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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 -
Scientific Reports Aug 2023Ketamine is a rapid-acting antidepressant that also influences neural reactivity to affective stimuli. However, the effect of ketamine on behavioral affective reactivity... (Randomized Controlled Trial)
Randomized Controlled Trial
Ketamine is a rapid-acting antidepressant that also influences neural reactivity to affective stimuli. However, the effect of ketamine on behavioral affective reactivity is yet to be elucidated. The affect-modulated startle reflex paradigm (AMSR) allows examining the valence-specific aspects of behavioral affective reactivity. We hypothesized that ketamine alters the modulation of the startle reflex during processing of unpleasant and pleasant stimuli and weakens the resting-state functional connectivity (rsFC) within the modulatory pathway, namely between the centromedial nucleus of the amygdala and nucleus reticularis pontis caudalis. In a randomized, double-blind, placebo-controlled, cross-over study, thirty-two healthy male participants underwent ultra-high field resting-state functional magnetic resonance imaging at 7 T before and 24 h after placebo and S-ketamine infusions. Participants completed the AMSR task at baseline and one day after each infusion. In contrast to our hypothesis, ketamine infusion did not impact startle potentiation during processing of unpleasant stimuli but resulted in diminished startle attenuation during processing of pleasant stimuli. This diminishment significantly correlated with end-of-infusion plasma levels of ketamine and norketamine. Furthermore, ketamine induced a decrease in rsFC within the modulatory startle reflex pathway. The results of this first study on the effect of ketamine on the AMSR suggest that ketamine might attenuate the motivational significance of pleasant stimuli in healthy participants one day after infusion.
Topics: Male; Humans; Reflex, Startle; Cross-Over Studies; Ketamine; Brain; Emotions
PubMed: 37587171
DOI: 10.1038/s41598-023-40099-4 -
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 -
Brain, Behavior, and Immunity Mar 2023Prenatal infections can increase the risk of developing psychiatric disorders such as schizophrenia in the offspring, especially when combined with other postnatal...
Prenatal infections can increase the risk of developing psychiatric disorders such as schizophrenia in the offspring, especially when combined with other postnatal insults. Here, we tested, in a rat model of prenatal immune challenge by the viral mimic polyriboinosinic-polyribocytidilic acid, whether maternal immune activation (MIA) affects the endocannabinoid system and endocannabinoid-mediated modulation of dopamine functions. Experiments were performed during adolescence to assess i) the behavioral endophenotype (locomotor activity, plus maze, prepulse inhibition of startle reflex); ii) the locomotor activity in response to Δ9-Tetrahydrocannabinol (THC) and iii) the properties of ventral tegmental area (VTA) dopamine neurons in vivo and their response to THC; iv) endocannabinoid-mediated synaptic plasticity in VTA dopamine neurons; v) the expression of cannabinoid receptors and enzymes involved in endocannabinoid synthesis and catabolism in mesolimbic structures and vi) MIA-induced neuroinflammatory scenario evaluated by measurements of levels of cytokine and neuroinflammation markers. We revealed that MIA offspring displayed an altered locomotor activity in response to THC, a higher bursting activity of VTA dopamine neurons and a lack of response to cumulative doses of THC. Consistently, MIA adolescence offspring showed an enhanced 2-arachidonoylglycerol-mediated synaptic plasticity and decreased monoacylglycerol lipase activity in mesolimbic structures. Moreover, they displayed a higher expression of cyclooxygenase 2 (COX-2) and ionized calcium-binding adaptor molecule 1 (IBA-1), associated with latent inflammation and persistent microglia activity. In conclusion, we unveiled neurobiological mechanisms whereby inflammation caused by MIA influences the proper development of endocannabinoid signaling that negatively impacts the dopamine system, eventually leading to psychotic-like symptoms in adulthood.
