Choline Metabolites Reverse Differentially the Habituation Deficit and Elevated Memory of Tau Null Drosophila.

Impaired neuronal plasticity and cognitive decline are cardinal features of Alzheimer's disease and related Tauopathies. Aberrantly modified Tau protein and neurotransmitter imbalance, predominantly involving acetylcholine, have been linked to these symptoms. In Drosophila, we have shown that dTau loss specifically enhances associative long-term olfactory memory, impairs foot shock habituation, and deregulates proteins involved in the regulation of neurotransmitter levels, particularly acetylcholine. Interestingly, upon choline treatment, the habituation and memory performance of mutants are restored to that of control flies. Based on these surprising results, we decided to use our well-established genetic model to understand how habituation deficits and memory performance correlate with different aspects of choline physiology as an essential component of the neurotransmitter acetylcholine, the lipid phosphatidylcholine, and the osmoregulator betaine. The results revealed that the two observed phenotypes are reversed by different choline metabolites, implying that they are governed by different underlying mechanisms. This work can contribute to a broader knowledge about the physiologic function of Tau, which may be translated into understanding the mechanisms of Tauopathies.

Environmental conditions shape learning in larval zebrafish.

Growing evidence reveals notable phenotypic plasticity in cognition among teleost fishes. One compelling example is the positive impact of enriched environments on learning performance. Most studies on this effect have focused on juvenile or later life stages, potentially overlooking the importance of early life plasticity. To address this gap, we investigated whether cognitive plasticity in response to environmental factors emerges during the larval stage in zebrafish. Our findings indicate that larvae exposed to an enriched environment after hatching exhibited enhanced habituation learning performance compared to their counterparts raised in a barren environment. This work underscores the presence of developmental phenotypic plasticity in cognition among teleost fish, extending its influence to the very earliest stages of an individual's life.

Long-term disgust habituation with limited generalisation in care home workers.

Countless workers handle bodily effluvia and body envelope violations every working day, and consequentially face deeply unpleasant levels of disgust. Understanding if and how they adapt can help inform policies to improve worker satisfaction and reduce staff turnover. So far, limited evidence exist that self-reported disgust is reduced (or lower to begin with) among those employed in high-disgust environments. However, it is unclear if this is due to demand effects or translates into real behavioural changes. Here, we tested healthcare assistants (N = 32) employed in UK care homes and a control sample (N = 50). We replicated reduced self-reported pathogen disgust sensitivity in healthcare workers compared to controls. We also found it negatively correlated with career duration, suggesting long-term habituation. Furthermore, we found that healthcare assistants showed no behavioural disgust avoidance on a web-based preferential looking task (equivalent to eye tracking). Surprisingly, this extended to disgust elicitors found outside care homes, suggesting generalisation of disgust habituation. While we found no difference between bodily effluvia (core disgust) and body envelope violations (gore disgust), generalisation did not extend to other domains: self-reported sexual and moral disgust sensitivity were not different between healthcare assistants and the control group, nor was there a correlation with career duration. In sum, our work confirms that people in high-frequency disgust employment are less sensitive to pathogen disgust. Crucially, we provide preliminary evidence that this is due to a process of long-term habituation with generalisation to disgust-elicitors within the pathogen domain, but not beyond it.

Electrodermal and central measures of the tonic orienting reflex (OR).

Sokolov described both phasic and tonic aspects of the Orienting Reflex (OR), but subsequent research and theory development has focussed primarily on the phasic OR at the expense of the tonic OR. The present study used prestimulus skin conductance level (SCL) during a dishabituation paradigm to model the tonic OR, examining its amplitude patterning over repeated standard stimulus presentations and a change stimulus. We expected sensitisation (increased amplitude) following the initial and change trials, and habituation (decrement) over the intervening trials. Prestimulus EEG alpha level was explored as a potential central measure of the tonic OR (as an inverse correlate), examining its pattern over stimulus repetition and change in relation to the SCL model. We presented a habituation series of innocuous auditory stimuli to two groups (each N = 20) at different ISIs (Long 13-15 s and Short 5-7 s) and recorded electrodermal and EEG data during two counterbalanced conditions; Indifferent: no task requirements; Significant: silent counting. Across groups and conditions, prestimulus SCLs and alpha amplitudes generally showed the expected trials patterns, confirming our main hypotheses. Findings have important implications for including the assessment of Sokolov's tonic OR in modelling central and autonomic nervous system interactions of fundamental attention and learning processes.

