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Psychopharmacology Aug 2008Preclinical data indicates that threat stimuli elicit two classes of defensive behaviors, those that are associated with imminent danger and are characterized by flight... (Review)
Review
RATIONALE
Preclinical data indicates that threat stimuli elicit two classes of defensive behaviors, those that are associated with imminent danger and are characterized by flight or fight (fear), and those that are associated with temporally uncertain danger and are characterized by sustained apprehension and hypervigilance (anxiety).
OBJECTIVE
The objectives of the study are 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.
Topics: Animals; Anti-Anxiety Agents; Anxiety; Conditioning, Psychological; Fear; Humans; Reflex, Startle
PubMed: 18058089
DOI: 10.1007/s00213-007-1019-1 -
Journal of Physiology and Pharmacology... Feb 2010Re-evaluation of our earlier c-Fos-like immuno-reactive studies and brainstem transection/lesion experiments in over 40 anaesthetized, non-paralyzed cats allowed... (Review)
Review
Re-evaluation of our earlier c-Fos-like immuno-reactive studies and brainstem transection/lesion experiments in over 40 anaesthetized, non-paralyzed cats allowed comparison of two distinct airway defensive reflexes with the distinct generators for inspiration (I) and expiration (E), described recently in juvenile rats. The spiration reflex (AspR) is characterized by solitary rapid and strong inspiratory effort with a reciprocal inhibition, preventing a subsequent active expiration, while the expiration reflex (ExpR) manifests by rapid and strong expiratory effort, starting without a preceding, inspiration, or reciprocal inhibition of occasional spontaneous inspiration. The retro-trapezoid nucleus/parafacial respiratory group neurones described as the distinct generator for active E in rats, are activated also during the ExpR in adult cats. Brainstem transection 5 mm above the obex eliminates the E generator and the ExpR, but preserves the I generator located in the pre-Bötzinger Complex, and also the AspR. This suggests the existence of a distinct I generator in cats as well as rats, and its contribution to the generation of the AspR. Persistence of the AspR in adult cats during asphyxic gasping, their similar character and the strong activation of I neurones at many places in the medulla and pons, suggest a common brainstem neuronal circuit contributing to generation of both the gasping and the gasp-like AspR. That the AspR and ExpR have distinct multilevel brainstem control mechanisms supports the dual theory of control and provides unique models for testing respiratory rhythm and pattern generation. The AspR may be compared with the powerful "auto-resuscitation effects of asphyxic gasping"; the ExpR may underly the effectiveness of the laryngeal chemoreflexes in prevention of lung diseases.
Topics: Animals; Brain Stem; Exhalation; Humans; Inhalation; Reflex, Startle; Respiratory Mechanics
PubMed: 20228409
DOI: No ID Found -
Scientific Reports Jan 2021Zebrafish is an established animal model for the reproduction and study of neurobiological pathogenesis of human neurological conditions. The 'startle reflex' in...
Zebrafish is an established animal model for the reproduction and study of neurobiological pathogenesis of human neurological conditions. The 'startle reflex' in zebrafish larvae is an evolutionarily preserved defence response, manifesting as a quick body-bend in reaction to sudden sensory stimuli. Changes in startle reflex habituation characterise several neuropsychiatric disorders and hence represent an informative index of neurophysiological health. This study aimed at establishing a simple and reliable experimental protocol for the quantification of startle reflex response and habituation. The fish were stimulated with 20 repeated pulses of specific vibratory frequency, acoustic intensity/power, light-intensity and interstimulus-interval, in three separate studies. The cumulative distance travelled, namely the sum of the distance travelled (mm) during all 20 stimuli, was computed as a group-level description for all the experimental conditions in each study. Additionally, by the use of bootstrapping, the data was fitted to a model of habituation with a first-order exponential representing the decay of locomotor distance travelled over repeated stimulation. Our results suggest that startle habituation is a stereotypic first-order process with a decay constant ranging from 1 to 2 stimuli. Habituation memory lasts no more than 5 min, as manifested by the locomotor activity recovering to baseline levels. We further observed significant effects of vibratory frequency, acoustic intensity/power and interstimulus-interval on the amplitude, offset, decay constant and cumulative distance travelled. Instead, the intensity of the flashed light did not contribute to significant behavioural variations. The findings provide novel insights as to the influence of different stimuli parameters on the startle reflex habituation and constitute a helpful reference framework for further investigation.
