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Current Topics in Behavioral... 2016Animal models of impaired sensorimotor gating, as assessed by prepulse inhibition (PPI) of startle, have demonstrated clear validity at face, predictive, and construct... (Review)
Review
Animal models of impaired sensorimotor gating, as assessed by prepulse inhibition (PPI) of startle, have demonstrated clear validity at face, predictive, and construct levels for schizophrenia therapeutics, neurophysiological endophenotypes, and potential causative insults for this group of disorders. However, with the growing recognition of the heterogeneity of the schizophrenias, and the less sanguine view of the clinical value of antipsychotic (AP) medications, our field must look beyond "validity," to assess the actual utility of these models. At a substantial cost in terms of research support and intellectual capital, what has come from these models, that we can say has actually helped schizophrenia patients? Such introspection is timely, as we are reassessing not only our view of the genetic and pathophysiological diversity of these disorders, but also the predominant strategies for SZ therapeutics; indeed, our field is gaining awareness that we must move away from a "find what's broke and fix it" approach, toward identifying spared neural and cognitive function in SZ patients, and matching these residual neural assets with learning-based therapies. Perhaps, construct-valid models that identify evidence of "spared function" in neural substrates might reveal opportunities for future therapeutics and allow us to study these substrates at a mechanistic level to maximize opportunities for neuroplasticity. Such an effort will require a retooling of our models, and more importantly, a re-evaluation of their utility. For animal models to remain relevant in the search for schizophrenia therapeutics, they will need to focus less on what is valid and focus more on what is useful.
Topics: Acoustic Stimulation; Animals; Disease Models, Animal; Humans; Reflex, Startle; Schizophrenia; Schizophrenic Psychology; Sensory Gating
PubMed: 27311762
DOI: 10.1007/7854_2015_5012 -
Psychophysiology Jun 2021During fear conditioning, a cue (CS) signals an inevitable distal threat (US) and evokes a conditioned response that can be described as attentive immobility (freezing)....
During fear conditioning, a cue (CS) signals an inevitable distal threat (US) and evokes a conditioned response that can be described as attentive immobility (freezing). The organism remains motionless and monitors the source of danger while startle responses are potentiated, indicating a state of defensive hypervigilance. Although in animals vagally mediated fear bradycardia is also reliably observed under such circumstances, results are mixed in human fear conditioning. Using a single-cue fear conditioning and extinction protocol, we tested cardiac reactivity and startle potentiation indexing low-level defensive strategies in a fear-conditioned (n = 40; paired presentations of CS and US) compared with a non-conditioned control group (n = 40; unpaired presentations of CS and US). Additionally, we assessed shock expectancy ratings on a trial-by-trial basis indexing declarative knowledge of the previous contingencies. Half of each group underwent extinction under sham or active transcutaneous vagus nerve stimulation (tVNS), serving as additional proof of concept. We found stronger cardiac deceleration during CS presentation in the fear learning relative to the control group. This learned fear bradycardia was positively correlated with conditioned startle potentiation but not with declarative knowledge of CS-US contingencies. TVNS abolished differences in heart rate changes between both groups and removed the significant correlation between late cardiac deceleration and startle potentiation in the fear learning group. Results suggest, fear-conditioned cues evoke attentive immobility in humans, characterized by cardiac deceleration and startle potentiation. Such defensive response pattern is elicited by cues predicting inevitable distal threat and resembles conditioned fear responses observed in rodents.
Topics: Adult; Anxiety; Attention; Bradycardia; Conditioning, Classical; Cues; Emotions; Fear; Female; Humans; Learning; Male; Reflex, Startle; Transcutaneous Electric Nerve Stimulation; Vagus Nerve; Young Adult
PubMed: 33759212
DOI: 10.1111/psyp.13812 -
Cognitive, Affective & Behavioral... Aug 2023A widely shared framework suggests that anxiety maps onto two dimensions: anxious apprehension and anxious arousal. Previous research linked individual differences in...