Tracking the habituation of the event-related EEG potential in automatic change detection using an auditory two-tone oddball paradigm.

The mismatch negativity and the P3a of the event-related EEG potential reflect the electrocortical response to a deviant stimulus in a series of stimuli. Although both components have been investigated in various paradigms, these paradigms usually incorporate many repetitions of the same deviant, thus leaving open whether both components vary as a function of the deviant's position in a series of deviant stimuli-i.e. whether they are subject to qualitative/quantitative habituation from one instantiation of a deviant to the next. This is so because the detection of mismatch negativity/P3a in the event-related EEG potential requires an averaging over dozens or hundreds of stimuli, i.e. over many instantiations of the deviant per participant. The present study addresses this research gap. We used a two-tone oddball paradigm implementing only a small number of (deviant) stimuli per participant, but applying it to a large number of participants (n > 230). Our data show that the mismatch negativity amplitude exhibits no decrease as a function of the deviant's position in a series of (standard and) deviant stimuli. Importantly, only after the very first deviant stimulus, a distinct P3a could be detected, indicative of an orienting reaction and an attention shift, and thus documenting a dissociation of mismatch negativity and P3a.

Habituation to a predatory stimulus in a harvester (Arachnida, Opiliones).

Several studies have investigated habituation in a defensive context, but few have addressed responses to dangerous stimuli. In such cases, animals should not habituate since this could cost their lives. Here we have stimulated individuals of the harvester Mischonyx squalidus with a predatory stimulus (squeezing with tweezers) in repeated trials within and between days, and measured the occurrence and magnitude of nipping, a defensive behavior. Contrary to our expectations, they did habituate to this stimulus. The probability and magnitude of response declined over trials during each of three days of testing in a typical habituation pattern. During the trials we also observed other defensive behaviors. We discuss our results mainly considering alternative defensive responses. Our data show that we lack information on (1) the role played by the ambiguity of stimuli, (2) the role played by subsequent stimuli and (3) the importance of the array of defensive behaviors of a species in understanding habituation. Although ubiquitous across animals and therefore expected, habituation is described for the first time in the order Opiliones.

Rhesus monkeys show greater habituation to repeated computer-generated images than do orangutans.

Humans and several other species of animals have demonstrated the ability to use familiarity to recognize that they have seen images before. In prior experiments, orangutans failed to show use of familiarity in memory tasks, even when other solutions were not available. We tested for evidence of habituation, a decreased response to repeated stimuli, as a behavioral indicator that repeated images were familiar to subjects. Monkeys and orangutans selected the smallest target out of four while computerized images were presented as distractors. Latency to complete the target-finding task was compared between conditions in which the distractor image was a familiar, repeating image, a novel, never-before-seen image, or no distractor was present. Rhesus macaques showed significant habituation, and significantly more habituation than orangutans, in each of four experiments. Orangutans showed statistically reliable habituation in only one of the four experiments. These results are consistent with previous research in which orangutans failed to demonstrate familiarity. Because we expect that familiarity and habituation are evolutionarily ancient memory processes, we struggle to explain these surprising, but consistent findings. Future research is needed to determine why orangutans respond to computerized images in this peculiar way.

Repeated exposure to body-related memories in women with high body-related self-disgust: Impact on disgust, avoidance, and acceptance.

