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    Behavioural variability and repeatability in adult zebrafish (Danio rerio) using the novel tank dive test
    (2025) Johnson, Andréa L.; Hurd, Peter L.; Mathot, Kimberley J.; Hamilton, Trevor
    Zebrafish (Danio rerio) are widely used in behavioural neuroscience as a model for studying anxiety-like and stress-related behaviours. However, substantial variability exists within and among individuals, influenced by factors such as sex, age, and environmental conditions, making the interpretation of anxiety-related behaviours challenging. Here we characterized longitudinal patterns of stability and variability in anxiety-like behaviours across individual adult zebrafish and assessed whether distinct behavioural profiles emerged over time. Using the novel tank dive test, we tracked anxiety-related behaviours in zebrafish across multiple time points over a 21-week period (90, 120, and 150 days post-fertilization). Behavioural metrics, including time spent in tank zones, swimming velocity, and immobility, were analyzed for age- and sex-related effects, repeatability, and group variation. Results indicated significant changes in anxiety-like behaviours with age, with fish spending more time in the upper zone and displaying increased swimming velocity over time. While no significant sex differences were observed in zone preference, males exhibited greater within-individual variation in time spent in the lower zone, while females demonstrated higher among-individual variation and repeatability over time. Furthermore, zebrafish were classified into high, medium, and low-anxiety groups based on cumulative behavioural scores, revealing stable individual differences in anxiety-like behaviours. These findings highlight the importance of considering age, sex and both intra- and inter-individual variation when interpreting zebrafish behaviour and provide a foundation for future research exploring selective breeding, anxiety level interactions, and pharmacological modulation of anxiety-related phenotypes.
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    Exploring the impact of acute solvent exposure on larval zebrafish behaviour
    (2025) Hagen, Ethan V.; Harper, Matthew M. M.; Zhang, Yanbo; Hamilton, Trevor
    Zebrafish (Danio rerio) are commonly used to test the impact of pharmacological and toxicological compounds. Larval zebrafish are extensively used because of high throughput procedures allowing simultaneous behavioural measurement in 24-, 48-, or 96-well plates. Often solvents are used as a vehicle for poorly soluble or insoluble compounds, however, the impact of dimethyl sulfoxide (DMSO), methanol, and ethanol after acute administration is not well characterized. Here we investigated the impact of 30-min exposures of DMSO, methanol, and ethanol (0.01%, 0.1%, and 1.0% vol/vol) on 5-day old larval zebrafish locomotion and startle responses. We found no effect of DMSO on distance moved and thigmotaxis in a spontaneous swimming test, and no effect on dark-, light-, or tap-startle responses compared to controls. Methanol and ethanol, both at 1.0% increased the distance moved, and ethanol decreased the dark startle response at 1.0%. Neither ethanol nor methanol had any impact on time in thigmotaxis zone, light- or tap-startle responses. Results from this study suggest that with acute exposure to experimental compounds requiring a solvent, the least impact on behaviour would occur with DMSO, followed by methanol, then ethanol.
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    Plating larval zebrafish prior to the day of experimentation has no impact on spontaneous swimming and startle responses
    (2025) Harper, Matthew M. M.; Hagen, Ethan V.; Zhang, Yanbo; Hamilton, Trevor
    Behavioural testing in larval zebrafish often involves pipetting the larvae into well plates for individual testing. Transferring larvae into plates the day prior to experimentation can increase efficiency of testing. Furthermore, pharmacological and toxicological studies can require a prolonged dosing period requiring the larvae to be pre-plated into the well plate the day prior to experimentation. Here, we compared the behavioural impact of pre-plating larval zebrafish at 4 days post-fertilization (dpf) to fish transferred at 5 dpf on the day of testing. Motion-tracking software was used to examine locomotion and zone preference, and responses to light, dark, and mechanical startle stimuli. We found no significant differences in distance moved, time spent in the thigmotaxis zone (outside edge of the arena), high mobility, immobility, light startle, dark startle, and mechanical startle responses. This data suggests that pre-plating larval zebrafish one day prior to testing does not have a significant impact on behaviour in a spontaneous swim task, dark startle test, light startle test, or mechanical startle test. Pre-plating larval zebrafish can increase the efficiency of behavioural testing. • Compare plating larvae one day prior to testing to plating day of testing. • Test the behaviour in a spontaneous swimming test, and measure light-, dark-, and mechanical-startle responses. • There were no significant differences in locomotion or startle responses.