A widely shared framework suggests that anxiety maps onto two dimensions: anxious apprehension and anxious arousal. Previous research linked individual differences in these dimensions to differential neural response patterns in neuropsychological, imaging, and physiological studies. Differential effects of the anxiety dimensions might contribute to inconsistencies in prior studies that examined neural processes underlying anxiety, such as hypersensitivity to unpredictable threat. We investigated the association between trait worry (as a key component of anxious apprehension), anxious arousal, and the neural processing of anticipated threat. From a large online community sample (N = 1,603), we invited 136 participants with converging and diverging worry and anxious arousal profiles into the laboratory. Participants underwent the NPU-threat test with alternating phases of unpredictable threat, predictable threat, and safety, while physiological responses (startle reflex and startle probe locked event-related potential components N1 and P3) were recorded. Worry was associated with increased startle responses to unpredictable threat and increased attentional allocation (P3) to startle probes in predictable threat anticipation. Anxious arousal was associated with increased startle and N1 in unpredictable threat anticipation. These results suggest that trait variations in the anxiety dimensions shape the dynamics of neural processing of threat. Specifically, trait worry seems to simultaneously increase automatic defensive preparation during unpredictable threat and increase attentional responding to threat-irrelevant stimuli during predictable threat anticipation. The current study highlights the utility of anxiety dimensions to understand how physiological responses during threat anticipation are altered in anxiety and supports that worry is associated with hypersensitivity to unpredictable, aversive contexts.
Topics: Humans; Reflex, Startle; Anxiety; Evoked Potentials; Anxiety Disorders; Arousal; Anticipation, Psychological
PubMed: 37106311
DOI: 10.3758/s13415-023-01094-4 -
The Journal of Neuroscience : the... Jan 2023Despite the clinical significance of prepulse inhibition (PPI), the mechanisms are not well understood. Herein, we present our investigation of PPI in the R1 component...
Despite the clinical significance of prepulse inhibition (PPI), the mechanisms are not well understood. Herein, we present our investigation of PPI in the R1 component of electrically induced blink reflexes. The effect of a prepulse was explored with varying prepulse test intervals (PTIs) of 20-600 ms in 4 females and 12 males. Prepulse-test combinations included the following: stimulation of the supraorbital nerve (SON)-SON [Experiment (Exp) 1], sound-sound (Exp 2), the axon of the facial nerve-SON (Exp 3), sound-SON (Exp 4), and SON-SON with a long trial-trial interval (Exp 5). Results showed that (1) leading weak SON stimulation reduced SON-induced ipsilateral R1 with a maximum effect at a PTI of 140 ms, (2) the sound-sound paradigm resulted in a U-shaped inhibition time course of the auditory startle reflex (ASR) peaking at 140 ms PTI, (3) facial nerve stimulation showed only a weak effect on R1, (4) a weak sound prepulse facilitated R1 but strongly inhibited SON-induced late blink reflexes (LateRs) with a similar U-shaped curve, and (5) LateR in Exp 5 was almost completely absent at PTIs >80 ms. These results indicate that the principal sensory nucleus is responsible for R1 PPI. Inhibition of ASR or LateR occurs at a point in the startle reflex circuit where auditory and somatosensory signals converge. Although the two inhibitions are different in location, their similar time courses suggest similar neural mechanisms. As R1 has a simple circuit and is stable, R1 PPI helps to clarify PPI mechanisms. Prepulse inhibition (PPI) is a phenomenon in which the startle response induced by a startle stimulus is suppressed by a preceding nonstartle stimulus. This study demonstrated that the R1 component of the trigeminal blink reflex shows clear PPI despite R1 generation within a circuit consisting of the trigeminal and facial nuclei, without startle reflex circuit involvement. Thus, PPI is not specific to the startle reflex. In addition, PPI of R1, the auditory startle reflex, and the trigeminal late blink reflex showed similar time courses in response to the prepulse test interval, suggesting similar mechanisms regardless of inhibition site. R1 PPI, in conjunction with other paradigms with different prepulse-test combinations, would increase understanding of the underlying mechanisms.
Topics: Male; Female; Humans; Prepulse Inhibition; Blinking; Reflex, Startle; Sound; Acoustic Stimulation
PubMed: 36443001
DOI: 10.1523/JNEUROSCI.1468-22.2022 -
International Journal of... Sep 2017Anticipated emotional category and temporal predictability are key characteristics that have both been shown to impact psychophysiological indices of defensive...