Disgust-based body image concerns can bias autobiographical memory towards the recall and avoidant processing of disgust-related memories of the own body. Repeated exposure to such memories may help breaking avoidance and promote the habituation of disgust, thereby lowering body concerns. Using a pre-post within-participant experimental design, we tested if repeatedly exposing women with high self-disgust (N = 61) to disgust-focused body memories vs. neutral memories led to changes in disgust, body acceptance, and reactive avoidance. Contrary to expectations, state disgust towards the body itself only decreased following exposure to neutral memories. Yet, disgust elicited by body-related memories decreased following both repeated exposure to neutral and body memories. Although acceptance was not found to significantly change in either exposure session, pre-post decreases in state disgust were associated with increases in acceptance following the disgust-focused exposure. In contrast to expectations, reactive avoidance increased from pre to post in the disgust-focused exposure. Overall, the results indicate that repeated exposure to disgust-focused body memories may help reduce disgust elicited by these memories and promote body acceptance. Yet, the effect of this repeated exposure to body memories did not extend to changing state disgust towards the body, possibly due to reactive avoidance.

A partial habituation method to test for anterograde and retrograde amnestic treatment effects: Evidence that antagonism of the NMDA receptor can induce anterograde but not retrograde amnestic effects.

BACKGROUND: A progressive decrease in spontaneous locomotion with repeated exposure to a novel environment has been assessed using both within and between-session measures. While both are well-established and reliable measurements, neither are useful alone as methods to concurrently assess treatment effects on acquisition and retention of habituation. NEW METHOD: We report a behavioral method that measures habituation by combining the within and between measurements of locomotion. We used a 30 min session divided into 6 five min blocks. In the first novel environment session activity was maximal in the first 5 min block but was reduced to a low level by the sixth block, indicative of within-session habituation. Using 8 daily sessions, we showed that this terminal block low level of activity progressed incrementally to the first block to achieve complete habituation. RESULTS/COMPARISON WITH EXISTING METHODS: Within-session activity across sessions was used to identify different stages of between session habituation. It was then possible to assess drug treatment effects from partial to complete habituation, so that treatment effects on retention of the previously acquired partial habituation, expressed as a reversion to an earlier within session habituation pattern (retrograde amnesia assessment), as well as the effects on new learning by the failure in subsequent sessions to acquire complete between-session habituation (anterograde amnesia assessment). CONCLUSIONS: The use of spontaneous motor activity to assess learning and memory effects provides the opportunity to assess direct treatment effects on behavior and motor activity in contrast to many learning and memory models.

Habituation of the cold shock response: A systematic review and meta-analysis.

Cold water immersion (CWI) evokes the life-threatening reflex cold shock response (CSR), inducing hyperventilation, increasing cardiac arrhythmias, and increasing drowning risk by impairing safety behaviour. Repeated CWI induces CSR habituation (i.e., diminishing response with same stimulus magnitude) after ∼4 immersions, with variation between studies. We quantified the magnitude and coefficient of variation (CoV) in the CSR in a systematic review and meta-analysis with search terms entered to Medline, SportDiscus, PsychINFO, Pubmed, and Cochrane Central Register. Random effects meta-analyses, including effect sizes (Cohen's d) from 17 eligible groups (k), were conducted for heart rate (HR, n = 145, k = 17), respiratory frequency (fR, n = 73, k = 12), minute ventilation (Ve, n = 106, k = 10) and tidal volume (Vt, n = 46, k=6). All CSR variables habituated (p < 0.001) with large or moderate pooled effect sizes: ΔHR -14 (10) bt. min-1 (d: -1.19); ΔfR -8 (7) br. min-1 (d: -0.78); ΔVe, -21.3 (9.8) L. min-1 (d: -1.64); ΔVt -0.4 (0.3) L -1. Variation was greatest in Ve (control vs comparator immersion: 32.5&24.7%) compared to Vt (11.8&12.1%). Repeated CWI induces CSR habituation potentially reducing drowning risk. We consider the neurophysiological and behavioural consequences.

