Startle Measures Research Articles

Longterm-habituation of the startle response in mice is stimulus modality, but not context specific

In mice, the specificity of longterm-habituation (LTH) of startle was tested in two experiments. In two strains of mice (C57Bl/6 and C3H) there was pronounced LTH over 10 days of acoustic stimulation in two different contexts of startle measurement. (We found LTH to be greater after stimulation with 14 kHz sine stimuli compared to noise or tactile stimuli). A change of context showed LTH to be independent of context, i.e., startle LTH in mice is a non-associative learning process. In the second experiment, 9 days of acoustic or tactile stimulation were given to C57B/6 mice. Both stimulus modalities produced LTH. When on the 10th day stimuli of the other modality were given, in both cases the long term habituated group showed no lower startle amplitude than a non-stimulated control group. This indicates LTH is stimulus-modality specific. Altogether, our results show that in mice—very similar to rats—LTH of startle is stimulus modality, but not context specific. In addition we found two indications that the LTH action site is on the sensory branch of the startle circuit.

Video-Based Analysis of Bodily Startle and Subsequent Emotional Facial Expression in Posttraumatic Stress Disorder.

Exaggerated startle is a core hyperarousal symptom of Posttraumatic Stress Disorder (PTSD). Observational studies on the characteristics of this response are strikingly lacking. Previous research has demonstrated that detailed video analysis of facial and bodily responses to startling stimuli enables the differentiation of an initial, primarily reflexive response and a secondary, primary emotional response. We exposed PTSD patients (n = 34) and trauma-exposed but healthy participants (TE group, n = 26) to startling electric stimuli while acquiring observational behavioral, psychophysiological, and experiential measures. Videographic results indicate that PTSD patients' initial bodily startle response was stronger than in the TE group, and their secondary facial expression was more negatively valenced, largely due to elevated anger expression. Videographic assessment of primary and secondary startle responses provides a new window into reflexive and emotional functioning of PTSD and may therefore complement existing startle measures. PTSD treatments should address bodily startle, negative symptom appraisals, and anger more specifically.

Between-site reliability of startle prepulse inhibition across two early psychosis consortia

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; however, between-site stability has not been established. In two separate consortia investigating biomarkers of early psychosis, traveling participants studies were carried out as a part of quality assurance procedures to assess the fidelity of data across sites. In the North American Prodromal Longitudinal Studies (NAPLS) consortium, eight normal participants traveled to each of the eight NAPLS sites and were tested twice at each site on the startle PPI paradigm. In preparation for a binational study, 10 healthy participants 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 multisite studies, it is essential to institute quality assurance procedures early and establish between-site reliability to assure comparable data across sites.

Increased Sensorimotor Gating in Recreational and Dependent Cocaine Users Is Modulated by Craving and Attention-Deficit/Hyperactivity Disorder Symptoms

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.

ACUTE STRESS DISORDER VERSUS CHRONIC POSTTRAUMATIC STRESS DISORDER: INHIBITION OF FEAR AS A FUNCTION OF TIME SINCE TRAUMA

Previous work has shown that inhibition of fear is impaired in posttraumatic stress disorder (PTSD) resulting from both civilian and combat trauma. The purpose of the present study was to investigate the inhibition of learned fear in traumatized individuals diagnosed with either acute stress disorder (ASD) or PTSD. This is the first study to use a conditioned inhibition paradigm with traumatized individuals within a month of trauma exposure. We hypothesized that impaired fear inhibition would be evident in PTSD, but not ASD. Using established translational, psychophysiological methods including fear-potentiated startle, and skin conductance, we examined fear acquisition, stimulus discrimination, and the transfer of learned safety in a Croatian population with ASD or PTSD. This cross-sectional study included three age-matched groups: healthy nontrauma controls (n = 27), a group with chronic PTSD (10 or more years since trauma exposure, n = 24), and a group with ASD (30 days or less since trauma exposure, n = 27). The presence of trauma-related psychopathology, whether acute or chronic, was associated with an impaired ability to transfer learned safety based on fear-potentiated startle measures, while healthy control subjects showed significant fear inhibition in the presence of the safety cue compared to the danger cue, F(1,26) = 12.64, P = .001. These data expand our previously observed findings of PTSD-associated fear inhibition deficits by demonstrating that trauma-related impairments in safety learning are evident within 30 days of trauma exposure.

Is startle a lateralised response in early infancy?