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    Brief exposure to (-) THC affects zebrafish embryonic locomotion with effects that persist into the next generation
    (2025) Amin, Md Ruhul; Khara, Lakhan; Szaszkiewicz, Joshua; Kim, Andrew M.; Hamilton, Trevor; Ali, Declan W.
    Cannabis is one of the most widely used drugs, and yet an understanding of its impact on the human brain and body is inconclusive. Medicinal and recreational use of cannabis has increased in the last decade with a concomitant increase in use by pregnant women. The major psychoactive compound in cannabis, Δ9-tetrahydrocannabinol (THC), exists in different isomers, with the (-) trans isomer most common. Prenatal exposure to THC can alter neural and behavioral development, but it is unknown how exposure to (-) trans-THC ((-)THC) during very early stages of development impacts fetal growth and movement, and whether effects persist to adulthood, or into the next generation. Here we exposed zebrafish (Danio rerio) to a single exposure of (-)THC (0.001 mg/L (3.2 nM) to 20 mg/L (63.6 µM), for 5 h) during gastrulation (5.25 hpf to 10.75 hpf) when key neurons involved in locomotion such as the primary motor neurons and Mauthner cell first appear. We then examined the impact on embryo morphology and locomotion, adult behavior, and locomotion in the next (F1) generation. Embryos treated with (-)THC experienced changes in morphology, were shorter in length and experienced altered hatching and survival. Spontaneous coiling of 1 dpf embryos was reduced, swimming after touch-evoked responses was reduced and basal swimming in 5 dpf larvae was also reduced. Adult zebrafish tested in the open field test and novel object approach test demonstrated no differences in locomotion, anxiety-like behavior, nor boldness, compared to controls. The (-)THC F1 generation embryos at 1 dpf showed reduced coiling activity, while swimming after touch-evoked responses was reduced in 2 dpf animals but basal swimming at 5 dpf remained similar to controls. Taken together, exposure to (-)THC only once for 5 h during gastrulation has a significant impact on locomotion in embryos and larvae, a minimal impact on adult behavior, and effects that persist into the next generation.
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    Instrumental and reactive intimate partner violence: offender characteristics, reoffence rates, and risk management
    (2017) Ennis, Liam; Toop, Carissa; Jung, Sandy; Bois, Sean
    Intimate partner violence (IPV) research has consistently demonstrated that abusive men are a heterogeneous group comprising men who differ in terms of individual characteristics, psychopathology, and presumably, also in terms of the nature and severity of their violent behavior. Some partner-violent men use violence instrumentally in a way that is planned, methodical, and goal-oriented, whereas other partner-violent men are reactive by acting out of anger, in response to a perceived threat (e.g., sexual jealousy). By extension, it would be expected that these subtypes may be differentiated by their risk for recidivism and in terms of the strategies that most likely to mitigate violence risk. The aim of the current study was to determine differences between instrumental and reactive intimate partner abusers that might be relevant for offender management and treatment. The files of 105 partner-violent men whose files were referred for threat assessment were reviewed and their data were coded. Instrumental partner-violent men were differentiated from reactive partner-violent men by higher overall risk scores, IPV supportive attitudes, offense characteristics and a lower prevalence of early life trauma. Discrepancies between predicted and observed recidivism outcomes suggest that factors that were unaccounted for in the current research may have differentially influenced outcomes for instrumental and reactive abusers.