Health protective behaviours during the COVID-19 pandemic: Risk adaptation or habituation?

Many epidemiological works show that human behaviours play a fundamental role in the spread of infectious diseases. However, we still do not know much about how people modify their Health Protective Behaviours (HPB), such as hygiene or social distancing measures, over time in response to the health threat during an epidemic. In this study, we examined the role of the epidemiological context in engagement in HPB through two possible mechanisms highlighted by research into decision-making under risk: risk adaptation and risk habituation. These two different mechanisms were assumed to explain to a large extent the temporal variations in the public's responsiveness to the health threat during the COVID-19 pandemic. To test them, we used self-reported data collected through a series of 25 cross-sectional surveys conducted in France among representative samples of the adult population, from March 2020 to September 2021 (N = 50,019). Interestingly, we found that both mechanisms accounted relatively well for the temporal variation in the adoption of social distancing during the pandemic, which is remarkable given their different assumptions about the underlying social cognitive processes involved in response to a health threat. These results suggest that strengthening the incentives to encourage people to maintain health protective behaviours and to counter risk habituation effects is crucial to disease control and prevention over time.

Brain Signatures of Early and Late Neural Measures of Auditory Habituation and Discrimination in Autism and Their Relationship to Autistic Traits and Sensory Overresponsivity.

Sensory differences are included in the DSM-5 criteria of autism for the first time, yet it is unclear how they relate to neural indicators of perception. We studied early brain signatures of perception and examined their relationship to sensory behaviors and autistic traits. Thirteen autistic children and 13 Typically Developing (TD) children matched on age and nonverbal IQ participated in a passive oddball task, during which P1 habituation and P1 and MMN discrimination were evoked by pure tones. Autistic children had less neural habituation than the TD comparison group, and the MMN, but not P1, mapped on to sensory overresponsivity. Findings highlight the significance of temporal and contextual factors in neural information processing as it relates to autistic traits and sensory behaviors.

Using Anticipatory Behavior to Detect the Change in Interest in an Activity Repeated Several Times and Avoid Habituation in Bottlenose Dolphins (Tursiops Truncatus).

Environmental enrichment is an essential component of the management policies used by zoos and aquaria to promote animals' welfare. However, when enrichments are provided several times, they can cause habituation and lose their enrichment effects. A simple method to avoid it could be making a preventive assessment about the trend of animals' interest in a stimulus provided several times. Here, we hypothesized that anticipatory behavior could be used to assess the decrease in interest in playing with objects when the activity is repeated. Moreover, we also assumed that this could be done before providing objects to play with. Our results support this hypothesis. Specifically, we found a positive correlation between the time the 7 dolphins tested spent performing anticipatory behavior before the enrichment sessions and the time they spent playing with objects during those sessions. As a result, anticipatory behavior performed before enrichment sessions predicted dolphins' interest in the session and allowed us to assess whether the sessions had lost their enrichment effect.

Habituation to pain: self-report, electroencephalography, and functional magnetic resonance imaging in healthy individuals. A scoping review and future recommendations.

ABSTRACT: Habituation to pain is a fundamental learning process and important adaption. Yet, a comprehensive review of the current state of the field is lacking. Through a systematic search, 63 studies were included. Results address habituation to pain in healthy individuals based on self-report, electroencephalography, or functional magnetic resonance imaging. Our findings indicate a large variety in methods, experimental settings, and contexts, making habituation a ubiquitous phenomenon. Habituation to pain based on self-report studies shows a large influence of expectations, as well as the presence of individual differences. Furthermore, widespread neural effects, with sometimes opposing effects in self-report measures, are noted. Electroencephalography studies showed habituation of the N2-P2 amplitude, whereas functional magnetic resonance imaging studies showed decreasing activity during painful repeated stimulation in several identified brain areas (cingulate cortex and somatosensory cortices). Important considerations for the use of terminology, methodology, statistics, and individual differences are discussed. This review will aid our understanding of habituation to pain in healthy individuals and may lead the way to improving methods and designs for personalized treatment approaches in chronic pain patients.