Topics: Pregnancy; Female; Rats; Male; Animals; Humans; Endocannabinoids; Dopamine; Signal Transduction; Schizophrenia; Dopaminergic Neurons; Prenatal Exposure Delayed Effects
PubMed: 36746342
DOI: 10.1016/j.bbi.2023.02.002 -
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 -
Evolutionary Human Sciences 2022Why do we leak lubricant from the eyes to solicit comfort from others? Why do we bare our teeth and crinkle our faces to express non-aggression? The defensive mimic... (Review)
Review
Why do we leak lubricant from the eyes to solicit comfort from others? Why do we bare our teeth and crinkle our faces to express non-aggression? The defensive mimic theory proposes that a broad range of human emotional expressions evolved originally as exaggerated, temporally extended mimics of the fast, defensive reflexes that normally protect the body surface. Defensive reflexes are so important to survival that they cannot be safely suppressed; yet they also broadcast information about an animal's internal state, information that can potentially be exploited by other animals. Once others can observe and exploit an animal's defensive reflexes, it may be advantageous to the animal to run interference by creating mimic defensive actions, thereby manipulating the behaviour of others. Through this interaction over millions of years, many human emotional expressions may have evolved. Here, human social signals including smiling, laughing and crying, are compared component-by-component with the known, well-studied features of primate defensive reflexes. It is suggested that the defensive mimic theory can adequately account for the physical form of not all, but a large range of, human emotional expression.
PubMed: 37588928
DOI: 10.1017/ehs.2022.5 -
Brain Sciences Sep 2020When a low-salience stimulus of any type of sensory modality-auditory, visual, tactile-immediately precedes an unexpected startle-like stimulus, such as the acoustic... (Review)
Review
When a low-salience stimulus of any type of sensory modality-auditory, visual, tactile-immediately precedes an unexpected startle-like stimulus, such as the acoustic startle reflex, the startle motor reaction becomes less pronounced or is even abolished. This phenomenon is known as prepulse inhibition (PPI), and it provides a quantitative measure of central processing by filtering out irrelevant stimuli. As PPI implies plasticity of a reflex and is related to automatic or attentional processes, depending on the interstimulus intervals, this behavioral paradigm might be considered a potential marker of short- and long-term plasticity. Assessment of PPI is directly related to the examination of neural sensorimotor gating mechanisms, which are plastic-adaptive operations for preventing overstimulation and helping the brain to focus on a specific stimulus among other distracters. Despite their obvious importance in normal brain activity, little is known about the intimate physiology, circuitry, and neurochemistry of sensorimotor gating mechanisms. In this work, we extensively review the current literature focusing on studies that used state-of-the-art techniques to interrogate the neuroanatomy, connectomics, neurotransmitter-receptor functions, and sex-derived differences in the PPI process, and how we can harness it as biological marker in neurological and psychiatric pathology.
PubMed: 32947873
DOI: 10.3390/brainsci10090639 -
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 -
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 -
Iranian Journal of Basic Medical... Oct 2022Tinnitus is defined as ringing of the ears that is experienced when there is no external sound source, and is an auditory phantom sensation. The insula as a multimodal...
OBJECTIVES
Tinnitus is defined as ringing of the ears that is experienced when there is no external sound source, and is an auditory phantom sensation. The insula as a multimodal cortex has been shown to be involved in the processing of auditory stimuli rather than other sensory and motor processing and reported to correlate with some aspects of tinnitus. However, its exact role is not clear. The present study aimed to investigate the effect of excitotoxic lesions limited to the insular cortex on the ability to detect a gap in background noise.
MATERIALS AND METHODS
Gap detection test and prepulse inhibition, two objective measurements of auditory startle response, were measured, in 33 male Wistar rats, before and up to four weeks after insular lesion in three experimental groups (sham, control, and lesion).
RESULTS
The ability to detect the gap interposed between 60 db background noise was impaired at weeks 2, 3, and 4 following insular lesion, while prepulse inhibition remained intact up to four weeks after surgery.
CONCLUSION
These findings indicated that excitotoxic lesions of the insular cortex may produce a tinnitus-like phenomenon in rats while sparing the hearing sensitivity; suggesting that the insular cortex may have a role in the development of tinnitus.
PubMed: 36311202
DOI: 10.22038/IJBMS.2022.63698.14083