical commercial wire-top cages, and allows large numbers of mice to train independently in their home cages on positive reinforcement tasks. We found that groups of mice trained together learned to accurately detect sounds within 2 weeks of training. In addition, individual mice isolated from groups also showed good task performance. The Psibox facilitates high-throughput testing of sensory, motor, and cognitive skills in mice, and provides a readily available animal population for studies ranging from experience-dependent neural plasticity to rodent models of mental disorders.

Role of Corticotropin Releasing Factor in Anxiety Disorders: A Translational Research Perspective

PubMed Central

Risbrough, Victoria B.; Stein, Murray B.

2007-01-01

Anxiety disorders are a group of mental disorders that include generalized anxiety disorder (GAD), panic disorder, phobic disorders (e.g., specific phobias, agoraphobia, social phobia) and posttraumatic stress disorder (PTSD). Anxiety disorders are among the most common of all mental disorders and, when coupled with an awareness of the disability and reduced quality of life they convey, they must be recognized as a serious public health problem. Over 20 years of preclinical studies point to a role for the CRF system in anxiety and stress responses. Clinical studies have supported a model of CRF dysfunction in depression and more recently a potential contribution to specific anxiety disorders (i.e., panic disorder and PTSD). Much work remains in both the clinical and preclinical fields to inform models of CRF function and its contribution to anxiety. First, we will review the current findings of CRF and HPA axis abnormalities in anxiety disorders. Second, we will discuss startle reflex measures as a tool for translational research to determine the role of the CRF system in development and maintenance of clinical anxiety. PMID:16870185

Capsaicin-sensitive muscle afferents modulate the monosynaptic reflex in response to muscle ischemia and fatigue in the rat.

PubMed

Della Torre, G; Brunetti, O; Pettorossi, V E

2002-01-01

The role of muscle ischemia and fatigue in modulating the monosynaptic reflex was investigated in decerebrate and spinalized rats. Field potentials and fast motoneuron single units in the lateral gastrocnemious (LG) motor pool were evoked by dorsal root stimulation. Muscle ischemia was induced by occluding the LG vascular supply and muscle fatigue by prolonged tetanic electrical stimulation of the LG motor nerve. Under muscle ischemia the monosynaptic reflex was facilitated since the size of the early and late waves of the field potential and the excitability of the motoneuron units increased. This effect was abolished after L3-L6 dorsal rhizotomy, but it was unaffected after L3-L6 ventral rhizotomy. By contrast, the monosynaptic reflex was inhibited by muscle fatiguing stimulation, and this effect did not fully depend on the integrity of the dorsal root. However, when ischemia was combined with repetitive tetanic muscle stimulation the inhibitory effect of fatigue was significantly enhanced. Both the ischemia and fatigue effects were abolished by capsaicin injected into the LG muscle at a dose that blocked a large number of group III and IV muscle afferents. We concluded that muscle ischemia and fatigue activate different groups of muscle afferents that are both sensitive to capsaicin, but enter the spinal cord through different roots. They are responsible for opposite effects, when given separately: facilitation during ischemia and inhibition during fatigue; however, in combination, ischemia enhances the responsiveness of the afferent fibres to fatigue.

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

Hypothyroidism impairs somatovisceral reflexes involved in micturition of female rabbits.

PubMed

Sánchez-García, Octavio; López-Juárez, Rhode; Rodríguez-Castelán, Julia; Corona-Quintanilla, Dora L; Martínez-Gómez, Margarita; Cuevas-Romero, Estela; Castelán, Francisco

2018-04-17

To determine the impact of hypothyroidism on the bladder and urethral functions as well as in the activation of the pubococcygeous (Pcm) and bulbospongiosus (Bsm) during micturition. Age-matched control and methimazole-induced hypothyroid female rabbits were used to simultaneously record cystometrograms, urethral pressure, and the reflex activation of Pcm and Bsm during the induced micturition. Urodynamic and urethral variables were measured. Activation or no activation of the Pcm and Bsm during the storage and voiding phases of micturition were categorized as 1 or 0. Significant differences (P ≤ 0.05) between control and hypothyroid groups were determined with unpaired Student-t or Mann-Whitney tests. One-month induced hypothyroidism increased the residual volume and threshold pressure while the opposite was true for the voided volume, maximal pressure, and voiding efficiency. Urethral pressure was also affected as supported by a notorious augmentation of the urethral resistance, among other changes in the rest of measured variables. Hypothyroidism also affected the reflex activation of the Pcm in the voiding phase of micturition. Our findings demonstrate hypothyroidism impairs the bladder and, urethral functions, and reflex activation of Pcm and Bsm affecting the micturition in female rabbits. © 2018 Wiley Periodicals, Inc.

Human H-reflexes are smaller in difficult beam walking than in normal treadmill walking.

PubMed

Llewellyn, M; Yang, J F; Prochazka, A

1990-01-01

Hoffman (H) reflexes were elicited from the soleus (SOL) muscle while subjects walked on a treadmill and on a narrow beam (3.5 cm wide, raised 34 cm from the floor). The speed of walking on the treadmill was selected for each subject to match the background activation level of their SOL muscle during beam walking. The normal reciprocal activation pattern of the tibialis anterior and SOL muscles in treadmill walking was replaced by a pattern dominated by co-contraction on the beam. In addition, the step cycle duration was more variable and the time spent in the swing phase was reduced on the beam. The H-reflexes were highly modulated in both tasks, the amplitude being high in the stance phase and low in the swing phase. The H-reflex amplitude was on average 40% lower during beam walking than treadmill walking. The relationship between the H-reflex amplitude and the SOL EMG level was quantified by a regression line relating the two variables. The slope of this line was on average 41% lower in beam walking than treadmill walking. The lower H-reflex gain observed in this study and the high level of fusimotor drive observed in cats performing similar tasks suggest that the two mechanisms which control the excitability of this reflex pathway (i.e. fusimotor action and control of transmission at the muscle spindle to moto-neuron synapse) may be controlled independently.

Task-dependent changes of corticospinal excitability during observation and motor imagery of balance tasks.

PubMed

Mouthon, A; Ruffieux, J; Wälchli, M; Keller, M; Taube, W

2015-09-10

Non-physical balance training has demonstrated to be efficient to improve postural control in young people. However, little is known about the potential to increase corticospinal excitability by mental simulation in lower leg muscles. Mental simulation of isolated, voluntary contractions of limb muscles increase corticospinal excitability but more automated tasks like walking seem to have no or only minor effects on motor-evoked potentials (MEPs) evoked by transcranial magnetic stimulation (TMS). This may be related to the way of performing the mental simulation or the task itself. Therefore, the present study aimed to clarify how corticospinal excitability is modulated during AO+MI, MI and action observation (AO) of balance tasks. For this purpose, MEPs and H-reflexes were elicited during three different mental simulations (a) AO+MI, (b) MI and (c) passive AO. For each condition, two balance tasks were evaluated: (1) quiet upright stance (static) and (2) compensating a medio-lateral perturbation while standing on a free-swinging platform (dynamic). AO+MI resulted in the largest facilitation of MEPs followed by MI and passive AO. MEP facilitation was significantly larger in the dynamic perturbation than in the static standing task. Interestingly, passive observation resulted in hardly any facilitation independent of the task. H-reflex amplitudes were not modulated. The current results demonstrate that corticospinal excitability during mental simulation of balance tasks is influenced by both the type of mental simulation and the task difficulty. As H-reflexes and background EMG were not modulated, it may be argued that changes in excitability of the primary motor cortex were responsible for the MEP modulation. From a functional point of view, our findings suggest best training/rehabilitation effects when combining MI with AO during challenging postural tasks. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Involvement of α2-adrenoceptors in inhibitory and facilitatory pain modulation processes.

PubMed

Vo, L; Drummond, P D

2016-03-01

In healthy humans, high-frequency electrical stimulation (HFS) of the forearm not only produces hyperalgesia at the site of stimulation but also reduces sensitivity to pressure-pain on the ipsilateral side of the forehead. In addition, HFS augments the ipsilateral trigeminal nociceptive blink reflex and intensifies the ipsilateral component of conditioned pain modulation. The aim of this study was to determine whether α2-adrenoceptors mediate these ipsilateral nociceptive influences. The α2-adrenoceptor antagonist yohimbine was administered to 22 participants in a double-blind, placebo-controlled crossover study. In each session, thermal and mechanical sensitivity in the forearms and forehead was assessed before and after HFS. In addition, the combined effect of HFS and yohimbine on the nociceptive blink reflex and on conditioned pain modulation was explored. In this paradigm, the conditioning stimulus was cold pain in the ipsilateral or contralateral temple, and the test stimulus was electrically evoked pain in the forearm. Blood pressure and electrodermal activity increased for several hours after yohimbine administration, consistent with blockade of central α2-adrenoceptors. Yohimbine not only augmented the nociceptive blink reflex ipsilateral to HFS but also intensified the inhibitory influence of ipsilateral temple cooling on electrically evoked pain at the HFS-treated site in the forearm. Yohimbine had no consistent effect on primary or secondary hyperalgesia in the forearm or on pressure-pain in the ipsilateral forehead. These findings imply involvement of α2-adrenoceptors both in ipsilateral antinociceptive and pronociceptive pain modulation processes. However, a mechanism not involving α2-adrenoceptors appears to mediate analgesia in the ipsilateral forehead after HFS. © 2015 European Pain Federation - EFIC®

[The role of the somatosensory cortex in the development of reflex analgesia].