Topics: Acoustic Stimulation; Animals; Computer Simulation; Habituation, Psychophysiologic; Larva; Models, Animal; Reflex, Startle; Zebrafish
PubMed: 33436805
DOI: 10.1038/s41598-020-79923-6 -
Postgraduate Medical Journal Sep 2001Hyperekplexia (startle disease) is a rare non-epileptic disorder characterised by an exaggerated persistent startle reaction to unexpected auditory, somatosensory and... (Review)
Review
Hyperekplexia (startle disease) is a rare non-epileptic disorder characterised by an exaggerated persistent startle reaction to unexpected auditory, somatosensory and visual stimuli, generalised muscular rigidity, and nocturnal myoclonus. The genetic basis is a mutation usually of the arginine residue 271 leading to neuronal hyperexcitability by impairing glycinergic inhibition. Hyperekplexia is usually familial, most often autosomal dominant with complete penetrance and variable expression. It can present in fetal life as abnormal intrauterine movements, or later at any time from the neonatal period to adulthood. Early manifestations include abnormal responses to unexpected auditory, visual, and somatosensory stimuli such as sustained tonic spasm, exaggerated startle response, and fetal posture with clenched fists and anxious stare. The tonic spasms may mimic generalised tonic seizures, leading to apnoea and death. Consistent generalised flexor spasm in response to tapping of the nasal bridge (without habituation) is the clinical hallmark of hyperekplexia. Electroencephalography may show fast spikes initially during the tonic spasms, followed by slowing of background activity with eventual flattening corresponding to the phase of apnoea bradycardia and cyanosis. Electromyography shows a characteristic almost permanent muscular activity with periods of electrical quietness. Nerve conduction velocity is normal. No specific computed tomography findings have been reported yet. Clonazepam, a gamma aminobutyric acid (GABA) receptor agonist, is the treatment of choice for hypertonia and apnoeic episodes. It, however, may not influence the degree of stiffness significantly. A simple manoeuvre like forced flexion of the head and legs towards the trunk is known to be life saving when prolonged stiffness impedes respiration.
Topics: Diagnosis, Differential; Humans; Infant, Newborn; Muscle Rigidity; Reflex, Abnormal; Reflex, Startle
PubMed: 11524514
DOI: 10.1136/pmj.77.911.570 -
Depression and Anxiety Apr 2012Guided by the diagnostic nosology, anxiety patients are expected to show defensive hyperarousal during affective challenge, irrespective of the principal phenotype. In... (Review)
Review
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.
Topics: Amygdala; Anxiety Disorders; Chronic Disease; Defense Mechanisms; Fear; Humans; Neuropsychological Tests; Reflex, Startle
PubMed: 22511362
DOI: 10.1002/da.21891 -
Journal of Psychopharmacology (Oxford,... Oct 2015Most smokers who attempt to quit lapse within the first week and are ultimately unsuccessful in their quit attempt. Nicotine withdrawal exacerbates cognitive and...
Most smokers who attempt to quit lapse within the first week and are ultimately unsuccessful in their quit attempt. Nicotine withdrawal exacerbates cognitive and attentional problems and may be one factor in smoking relapse. The startle reflex response and prepulse inhibition (PPI) of the response are sensitive to arousal and early attentional dysregulation. The current study examined whether startle response and PPI are related to early smoking lapse, and if this differs in people with and without posttraumatic stress disorder (PTSD). Participants with (N = 34) and without (N = 57) PTSD completed a startle reflex and PPI assessment during (1) ad lib smoking (2) on the first day of abstinence during a quit attempt. Most (88%) participants lapsed within the first week of the quit attempt. PTSD status predicted shorter time to lapse. Larger startle magnitude and greater PPI predicted a longer duration before smoking lapse. When diagnostic groups were examined separately, greater PPI predicted a longer successful quit attempt only in participants with a PTSD diagnosis. The startle reflex response and PPI may provide an objective, neurophysiological evaluation of regulation of arousal and early attentional processes by nicotine, which are important factors in smoking cessation success.
Topics: Acoustic Stimulation; Adult; Arousal; Attention; Humans; Male; Nicotine; Prepulse Inhibition; Recurrence; Reflex, Startle; Smoking; Smoking Cessation; Stress Disorders, Post-Traumatic; Substance Withdrawal Syndrome; Time Factors
PubMed: 26253620
DOI: 10.1177/0269881115598319 -
Sheng Li Xue Bao : [Acta Physiologica... Dec 2014Prepulse inhibition (PPI) is suppression of the startle reflex when an intense startling stimulus is preceded by a weaker sensory stimulus (the prepulse). It is an... (Review)
Review
Prepulse inhibition (PPI) is suppression of the startle reflex when an intense startling stimulus is preceded by a weaker sensory stimulus (the prepulse). It is an operational measurement of sensorimotor gating mechanism to help human adapt to complex environment. This weak prepulse protect central cognitive processing by damping the effect of intense stimuli. Autistics cannot select out behaviorally important information from a lot of irrelevant resources and reflect abnormal gating mechanism and attentional abnormalities. Previous studies have not made agreement on whether autistic patients demonstrated deficits in PPI, because the results depend on age, sex, severity of the disease as well as the experimental parameters used. Moreover, these studies have not covered whether autistics have suffered deficits in higher-order processing. In this review, the "top-down" modulation of selective attention and subjective emotion are introduced into the PPI experiment. We also introduce fear conditioning and perceived spatial separation paradigm to further explore the interaction between autistic cognitive process and gating mechanism.