That sounds awful! Does sound unpleasantness modulate the mismatch negativity and its habituation?

There are sounds that most people perceive as highly unpleasant, for instance, the sound of rubbing pieces of polystyrene together. Previous research showed larger physiological and neural responses for such aversive compared to neutral sounds. Hitherto, it remains unclear whether habituation, i.e., diminished responses to repeated stimulus presentation, which is typically reported for neutral sounds, occurs to the same extent for aversive stimuli. We measured the mismatch negativity (MMN) in response to rare occurrences of aversive or neutral deviant sounds within an auditory oddball sequence in 24 healthy participants, while they performed a demanding visual distractor task. Deviants occurred as single events (i.e., between two standards) or as double deviants (i.e., repeating the identical deviant sound in two consecutive trials). All deviants elicited a clear MMN, and amplitudes were larger for aversive than for neutral deviants (irrespective of their position within a deviant pair). This supports the claim of preattentive emotion evaluation during early auditory processing. In contrast to our expectations, MMN amplitudes did not show habituation, but increased in response to deviant repetition-similarly for aversive and neutral deviants. A more fine-grained analysis of individual MMN amplitudes in relation to individual arousal and valence ratings of each sound item revealed that stimulus-specific MMN amplitudes were best predicted by the interaction of deviant position and perceived arousal, but not by valence. Deviants with perceived higher arousal elicited larger MMN amplitudes only at the first deviant position, indicating that the MMN reflects preattentive processing of the emotional content of sounds.

Individual differences in processing speed and curiosity explain infant habituation and dishabituation performance.

Habituation and dishabituation are the most prevalent measures of infant cognitive functioning, and they have reliably been shown to predict later cognitive outcomes. Yet, the exact mechanisms underlying infant habituation and dishabituation are still unclear. To investigate them, we tested 106 8-month-old infants on a classic habituation task and a novel visual learning task. We used a hierarchical Bayesian model to identify individual differences in sustained attention, learning performance, processing speed and curiosity from the visual learning task. These factors were then related to habituation and dishabituation. We found that habituation time was related to individual differences in processing speed, while dishabituation was related to curiosity, but only for infants who did not habituate. These results offer novel insights in the mechanisms underlying habituation and serve as proof of concept for hierarchical models as an effective tool to measure individual differences in infant cognitive functioning. RESEARCH HIGHLIGHTS: We used a hierarchical Bayesian model to measure individual differences in infants' processing speed, learning performance, sustained attention, and curiosity. Faster processing speed was related to shorter habituation time. High curiosity was related to stronger dishabituation responses, but only for infants who did not habituate.

Long-term root electrotropism reveals habituation and hysteresis.

Plant roots sense many physical and chemical cues in soil, such as gravity, humidity, light, and chemical gradients, and respond by redirecting their growth toward or away from the source of the stimulus. This process is called tropism. While gravitropism is the tendency to follow the gravitational field downwards, electrotropism is the alignment of growth with external electric fields and the induced ionic currents. Although root tropisms are at the core of their ability to explore large volumes of soil in search of water and nutrients, the molecular and physical mechanisms underlying most of them remain poorly understood. We have previously provided a quantitative characterization of root electrotropism in Arabidopsis (Arabidopsis thaliana) primary roots exposed for 5 h to weak electric fields, showing that auxin asymmetric distribution is not necessary for root electrotropism but that cytokinin biosynthesis is. Here, we extend that study showing that long-term electrotropism is characterized by a complex behavior. We describe overshoot and habituation as key traits of long-term root electrotropism in Arabidopsis and provide quantitative data about the role of past exposures in the response to electric fields (hysteresis). On the molecular side, we show that cytokinin, although necessary for root electrotropism, is not asymmetrically distributed during the bending. Overall, the data presented here represent a step forward toward a better understanding of the complexity of root behavior and provide a quantitative platform for future studies on the molecular mechanisms of electrotropism.