PubMed

Kukushkin, M L; Reshetniak, V K; Durinian, R A

1986-06-01

The effects of reflex stimulation on the changes of nociception thresholds in animals before and after ablation of the somatosensory cortex were studied in behavioural experiments on adult cats. Electroacupuncture stimulation (EAP) was shown to increase nociception thresholds at all levels of the conventional scale. The ablation of both the first (S1) and the second (S2) somatosensory cortex led to EAP inefficiency at the side opposite to the ablation. Partial lesion of the lateral and suprasylvian gyri, used as control, did not affect the efficiency of reflex analgesia. It is concluded that somatosensory areas of the cortex, especially 2, are involved in reflex analgesia.

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.

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

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.

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

METHOD FOR STABILIZING KLYSTRONS

DOEpatents

Magnuson, D.W.; Smith, D.F.

1959-04-14

High-frequency oscillators for the generation of microwaves, particularly a system for stabilizing frequency-modulated klystron oscillators of the reflex type, are described. The system takos advantage of the fact that a change in oscillator frequency will alter the normal phase displacement between the cavity and its modulator, creating an error voltage which is utilized to regulate the frequency of the oscillator and stabilize it.

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

Neuromuscular properties of different spastic human joints vary systematically.

PubMed

Mirbagheri, M M; Settle, K

2010-01-01

We quantified the mechanical abnormalities of the spastic wrist in chronic stroke survivors, and determined whether these findings were representative of those recorded at the elbow and ankle joints. System identification techniques were used to characterize the mechanical abnormalities of these joints and to identify the contribution of intrinsic and reflex stiffness to these abnormalities. Modulation of intrinsic and reflex stiffness with the joint angle was studied by applying PRBS perturbations to the joints at different joint angles over the range of motion. Age-matched healthy subjects were used as control.

Anatomically remote muscle contraction facilitates patellar tendon reflex reinforcement while mental activity does not: a within-participants experimental trial.

PubMed

Passmore, Steven R; Bruno, Paul A

2012-09-07

The Jendrassik maneuver (JM) is a remote facilitation muscular contraction shown to affect amplitude and temporal components of the human stretch reflex. Conflicting theoretical models exist regarding the neurological mechanism related to its ability to reinforce reflex parameters. One mechanism involves the gamma motoneurons of the fusimotor system, which are subject to both physical and mental activity. A second mechanism describes reduced alpha motoneuron presynaptic inhibition, which is not subject to mental activity. In the current study, we determined if mental activity could be used to create a reflex facilitation comparable to a remote muscle contraction. Using a within-participants design, we investigated the relative effect of the JM and a successfully employed mental task (Stroop task) on the amplitude and temporal components of the patellar tendon reflex. We found that the addition of mental activity had no influence on the patellar tendon reflex parameters measured, while the JM provided facilitation (increased reflex amplitude, decreased total reflex time). The findings from this study support the view that the mechanism for the JM is a reduction in presynaptic inhibition of alpha motoneurons as it is influenced by physical and not mental activity.

Emotional Dissonance and Burnout: The Moderating Role of Team Reflexivity and Re-Evaluation.

PubMed

Andela, Marie; Truchot, Didier

2017-08-01

The aim of the present study was to better understand the relationship between emotional dissonance and burnout by exploring the buffering effects of re-evaluation and team reflexivity. The study was conducted with a sample of 445 nurses and healthcare assistants from a general hospital. Team reflexivity was evaluated with the validation of the French version of the team reflexivity scale (Facchin, Tschan, Gurtner, Cohen, & Dupuis, 2006). Burnout was measured with the MBI General Survey (Schaufeli, Leiter, Maslach, & Jackson, 1996). Emotional dissonance and re-evaluation were measured with the scale developed by Andela, Truchot, & Borteyrou (2015). With reference to Rimé's theoretical model (2009), we suggested that both dimensions of team reflexivity (task and social reflexivity) respond to both psychological necessities induced by dissonance (cognitive clarification and socio-affective necessities). Firstly, results indicated that emotional dissonance was related to burnout. Secondly, regression analysis confirmed the buffering role of re-evaluation and social reflexivity on the emotional exhaustion of emotional dissonance. Overall, results contribute to the literature by highlighting the moderating effect of re-evaluation and team reflexivity in analysing the relationship between emotional dissonance and burnout. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Multiple sites and actions of gabapentin-induced relief of ongoing experimental neuropathic pain.

PubMed

Bannister, Kirsty; Qu, Chaoling; Navratilova, Edita; Oyarzo, Janice; Xie, Jennifer Yanhua; King, Tamara; Dickenson, Anthony H; Porreca, Frank

2017-12-01

Gabapentin (GBP) is a first-line therapy for neuropathic pain, but its mechanisms and sites of action remain uncertain. We investigated GBP-induced modulation of neuropathic pain following spinal nerve ligation (SNL) in rats. Intravenous or intrathecal GBP reversed evoked mechanical hypersensitivity and produced conditioned place preference (CPP) and dopamine (DA) release in the nucleus accumbens (NAc) selectively in SNL rats. Spinal GBP also significantly inhibited dorsal horn wide-dynamic-range neuronal responses to a range of evoked stimuli in SNL rats. By contrast, GBP microinjected bilaterally into the rostral anterior cingulate cortex (rACC), produced CPP, and elicited NAc DA release selectively in SNL rats but did not reverse tactile allodynia and had marginal effects on wide-dynamic-range neuronal activity. Moreover, blockade of endogenous opioid signaling in the rACC prevented intravenous GBP-induced CPP and NAc DA release but failed to block its inhibition of tactile allodynia. Gabapentin, therefore, can potentially act to produce its pain relieving effects by (a) inhibition of injury-induced spinal neuronal excitability, evoked hypersensitivity, and ongoing pain and (b) selective supraspinal modulation of affective qualities of pain, without alteration of reflexive behaviors. Consistent with previous findings of pain relief from nonopioid analgesics, GBP requires engagement of rACC endogenous opioid circuits and downstream activation of mesolimbic reward circuits reflected in learned pain-motivated behaviors. These findings support the partial separation of sensory and affective dimensions of pain in this experimental model and suggest that modulation of affective-motivational qualities of pain may be the preferential mechanism of GBP's analgesic effects in patients.

Multiple sites and actions of gabapentin-induced relief of ongoing experimental neuropathic pain

PubMed Central

Bannister, Kirsty; Qu, Chaoling; Navratilova, Edita; Oyarzo, Janice; Xie, Jennifer Yanhua; King, Tamara; Dickenson, Anthony H.; Porreca, Frank

2017-01-01

Gabapentin is a first-line therapy for neuropathic pain but its mechanisms and sites of action remain uncertain. We investigated gabapentin-induced modulation of neuropathic pain following spinal nerve ligation (SNL) in rats. Intravenous or intrathecal gabapentin reversed evoked mechanical hypersensitivity, produced conditioned place preference (CPP) and dopamine release in the nucleus accumbens (NAc) selectively in SNL rats. Spinal gabapentin also significantly inhibited dorsal horn wide dynamic range (WDR) neuronal responses to a range of evoked stimuli in SNL rats. In contrast, gabapentin microinjected bilaterally into the rostral anterior cingulate cortex (rACC), produced CPP and elicited NAc dopamine release selectively in SNL rats but did not reverse tactile allodynia and had marginal effects on WDR neuronal activity. Moreover, blockade of endogenous opioid signaling in the rACC prevented intravenous gabapentin-induced CPP and NAc dopamine release but failed to block its inhibition of tactile allodynia. Gabapentin therefore can potentially act to produce its pain relieving effects by (a) inhibition of injury-induced spinal neuronal excitability, evoked hypersensitivity and ongoing pain and (b) selective supraspinal modulation of affective qualities of pain, without alteration of reflexive behaviors. Consistent with previous findings of pain relief from non-opioid analgesics, gabapentin requires engagement of rACC endogenous opioid circuits and downstream activation of mesolimbic reward circuits reflected in learned pain motivated behaviors. These findings support the partial separation of sensory and affective dimensions of pain in this experimental model and suggest that modulation of affective-motivational qualities of pain may be the preferential mechanism of gabapentin’s analgesic effects in patients. PMID:28832395

Pre- and post-alpha motoneuronal control of the soleus H-reflex during sinusoidal hip movements in human spinal cord injury

PubMed Central

Knikou, Maria; Chaudhuri, Debjani; Kay, Elizabeth; Schmit, Brian D.