Anticipated emotional category and temporal predictability are key characteristics that have both been shown to impact psychophysiological indices of defensive motivation (e.g., the startle reflex). To date, research has primarily examined these features in isolation, and it is unclear whether they have additive or interactive effects on defensive motivation. In the present study, the startle reflex was measured in anticipation of low arousal neutral, moderate arousal pleasant, and high arousal unpleasant pictures that were presented with either predictable or unpredictable timing. Linear mixed-effects modeling was conducted to examine startle magnitude across time, and the intercept at the beginning and end of the task. Across the entire task, the anticipation of temporally unpredictable (relative to predictable) pictures and emotional (relative to neutral) pictures potentiated startle magnitude, but there was no interaction between the two features. However, examination of the intercept at the beginning of the task indicated a Predictability by Emotional Category interaction, such that temporal unpredictability enhanced startle potentiation in anticipation of unpleasant pictures only. Examination of the intercept at the end of the task indicated that the effects of predictability and emotional category on startle magnitude were largely diminished. The present study replicates previous reports demonstrating that emotional category and temporal predictability impact the startle reflex, and provides novel evidence suggesting an interactive effect on defensive motivation at the beginning of the task. This study also highlights the importance of examining the time course of the startle reflex.
Topics: Adult; Anticipation, Psychological; Electromyography; Emotions; Female; Humans; Male; Pattern Recognition, Visual; Reflex, Startle; Time Perception; Young Adult
PubMed: 28315361
DOI: 10.1016/j.ijpsycho.2017.03.003 -
Psychophysiology Dec 2015Previous research indicates that predictive cues can dampen subsequent defensive reactions. The present study investigated whether effects of cuing are specific to...
Previous research indicates that predictive cues can dampen subsequent defensive reactions. The present study investigated whether effects of cuing are specific to aversive stimuli, using modulation of the blink startle reflex as a measure of emotional reactivity. Participants viewed pictures depicting violence, romance/erotica, or mundane content. On half of all trials, a cue (color) predicted the content of the upcoming picture; on the remaining trials, scenes were presented without a cue. Acoustic startle probes were presented during picture viewing on trials with predictive cues and trials without a cue. Replicating previous studies, blink reflexes elicited when viewing violent pictures that had not been preceded by a cue were potentiated compared to uncued mundane scenes, and reflexes were attenuated when viewing scenes of erotica/romance that had not been cued. On the other hand, reflex potentiation when viewing scenes of violence (relative to mundane scenes) was eliminated when these pictures were preceded by a predictive cue, whereas scenes of romance prompted reliable reflex attenuation regardless of whether pictures were cued or not. Taken together, the data suggest that cuing elicits an anticipatory coping process that is specific to aversive stimuli.
Topics: Adolescent; Blinking; Cues; Emotions; Female; Humans; Male; Photic Stimulation; Reflex; Reflex, Startle; Young Adult
PubMed: 26399464
DOI: 10.1111/psyp.12546 -
International Journal of... Feb 2023There is growing evidence of beneficial effects of mindfulness developed through engaging in mindfulness training/practices on sensory and cognitive processing, emotion...
There is growing evidence of beneficial effects of mindfulness developed through engaging in mindfulness training/practices on sensory and cognitive processing, emotion regulation and mental health. Mindfulness has also been conceptualised as a dispositional 'trait', i.e. the naturally-occurring ability of meditation-naïve individuals to display, in varying degree, a non-judgmental non-reactive present-moment awareness in everyday life. In this study we examined possible associations between dispositional mindfulness, alexithymia and sensory processing. Eye-blink startle responses to acoustic stimuli of varying intensity [90-dB or 100-dB over 70-dB (A) background] were assessed in 26 meditation-naïve adults (50 % men) using electromyographic recordings of the orbicularis muscle. All participants completed the Five Facet Mindfulness Questionnaire and the 20-item Toronto Alexithymia Scale. A negative association was found between dispositional mindfulness and alexithymia (r = -0.513). There was stronger startle habituation to 100-dB, compared to 90-dB probes. Stronger startle habituation (larger negative habitation slope values) to 100-dB probes was significantly associated with higher dispositional mindfulness (r = -0.528) and with lower alexithymia at trend level (r = 0.333). As indicated by commonality analysis, 10.6 % of explained variance in habituation (100-dB probes) was common to both alexithymia and mindfulness, 17.3 % was unique to mindfulness, but alexithymia made negligible unique contribution (0.5 %). These findings indicate similar startle habituation pattern in people with a high level of dispositional mindfulness to that reported previously by Antonova et al. (2015) in people with moderate mindfulness meditation practice intensity. Future studies should investigate the mechanisms, such as interoceptive awareness, that might underly these relationships.
