-
Hearing Research Feb 2023The startle reflex (SR), a robust, motor response elicited by an intense auditory, visual, or somatosensory stimulus has been widely used as a tool to assess...
The startle reflex (SR), a robust, motor response elicited by an intense auditory, visual, or somatosensory stimulus has been widely used as a tool to assess psychophysiology in humans and animals for almost a century in diverse fields such as schizophrenia, bipolar disorder, hearing loss, and tinnitus. Previously, SR waveforms have been ignored, or assessed with basic statistical techniques and/or simple template matching paradigms. This has led to considerable variability in SR studies from different laboratories, and species. In an effort to standardize SR assessment methods, we developed a machine learning algorithm and workflow to automatically classify SR waveforms in virtually any animal model including mice, rats, guinea pigs, and gerbils obtained with various paradigms and modalities from several laboratories. The universal features common to SR waveforms of various species and paradigms are examined and discussed in the context of each animal model. The procedure describes common results using the SR across species and how to fully implement the open-source R implementation. Since SR is widely used to investigate toxicological or pharmaceutical efficacy, a detailed and universal SR waveform classification protocol should be developed to aid in standardizing SR assessment procedures across different laboratories and species. This machine learning-based method will improve data reliability and translatability between labs that use the startle reflex paradigm.
Topics: Humans; Rats; Mice; Animals; Guinea Pigs; Reflex, Startle; Acoustic Stimulation; Reproducibility of Results; Tinnitus; Disease Models, Animal; Gerbillinae
PubMed: 36566642
DOI: 10.1016/j.heares.2022.108667 -
Behavioural Brain Research Feb 2023Sensory-motor gating, the process of filtering sensory stimuli to modulate motor responses, is impaired in many psychiatric diseases but especially schizophrenia....
Sensory-motor gating, the process of filtering sensory stimuli to modulate motor responses, is impaired in many psychiatric diseases but especially schizophrenia. Sensory-motor gating assessed with the prepulse inhibition paradigm (PPI) measures startle in response to preceding acoustic stimuli. PPI studies in rodents have consistently found that neonatal hippocampal lesions impair sensory-motor gating in adult animals, but its applicability to primates has yet to be tested. The study examined acoustic startle responses and PPI in adult rhesus monkeys with neonatal lesions of the hippocampus (Neo-Hibo), amygdala (Neo-Aibo), and orbital frontal cortex areas 11 and 13 (Neo-Oasp) and with sham-operations (Neo-C). All monkeys were initially habituated to the startle apparatus and assayed for acoustic startle response curves. Subsequently, PPI was measured with the prepulse occurring at 60, 120, 240, 480, 1000 and 5000 msec prior to the pulse onset. No significant group differences in baseline startle were found. Compared to Neo-C monkeys, Neo-Hibo monkeys showed normal startle curves as well as normal PPI at short prepulse delays but prepulse facilitation (PPF) at longer prepulse intervals. Neo-Aibo monkeys displayed enhanced startle responses with only minor changes in PPI, whereas Neo-Oasp monkeys had severe dampening of startle responses and impaired PPI at shorter prepulse intervals. These results support prior evidence from rodent literature of the involvement of each of these areas in the development of the complex cortico-limbic circuit modulating sensory-motor gating and may shade light on the specific neural structures associated with deficits in PPI reported in neuropsychiatric disorders, such as schizophrenia, autism spectrum disorders, and post-traumatic disorders.