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    Forensic assessment with the PAI in correctional samples: implications for RNR
    (2019) Toop, Carissa; Olver, Mark E.; Jung, Sandy
    The present investigation examined Risk-Need-Responsivity (RNR) correlates of Personality Assessment Inventory (PAI) scores in a sample (N = 377) of offenders with diverse criminal histories. It was hypothesized that PAI scales with content reflective of criminogenic needs would be associated with recidivism while those indicative of major mental illness and behavioral disruption would be positively linked to responsivity variables. Several PAI scales predicted general and violent recidivism, particularly those reflective of criminogenic need. More serious profile patterns were associated with younger age, less education, lower cognitive ability, and sexual offense treatment attrition, per the responsivity principle. Finally, an exploratory factor analysis identified four PAI factors: Major Mental Illness, Extraversion, Paranoia, and Antisociality. Antisociality scores were the most predictive of general and violent recidivism. Antisociality and Major Mental Illness scores also predicted treatment attrition. Study findings suggest that the PAI can be a useful adjunct to standardized risk and need measures for RNR-informed assessment.
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    Identifying criminogenic needs using the personality assessment inventory with males who have sexually offended
    (2017) Jung, Sandy; Toop, Carissa; Ennis, Liam
    The present study investigated the relationships between the scales of the Personality Assessment Inventory (PAI) and variables relevant to recidivism risk and criminogenic need to inform clinicians’ use of the PAI for purposes of treatment planning and risk management. PAI profiles, risk measure and domain scores, and recidivism data were collected for 158 males who have been convicted of sexually offending. Data were analyzed to investigate whether select clinical scales of the PAI correlated with conceptually relevant domains of risk and/or recidivism. Our findings demonstrated that the antisocial scales were consistently associated with risk constructs and recidivism, while very few clinical and personality scales showed relationships with risk constructs. The PAI seems to include select scales that represent risk-related needs, but also, other scales that may be more related to responsivity issues, and therefore may have utility to address two of the risk, need, and responsivity principles.
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    Empirically-based dynamic risk and protective factors for sexual offending
    (2023) Seto, Michael C.; Augustyn, Carissa; Roche, Kailey M.; Hilkes, Gabriella
    This review provides an overview and update of empirical evidence for psychologically meaningful dynamic risk factors and protective factors for sexual offending. Using the review by Mann et al. (2010) as a starting point, we reviewed relevant literature that has appeared since this publication, focusing on meta-analyses, systematic and scoping reviews of dynamic risk factors, recent evaluations of commonly used dynamic assessment tools, and studies of dynamic risk and protective factors in community samples in addition to clinical or forensic samples. Two risk factors previously deemed promising by Mann et al. (2010), hostility towards women and dysfunctional coping (conceptualized as hostile masculinity and emotional regulation deficits, respectively, in this review), could now be considered supported using this review's criteria of three or more studies demonstrating an effect size of 0.15 or greater. No new risk factors were identified. We conducted a broader search of protective factors in recognition of the relative newness of this literature: Positive social support was the only protective factor identified as empirically supported. We also discuss situational risk and protective factors.
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    Therapeutic and risk relevance of psychopathy and general criminal attitude change in an institutional sexual offense program
    (2024) Augustyn, Carissa M.; Olver, Mark E.
    We examined the interrelationships between psychopathy, changes in general criminal attitudes, and community recidivism in a sample of 212 men who attended an institutional sexual offense treatment program (SOTP) and were followed for an average of 12.73 years post-release. The men completed a self-report measure of general criminal attitudes, the Criminal Sentiments Scale, as part of routine SOTP service delivery, Psychopathy Checklist-Revised (PCL-R) ratings were completed via file review, and recidivism data were obtained from official criminal records. Criminal attitude endorsement and criminal attitude change had clinically meaningful, but differential, associations with the antisocial and interpersonal features of psychopathy. Further, positive changes in criminal attitudes—particularly tolerance of law violations (i.e., rationalizations for criminal behavior)—were significantly predictive of reductions in community violent and general recidivism after controlling for PCL-R score. Results demonstrate that general criminal attitude change has risk relevance in the treatment of high psychopathy persons with sexual offense histories.