2006-01-01

The aim of this study was to establish the contribution of hip-mediated sensory feedback to spinal interneuronal circuits during dynamic conditions in people with incomplete spinal cord injury (SCI). Specifically, we investigated the effects of synergistic and antagonistic group I afferents on the soleus H-reflex during imposed sinusoidal hip movements. The soleus H-reflex was conditioned by stimulating the common peroneal nerve (CPN) at short (2, 3, and 4 ms) and long (80, 100, and 120 ms) conditioning test (C-T) intervals to assess the reciprocal and pre-synaptic inhibition of the soleus H-reflex, respectively. The soleus H-reflex was also conditioned by medial gastrocnemius (MG) nerve stimulation at C-T intervals ranging from 4 to 7 ms to assess changes in autogenic Ib inhibition during hip movement. Sinusoidal hip movements were imposed to the right hip joint at 0.2 Hz by the Biodex system while subjects were supine. The effects of sinusoidal hip movement on five leg muscles along with hip, knee, and ankle joint torques were also established during sensorimotor conditioning of the reflex. Phase-dependent modulation of antagonistic and synergistic muscle afferents was present during hip movement, with the reciprocal, pre-synaptic, and Ib inhibition to be significantly reduced during hip extension and reinforced during hip flexion. Reflexive muscle and joint torque responses – induced by the hip movement – were entrained to specific phases of hip movement. This study provides evidence that hip-mediated input acts as a controlling signal of pre- and post-alpha motoneuronal control of the soleus H-reflex. The expression of these spinal interneuronal circuits during imposed sinusoidal hip movements is discussed with respect to motor recovery in humans after SCI. PMID:16782072

Glycine Receptors Containing α2 or α3 Subunits Regulate Specific Ethanol-Mediated Behaviors

PubMed Central

Blednov, Yuri A.; Benavidez, Jillian M.; Black, Mendy; Leiter, Courtney R.; Osterndorff-Kahanek, Elizabeth

2015-01-01

Glycine receptors (GlyRs) are broadly expressed in the central nervous system. Ethanol enhances the function of brain GlyRs, and the GlyRα1 subunit is associated with some of the behavioral actions of ethanol, such as loss of righting reflex. The in vivo role of GlyRα2 and α3 subunits in alcohol responses has not been characterized despite high expression levels in the nucleus accumbens and amygdala, areas that are important for the rewarding properties of drugs of abuse. We used an extensive panel of behavioral tests to examine ethanol actions in mice lacking Glra2 (the gene encoding the glycine receptor alpha 2 subunit) or Glra3 (the gene encoding the glycine receptor alpha 3 subunit). Deletion of Glra2 or Glra3 alters specific ethanol-induced behaviors. Glra2 knockout mice demonstrate reduced ethanol intake and preference in the 24-hour two-bottle choice test and increased initial aversive responses to ethanol and lithium chloride. In contrast, Glra3 knockout mice show increased ethanol intake and preference in the 24-hour intermittent access test and increased development of conditioned taste aversion to ethanol. Mutants and wild-type mice consumed similar amounts of ethanol in the limited access drinking in the dark test. Other ethanol effects, such as anxiolysis, motor incoordination, loss of righting reflex, and acoustic startle response, were not altered in the mutants. The behavioral changes in mice lacking GlyRα2 or α3 subunits were distinct from effects previously observed in mice with knock-in mutations in the α1 subunit. We provide evidence that GlyRα2 and α3 subunits may regulate ethanol consumption and the aversive response to ethanol. PMID:25678534

Recording Field Potentials From Zebrafish Larvae During Escape Responses

PubMed Central

Monesson-Olson, Bryan D.; Troconis, Eileen L.; Trapani, Josef G.

2014-01-01

Among vertebrates, startle responses are a ubiquitous method for alerting, and avoiding or escaping from alarming or dangerous stimuli. In zebrafish larvae, fast escape behavior is easily evoked through either acoustic or tactile stimuli. For example, a light touch to the head will excite trigeminal neurons that in turn excite a large reticulospinal neuron in the hindbrain called the Mauthner cell (M-cell). The M-cell action potential then travels down the contralateral trunk of the larva exciting motoneurons, which subsequently excite the entire axial musculature, producing a large amplitude body bend away from the source of the stimulus. This body conformation is known as the “C-bend” due to the shape of the larva during the behavior. As a result of the semi-synchronized activation of the M-cell, the population of motor neurons, and the axial trunk muscles, a large field potential is generated and can be recorded from free-swimming or fixed-position larvae. Undergraduate laboratories that record field potentials during escape responses in larval zebrafish are relatively simple to setup and allow students to observe and study the escape reflex circuit. Furthermore, by testing hypotheses, analyzing data and writing journal-style laboratory reports, students have multiple opportunities to learn about many neuroscience topics including vertebrate reflexes; sensory transduction; synaptic-, neuro-, and muscle-physiology; the M-cell mediated escape response; and the zebrafish as a model organism. Here, we detail the equipment, software, and recording setup necessary to observe field potentials in an undergraduate teaching lab. Additionally, we discuss potential advanced laboratory exercises and pedagogical outcomes. Finally, we note possible low-cost alternatives for recording field potentials. PMID:25565920

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

PubMed

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

2017-10-15

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

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

PubMed

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

2017-12-01

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

The application of conditioning paradigms in the measurement of pain.

PubMed

Li, Jun-Xu

2013-09-15

Pain is a private experience that involves both sensory and emotional components. Animal studies of pain can only be inferred by their responses, and therefore the measurement of reflexive responses dominates the pain literature for nearly a century. It has been argued that although reflexive responses are important to unveil the sensory nature of pain in organisms, pain affect is equally important but largely ignored in pain studies primarily due to the lack of validated animal models. One strategy to begin to understand pain affect is to use conditioning principles to indirectly reveal the affective condition of pain. This review critically analyzed several procedures that are thought to measure affective learning of pain. The procedures regarding the current knowledge, the applications, and their advantages and disadvantages in pain research are discussed. It is proposed that these procedures should be combined with traditional reflex-based pain measurements in future studies of pain, which could greatly benefit both the understanding of neural underpinnings of pain and preclinical assessment of novel analgesics. © 2013 Elsevier B.V. All rights reserved.

Basal μ-opioid receptor availability in the amygdala predicts the inhibition of pain-related brain activity during heterotopic noxious counter-stimulation.

PubMed

Piché, Mathieu; Watanabe, Nobuhiro; Sakata, Muneyuki; Oda, Keiichi; Toyohara, Jun; Ishii, Kenji; Ishiwata, Kiichi; Hotta, Harumi

2014-01-01

The aim of this study was to investigate the association between the magnitude of anti-nociceptive effects induced by heterotopic noxious counter-stimulation (HNCS) and the basal μ-opioid receptor availability in the amygdala. In 8 healthy volunteers (4 females and 4 males), transcutaneous electrical stimulation was applied to the right sural nerve to produce the nociceptive flexion reflex (RIII-reflex), moderate pain, and scalp somatosensory evoked potentials (SEPs). Immersion of the left hand in cold water for 20min was used as HNCS. In a separate session, basal μ-opioid receptor availability was measured using positron emission tomography with the radiotracer [(11)C]carfentanil. HNCS produced a reduction of the P260 amplitude (p<0.05), a late component of SEP that reflects activity in the anterior cingulate cortex. This reduction was associated with higher basal μ-opioid receptor availability in the amygdala on the right (R(2)=0.55, p=0.03) with a similar trend on the left (R(2)=0.24, p=0.22). Besides, HNCS did not induce significant changes in pain and RIII-reflex amplitude (p>0.05). These results suggest that activation of μ-opioid receptors in the amygdala may contribute to the anti-nociceptive effects of HNCS. The lack of RIII-reflex modulation further suggests that μ-opioid receptor activation in the amygdala contributes to decrease pain-related brain activity through a cerebral mechanism independent of descending modulation. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Parasympathetic reflex vasodilation in the cerebral hemodynamics of rats.

PubMed

Ishii, Hisayoshi; Sato, Toshiya; Izumi, Hiroshi

2014-04-01

We investigated the role of parasympathetic reflex vasodilation in the regulation of the cerebral hemodynamics, and whether GABAA receptors modulate the response. We examined the effects of activation of the parasympathetic fibers through trigeminal afferent inputs on blood flow in the internal carotid artery (ICABF) and the cerebral blood vessels (rCBF) in parietal cortex in urethane-anesthetized rats. Electrical stimulation of the central cut end of the lingual nerve (LN) elicited intensity- and frequency-dependent increases in ICABF that were independent of changes in external carotid artery blood flow. Increases in ICABF were elicited by LN stimulation regardless of the presence or absence of sympathetic innervation. The ICABF increases evoked by LN stimulation were almost abolished by the intravenous administration of hexamethonium (10 mg kg(-1)) and were reduced significantly by atropine administration (0.1 mg kg(-1)). Although the LN stimulation alone had no significant effect on rCBF, LN stimulation in combination with a blocker of the GABAA receptor pentylenetetrazole increased the rCBF markedly. This increase in rCBF was reduced significantly by the administration of hexamethonium and atropine. These observations indicate that the increases in both ICABF and rCBF are evoked by parasympathetic activation via the trigeminal-mediated reflex. The rCBF increase evoked by LN stimulation is thought to be limited by the GABAA receptors in the central nervous system. These results suggest that the parasympathetic reflex vasodilation and its modulation mediated by GABA receptors within synaptic transmission in the brainstem are involved in the regulation of the cerebral hemodynamics during trigeminal afferent inputs.