Topics: Animals; Prepulse Inhibition; Reflex, Startle; Amygdala; Acoustic Stimulation; Hippocampus; Frontal Lobe; Acoustics; Neural Inhibition
PubMed: 36283567
DOI: 10.1016/j.bbr.2022.114170 -
Neurological Sciences : Official... Oct 2022Tic related disorders affect 4-20% of the population, mostly idiopathic, can be grouped in a wide spectrum of severity, where the most severe end is Tourette Syndrome... (Review)
Review
Tic related disorders affect 4-20% of the population, mostly idiopathic, can be grouped in a wide spectrum of severity, where the most severe end is Tourette Syndrome (TS). Tics are arrhythmic hyperkinesias to whom execution the subject is forced by a "premonitory urge" that can be classified as sensory tic, just-right experience or urge without obsession. If an intact volitional inhibition allows patients to temporarily suppress tics, a lack or deficit in automatic inhibition is involved in the genesis of the disorder. Studies have assessed the presence of intrinsic microscopic and macroscopic anomalies in striatal circuits and relative cortical areas in association with a hyperdopaminergic state in the basal forebrain. Prepulse inhibition (PPI) of the startle reflex is a measure of inhibitory functions by which a weak sensory stimulus inhibits the elicitation of a startle response determined by a sudden intense stimulus. It is considered an operation measure of sensorimotor gating, a neural process by which unnecessary stimuli are eliminated from awareness. Evidence points out that the limbic domain of the CSTC loops, dopamine and GABA receptors within the striatum play an important role in PPI modulation. It is conceivable that a sensorimotor gating deficit may be involved in the genesis of premonitory urge and symptoms. Therefore, correcting the sensorimotor gating deficit may be considered a target for tic-related disorders therapies; in such case PPI (as well as other indirect estimators of sensorimotor gating) could represent therapeutic impact predictors.
Topics: Humans; Prepulse Inhibition; Reflex, Startle; Sensory Gating; Tics; Tourette Syndrome
PubMed: 35781754
DOI: 10.1007/s10072-022-06235-0 -
International Journal of... Dec 2023Examining appetitive and aversive responses toward body image stimuli of those with disordered eating may illuminate motivational systems unique to eating pathology. The...
Facial EMG startle response and self-report reactions after exposure to severely underweight and severely obese body images in individuals with disordered eating: An examination of motivational responses.
Examining appetitive and aversive responses toward body image stimuli of those with disordered eating may illuminate motivational systems unique to eating pathology. The current study extended previous literature by examining self-report and startle responses to a range of body sizes. In this cross-sectional design, female, adult participants (n = 45) were sorted into disordered eating (DE; n = 22) and healthy control (HC; n = 23) groups based on Eating Disorder Examination Questionnaire global scores that were one standard deviation above or below normative values. Participants viewed eight computer-generated female body pictures from each group: severely underweight (BMI < 16.0), average (BMI 18.5-24.99), and severely obese (BMI > 40.0). Startle responses and self-reported valence and anxiety scores were collected to assess implicit and explicit reactions. 2 × 3 ANCOVA/ANOVAs were used to examine startle responses and self-report differences between groups, in response to image types. Results indicated startle responses did not differ between groups. There was a significant main effect for body picture type (p < .001), after controlling for psychotropic medication. Startle responses were higher for severely underweight body images compared to severely obese body images, although non-significant at post-hoc. The DE group reported higher levels of anxiety and sadness when viewing body images compared to the HC group. Average bodies were rated as less anxiety provoking and more positive than severely underweight and obese bodies. Group differences in anxiety and valence scores could be due to more maladaptive cognitions related to fear of weight gain among people with disordered eating.
Topics: Adult; Humans; Female; Body Image; Self Report; Reflex, Startle; Cross-Sectional Studies; Thinness; Feeding and Eating Disorders; Obesity
PubMed: 37802389
DOI: 10.1016/j.ijpsycho.2023.112249 -
PloS One 2022Duchenne muscular dystrophy (DMD), an X-linked childhood-onset muscular dystrophy caused by loss of the protein dystrophin, can be associated with neurodevelopmental,...
Duchenne muscular dystrophy (DMD), an X-linked childhood-onset muscular dystrophy caused by loss of the protein dystrophin, can be associated with neurodevelopmental, emotional and behavioural problems. A DMD mouse model also displays a neuropsychiatric phenotype, including increased startle responses to threat which normalise when dystrophin is restored in the brain. We hypothesised that startle responses may also be increased in humans with DMD, which would have potential translational therapeutic implications. To investigate this, we first designed a novel discrimination fear-conditioning task and tested it in six healthy volunteers, followed by male DMD (n = 11) and Control (n = 9) participants aged 7-12 years. The aims of this methodological task development study were to: i) confirm the task efficacy; ii) optimise data processing procedures; iii) determine the most appropriate outcome measures. In the task, two neutral visual stimuli were presented: one 'safe' cue presented alone; one 'threat' cue paired with a threat stimulus (aversive noise) to enable conditioning of physiological startle responses (skin conductance response, SCR, and heart rate). Outcomes were the unconditioned physiological startle responses to the initial threat, and retention of conditioned responses in the absence of the threat stimulus. We present the protocol development and optimisation of data processing methods based on empirical data. We found that the task was effective in producing significantly higher physiological startle SCR in reinforced 'threat' trials compared to 'safe' trials (P < .001). Different data extraction methods were compared and optimised, and the optimal sampling window was derived empirically. SCR amplitude was the most effective physiological outcome measure when compared to SCR area and change in heart rate, with the best profile on data processing, the least variance, successful conditioned response retention (P = .01) and reliability assessment in test-retest analysis (rho = .86). The definition of this novel outcome will allow us to study this response in a DMD population.