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    Measuring many mindsets: a systematic review of growth mindset domains, and discussion of domain relationships, with implications for growth mindset interventions
    (2024) Kyler, E. Nathan; Moscicki, Michele K.
    Research into growth mindset, the belief that attributes are malleable, has increased dramatically in the last 30 years, leading to an explosion in the number of mindset domains studied. Given this plethora of mindset domains, there is comparatively little work investigating mindset domain relationships. Further, with expanding interest in growth mindset has come an increase in mindset interventions aimed at increasing growth mindset beliefs, with mixed results. The mindset domain used in intervention messaging is an understudied potential moderator of intervention efficacy, as few domains have been used in interventions, despite the number of domains studied. In this article we raise three questions: (1) How many mindset domains have been studied and what are those domains?; (2) How are beliefs in different mindset domains related to one another?; and (3) How can we use information about existing mindset domains and their relationships to improve mindset intervention efficacy? To address question one, we systematically reviewed the mindset literature between 1995 and 2022 to document studied mindset domains. We then discuss heterogeneity in mindset domain relationship research and suggest how our review can be used to address gaps in this field. Lastly, we describe heterogeneity in mindset intervention efficacy and suggest how to apply our review of mindset domains to examine the impact of the domain used in intervention messaging on efficacy. We aim to stimulate research into understanding mindset domain relationships and how this insight may be applied to mindset interventions to improve people's lives through effectively enhancing their growth mindset beliefs.
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    Relationships among sex, sexual orientation, dark triad traits, sociosexuality, and sexual excitation/inhibition
    (2025) Semenyna, Scott W.; Vasey, Paul L.; Honey, P. Lynne
    Subclinical narcissism, psychopathy, and Machiavellianism are a cluster of manipulative, callous, and entitled traits known as the Dark Triad (DT). These traits have been repeatedly linked to short-term mating strategies and a tolerance for uncommitted sexual behavior (i.e., unrestricted sociosexuality) in both men and women, a pattern interpreted as consistent with life history theory. Alongside sociosexuality, individuals vary in their distinct capacities toward sexual excitation and sexual inhibition. Although much research has examined the relationships between DT traits and sociosexuality, and between sociosexuality and sexual excitation/inhibition, none has simultaneously evaluated the links among all three. In a large undergraduate sample, DT traits and sexual excitation/inhibition showed unique multivariate associations with sociosexuality, even when accounting for age, sex, relationship status, and sexual orientation. Results suggest that DT traits, elevated sexual excitation, lower inhibition and bisexuality, facilitate fast life history strategies in both males and females.
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    From colours to cravings: exploring conditioned colour preference to ethanol in zebrafish
    (2025) Hagen, Ethan V.; Zhang, Yanbo; Hamilton, Trevor
    Conditioned preference paradigms like conditioned colour preference tests (CCP) can be used to investigate addictive drug seeking in zebrafish (Danio rerio), but many aspects of this procedure require further study. Conditioned preference can be tested with either biased or unbiased conditioning methods, each with their own strengths and weaknesses. The present study used unbiased stimuli to test seeking behaviour in ethanol-exposed zebrafish at different durations of drug withdrawal. Zebrafish were exposed to one of two equally preferred colours (red or yellow) while dosed with 0.8 % vol/vol ethanol or with habitat water (controls) for 1 h each day for 21 days. Next, fish experienced withdrawal for either 2-, 4-, or 8-days then were tested in a two-way red and yellow task for 10 min with their movement recorded via motion-tracking software. Fish conditioned to red showed a main effect of ethanol and a significant preference for red compared to yellow at 8-days of withdrawal but not at 2-days or 4-days of withdrawal. Fish conditioned to yellow did not show any colour preference during the 2-, 4-, or 8-days of withdrawal, but did show a main effect of withdrawal duration. This work expands our understanding of CCP paradigms in zebrafish and highlights the capacity of zebrafish to develop an association to red but not yellow under our experimental conditions.