Topics: Attention; Autistic Disorder; Fear; Humans; Prepulse Inhibition; Reflex, Startle
PubMed: 25516523
DOI: No ID Found -
Journal of Psychopharmacology (Oxford,... Nov 2022Prepulse-induced startle modulation occurs when a weak sensory stimulus ('prepulse') is presented before a startling sensory stimulus ('pulse'), producing an inhibited...
The influence of stimulus onset asynchrony, task order, sex and hormonal contraception on prepulse inhibition and prepulse facilitation: Methodological considerations for drug and imaging research.
BACKGROUND
Prepulse-induced startle modulation occurs when a weak sensory stimulus ('prepulse') is presented before a startling sensory stimulus ('pulse'), producing an inhibited (Prepulse Inhibition, PPI) or facilitated (Prepulse Facilitation, PPF) startle response. We recently identified several gaps and outlined future lines of enquiry to enable a fuller understanding of the neurobiology of PPI and PPF in healthy and clinical populations. However, before embarking on these studies, it is important to consider how task and population characteristics affect these phenomena in healthy humans.
METHODS
We examined PPI and PPF in separate tasks, with counterbalanced task order across participants in one session, using a range of stimulus onset asynchronies (SOAs), in 48 healthy adults (23 men, 25 women; 10 hormonal contraceptive users) to determine which SOAs produce the strongest PPI and PPF and also explored how sex and hormonal contraception might influence PPI and PPF under these experimental conditions.
RESULTS
Both PPI and PPF were affected by SOA, with greatest PPI observed at 60 and 120 ms, and greatest PPF at 4500 and 6000 ms. PPI was influenced by sex (more PPI in men than women) and hormonal contraception, whereas PPF was affected by task order (greater PPF when the PPF task followed, rather than preceded, the PPI task).
CONCLUSIONS
Our findings indicate that studies of PPI and PPF need to consider, not only sex and hormonal status of study participants, but also task characteristics and presentation order to reduce variance and increase replicability across studies.
Topics: Adult; Male; Humans; Female; Prepulse Inhibition; Acoustic Stimulation; Hormonal Contraception; Reflex, Startle
PubMed: 36268723
DOI: 10.1177/02698811221133469 -
Neuroscience and Biobehavioral Reviews May 2023The startle response consists of whole-body muscle contractions, eye-blink, accelerated heart rate, and freezing in response to a strong, sudden stimulus. It is... (Review)
Review
The startle response consists of whole-body muscle contractions, eye-blink, accelerated heart rate, and freezing in response to a strong, sudden stimulus. It is evolutionarily preserved and can be observed in any animal that can perceive sensory signals, indicating the important protective function of startle. Startle response measurements and its alterations have become a valuable tool for exploring sensorimotor processes and sensory gating, especially in the context of pathologies of psychiatric disorders. The last reviews on the neural substrates underlying acoustic startle were published around 20 years ago. Advancements in methods and techniques have since allowed new insights into acoustic startle mechanisms. This review is focused on the neural circuitry that drives the primary acoustic startle response in mammals. However, there have also been very successful efforts to identify the acoustic startle pathway in other vertebrates and invertebrates in the past decades, so at the end we briefly summarize these studies and comment on the similarities and differences between species.
Topics: Animals; Reflex, Startle; Acoustic Stimulation; Mammals
PubMed: 36914078
DOI: 10.1016/j.neubiorev.2023.105129 -
Scientific Reports Aug 2023Two studies examined the amplitude of the startle response as a function of the Dark Tetrad of personality (narcissism, Machiavellianism, psychopathy, and sadism). We...
Two studies examined the amplitude of the startle response as a function of the Dark Tetrad of personality (narcissism, Machiavellianism, psychopathy, and sadism). We measured electromyographic activity of the orbicularis oculi muscle evoked by a startle stimulus while participants viewed images on a computer screen. Both studies revealed a negative correlation between general startle reactivity (averaged across positive, negative, and neutral images) and sadistic tendencies. In Study 2, all four dark traits were negative correlates of general startle reactivity. Study 2 also examined the personality correlates of aversive startle potentiation (ASP; indexed by greater reactivity while viewing negatively-valenced images than positive or neutral images). ASP correlated negatively with a variety of personality measures of psychopathy and sadism, their facets, and related personality tendencies (callousness, risk-taking, and restricted affect). These findings suggest that ordinary people with high levels of callousness and antagonism display physiological evidence of non-reactivity (i.e., blunted acoustic startle in general), whereas psychopathy and sadism are preferentially associated with reduced ASP.
Topics: Humans; Reflex, Startle; Sadism; Antisocial Personality Disorder; Personality Disorders; Personality
PubMed: 37648765
DOI: 10.1038/s41598-023-41043-2