Activity of masticatory muscles in subjects with different orofacial pain conditions.

PubMed

Bodéré, Céline; Téa, Say Hack; Giroux-Metges, Marie Agnes; Woda, Alain

2005-07-01

The existence of a pathophysiological link between tonic muscle activity and chronic muscle pain is still being debated. The purpose of this retrospective, controlled study was to evaluate the electromyographic (EMG) activity of masticatory muscles in subjects with different orofacial pain conditions. The temporal and masseter EMG activity at rest and the masseteric reflex were recorded in two groups of patients with either myofascial pain (n=33) or neuropathic pain (n=20), one group of non-pain patients with disc derangement disorders (n=27) and one control group of healthy, asymptomatic subjects (n=32). The EMG activities of both muscles at rest were significantly higher in the pain patient groups compared to the asymptomatic control group. There was no significant difference between the disc derangement disorder group and the control group. The masseteric reflex amplitude was reduced in all patient groups when compared with the control group. In pain patient groups, the increased EMG activity at rest and the reduction of the masseteric reflex amplitude were equally distributed in the pain and non-pain sides. In addition, subjects presenting with bilateral pain showed higher EMG activity at rest than those with unilateral pain. These results suggested that the modulation of muscle activity was not the direct consequence of a peripheral nociceptive mechanism and seemed to indicate that a central mechanism was at work. The contrast between the increased EMG activity at rest and the reduction of the masseteric reflex amplitude may reflect modulations of motoneurones that differed in tonic versus phasic conditions in chronic pain patients.

Effect of afferent feedback and central motor commands on soleus H-reflex suppression during arm cycling.

PubMed

Hundza, S R; de Ruiter, Geoff C; Klimstra, M; Zehr, E Paul

2012-12-01

Suppression of soleus H-reflex amplitude in stationary legs is seen during rhythmic arm cycling. We examined the influence of various arm-cycling parameters on this interlimb reflex modulation to determine the origin of the effect. We previously showed the suppression to be graded with the frequency of arm cycling but not largely influenced by changes in peripheral input associated with crank length. Here, we more explicitly explored the contribution of afferent feedback related to arm movement on the soleus H-reflex suppression. We explored the influence of load and rate of muscle stretch by manipulating crank-load and arm-muscle vibration during arm cycling. Furthermore, internally driven ("Active") and externally driven ("Passive") arm cycling was compared. Soleus H-reflexes were evoked with tibial nerve stimulation during stationary control and rhythmic arm-cycling conditions, including: 1) six different loads; 2) with and without vibration to arm muscles; and 3) Active and Passive conditions. No significant differences were seen in the level of suppression between the different crank loads or between conditions with and without arm-muscle vibration. Furthermore, in contrast to the clear effect seen during active cycling, passive arm cycling did not significantly suppress the soleus H-reflex amplitude. Current results, in conjunction with previous findings, suggest that the afferent feedback examined in these studies is not the primary source responsible for soleus H-reflex suppression. Instead, it appears that central motor commands (supraspinal or spinal in origin) associated with frequency of arm cycling are relatively more dominant sources.

Effect of transcranial direct current stimulation on vestibular-ocular and vestibulo-perceptual thresholds.

PubMed

Kyriakareli, Artemis; Cousins, Sian; Pettorossi, Vito E; Bronstein, Adolfo M

2013-10-02

Transcranial direct current stimulation (tDCS) was used in 17 normal individuals to modulate vestibulo-ocular reflex (VOR) and self-motion perception rotational thresholds. The electrodes were applied over the temporoparietal junction bilaterally. Both vestibular nystagmic and perceptual thresholds were increased during as well as after tDCS stimulation. Body rotation was labeled as ipsilateral or contralateral to the anode side, but no difference was observed depending on the direction of rotation or hemisphere polarity. Threshold increase during tDCS was greater for VOR than for motion perception. 'Sham' stimulation had no effect on thresholds. We conclude that tDCS produces an immediate and sustained depression of cortical regions controlling VOR and movement perception. Temporoparietal areas appear to be involved in vestibular threshold modulation but the differential effects observed between VOR and perception suggest a partial dissociation between cortical processing of reflexive and perceptual responses.

Effects of Predictability of Load Magnitude on the Response of the Flexor Digitorum Superficialis to a Sudden Fingers Extension

PubMed Central

Aimola, Ettore; Valle, Maria Stella; Casabona, Antonino

2014-01-01

Muscle reflexes, evoked by opposing a sudden joint displacement, may be modulated by several factors associated with the features of the mechanical perturbation. We investigated the variations of muscle reflex response in relation to the predictability of load magnitude during a reactive grasping task. Subjects were instructed to flex the fingers 2–5 very quickly after a stretching was exerted by a handle pulled by loads of 750 or 1250 g. Two blocks of trials, one for each load (predictable condition), and one block of trials with a randomized distribution of the loads (unpredictable condition) were performed. Kinematic data were collected by an electrogoniometer attached to the middle phalanx of the digit III while the electromyography of the Flexor Digitorum Superficialis muscle was recorded by surface electrodes. For each trial we measured the kinematics of the finger angular rotation, the latency of muscle response and the level of muscle activation recorded below 50 ms (short-latency reflex), between 50 and 100 ms (long-latency reflex) and between 100 and 140 ms (initial portion of voluntary response) from the movement onset. We found that the latency of the muscle response lengthened from predictable (35.5±1.3 ms for 750 g and 35.5±2.5 ms for 1250 g) to unpredictable condition (43.6±1.3 ms for 750 g and 40.9±2.1 ms for 1250 g) and the level of muscle activation increased with load magnitude. The parallel increasing of muscle activation and load magnitude occurred within the window of the long-latency reflex during the predictable condition, and later, at the earliest portion of the voluntary response, in the unpredictable condition. Therefore, these results indicate that when the amount of an upcoming perturbation is known in advance, the muscle response improves, shortening the latency and modulating the muscle activity in relation to the mechanical demand. PMID:25271638

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.

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.

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.

Emotion and anxiety potentiate the way attention alters visual appearance.

PubMed

Barbot, Antoine; Carrasco, Marisa

2018-04-12

The ability to swiftly detect and prioritize the processing of relevant information around us is critical for the way we interact with our environment. Selective attention is a key mechanism that serves this purpose, improving performance in numerous visual tasks. Reflexively attending to sudden information helps detect impeding threat or danger, a possible reason why emotion modulates the way selective attention affects perception. For instance, the sudden appearance of a fearful face potentiates the effects of exogenous (involuntary, stimulus-driven) attention on performance. Internal states such as trait anxiety can also modulate the impact of attention on early visual processing. However, attention does not only improve performance; it also alters the way visual information appears to us, e.g. by enhancing perceived contrast. Here we show that emotion potentiates the effects of exogenous attention on both performance and perceived contrast. Moreover, we found that trait anxiety mediates these effects, with stronger influences of attention and emotion in anxious observers. Finally, changes in performance and appearance correlated with each other, likely reflecting common attentional modulations. Altogether, our findings show that emotion and anxiety interact with selective attention to truly alter how we see.

Psychotomimetic effects of different doses of MK-801 and the underlying mechanisms in a selective memory impairment model.

PubMed

Liu, Weiqing; Wang, Dong; Hong, Wenjuan; Yu, Yi; Tang, Jinsong; Wang, Jicai; Liu, Fang; Xu, Xiufeng; Tan, Liwen; Chen, Xiaogang

2017-03-01

Although N-methyl-d-aspartate receptor antagonists-induced hypoglutamate rodent models are the most well-established models for preclinical studies of schizophrenia-related deficits, they also evoke a wide spectrum of psychotomimetic side effects. It is significant to increase the specificity of hypoglutamate rodent models. In this study, the recognition memory was evaluated in rats by object recognition test (ORT), sensorimotor gating was evaluated by prepulse inhibition of the startle reflex (PPI), and locomotor activity was measured using open field test. High-performance liquid chromatography was used to measure neurotransmitters content in the medial prefrontal cortex (mPFC) and thalamus (THA). Total Akt and phospho-Akt protein was measured by Western blots. Results showed that 0.3mg/kg of MK-801 was most effective in inducing locomotion. 0.3mg/kg of MK-801 was most effective in decreasing PPI. 0.03mg/kg of MK-801 was most effective in decreasing object memory while not affecting exploration manners in the training session. 0.03mg/kg of MK-801 significantly increased HVA and Glu content in the mPFC. 0.1mg/kg of MK-801 significantly decreased GABA content in the THA. 0.03mg/kg of MK-801 significantly decreased Akt phosphorylation in the mPFC, which was related to the ORT index. In conclusion, a dose of 0.03mg/kg MK-801 can establish a "pure" memory impairment model without contaminations of sensorimotor gating and locomotor activity. MK-801-induced cognitive deficits is associated with increased DA metabolites and glutamate content in the mPFC and decreased GABA content in the THA as well as decrease in Akt phosphorylation in the mPFC. Copyright © 2016. Published by Elsevier B.V.

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.