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    Greater realism in authentic assessments promotes student motivation and engagement
    (2025) Pacher, Constanza; Honey, P. Lynne
    Student motivation is an important predictor of both performance and attitudes toward schoolwork. Higher levels of intrinsic, or autonomous, motivation are facilitated by high-impact teaching practices, including experiential learning and using authentic experiences and evaluations. The present study was inspired by instructor perception that students in their third semester in a four-year undergraduate design program were more engaged with, and more motivated by, one course project over another. Although both projects were authentic assessments, the preferred project had more realism, including real external stakeholders and context. We assessed students’ subjective experience while working with two projects taught in the same course over two years, where the projects varied in level of realism. Phase 1 of the study measured students’ intrinsic motivation for the two projects using a questionnaire based on the Intrinsic Motivation Inventory. Phase 2 of the study again measured students’ intrinsic motivation for the two projects after the less-preferred project was adjusted to be more realistic. This study showed evidence that students experienced higher levels of engagement and intrinsic motivation when working with more realistic projects involving real external stakeholders and context, compared to a project with less realism. Projects with real problems, goals, and outcomes seem to give students a higher sense of autonomy, competence, and relatedness than fictitious ones—improving their self-regulation, engagement, and well-being.
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    Sex and sexual orientation differences in Dark Triad traits, sexual excitation/inhibition, and sociosexuality
    (2023) Semenyna, Scott W.; Vasey, Paul L.; Honey, P. Lynne
    The present study sought to investigate sex and sexual orientation differences in several traits related to sexuality and sexual behavior. Examining sexual orientation differences alongside basic sex differences to help identify correlates of sexual orientation diversity, and whether individuals with varying degrees of same-sex attraction show concurrent sex-atypical shifts in other domains. Males tend to score higher than females in the Dark Triad (DT) traits of sub-clinical narcissism, psychopathy, and Machiavellianism. Similarly, females tend to be more cautious than males in their attitudes and desires toward casual sex activity (i.e., sociosexuality). These sex differences may be related to the propensity for individuals to become easily sexually excited, which is higher in males, or to instead inhibit sexual arousal, which is higher in females. In a large undergraduate sample (N = 2047), we replicated expected sex differences in DT traits, sociosexuality, and sexual excitation/inhibition. We found that non-heterosexual females were “male-shifted” in some of these traits, but these shifts tended to be strongest among mostly heterosexual and bisexual individuals. Furthermore, we found that within-sex variation in sociosexuality, sexual excitation, and sexual inhibition was not related to sexual orientation in a linear fashion. Instead, sociosexuality and sexual excitation were related to sexual orientation in a curvilinear (inverted-U) fashion, especially among females. The fact that traits correlated with bisexuality and homosexuality were somewhat distinct is consistent with the idea that different developmental pathways may lead to these discrete sexual attraction patterns.
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    Sex, drugs, and zebrafish: acute exposure to anxiety-modulating compounds in a modified novel tank dive test
    (2024) Johnson, Andréa L.; Hurd, Peter L.; Hamilton, Trevor
    This study investigated the effects of anxiogenic and anxiolytic drugs on zebrafish (Danio rerio) behaviour using a modified novel tank dive test with higher walls and a narrower depth. Zebrafish were administered chondroitin sulfate, beta-carboline, delta-9-tetrahydrocannabinol (THC), ethanol, and beta-caryophyllene, and their behaviours were evaluated for geotaxis, swimming velocity, and immobility. Both anxiogenic and anxiolytic compounds generally increased bottom-dwelling behaviour, suggesting that the tank's modified dimensions significantly influence zebrafish responses. EC50 values for ethanol showed a lower threshold for velocity reduction compared to zone preference. Chondroitin sulfate uniquely caused a sex-specific increase in male swimming velocity, whereas no other sex-differences were observed with any compound. Interestingly, the presence of drug-treated fish did not alter the behaviour of observer fish, suggesting limited social buffering effects. The findings underscore the complexity of zebrafish behavioural phenotypes and highlight the need for considering tank dimensions and multiple behavioural parameters to accurately assess the effects of anxiety-modulating drugs. This study demonstrates the utility of the modified novel tank dive test in providing nuanced insights into the behavioural effects of different pharmacological agents in zebrafish.