The aim of the study was to explore whether the acoustic startle response shows signs of early lateralisation. Using non-invasive startle measurements (Automated Infant Motor Movement Startle Seat and Facial Action Coding System), an analysis of response latencies and intensities on the right and left body sides was performed, investigating the presence of asymmetries on the whole-body startle and on the facial component of the startle motor pattern in a group of 5-month-old infants. The findings suggest that the infant whole-body startle is a lateralised response, characterised by a right bias latency. This lateralisation could reflect an underlying lateralised organisation of the infant startle neural circuitry. On the other hand, the analysis of the facial component of the startle motor pattern did not reveal any significant asymmetry. The discrepancy found in the whole-body response and in the startle facial component will be discussed, reflecting on the limits of the adopted methodologies. The use of a high-speed camcorder might allow future research to analyse more in depth the startle fast face responses.

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

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.

Lack of relationship between acoustic startle and cognitive variables in schizophrenia and control subjects

Measures of acoustic startle such as prepulse inhibition (PPI) and startle latency have been found to be impaired in schizophrenia, and are commonly thought to be related to cognitive deficits in this disease. However, findings about the relationship between startle variables and cognitive performance have been equivocal. In this study, we examined correlations between startle measures (baseline startle magnitude, latency, habituation and PPI) and cognitive performance (using the Benton Visual Retention Test, Conner's Continuous Performance Test, California Verbal Learning Test, Finger Tapping Test, and Wisconsin Card Sort Test) in 107 schizophrenia patients and 94 healthy controls. Overall, there was a lack of any significant relationship between these constructs in both populations when correcting for multiple comparisons. This suggests that alterations in startle measures seen in schizophrenia may not reflect elements of information processing that cause cognitive deficits in the disease.

Emotional reactivity in nonsuicidal self-injury: Divergence between self-report and startle measures

The current study examined emotional reactivity in nonsuicidal self-injurers and noninjuring controls using self-report (the Emotional Reactivity Scale: ERS) and psychophysiological measures (the startle reflex was measured during and after the presentation of IAPS images). Self-injurers reported greater emotional reactivity on the ERS, but did not exhibit differences in startle modulation during or after picture viewing compared to controls. Results suggest a divergence between self-report and psychophysiological measures of emotion in NSSI.

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

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.

Prepulse inhibition of the startle response with chronic schizophrenia: A replication study

Prepulse inhibition (PPI) deficit, the acoustic startle reflex (ASR) and habituation (HAB) impairment are considered to be endophenotypes for schizophrenia. The recent two studies have reported that a PPI deficit was detected in Japanese schizophrenic patients. We replicated that study using larger samples (115 schizophrenic patients and 111 normal controls) than the original study and a method same as original study. A startle response monitoring system was used to deliver acoustic startle stimuli, and to record and score the electromyographic activity of the orbicularis oculi muscle. We evaluated the startle measures of mean magnitude of ASR, HAB, and PPI at prepulse sound pressure intensities of 82 dB (PPI82), 86 dB (PPI86), and 90 dB (PPI90). ASR was significantly different between schizophrenic patients and controls. HAB and all PPI session data from schizophrenic patients were significantly lower than in controls. In addition, we detected significant differences for ASR, HAB and each PPI (82, 86 and 90 dB) between schizophrenic patients and controls with the use of multiple regression analysis. The gender and smoking state were not correlated with ASR, HAB or any PPI in multiple regression analysis. In conclusion, we were able to replicate the finding of HAB impairment and PPI deficit in chronic Japanese schizophrenic patients.

Test‐retest reliability of voluntary emotion regulation

Despite growing interest in emotion regulation, the degree to which psychophysiological measures of emotion regulation are stable over time remains unknown. We examined four-week test-retest reliability of corrugator electromyographic and eyeblink startle measures of negative emotion and its regulation. Both measures demonstrated similar sensitivity to the emotion manipulation, but only individual differences in corrugator modulation and regulation showed adequate reliability. Startle demonstrated diminished sensitivity to the regulation instructions across assessments and poor reliability. This suggests that corrugator represents a trait-like measure of voluntary emotion regulation, whereas startle should be used with caution for assessing individual differences. The data also suggest that corrugator and startle might index partially dissociable constructs and underscore the need to collect multiple measures of emotion.

Effects of cocaine self-administration history under limited and extended access conditions on in vivo striatal dopamine neurochemistry and acoustic startle in rhesus monkeys

The transition from infrequent and controlled cocaine use to dependence may involve enduring changes in neurobiology as a consequence of persistent drug use. The present study utilized an intravenous drug self-administration protocol of increasing cocaine access to evaluate potential changes in dopamine function in vivo, including changes in sensitivity to psychostimulants. Drug-naïve rhesus monkeys were provided limited access (1 h) to cocaine self-administration for 60 days followed by 60 days under an extended access condition (4 h). Basal levels of striatal extracellular dopamine and its metabolites, as well as the effectiveness of cocaine and amphetamine to elevate dopamine, were determined with in vivo microdialysis before the initiation of cocaine self-administration and during limited and extended access. The effect of cocaine and amphetamine on the acoustic startle response was also examined to assess complementary behavioral changes as a function of drug history. Extended access to cocaine self-administration lead to increased daily intake compared to limited access conditions but did not result in escalated intake over time. However, cocaine- and amphetamine-induced increases in striatal dopamine were diminished as a function of cocaine self-administration history. Surprisingly, there was no effect of drug-taking history on sensitivity to psychostimulant-induced enhancement of startle amplitude. The present experiments provide evidence of a hypofunctional dopamine system that is not associated with an escalation in drug intake or reflected in measures of acoustic startle.