Topics: Animals; Child; Conditioning, Classical; Dystrophin; Humans; Male; Mice; Muscular Dystrophy, Duchenne; Reflex, Startle; Reproducibility of Results
PubMed: 35439255
DOI: 10.1371/journal.pone.0264091 -
Molecular Psychiatry Jun 2021Measuring animal behavior in the context of experimental manipulation is critical for modeling, and understanding neuropsychiatric disease. Prepulse inhibition of the...
Measuring animal behavior in the context of experimental manipulation is critical for modeling, and understanding neuropsychiatric disease. Prepulse inhibition of the acoustic startle response (PPI) is a behavioral phenomenon studied extensively for this purpose, but the results of PPI studies are often inconsistent. As a result, the utility of this phenomenon remains uncertain. Here, we deconstruct the phenomenon of PPI and confirm several limitations of the methodology traditionally utilized to describe PPI, including that the underlying startle response has a non-Gaussian distribution, and that the traditional PPI metric changes with different stimuli. We then develop a novel model that reveals PPI to be a combination of the previously appreciated scaling of the startle response, as well as a scaling of sound processing. Using our model, we find no evidence for differences in PPI in a rat model of Fragile-X Syndrome (FXS) compared with wild-type controls. These results in the rat provide a reliable methodology that could be used to clarify inconsistent PPI results in mice and humans. In contrast, we find robust differences between wild-type male and female rats. Our model allows us to understand the nature of these differences, and we find that both the startle-scaling and sound-scaling components of PPI are a function of the baseline startle response. Males and females differ specifically in the startle-scaling, but not the sound-scaling, component of PPI. These findings establish a robust experimental and analytical approach that has the potential to provide a consistent biomarker of brain function.
Topics: Acoustic Stimulation; Acoustics; Animals; Female; Fragile X Syndrome; Male; Mice; Prepulse Inhibition; Rats; Reflex, Startle
PubMed: 32144356
DOI: 10.1038/s41380-020-0703-y -
Psychophysiology Sep 2023A heightened sensitivity to unpredictable threat has been identified as a potential transdiagnostic mechanism of psychopathology. The majority of supporting research has...
A heightened sensitivity to unpredictable threat has been identified as a potential transdiagnostic mechanism of psychopathology. The majority of supporting research has been conducted in adults, and it is unclear whether psychophysiological indicators of sensitivity to unpredictable threat are comparable in youth during developmental periods associated with increased risk for psychopathology. In addition, no studies have examined whether sensitivity to unpredictable threat is correlated between parents and their offspring. The present study examined defensive motivation (startle reflex) and attentional engagement (probe N100, P300) in anticipation of predictable and unpredictable threat in a sample of 15-year-old adolescents (N = 395) and a biological parent (N = 379). Adolescents, compared to their parents, demonstrated greater startle potentiation and probe N100 enhancement in anticipation of unpredictable threat. In addition, overall startle potentiation in anticipation of threat was correlated between the adolescents and their parents. Adolescence is a key developmental period characterized by heightened defensive motivation and attentional engagement in anticipation of both predictable and unpredictable threat. Sensitivity to threat might index is one mechanism of vulnerability that is at least partially shared between parents and their offspring.
Topics: Adult; Humans; Adolescent; Reflex, Startle; Anticipation, Psychological; Evoked Potentials; Motivation; Parents; Anxiety
PubMed: 37076982
DOI: 10.1111/psyp.14311 -
Developmental Science Jan 2021Risk for adverse outcomes, including the onset of mental illness, increases during adolescence. This increase may be linked to both new exposures, such as violence at...