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    One hundred years of EEG for brain and behaviour research
    (2024) Mushtaq, Faisal; Welke, Dominik; Gallagher, Anne; Pavlov, Yuri G.; Kouara, Layla; Bosch-Bayard, Jorge; van den Bosch, Jasper J. F.; Arvaneh, Mahnaz; Bland, Amy R.; Chaumon, Maximilien; Borck, Cornelius; He, Xun; Luck, Steven J.; Machizawa, Maro G.; Pernet, Cyril; Puce, Aina; Segalowitz, Sidney J.; Rogers, Christine; Awais, Muhammad; Babiloni, Claudio; Bailey, Neil W.; Baillet, Sylvain; Bendall, Robert C. A.; Brady, Daniel; Bringas-Vega, Maria L.; Busch, Niko A.; Calzada-Reyes, Ana; Chatard, Armand; Clayson, Peter E.; Cohen, Michael X.; Cole, Jonathan; Constant, Martin; Corneyllie, Alexandra; Coyle, Damien; Cruse, Damian; Delis, Ioannis; Delorme, Arnaud; Fair, Damien; Falk, Tiago H.; Gamer, Matthias; Ganis, Giorgio; Gloy, Kilian; Gregory, Samantha; Hassall, Cameron D.; Hiley, Katherine E.; Ivry, Richard B.; Jerbi, Karim; Jenkins, Michael; Kaiser, Jakob; Keil, Andreas; Knight, Robert T.; Kochen, Silvia; Kotchoubey, Boris; Krigolson, Olave E.; Langer, Nicolas; Liesefeld, Heinrich R.; Lippé, Sarah; London, Raquel E.; MacNamara, Annmarie; Makeig, Scott; Marinovic, Welber; Martínez-Montes, Eduardo; Marzuki, Aleya A.; Mathew, Ryan K.; Michel, Christoph; Millán, José D. R.; Mon-Williams, Mark; Morales-Chacón, Lilia; Naar, Richard; Nilsonne, Gustav; Niso, Guiomar; Nyhus, Erika; Oostenveld, Robert; Paul, Katharina; Paulus, Walter; Pfabigan, Daniela M.; Pourtois, Gilles; Rampp, Stefan; Rausch, Manuel; Robbins, Kay; Rossini, Paolo M.; Ruzzoli, Manuela; Schmidt, Barbara; Senderecka, Magdalena; Srinivasan, Narayanan; Stegmann, Yannik; Thompson, Paul M.; Valdes-Sosa, Mitchell; van der Molen, Melle J. W.; Veniero, Domenica; Verona, Edelyn; Verona, Edelyn; Voytek, Bradley; Yao, Dezhong; Evans, Alan C.; Valdes Sosa, Pedro
    On the centenary of the first human EEG recording, more than 500 experts reflect on the impact that this discovery has had on our understanding of the brain and behaviour. We document their priorities and call for collective action focusing on validity, democratization and responsibility to realize the potential of EEG in science and society over the next 100 years.
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    Reward positivity affects temporal interval production in a continuous timing task
    (2024) Yan, Yan; Hunt, Laurence T.; Hassall, Cameron D.
    The neural circuits of reward processing and interval timing (including the perception and production of temporal intervals) are functionally intertwined, suggesting that it might be possible for momentary reward processing to influence subsequent timing behavior. Previous animal and human studies have mainly focused on the effect of reward on interval perception, whereas its impact on interval production is less clear. In this study, we examined whether feedback, as an example of performance-contingent reward, biases interval production. We recorded EEG from 20 participants while they engaged in a continuous drumming task with different realistic tempos (1728 trials per participant). Participants received color-coded feedback after each beat about whether they were correct (on time) or incorrect (early or late). Regression-based EEG analysis was used to unmix the rapid occurrence of a feedback response called the reward positivity (RewP), which is traditionally observed in more slow-paced tasks. Using linear mixed modeling, we found that RewP amplitude predicted timing behavior for the upcoming beat. This performance-biasing effect of the RewP was interpreted as reflecting the impact of fluctuations in reward-related anterior cingulate cortex activity on timing, and the necessity of continuous paradigms to make such observations was highlighted.
