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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 -
Brain : a Journal of Neurology Jul 2020Neurological examination of non-communicating patients relies on a few decisive items that enable the crucial distinction between vegetative state (VS)-also coined...
Neurological examination of non-communicating patients relies on a few decisive items that enable the crucial distinction between vegetative state (VS)-also coined unresponsive wakefulness syndrome (UWS)-and minimally conscious state. Over the past 10 years, this distinction has proven its diagnostic value as well as its important prognostic value on consciousness recovery. However, clinicians are currently limited by three factors: (i) the current behavioural repertoire of minimally conscious state items is limited and restricted to a few cognitive domains in the goldstandard revised version of the Coma Recovery Scale; (ii) a proportion of ∼15-20% clinically VS/UWS patients are actually in a richer state than VS/UWS as evidenced by functional brain imaging; and (iii) the neurophysiological and cognitive interpretation of each minimally conscious state item is still unclear and debated. In the current study we demonstrate that habituation of the auditory startle reflex (hASR) tested at bedside constitutes a novel, simple and powerful behavioural sign that can accurately distinguish minimally conscious state from VS/UWS. In addition to enlarging the minimally conscious state items repertoire, and therefore decreasing the low sensitivity of current behavioural measures, we also provide an original and rigorous description of the neurophysiological basis of hASR through a combination of functional (high density EEG and 18F-fluorodeoxyglucose PET imaging) and structural (diffusion tensor imaging MRI) measures. We show that preservation of hASR is associated with the functional and structural integrity of a brain-scale fronto-parietal network, including prefrontal regions related to control of action and inhibition, and meso-parietal areas associated with minimally conscious and conscious states. Lastly, we show that hASR predicts 6-month improvement of consciousness. Taken together, our results show that hASR is a cortically-mediated behaviour, and suggest that it could be a new clinical item to clearly and accurately identify non-communicating patients who are in the minimally conscious state.
Topics: Adult; Brain; Female; Habituation, Psychophysiologic; Humans; Male; Middle Aged; Persistent Vegetative State; Recovery of Function; Reflex, Startle
PubMed: 32582938
DOI: 10.1093/brain/awaa159 -
Psychophysiology Sep 2008The acoustic startle reflex and its modulation by a prepulse are psychophysiological phenomena that are commonly studied to evaluate various aspects of information... (Comparative Study)
Comparative Study
The acoustic startle reflex and its modulation by a prepulse are psychophysiological phenomena that are commonly studied to evaluate various aspects of information processing. Recent reports in human populations suggest that subjects from disparate racial backgrounds may have significant differences in the startle response. To determine if this pattern could be observed in our subject population and whether it extended to prepulse inhibition (PPI), we evaluated baseline startle parameters and PPI in 53 African-Americans (AA) and 38 European-Americans (EA). In AA compared to EA, mean startle magnitude and probability of blink response were lower, with no difference in habituation. PPI was greater in AA than EA when groups were matched on baseline startle magnitude. These findings support the idea of racial differences in startle response. Implications for study design are highlighted, and possible environmental and genetic influences are considered.
Topics: Acoustic Stimulation; Adult; Black or African American; Electromyography; Ethnicity; Female; Humans; Male; Middle Aged; Reflex, Startle; White People
PubMed: 18665868
DOI: 10.1111/j.1469-8986.2008.00680.x -
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 -
PloS One 2013A working model of the neurophysiology of hypnosis suggests that highly hypnotizable individuals (HHs) have more effective frontal attentional systems implementing...
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.
Topics: Adult; Electromyography; Evoked Potentials; Female; Gyrus Cinguli; Humans; Hypnosis; Male; Parietal Lobe; Reaction Time; Reflex, Startle; Young Adult
PubMed: 24278150
DOI: 10.1371/journal.pone.0079605 -
Research on Child and Adolescent... Oct 2022Numerous studies in children, adolescents and adults have reported that anxiety disorders and symptoms are associated with greater threat-potentiated startle responses....
Numerous studies in children, adolescents and adults have reported that anxiety disorders and symptoms are associated with greater threat-potentiated startle responses. This suggests that it may also be related to risk factors that have been implicated in the genesis of anxiety disorders. Therefore, we examined the roles of early childhood temperamental behavioral inhibition (BI) and parental history of anxiety disorders in predicting threat-potentiated startle response in a community sample of 346 adolescents. Parental history of anxiety disorders moderated the effects of BI on subsequent startle responses. For both total startle response and unpredictable threat startle potentiation, higher levels of BI at age 3 predicted larger startle responses at age 15, but only among offspring of parents with a history of anxiety disorders. Among offspring of parents with no lifetime history of anxiety disorder, BI was unrelated to startle magnitude. These findings were evident even after adjusting for youth's biological sex, concurrent anxiety symptoms, and lifetime history of anxiety disorders. In contrast, neither BI nor parental anxiety significantly predicted startle potentiation to predictable threat. These findings have implications for tracing pathways to the development of anxiety disorders.
Topics: Child; Adult; Humans; Adolescent; Child, Preschool; Reflex, Startle; Fear; Inhibition, Psychological; Anxiety Disorders; Parents
PubMed: 35689731
DOI: 10.1007/s10802-022-00942-0 -
Journal of Abnormal Child Psychology Feb 2017There is growing evidence that heightened sensitivity to unpredictability is a core mechanism of anxiety disorders. In adults, multiple anxiety disorders have been...
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.
Topics: Adolescent; Anticipation, Psychological; Anxiety; Child; Depression; Female; Humans; Reflex, Startle
PubMed: 27224989
DOI: 10.1007/s10802-016-0169-1 -
Biological Psychiatry. Cognitive... Jul 2018The National Institute of Mental Health Research Domain Criteria initiative encourages a search for dimensional biological measures of psychopathology unconstrained by...
BACKGROUND
The National Institute of Mental Health Research Domain Criteria initiative encourages a search for dimensional biological measures of psychopathology unconstrained by current diagnostic categories. Consistent with this aim, the presented research studies a large sample of anxiety and mood disorder patients, assessing differences in principal diagnoses and comorbidity patterns, clinicians' ratings, and questionnaire measures of negative affect and life dysfunction as they relate to a potential brain marker of pathology: the amplitude of the event-related potential (ERP) elicited by a startle-evoking stimulus.
METHODS
Patients seeking evaluation or treatment for anxiety and mood disorders (N = 208) participated in two tasks at the University of Florida (Gainesville, FL): 1) imagining emotional and neutral events and 2) viewing emotional and neutral pictures while acoustic startle probes were presented and the ERP was recorded. For a comparison patient group (N = 120), startle probes were administered and ERPs recorded at the University of Greifswald (Greifswald, Germany) while performing the same imagery task.
RESULTS
Reduced positive amplitude of a centroparietal startle-evoked ERP (156-352 ms after onset) significantly predicted higher questionnaire scores of anxiety/depression, reports of increased life dysfunction, greater comorbidity, and clinician ratings of heightened severity and poorer prognosis. The effect was general across principal diagnoses, found for both the Florida and German samples, and consistent in pattern despite differences in the tasks administered.
CONCLUSIONS
The startle-evoked ERP reliably predicts severity and breadth of psychopathology, independent of task context. It is a potential significant contributor to a needed array of biological measures that might improve classification of anxiety and mood disorders.
Topics: Adult; Anxiety Disorders; Auditory Perception; Cerebral Cortex; Electroencephalography; Evoked Potentials; Female; Humans; Male; Mood Disorders; Pattern Recognition, Visual; Reflex, Startle; Severity of Illness Index
PubMed: 30047478
DOI: 10.1016/j.bpsc.2017.07.006 -
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 -
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