Reflexive journaling on emotional research topics: ethical issues for team researchers.

PubMed

Malacrida, Claudia

2007-12-01

Traditional epistemological concerns in qualitative research focus on the effects of researchers' values and emotions on choices of research topics, power relations with research participants, and the influence of researcher standpoints on data collection and analysis. However, the research process also affects the researchers' values, emotions, and standpoints. Drawing on reflexive journal entries of assistant researchers involved in emotionally demanding team research, this article explores issues of emotional fallout for research team members, the implications of hierarchical power imbalances on research teams, and the importance of providing ethical opportunities for reflexive writing about the challenges of doing emotional research. Such reflexive approaches ensure the emotional safety of research team members and foster opportunities for emancipatory consciousness among research team members.

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

Effect of Spaceflight on Vestibulo-Ocular Reflexes (VORS) During Angular Head Motion

NASA Technical Reports Server (NTRS)

Tomko, David L.; Clifford, James O.; Hargens, Alan R. (Technical Monitor)

1996-01-01

Vestibulo-ocular reflexes (VORs) stabilize the eyes during head motion. During Earth-horizontal (E-H) pitch or roll rotations, canal and otolith stimuli occur together. In Earth-vertical (E-V) pitch or roll rotations, only canal signals occur. In cats and squirrel monkeys, pitch/roll VOR gains during E-H motion have been shown to be larger than during E-V motion, implying that otolith modulation plays a role in producing angular VORs (aVORs). The present experiments replicated this experiment in rhesus monkeys, and examined how spaceflight affected AVOR gain. During yaw, pitch and roll (0.5 - 1.0 Hz, 40-50 deg/s pk) motion, 3-d eye movements were recorded in four Rhesus monkeys using scleral search coils. Mean E-H and E-V pitch VOR gains were 0.85 and 0.71. Torsional VOR gains during E-H and E-V were 0.47 and 0.39. Gains are more compensatory during E-H pitch or roll. Two of the four monkeys flew for 11 days on the COSMOS 2229 Biosatellite. E-H pitch VOR gains were attenuated immediately (72 hrs) post-flight, with similar values to pre-flight E-V pitch gains. Horizontal yaw VOR gains were similar pre- and post-flight.

Role of phosphodiesterase-4 on ethanol elicited locomotion and narcosis.

PubMed

Baliño, Pablo; Ledesma, Juan Carlos; Aragon, Carlos M G

2016-02-01

The cAMP signaling pathway has emerged as an important modulator of the pharmacological effects of ethanol. In this respect, the cAMP-dependent protein kinase has been shown to play an important role in the modulation of several ethanol-induced behavioral actions. Cellular levels of cAMP are maintained by the activity of adenylyl cyclases and phosphodiesterases. In the present work we have focused on ascertaining the role of PDE4 in mediating the neurobehavioral effects of ethanol. For this purpose, we have used the selective PDE4 inhibitor Ro 20-1724. This compound has been proven to enhance cellular cAMP response by PDE4 blockade and can be administered systemically. Swiss mice were injected intraperitoneally (i.p.) with Ro 20-1724 (0-5 mg/kg; i.p.) at different time intervals before ethanol (0-4 g/kg; i.p.) administration. Immediately after the ethanol injection, locomotor activity, loss of righting reflex, PKA footprint and enzymatic activity were assessed. Pretreatment with Ro 20-1724 increased ethanol-induced locomotor stimulation in a dose-dependent manner. Doses that increased locomotor stimulation did not modify basal locomotion or the suppression of motor activity produced by high doses of this alcohol. Ro 20-1724 did not alter the locomotor activation produced by amphetamine or cocaine. The time of loss of righting reflex evoked by ethanol was increased after pretreatment with Ro 20-1724. This effect was selective for the narcotic effects of ethanol since Ro 20-1724 did not affect pentobarbital-induced narcotic effects. Moreover, Ro 20-1724 administration increased the PKA footprint and enzymatic activity response elicited by ethanol. These data provide further evidence of the key role of the cAMP signaling pathway in the central effects of ethanol. Copyright © 2015 Elsevier Ltd. All rights reserved.

Locomotor training improves premotoneuronal control after chronic spinal cord injury.

PubMed

Knikou, Maria; Mummidisetty, Chaithanya K

2014-06-01

Spinal inhibition is significantly reduced after spinal cord injury (SCI) in humans. In this work, we examined if locomotor training can improve spinal inhibition exerted at a presynaptic level. Sixteen people with chronic SCI received an average of 45 training sessions, 5 days/wk, 1 h/day. The soleus H-reflex depression in response to low-frequency stimulation, presynaptic inhibition of soleus Ia afferent terminals following stimulation of the common peroneal nerve, and bilateral EMG recovery patterns were assessed before and after locomotor training. The soleus H reflexes evoked at 1.0, 0.33, 0.20, 0.14, and 0.11 Hz were normalized to the H reflex evoked at 0.09 Hz. Conditioned H reflexes were normalized to the associated unconditioned H reflex evoked with subjects seated, while during stepping both H reflexes were normalized to the maximal M wave evoked after the test H reflex at each bin of the step cycle. Locomotor training potentiated homosynaptic depression in all participants regardless the type of the SCI. Presynaptic facilitation of soleus Ia afferents remained unaltered in motor complete SCI patients. In motor incomplete SCIs, locomotor training either reduced presynaptic facilitation or replaced presynaptic facilitation with presynaptic inhibition at rest. During stepping, presynaptic inhibition was modulated in a phase-dependent manner. Locomotor training changed the amplitude of locomotor EMG excitability, promoted intralimb and interlimb coordination, and altered cocontraction between knee and ankle antagonistic muscles differently in the more impaired leg compared with the less impaired leg. The results provide strong evidence that locomotor training improves premotoneuronal control after SCI in humans at rest and during walking. Copyright © 2014 the American Physiological Society.

Assessing TMS-induced D and I waves with spinal H-reflexes.

PubMed

Niemann, Niclas; Wiegel, Patrick; Kurz, Alexander; Rothwell, John C; Leukel, Christian

2018-03-01

Transcranial magnetic stimulation (TMS) of motor cortex produces a series of descending volleys known as D (direct) and I (indirect) waves. In the present study, we questioned whether spinal H-reflexes can be used to dissect D waves and early and late I waves from TMS. We therefore probed H-reflex facilitation at arrival times of D and I waves at the spinal level and thereby changed TMS parameters that have previously been shown to have selective effects on evoked D and different I waves. We changed TMS intensity and current direction and applied a double-pulse paradigm known as short-interval intracortical inhibition (SICI). Experiments were conducted in flexor carpi radialis (FCR) in the arm and soleus (SOL) in the leg. There were two major findings: 1) in FCR, H-reflex facilitation showed characteristic modulations with altered TMS parameters that correspond to the changes of evoked D and I waves; and 2) H-reflexes in SOL did not, possibly because of increased interference from other spinal circuits. Therefore, the most significant outcome of this study is that in FCR, H-reflexes combined with TMS seem to be a useful technique to dissect TMS-induced D and I waves. NEW & NOTEWORTHY Questions that relate to corticospinal function in pathophysiology and movement control demand sophisticated techniques to provide information about corticospinal mechanisms. We introduce a noninvasive electrophysiological technique that may be useful in describing such mechanisms in more detail by dissecting D and I waves from transcranial magnetic stimulation (TMS). Based on the combination of spinal H-reflexes and TMS in the flexor carpi radialis muscle, the technique was shown to measure selective effects on D and I waves from changing TMS parameters.

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.

Quantitative evaluation of the stretch reflex before and after hydro kinesy therapy in patients affected by spastic paresis.

PubMed

Pagliaro, P; Zamparo, P

1999-04-01

The aim of this study was the quantitative evaluation of the myotatic reflex in a group of 26 patients affected by stationary spastic paresis (6: hemiparesis; 5: paraparesis; 8: tetraparesis; 7: multiple sclerosis) before and after a treatment of hydro-kinesy therapy. The treatment was carried out in an indoor pool containing warm (32 degrees C) sea water and consisted of active and passive motion exercises, coordination exercises and immersion walking. The measured parameters were: (i) the peak input force (FpH) measured by means of an instrumented hammer with which the patellar tendon was hit; and (ii) the peak value of the corresponding reflex force of the quadriceps femoris (FpQ) measured by means of a load cell connected to the subject's ankle. The peak values of the reflex response (FpQ) were found to increase as a function of the intensity of the imposed stimulus and to reach a plateau between 15 and 30 N of FpH. A Student's t test applied to the paired values of FpQ (as measured at plateau conditions) on both the lower limbs, before and after therapy, showed no significant changes due to the treatment in the four groups of subjects. However, if all subjects were grouped regardless the type of illness: 1) the average reflex response of the affected limb (the one characterized before therapy by the higher FpQ values) was found to decrease following the treatment (75.1+/-26.7 N pre therapy and 69.1+/-29.3 N post therapy, p = 0.07, n = 26); and 2) the effect of the treatment was found to be significantly larger (p = 0.04, n = 26) on the affected limb (delta FpQ = 6.07+/-16.5 N) as respect with the contra lateral one (delta FpQ = -0.16+/-12.1 N).