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    The neural correlates of continuous feedback processing
    (2023) Hassall, Cameron D.; Yan, Yan; Hunt, Laurence T.
    Feedback processing is commonly studied by analyzing the brain's response to discrete rather than continuous events. Such studies have led to the hypothesis that rapid phasic midbrain dopaminergic activity tracks reward prediction errors (RPEs), the effects of which are measurable at the scalp via electroencephalography (EEG). Although studies using continuous feedback are sparse, recent animal work suggests that moment-to-moment changes in reward are tracked by slowly ramping midbrain dopaminergic activity. Some have argued that these ramping signals index state values rather than RPEs. Our goal here was to develop an EEG measure of continuous feedback processing in humans, then test whether its behavior could be accounted for by the RPE hypothesis. Participants completed a stimulus–response learning task in which a continuous reward cue gradually increased or decreased over time. A regression-based unmixing approach revealed EEG activity with a topography and time course consistent with the stimulus-preceding negativity (SPN), a scalp potential previously linked to reward anticipation and tonic dopamine release. Importantly, this reward-related activity depended on outcome expectancy: as predicted by the RPE hypothesis, activity for expected reward cues was reduced compared to unexpected reward cues. These results demonstrate the possibility of using human scalp-recorded potentials to track continuous feedback processing, and test candidate hypotheses of this activity.
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    Repeated microdoses of LSD do not alter anxiety or boldness in zebrafish
    (2024) Hagen, Ethan V.; Schalomon, Melike; Zhang, Yunhui; Hamilton, Trevor
    The therapeutic use of lysergic acid diethylamide (LSD) has resurfaced in the last decade, prompting further scientific investigation into its effectiveness in many animal models. Zebrafish (Danio rerio) are a popular model organism in medical sciences and are used to examine the repeated administration of pharmacological compounds. Previous zebrafish research found acute LSD altered behaviour and cortisol levels at high (250 µg/L) but not low (5–100 µg/L) levels. In this study, we used a motion tracking system to record and analyze the movement patterns of zebrafish after acute and repeated 10-day LSD exposure (1.5 µg/L, 15 µg/L, 150 µg/L) and after seven days of withdrawal. The open-field and novel object approach tests were used to examine anxiety-like behaviour, boldness, and locomotion. In the acute experiments we observed a significant decrease in high mobility with 1.5 µg/L, 15 µg/L, and 150 µg/L of LSD compared to the control and a decrease in velocity with 1.5 and 15 µg/L. In repeated experiments, there were no significant differences in the levels of anxiety, boldness, or locomotion between all LSD groups and controls immediately after 10-day treatment or after withdrawal.
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    β-Carboline (FG-7142) modulates fear but not anxiety-like behaviour in zebrafish
    (2024) Scatterty, Kale R.; Hamilton, Trevor
    The β-Carboline FG-7142 is a partial inverse agonist at the benzodiazepine allosteric site on the GABA-A receptor that induces anxiogenic, proconvulsant, and appetite-reducing effects in many species, including humans. Seizure-kindling effects have been well studied, however anxiogenic properties are relatively unexplored. This study aimed to investigate concentration-dependent effects of FG-7142 on anxiety-like behaviour and fear responses in zebrafish (Danio rerio) using the open-field test (OF) and novel object approach test (NOA). A U-shaped distribution was found with maximal responses in increased immobility and reduced distance moved at 10 µM in the NOA but not the OF. Follow up experiments demonstrated a lack of effect in repeated OF testing and no changes in opercular movements. Furthermore, the effect of FG-7142 was reversed with ethanol treatment. These results suggest that FG-7142 elicits a ‘freezing’ response in zebrafish via the introduction of novelty, suggesting fear-induction. These findings indicate that FG-7142 may act as an agent to promote acute fear responses in zebrafish.