Impaired prepulse inhibition and habituation of acoustic startle response in Japanese patients with schizophrenia

Prepulse inhibition (PPI) and habituation of the acoustic startle reflex (ASR) are considered to be candidate endophenotypes of schizophrenia. However, to our knowledge, only one group has investigated these startle measures in Asian patients with schizophrenia. In the present study, we evaluated these startle measures in 51 Japanese patients with schizophrenia and compared them with those of 55 healthy age- and sex-matched Japanese controls. A human startle response monitoring system was used to deliver acoustic startle stimuli, and record and score the electromyographic activity of the orbicularis oculi muscle. The startle measures examined were mean magnitude of ASR to pulse alone trials in initial block (SR), habituation of ASR during the session (HAB), and PPI at prepulse intensities of 82 dB (PPI82), 86 dB (PPI86), and 90 dB (PPI90) sound pressure level. SR was not significantly different between the patients and controls. Patients displayed significantly reduced HAB and PPI for all prepulse intensities compared to controls. The greatest statistical difference in PPI between patients and controls was found with PPI86. This did not correlate with any clinical variable in each group. Our results indicate that PPI and habituation of ASR are impaired in Asian patients with schizophrenia.

Influence of Exercise on Stress and Depression

LANGUAGE NOTE | Document text in English; abstract also in Chinese.
 There is evidence in human subjects that aerobic physical exercise boosts the immune system, influences stress hormone levels and depressive feelings (Brenner, Shek, Zamecnik, & Shephard, 1998). Moderate physical exercise can prevent detrimental effects of stress and depression as a result of the interaction between the neuroendocrine system and the immune system post aerobic exercise (Fleshner, 2000). In this study, the contribution of intensity and duration of exercise to modulation of stress responses were assessed. Physical exercise modulation of the response to a stressful threatening event was examined in rats at the behavioral and biochemical levels. At the behavioral level, the following parameters were measured: anxiety (Elevated Plus Maze, Startle reflex response measures), depression (Learned helplessness) exploratory orientation (Open field) and of cognitive abilities (Spatial learning and memory, active avoidance). At the biochemical level, alterations in the basal concentrations of neurosteroids and in responsiveness to stress were measured.
 In response to acute stress there is a rapid increase in neurosteroids (Vllee, Rivera, Koob, Purdy, & Fitzgerald, 2000). The neurosteroid allopregnanolone has been shown to be a potent ligand of gamma-aminobutyric acid (GABA)-A receptors. It enhances its receptor-mediated inhibitory effects in the rat (Guo et al., 1995; Pericic, Svob, Jazvinscak, & Mirkovic, 2000). The neurosteroid 3 alpha, 5 alpha THP acts like an antidepressant drug. It interacts with the central delta receptor, which has antidepressant-like effects (Khisti, Chopde, & Jain, 2000; Reddy, Kaur, & Kulkani, 1998).
 進行適量運動能夠產生正面的健康影響，運動與身體免疫系統、壓力賀爾蒙和憂鬱情況的相關研究，經已得到確定。本文嘗試以不同的運動強度及時期，並用白鼠作用受試對象，去探討運動與壓力兩者的生理變化。

Acoustic Startle Reflex in Rhesus Monkeys: A Review

Modulation of the acoustic startle response is a simple and objective indicator of emotionality and attention in rodents and humans. This finding has proven extremely valuable for the analysis of neural systems associated with fear and anxiety. Until recently, there have been few efforts to develop acoustic startle measurement in non-human primates. Here we review recent work in which whole body acoustic startle amplitude has been measured in rhesus monkeys. Initial studies revealed that the amplitude of whole body startle in monkeys, as in rodents and humans, is directly proportional to acoustic stimulus intensity and gradually habituates with repeated exposures. Presentation of a weak acoustic stimulus 25-5,000 msec before a startle stimulus reduces startle amplitude by 40-50% depending on inter-stimulus interval length (prepulse inhibition). We have also measured significant fear-potentiated startle in the presence of a visual stimulus after pairing it with an inescapable pulse of pressurized air (fear-potentiated startle). This effect was reduced by diazepam and morphine, but not by buspirone. Ibotenic acid-induced lesions of the amygdala prevented the acquisition of fear-potentiated startle but, remarkably, did not prevent the expression of fear-potentiated startle when fear conditioning was carried out prior to the lesion. Finally, we have developed an objective measure of fear inhibition in monkeys using a novel conditioned inhibition procedure identical to one used in rats and humans. Our data demonstrate that acoustic startle in non-human primates successfully bridges rodent and human research. The opportunity now emerges to link concepts developed in rodents to the more complex neuroanatomical and cognitive processes common to monkeys and humans.