Mechanisms of inhibitory action of TRK-130 (Naltalimide), a μ-opioid receptor partial agonist, on the micturition reflex.

PubMed

Fujimura, Morihiro; Izumimoto, Naoki; Kanie, Sayoko; Kobayashi, Ryosuke; Yoshikawa, Satoru; Momen, Shinobu; Hirakata, Mikito; Komagata, Toshikazu; Okanishi, Satoshi; Iwata, Masashi; Hashimoto, Tadatoshi; Doi, Takayuki; Yoshimura, Naoki; Kawai, Koji

2017-04-01

To clarify the mechanism of inhibitory action of TRK-130 (Naltalimide), a unique µ-opioid receptor partial agonist, on the micturition reflex. The effect of TRK-130 on isovolumetric rhythmic bladder contractions (RBCs) was examined in guinea pigs, the effect of which was clarified by co-treatment with naloxone or in spinal cord transection. The effect of TRK-130 on urodynamic parameters was also observed in guinea pigs. In addition, the effect of TRK-130 on bladder contraction induced by peripheral stimulation of the pelvic nerve was investigated in rats. TRK-130 (0.001-0.01 mg/kg, iv) dose-dependently inhibited RBCs, which was dose-dependently antagonized by naloxone; however, the antagonism susceptibility was different from morphine (1 mg/kg, iv). The minimum effective dose (0.003 mg/kg) of TRK-130 remained similar in spinal cord-transected animals. TRK-130 (0.0025 mg/kg, iv) increased bladder capacity without changing the voiding efficiency, maximum flow rate, and intravesical pressure at the maximum flow rate, whereas oxybutynin (1 mg/kg, iv) increased the bladder capacity but affected the other parameters. TRK-130 (0.005 mg/kg, iv) did not produce significant changes on the bladder contractions induced by peripheral stimulation of the pelvic nerve, while oxybutynin (1 mg/kg, iv) significantly suppressed the bladder contractions. These results suggest that TRK-130 enhances the bladder storage function by modulating the afferent limb of the micturition reflex through µ-opioid receptors in the spinal cord. TRK-130 could be a more effective and safer therapeutic agent with a different fashion from antimuscarinics and conventional opioids for overactive bladder.

Bouncing on Mars and the Moon-the role of gravity on neuromuscular control: correlation of muscle activity and rate of force development.

PubMed

Ritzmann, Ramona; Freyler, Kathrin; Krause, Anne; Gollhofer, Albert

2016-11-01

On our astronomical neighbors Mars and the Moon, bouncing movements are the preferred locomotor techniques. During bouncing, the stretch-shortening cycle describes the muscular activation pattern. This study aimed to identify gravity-dependent changes in kinematic and neuromuscular characteristics in the stretch-shortening cycle. Hence, neuromuscular control of limb muscles as well as correlations between the muscles' pre-activation, reflex components, and force output were assessed in lunar, Martian, and Earth gravity. During parabolic flights, peak force (F max ), ground-contact-time, rate of force development (RFD), height, and impulse were measured. Electromyographic (EMG) activities in the m. soleus (SOL) and gastrocnemius medialis (GM) were assessed before (PRE) and during bounces for the reflex phases short-, medium-, and long-latency response (SLR, MLR, LLR). With gradually decreasing gravitation, F max , RFD, and impulse were reduced, whereas ground-contact time and height increased. Concomitantly, EMG_GM decreased for PRE, SLR, MLR, and LLR, and in EMG_SOL in SLR, MLR, and LLR. For SLR and MLR, F max and RFD were positively correlated to EMG_SOL. For PRE and LLR, RFD and F max were positively correlated to EMG_GM. Findings emphasize that biomechanically relevant kinematic adaptations in response to gravity variation were accompanied by muscle- and phase-specific modulations in neural control. Gravitational variation is anticipated and compensated for by gravity-adjusted muscle activities. Importantly, the pre-activation and reflex phases were differently affected: in SLR and MLR, SOL is assumed to contribute to the decline in force output with a decreasing load, and, complementary in PRE and LLR, GM seems to be of major importance for force generation. Copyright © 2016 the American Physiological Society.

Surgical injury in the neonatal rat alters the adult pattern of descending modulation from the rostroventral medulla.

PubMed

Walker, Suellen M; Fitzgerald, Maria; Hathway, Gareth J

2015-06-01

Neonatal pain and injury can alter long-term sensory thresholds. Descending rostroventral medulla (RVM) pathways can inhibit or facilitate spinal nociceptive processing in adulthood. As these pathways undergo significant postnatal maturation, the authors evaluated long-term effects of neonatal surgical injury on RVM descending modulation. Plantar hind paw or forepaw incisions were performed in anesthetized postnatal day (P)3 Sprague-Dawley rats. Controls received anesthesia only. Hind limb mechanical and thermal withdrawal thresholds were measured to 6 weeks of age (adult). Additional groups received pre- and post-incision sciatic nerve levobupivacaine or saline. Hind paw nociceptive reflex sensitivity was quantified in anesthetized adult rats using biceps femoris electromyography, and the effect of RVM electrical stimulation (5-200 μA) measured as percentage change from baseline. In adult rats with previous neonatal incision (n = 9), all intensities of RVM stimulation decreased hind limb reflex sensitivity, in contrast to the typical bimodal pattern of facilitation and inhibition with increasing RVM stimulus intensity in controls (n = 5) (uninjured vs. neonatally incised, P < 0.001). Neonatal incision of the contralateral hind paw or forepaw also resulted in RVM inhibition of hind paw nociceptive reflexes at all stimulation intensities. Behavioral mechanical threshold (mean ± SEM, 28.1 ± 8 vs. 21.3 ± 1.2 g, P < 0.001) and thermal latency (7.1 ± 0.4 vs. 5.3 ± 0.3 s, P < 0.05) were increased in both hind paws after unilateral neonatal incision. Neonatal perioperative sciatic nerve blockade prevented injury-induced alterations in RVM descending control. Neonatal surgical injury alters the postnatal development of RVM descending control, resulting in a predominance of descending inhibition and generalized reduction in baseline reflex sensitivity. Prevention by local anesthetic blockade highlights the importance of neonatal perioperative analgesia.

Comparison of Grammar in Neurodevelopmental Disorders: The Case of Binding in Williams Syndrome and Autism With and Without Language Impairment

PubMed Central

Modyanova, Nadya; Wexler, Ken

2013-01-01

This study investigates whether distinct neurodevelopmental disorders show distinct patterns of impairments in particular grammatical abilities and the relation of those grammatical patterns to general language delays and intellectual disabilities. We studied two disorders (autism and Williams syndrome [WS]) and two distinct properties (Principle A that governs reflexives and Principle B that, together with its associated pragmatic rule, governs pronouns) of the binding module of grammar. These properties are known to have markedly different courses of acquisition in typical development. We compare the knowledge of binding in children with autism with language impairment (ALI) and those with normal language (ALN) to that of children with WS, matched on age to the ALN group, and on age and nonverbal mental age (MA) to the ALI group, as well as to two groups of typically developing (TD) controls, matched on nonverbal MA to ALI and ALN groups. Our results reveal a remarkably different pattern of comprehension of personal pronouns and reflexives in ALI as opposed to ALN, WS, and two groups of TD controls. All five groups demonstrated an equal delay in their comprehension of personal pronouns, in line with widely reported delays in TD literature, argued to be due to delayed pragmatic abilities. However, and most strikingly, the ALI group also showed a pronounced difficulty in comprehension of reflexive pronouns, and particularly of the knowledge that the antecedent of a reflexive must c-command it. The revealed pattern confirms the existence of a particular impairment concerning Principle A in this module of grammar, unrelated to general language delays or cognitive deficits generally present in a large portion of individuals with autism as well as WS, or to general pragmatic deficits, known to be particularly prevalent in the population with autism. PMID:25170241

Chronic mercury exposure impairs the sympathovagal control of the rat heart.

PubMed

Simões, M R; Azevedo, B F; Fiorim, J; Jr Freire, D D; Covre, E P; Vassallo, D V; Dos Santos, L

2016-11-01

Mercury is known to cause harmful neural effects affecting the cardiovascular system. Here, we evaluated the chronic effects of low-dose mercury exposure on the autonomic control of the cardiovascular system. Wistar rats were treated for 30 days with HgCl 2 (1st dose 4.6 μg/kg followed by 0.07 μg/kg per day, intramuscular) or saline. The femoral artery and vein were then cannulated for evaluation of autonomic control of the hemodynamic function, which was evaluated in awake rats. The following tests were performed: baroreflex sensitivity, Von Bezold-Jarisch reflex, heart rate variability (HRV) and pharmacological blockade with methylatropine and atenolol to test the autonomic tone of the heart. Exposure to HgCl 2 for 30 days slightly increased the mean arterial pressure and heart rate (HR). There was a significant reduction in the baroreflex gain of animals exposed to HgCl 2 . Moreover, haemodynamic responses to the activation of the Von Bezold-Jarisch reflex were also reduced. The changes in the spectral analysis of HRV suggested a shift in the sympathovagal balance toward a sympathetic predominance after mercury exposure, which was confirmed by autonomic pharmacological blockade in the HgCl 2 group. This group also exhibited reduced intrinsic HR after the double block suggesting that the pacemaker activity of the sinus node was also affected. These findings suggested that the autonomic modulation of the heart was significantly altered by chronic mercury exposure, thus reinforcing that even at low concentrations such exposure might be associated with increased cardiovascular risk. © 2016 John Wiley & Sons Australia, Ltd.