Risk for adverse outcomes, including the onset of mental illness, increases during adolescence. This increase may be linked to both new exposures, such as violence at home or in the community, or to physiological changes driven by puberty. There are significant sex differences in adolescent risk, for instance, anxiety disorders are significantly more prevalent in girls than boys. Fear learning is linked to mental health and may develop during adolescence, but the role of puberty in adolescent-specific change has not yet been systematically evaluated. We conducted a longitudinal study of fear learning that tested fear-potentiated startle (FPS) in 78 children (40 girls) aged 8-16 years. Participants completed two to three visits that included a differential fear conditioning task and self-report of both pubertal status and violence exposure. We tested for effects of sex, pubertal status, and violence exposure on FPS over time with latent growth curve models. We also examined the association between FPS and later anxiety symptoms. We found significant changes in FPS to the threat cue, but not the safety cue, across visits. Higher pubertal status was significantly associated with increased FPS to threat cues at each visit, whereas sex and violence exposure were not. FPS to threat during the baseline visit also predicted later anxiety symptoms. These findings suggest that puberty drives increased fear response to threat cues similarly for girls and boys, and that this effect may not be significantly impacted by individual differences in violence exposure during early adolescence.
Topics: Adolescent; Anxiety; Child; Fear; Female; Humans; Longitudinal Studies; Male; Puberty; Reflex, Startle
PubMed: 32497415
DOI: 10.1111/desc.13000 -
Attention and affect in dysphoria: Insights from startle reflex modulation and cardiac deceleration.Behaviour Research and Therapy Aug 2020The present study investigated the interplay between attention and affective disposition during emotional processing in dysphoria. Attentional and affective startle...
The present study investigated the interplay between attention and affective disposition during emotional processing in dysphoria. Attentional and affective startle modulation and cardiac deceleration were assessed during the viewing of emotional pictures in 38 individuals with dysphoria and in 52 controls. Startle probes during picture viewing were presented at 300, 1500, 3500, 4500 ms after picture onset. Whereas controls showed the expected startle potentiation to unpleasant stimuli as compared to neutral and pleasant ones, individuals with dysphoria did not show any significant increase in startle reflex amplitude in response to unpleasant stimuli. Of note, startle potentiation during the viewing of unpleasant stimuli was significantly attenuated in the group with dysphoria relative to controls. Conversely, no significant effect concerning attentional startle modulation was noted. However, whereas individuals with dysphoria showed a prolonged cardiac deceleration when viewing unpleasant compared to neutral stimuli, the same effect was observed in controls only in the initial stage of stimuli processing. This study suggests that dysphoria is characterized by underactivation of the defensive motivational system and by prolonged attentional allocation to unpleasant stimuli. The assessment of affective startle modulation and cardiac deceleration is a valuable paradigm for unraveling dysfunctions in affective disposition and attention in dysphoria.
Topics: Affect; Attention; Depression; Emotions; Female; Heart Rate; Humans; Male; Reflex, Startle; Young Adult
PubMed: 32387705
DOI: 10.1016/j.brat.2020.103626 -
Scientific Reports Nov 2021The startle reflex in larval zebrafish describes a C-bend of the body occurring in response to sudden, unexpected, stimuli of different sensory modalities. Alterations...
The startle reflex in larval zebrafish describes a C-bend of the body occurring in response to sudden, unexpected, stimuli of different sensory modalities. Alterations in the startle reflex habituation (SRH) have been reported in various human and animal models of neurological and psychiatric conditions and are hence considered an important behavioural marker of neurophysiological function. The amplitude, offset and decay constant of the auditory SRH in larval zebrafish have recently been characterised, revealing that the measures are affected by variation in vibratory frequency, intensity, and interstimulus-interval. Currently, no study provides a model-based analysis of the effect of physical properties of light stimuli on the visual SRH. This study assessed the effect of incremental light-stimulus intensity on the SRH of larval zebrafish through a repeated-measures design. Their total locomotor responses were normalised for the time factor, based on the behaviour of a (non-stimulated) control group. A linear regression indicated that light intensity positively predicts locomotor responses due to larger SRH decay constants and offsets. The conclusions of this study provide important insights as to the effect of light properties on the SRH in larval zebrafish. Our methodology and findings constitute a relevant reference framework for further investigation in translational neurophysiological research.
Topics: Animals; Behavior, Animal; Habituation, Psychophysiologic; Larva; Light; Locomotion; Models, Animal; Reflex, Startle; Zebrafish
PubMed: 34789729
DOI: 10.1038/s41598-021-00535-9