Accessible and reliable neurometric testing in humans using a smartphone platform.

Tests of human brain circuit function typically require fixed equipment in lab environments. We have developed a smartphone-based platform for neurometric testing. This platform, which uses AI models like computer vision, is optimized for at-home use and produces reproducible, robust results on a battery of tests, including eyeblink conditioning, prepulse inhibition of acoustic startle response, and startle habituation. This approach provides a scalable, universal resource for quantitative assays of central nervous system function.

The impact of emotional valence and stimulus habituation on fMRI signal reliability during emotion generation.

BACKGROUND: The emotional domain is often impaired across many neurological diseases, for this reason it represents a relevant target of rehabilitation interventions. Functional changes in neural activity related to treatment can be assessed with functional MRI (fMRI) using emotion-generation tasks in longitudinal settings. Previous studies demonstrated that within-subject fMRI signal reliability can be affected by several factors such as repetition suppression, type of task and brain anatomy. However, the differential role of repetition suppression and emotional valence of the stimuli on the fMRI signal reliability and reproducibility during an emotion-generation task involving the vision of emotional pictures is yet to be determined. METHODS: Sixty-two healthy subjects were enrolled and split into two groups: group A (21 subjects, test-retest reliability on same-day and with same-task-form), group B (30 subjects, test-retest reproducibility with 4-month-interval using two equivalent-parallel forms of the task). Test-retest reliability and reproducibility of fMRI responses and patterns were evaluated separately for positive and negative emotional valence conditions in both groups. The analyses were performed voxel-wise, using the general linear model (GLM), and via a region-of-interest (ROI)-based approach, by computing the intra-class correlation coefficient (ICC) on the obtained contrasts. RESULTS: The voxel-wise GLM test yielded no significant differences for both conditions in reliability and reproducibility analyses. As to the ROI-based approach, across all areas with significant main effects of the stimuli, the reliability, as measured with ICC, was poor (<0.4) for the positive condition and ranged from poor to excellent (0.4-0.75) for the negative condition. The ICC-based reproducibility analysis, related to the comparison of two different parallel forms, yielded similar results. DISCUSSION: The voxel-wise GLM analysis failed to capture the poor reliability of fMRI signal which was instead highlighted using the ROI-based ICC analysis. The latter showed higher signal reliability for negative valence stimuli with respect to positive ones. The implementation of two parallel forms allowed to exclude neural suppression as the predominant effect causing low signal reliability, which could be instead ascribed to the employment of different neural strategies to cope with emotional stimuli over time. This is an invaluable information for a better assessment of treatment and rehabilitation effects in longitudinal studies of emotional neural processing.

A preliminary evaluation of habituation and dishabituation of operant responding in mice.

Previous research has suggested that operant response decrements within experimental sessions are due in part to habituation to the repeated presentation of reinforcers. One way to assess the role of habituation in within-session response decrements is to conduct a test for dishabituation, a phenomenon in which a habituated response to a given stimulus recovers following the presentation of some strong or novel stimulus other than the habituated stimulus. Dishabituation of operant responding has been demonstrated on several occasions in the literature, but studies with non-human subjects have thus far been limited to those using rats and pigeons. Two experiments attempting to replicate these findings with mice were conducted. Two groups of mice nose-poked for a sweetened condensed milk/water reinforcer on either a fixed-ratio 4 or variable-interval 15 s schedule of reinforcement. During testing, baseline sessions were then alternated with two test conditions and a control condition. Test conditions included a 5 s auditory stimulus or flashing of the house light presented mid-session. Control conditions were identical to baseline. Dishabituation was not observed for either group in Experiment 1. In Experiment 2, dishabituation was not observed for the fixed-ratio 4 group but was observed for the variable interval 15 s group. Considerations for further study of operant dishabituation in mice are discussed.