High Trait Anxiety: A Challenge for Disrupting Fear Memory Reconsolidation

PubMed Central

Soeter, Marieke; Kindt, Merel

2013-01-01

Disrupting reconsolidation may be promising in the treatment of anxiety disorders but the fear-reducing effects are thus far solely demonstrated in the average organism. A relevant question is whether disrupting fear memory reconsolidation is less effective in individuals who are vulnerable to develop an anxiety disorder. By collapsing data from six previous human fear conditioning studies we tested whether trait anxiety was related to the fear-reducing effects of a pharmacological agent targeting the process of memory reconsolidation - n = 107. Testing included different phases across three consecutive days each separated by 24 h. Fear responding was measured by the eye-blink startle reflex. Disrupting the process of fear memory reconsolidation was manipulated by administering the β-adrenergic receptor antagonist propranolol HCl either before or after memory retrieval. Trait anxiety uniquely predicted the fear-reducing effects of disrupting memory reconsolidation: the higher the trait anxiety, the less fear reduction. Vulnerable individuals with the propensity to develop anxiety disorders may need higher dosages of propranolol HCl or more retrieval trials for targeting and changing fear memory. Our finding clearly demonstrates that we cannot simply translate observations from fundamental research on fear reduction in the average organism to clinical practice. PMID:24260096

High trait anxiety: a challenge for disrupting fear memory reconsolidation.

PubMed

Soeter, Marieke; Kindt, Merel

2013-01-01

Disrupting reconsolidation may be promising in the treatment of anxiety disorders but the fear-reducing effects are thus far solely demonstrated in the average organism. A relevant question is whether disrupting fear memory reconsolidation is less effective in individuals who are vulnerable to develop an anxiety disorder. By collapsing data from six previous human fear conditioning studies we tested whether trait anxiety was related to the fear-reducing effects of a pharmacological agent targeting the process of memory reconsolidation--n = 107. Testing included different phases across three consecutive days each separated by 24 h. Fear responding was measured by the eye-blink startle reflex. Disrupting the process of fear memory reconsolidation was manipulated by administering the β-adrenergic receptor antagonist propranolol HCl either before or after memory retrieval. Trait anxiety uniquely predicted the fear-reducing effects of disrupting memory reconsolidation: the higher the trait anxiety, the less fear reduction. Vulnerable individuals with the propensity to develop anxiety disorders may need higher dosages of propranolol HCl or more retrieval trials for targeting and changing fear memory. Our finding clearly demonstrates that we cannot simply translate observations from fundamental research on fear reduction in the average organism to clinical practice.

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.

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

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.

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.

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.

Neurobiological mechanisms of acupuncture for some common illnesses: a clinician's perspective.

PubMed

Cheng, Kwokming James

2014-06-01

This paper presents some previously proposed neurobiological mechanisms on how acupuncture may work in some clinical applications from a clinician's perspective. For the treatment of musculoskeletal conditions, the proposed mechanisms included microinjury, increased local blood flow, facilitated healing, and analgesia. Acupuncture may trigger a somatic autonomic reflex, thereby affecting the gastric and cardiovascular functions. Acupuncture may also change the levels of neurotransmitters such as serotonin and dopamine, thereby affecting the emotional state and craving. This mechanism may form the basis for the treatment of smoking cessation. By affecting other pain-modulating neurotransmitters such as met-enkephalin and substance P along the nociceptive pathway, acupuncture may relieve headache. Acupuncture may affect the hypothalamus pituitary axis and reduce the release of the luteinizing hormone in the treatment of polycystic ovary syndrome. In addition, two other approaches to the acupuncture mechanism, the fascia connective tissue network and the primo vascular system, are briefly reviewed. Finally, the idea of true versus sham acupuncture points, which are commonly used in clinical trials, is examined because the difference between true and sham points does not exist in the neurobiological model. Copyright © 2013. Published by Elsevier B.V.

Modulating Tone to Promote Motor Development Using a Neurofacilitation of Developmental Reaction (NFDR) Approach in Children with Neurodevelopmental Delay

PubMed Central

Batra, Vijay; Batra, Meenakshi; Pandey, Ravindra Mohan; Sharma, Vijai Prakash; Agarwal, Girdhar Gopal

2015-01-01

Objective To compare the efficacy of a Neurofacilitation of Developmental Reaction (NFDR) approach with that of a Conventional approach in the modulation of tone in children with neurodevelopmental delay. Methods Experimental control design. A total of 30 spastic children ranging in age from 4 to 7 years with neurodevelopmental delay were included. Baseline evaluations of muscle tone and gross motor functional performance abilities were performed. The children were allocated into two intervention groups of 15 subjects each. In groups A and B, the NFDR and conventional approaches were applied, respectively, for 3 months and were followed by subsequent re-evaluations. Results Between group analyses were performed using independent t test for tone and primitive reflex intensity and a Mann-Whitney U test for gross motor functional ability. For the within-group analyses, paired t tests were used for tone and primitive reflex intensity, and a Wilcoxon signed-rank test was used for gross motor functional ability. Conclusion The NFDR approach/technique prepares the muscle to undergo tonal modulation and thereby enhances motor development and improves the motor functional performance abilities of the children with neurodevelopmental delay. PMID:28239268

Vestibuloocular reflex of rhesus monkeys after spaceflight

NASA Technical Reports Server (NTRS)

Cohen, Bernard; Kozlovskaia, Inessa; Raphan, Theodore; Solomon, David; Helwig, Denice; Cohen, Nathaniel; Sirota, Mikhail; Iakushin, Sergei

1992-01-01

The vestibuloocular reflex (VOR) of two rhesus monkeys was recorded before and after 14 days of spaceflight. The gain (eye velocity/head velocity) of the horizontal VOR, tested 15 and 18 h after landing, was approximately equal to preflight values. The dominant time constant of the animal tested 15 h after landing was equivalent to that before flight. During nystagmus induced by off-vertical axis rotation (OVAR), the latency, rising time constant, steady-state eye velocity, and phase of modulation in eye velocity and eye position with respect to head position were similar in both monkeys before and after flight. There were changes in the amplitude of modulation of horizontal eye velocity during steady-state OVAR and in the ability to discharge stored activity rapidly by tilting during postrotatory nystagmus (tilt dumping) after flight: OVAR modulations were larger, and tilt dumping was lost in the one animal tested on the day of landing and for several days thereafter. If the gain and time constant of the horizontal VOR exchange in microgravity, they must revert to normal soon after landing. The changes that were observed suggest that adaptation to microgravity had caused alterations in way that the central nervous system processes otolith input.

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.

Enhancement of the intrinsic defecation reflex by mosapride, a 5-HT4 agonist, in chronically lumbosacral denervated guinea pigs.

PubMed

Kojima, Yu; Fujii, Hisao; Katsui, Renta; Nakajima, Yoshiyuki; Takaki, Miyako

2006-10-01

The defecation reflex is composed of rectal distension-evoked rectal (R-R) reflex contractions and synchronous internal anal sphincter (R-IAS) reflex relaxations in guinea pigs. These R-R and R-IAS reflexes are controlled via extrinsic sacral excitatory nerve pathway (pelvic nerves), lumbar inhibitory nerve pathways (colonic nerves) and by intrinsic cholinergic excitatory and nitrergic inhibitory nerve pathways. The effect of mosapride (a prokinetic benzamide) on the intrinsic reflexes, mediated via enteric 5-HT(4) receptors, was evaluated by measuring the mechanical activity of the rectum and IAS in anesthetized guinea pigs using an intrinsic R-R and R-IAS reflex model resulting from chronic (two to nine days) lumbosacral denervation (PITH). In this model, the myenteric plexus remains undamaged and the distribution of myenteric and intramuscular interstitial cells of Cajal is unchanged. Although R-R and R-IAS reflex patterns markedly changed, the reflex indices (reflex pressure or force curve-time integral) of both the R-R contractions and the synchronous R-IAS relaxations were unchanged. The frequency of the spontaneous R and IAS motility was also unchanged. Mosapride (0.1-1.0 mg/kg) dose-dependently increased both intrinsic R-R (maximum: 1.82) and R-IAS reflex indices (maximum: 2.76) from that of the control (1.0) 6-9 days following chronic PITH. The dose-response curve was similar to that in the intact guinea pig, and had shifted to the left from that in the guinea pig after acute PITH. A specific 5-HT(4) receptor antagonist, GR 113808 (1.0 mg/kg), decreased both reflex indices by approximately 50% and antagonized the effect of mosapride 1.0 mg/kg. This was quite different from the result in the intact guinea pig where GR 113808 (1.0 mg/kg) did not affect either of the reflex indices. The present results indicate that mosapride enhanced the intrinsic R-R and R-IAS reflexes and functionally compensated for the deprivation of extrinsic innervation. The actions of mosapride were mediated through endogenously active, intrinsic 5-HT(4) receptors which may be post-synaptically located in the myenteric plexus of the anorectum.