Topics: Adult; Male; Humans; Female; Reflex, Startle; Affective Symptoms; Habituation, Psychophysiologic; Mindfulness; Perception
PubMed: 36513183
DOI: 10.1016/j.ijpsycho.2022.12.002 -
Neuroreport Mar 2023The potassium voltage-gated channel subfamily Q member 4 (KCNQ4) subunit forms channels responsible for M-current, a muscarine-sensitive potassium current regulating...
The potassium voltage-gated channel subfamily Q member 4 (KCNQ4) subunit forms channels responsible for M-current, a muscarine-sensitive potassium current regulating neuronal excitability. In contrast to other KCNQ subunits, its expression is restricted to the cochlear outer hair cells, the auditory brainstem and other brainstem nuclei in a great overlap with structures involved in startle reflex. We aimed to show whether startle reflexis affected by the loss of KCNQ4 subunit and whether these alterations are similar to the ones caused by brainstem hyperexcitability. Young adult KCNQ4 knockout mice and wild-type littermates, as well as mice expressing hM3D chemogenetic actuator in the pontine caudal nucleus and neurons innervating it were used for testing acoustic startle. The acoustic startle reflex was significantly increased in knockout mice compared with wild-type littermates. When mice expressing human M3 muscarinic (hM3D) in nuclei related to startle reflex were tested, a similar increase of the first acoustic startle amplitude and a strong habituation of the further responses was demonstrated. We found that the acoustic startle reflex is exaggerated and minimal habituation occurs in KCNQ4 knockout animals. These changes are distinct from the effects of the hyperexcitability of nuclei involved in startle. One can conclude that the exaggerated startle reflex found with the KCNQ4 subunit deletion is the consequence of both the cochlear damage and the changes in neuronal excitability of startle networks.
Topics: Animals; Mice; Brain Stem; KCNQ Potassium Channels; Mice, Knockout; Neurons; Reflex, Startle
PubMed: 36789839
DOI: 10.1097/WNR.0000000000001883 -
Scientific Reports Sep 2017Startle behavior is important for survival, and abnormal startle responses are related to several neurological diseases. Drosophila melanogaster provides a powerful...
Startle behavior is important for survival, and abnormal startle responses are related to several neurological diseases. Drosophila melanogaster provides a powerful system to investigate the genetic underpinnings of variation in startle behavior. Since mechanically induced, startle responses and environmental conditions can be readily quantified and precisely controlled. The 156 wild-derived fully sequenced lines of the Drosophila Genetic Reference Panel (DGRP) were used to identify SNPs and transcripts associated with variation in startle behavior. The results validated highly significant effects of 33 quantitative trait SNPs (QTSs) and 81 quantitative trait transcripts (QTTs) directly associated with phenotypic variation of startle response. We also detected QTT variation controlled by 20 QTSs (tQTSs) and 73 transcripts (tQTTs). Association mapping based on genomic and transcriptomic data enabled us to construct a complex genetic network that underlies variation in startle behavior. Based on principles of evolutionary conservation, human orthologous genes could be superimposed on this network. This study provided both genetic and biological insights into the variation of startle response behavior of Drosophila melanogaster, and highlighted the importance of genetic network to understand the genetic architecture of complex traits.
Topics: Animals; Drosophila melanogaster; Gene Regulatory Networks; Genes, Insect; Genome, Insect; Genome-Wide Association Study; Genomics; Humans; Phenotype; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Reflex, Startle
PubMed: 28959013
DOI: 10.1038/s41598-017-11676-1 -
Physiology & Behavior Feb 2017Circannual rhythms and seasonality have long been in the interest of research. In humans, seasonal changes in mood have been extensively investigated since a substantial...
Circannual rhythms and seasonality have long been in the interest of research. In humans, seasonal changes in mood have been extensively investigated since a substantial part of the population experiences worsening of mood during winter. Questions remain regarding accompanying physiological phenomena. We report seasonal effects on the acoustic startle response in a cross-sectional (n=124) and a longitudinal sample (n=23). Startle magnitudes were larger in winter (sample 1: p=0.026; sample 2: p=0.010) compared to summer months. Although the findings need to be replicated they may have implications regarding the timing of startle experiments.
Topics: Acoustic Stimulation; Adolescent; Adult; Affect; Analysis of Variance; Arousal; Cross-Sectional Studies; Female; Humans; Longitudinal Studies; Male; Reflex, Startle; Seasons; Young Adult
PubMed: 27940142
DOI: 10.1016/j.physbeh.2016.11.038