Antagonism of nucleus accumbens M 2 muscarinic receptors disrupts operant responding for sucrose under a progressive ratio reinforcement schedule

Diverse cholinergic signaling mechanisms regulate the excitability of striatal principal neurons and modulate striatal-dependent behavior. These effects are mediated, in part, by action at muscarinic receptors (mAChR), subtypes of which exhibit distinct patterns of expression across striatal neuronal populations. Non-selective mAChR blockade within the nucleus accumbens (NAc) has been shown to disrupt operant responding for food and to inhibit food consumption. However, the specific receptor subtypes mediating these effects are not known. Thus, we evaluated effects of intra-NAc infusions of pirenzepine and methoctramine, mAChR antagonisits with distinct binding affinity profiles, on operant responding for sucrose reward under a progressive ratio (PR) reinforcement schedule. Moderate to high doses of methoctramine disrupted operant responding and reduced behavioral breakpoint. In contrast, pirenzepine failed to impact operant performance at any dose tested. Methoctramine failed to affect latencies to complete appetitive-consummatory response sequences or to impact measures of acoustic startle, suggesting that its’ disruptive effects on operant behavior were not consequent to gross motor impairment. Since methoctramine has a greater affinity for M 2 receptors compared to pirenzepine, which has a greater relative affinity for M 1 and M 3 receptors, these findings suggest that M 2 mAChRs within the NAc regulate behavioral processes underling the acquisition of reward.

Sensorimotor gating in manic and mixed episode bipolar disorder

Few studies have examined acoustic startle sensorimotor gating in bipolar disorder (BPD) despite the fact that patients with BPD have exhibited inhibitory dysfunctions on a variety of early information processing tasks. The present study aimed to expand the current literature through the investigation of electromyographic (EMG) measures of acoustic startle prepulse inhibition (PPI) in manic and mixed episode BPD. Fourteen manic and 21 mixed episode BPD patients were compared to 32 healthy controls on acoustic startle measures of PPI using a 120-ms lead interval. Prepulse inhibition did not significantly differ across diagnostic groups (manic, mixed, control), and the presence of psychosis in the patient sample was not significantly related to PPI levels. With respect to startle response characteristics, patients in the mixed phase of the disorder showed prolonged prepulsed startle latency and attenuated responses to both probe-alone and prepulsed probes, though no differences in startle habituation were found across diagnostic groups. Although PPI deficits were not observed in either BPD sub-group, attenuated probe-alone and prepulsed startle magnitudes and reduced prepulse-induced latency facilitation in the mixed episode group is consistent with evidence that the mixed phase of BPD is associated with a more severe clinical outlook than other stages of the disorder. The absence of attenuated PPI in the patient sample may be due to the low incidence of psychosis in the BPD groups, though further studies are required to systematically assess the effects of symptom factors and clinical phase on sensorimotor gating in BPD.

Conditioned fear extinction and reinstatement in a human fear-potentiated startle paradigm

The purpose of this study was to analyze fear extinction and reinstatement in humans using fear-potentiated startle. Participants were fear conditioned using a simple discrimination procedure with colored lights as the conditioned stimuli (CSs) and an airblast to the throat as the unconditioned stimulus (US). Participants were extinguished 24 h after fear conditioning. Upon presentation of unsignaled USs after extinction, participants displayed significant fear reinstatement. In summary, these procedures produced robust fear-potentiated startle, significant CS+/CS- discrimination, within-session extinction, and significant reinstatement. This is the first demonstration of fear extinction and reinstatement in humans using startle measures.

Interleukin‐1β as a Mechanism for Stress‐Induced Startle Suppression in Females

Startle measures were taken 2 h following a systemic injection of interleukin-1beta (IL-1beta) (3 microg/kg) to intact or ovariectomy (OVX) female rats. Changes in startle responsivity (reduced startle magnitude) were evident in intact IL-1beta-treated rats, despite no significant effects on startle sensitivity (number of elicited startles). No significant changes in startle sensitivity or responsivity were evident in IL-1beta-treated OVX rats. These results are discussed as a possible mechanism for stress-induced suppression of startle responsivity seen in intact female rats.