FMRFamide produces biphasic modulation of the LFS motor neurons in the neural circuit of the siphon withdrawal reflex of Aplysia by activating Na+ and K+ currents.

PubMed

Belkin, K J; Abrams, T W

1993-12-01

The molluscan neuropeptide FMRFamide has an inhibitory effect on transmitter release from the presynaptic sensory neurons in the neural circuit for the siphon withdrawal reflex. We have explored whether FMRFamide also acts postsynaptically in motor neurons in this circuit, focusing on the LFS motor neurons. FMRFamide typically produces a biphasic response in LFS neurons: a fast excitatory response followed by a prolonged inhibitory response. We have analyzed these postsynaptic actions and compared them with the mechanism of FMRFamide's inhibition of the presynaptic sensory neurons. The transient excitatory effect of FMRFamide, which desensitizes rapidly, is due to activation of a TTX-insensitive, Na(+)-dependent inward current. The late hyperpolarizing phase of the FMRFamide response results from activation of at least two K+ currents. One component of the hyperpolarizing response is active at rest and at more hyperpolarized membrane potentials, and is blocked by 5 mM 4-aminopyridine, suggesting that it differs from the previously described FMRFamide-modulated K+ currents in the presynaptic sensory neurons. In addition, FMRFamide increases a 4-aminopyridine-insensitive K+ current. Presynaptically, FMRFamide increases K+ conductance, acting via release of arachidonic acid. In the LFS motor neurons, application of arachidonic acid mimicked the prolonged, hyperpolarizing phase of the FMRFamide response; 4-bromophenacyl bromide, an inhibitor of phospholipase A2, selectively blocked this component of the FMRFamide response. Thus, FMRFamide may act in parallel pre- and post-synaptically to inhibit the output of the siphon withdrawal reflex circuit, producing this inhibitory effect via the same second messenger in the sensory neurons and motor neurons, though a number of the K+ currents modulated in these two types of neurons are different.

Modulation of gastric contractions in response to tachykinins and bethanechol by extrinsic nerves.

PubMed Central

Holzer-Petsche, U.

1991-01-01

1. Extrinsic reflexes elicited by changes in gastric wall tension play an important role in regulating gastric tone. The present study investigated whether such reflexes modulate gastric contractions induced by close arterially administered neurokinin A (NKA), substance P (SP), SP-methylester and bethancehol in anaesthetized rats. 2. Reflex pathways were acutely interrupted by either subdiaphragmatic vagotomy or prevertebral ganglionectomy. C-fibre afferent nerve activity was abolished by pretreating rats with capsaicin 10 to 16 days before the experiments. 3. The order of potency in inducing gastric contractions was NKA greater than SP greater than bethanechol. SP-methylester was markedly less effective than SP and its effects did not fit sigmoid dose-response curves (DRCs). The maximal responses to NKA, SP, and bethanechol were similar, whilst the DRC for SP was significantly flatter than those for NKA or bethanechol. Pretreatment of the rats with the peptidase inhibitors phosphoramidon or captopril did not increase the contractile response to SP. 4. Prevertebral ganglionectomy had no significant effect on the DRCs for SP and NKA, whereas vagotomy shifted the DRCs for all three test substances to the left. 5. Capsaicin pretreatment did not change the DRC for NKA in rats with intact vagus but shifted that for bethanechol to the left. The leftward of the DRC for NKA caused by vagotomy was prevented in capsaicin-pretreated rats whereas the vagotomy-induced shift of the DRC for bethanechol remained unaltered. The shift of the DRC for SP seen in response to vagotomy was only slightly reduced by capsaicin pretreatment. 6. These data may be interpreted as demonstrating two neuronal mechanisms for modulating drug-induced gastric contractions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1717093

Interaction between vestibulosympathetic and skeletal muscle reflexes on sympathetic activity in humans

NASA Technical Reports Server (NTRS)

Ray, C. A.

2001-01-01

Evidence from animals indicates that skeletal muscle afferents activate the vestibular nuclei and that both vestibular and skeletal muscle afferents have inputs to the ventrolateral medulla. The purpose of the present study was to investigate the interaction between the vestibulosympathetic and skeletal muscle reflexes on muscle sympathetic nerve activity (MSNA) and arterial pressure in humans. MSNA, arterial pressure, and heart rate were measured in 17 healthy subjects in the prone position during three experimental trials. The three trials were 2 min of 1) head-down rotation (HDR) to engage the vestibulosympathetic reflex, 2) isometric handgrip (IHG) at 30% maximal voluntary contraction to activate skeletal muscle afferents, and 3) HDR and IHG performed simultaneously. The order of the three trials was randomized. HDR and IHG performed alone increased total MSNA by 46 +/- 16 and 77 +/- 24 units, respectively (P < 0.01). During the HDR plus IHG trial, MSNA increased 142 +/- 38 units (P < 0.01). This increase was not significantly different from the sum of the individual trials (130 +/- 41 units). This finding was also observed with mean arterial pressure (sum = 21 +/- 2 mmHg and HDR + IHG = 22 +/- 2 mmHg). These findings suggest that there is an additive interaction for MSNA and arterial pressure when the vestibulosympathetic and skeletal muscle reflexes are engaged simultaneously in humans. Therefore, no central modulation exists between these two reflexes with regard to MSNA output in humans.

Intramuscular Neurotrophin-3 normalizes low threshold spinal reflexes, reduces spasms and improves mobility after bilateral corticospinal tract injury in rats.

PubMed

Kathe, Claudia; Hutson, Thomas Haynes; McMahon, Stephen Brendan; Moon, Lawrence David Falcon

2016-10-19

Brain and spinal injury reduce mobility and often impair sensorimotor processing in the spinal cord leading to spasticity. Here, we establish that complete transection of corticospinal pathways in the pyramids impairs locomotion and leads to increased spasms and excessive mono- and polysynaptic low threshold spinal reflexes in rats. Treatment of affected forelimb muscles with an adeno-associated viral vector (AAV) encoding human Neurotrophin-3 at a clinically-feasible time-point after injury reduced spasticity. Neurotrophin-3 normalized the short latency Hoffmann reflex to a treated hand muscle as well as low threshold polysynaptic spinal reflexes involving afferents from other treated muscles. Neurotrophin-3 also enhanced locomotor recovery. Furthermore, the balance of inhibitory and excitatory boutons in the spinal cord and the level of an ion co-transporter in motor neuron membranes required for normal reflexes were normalized. Our findings pave the way for Neurotrophin-3 as a therapy that treats the underlying causes of spasticity and not only its symptoms.

Is temporal summation of pain and spinal nociception altered during normal aging?

PubMed Central

Marouf, Rafik; Piché, Mathieu; Rainville, Pierre

2015-01-01

Abstract This study examines the effect of normal aging on temporal summation (TS) of pain and the nociceptive flexion reflex (RIII). Two groups of healthy volunteers, young and elderly, received transcutaneous electrical stimulation applied to the right sural nerve to assess pain and the nociceptive flexion reflex (RIII-reflex). Stimulus intensity was adjusted individually to 120% of RIII-reflex threshold, and shocks were delivered as a single stimulus or as a series of 5 stimuli to assess TS at 5 different frequencies (0.17, 0.33, 0.66, 1, and 2 Hz). This study shows that robust TS of pain and RIII-reflex is observable in individuals aged between 18 and 75 years and indicates that these effects are comparable between young and older individuals. These results contrast with some previous findings and imply that at least some pain regulatory processes, including TS, may not be affected by normal aging, although this may vary depending on the method. PMID:26058038

The impact of harmfulness information on citric acid induced cough and urge-to-cough.

PubMed

Janssens, Thomas; Brepoels, Sarah; Dupont, Lieven; Van den Bergh, Omer

2015-04-01

The cough reflex is an automatic protective reflex, which can be modulated by conscious effort or other forms of top-down control. In this experiment, we investigated whether information about harmfulness of a cough-inducing substance would augment cough reflex sensitivity and associated urge-to-cough. Healthy participants (N = 39) were randomized to receive information that they were to inhale a harmless substance (natural citric acid), or a potentially harmful substance (a potent agro-chemical acid). Using dosimeter-controlled inhalations, the dose of citric acid eliciting at least three coughs (C3) was determined. Next, participants received 4 blocks of randomized presentations of citric acid at the C3 dose, a sub-threshold dose of citric acid and saline control. C3 was reached for 27/39 participants, and C3 thresholds were not influenced by harmfulness information. During repeated citric acid presentations, framing the cough-inducing substance as a potentially harmful chemical resulted in a greater urge-to-cough compared to information framing it as natural citric acid (p < .01). The experimental manipulation did not influence cough frequencies. Our findings show that harmfulness information influences urge-to-cough, corroborating the role of cortical mechanisms in modulating the urge-to-cough and suggesting that cognitive manipulations may contribute to cough treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.