Behavioural Brain Research

It is estimated that approximately fifty percent of the population will encounter at least one traumatic event during their lifetime; however, only six percent develop Posttraumatic Stress Disorder (PTSD), a trauma-related disorder characterized by persistent alterations in affect and cognition, including an exaggerated fear response. It is well established that females (9.7%) are more than twice as likely as males (3.6%) to be diagnosed with PTSD. Nevertheless, a significant challenge remains in understanding how the severity of traumas experienced in childhood versus adulthood influences PTSD development across sexes. To address this challenge effectively, the adoption of preclinical animal models that accurately reflect these key characteristics is crucial. The Stress Enhanced Fear Learning (SEFL) paradigm in rodents encapsulates some of these complexities associated with PTSD, such as persistent fear sensitization following exposure to acute trauma. This study investigates how stress severity and developmental timing affect the long-term maintenance of SEFL in male and female rats. Juvenile and adult rats were initially subjected to no stress (control, context only), low stress (1 footshock), moderate stress (3 footshocks), or high stress (15 footshocks), followed by an extinction session either one day (recent) or sixty days (remote) later. Subsequently, to evaluate SEFL in a new context, all subjects received a single footshock and were tested the following day. Shortly after stress induction, all groups displayed SEFL. Although the effects persisted for sixty days in adult males and juvenile females, even at the lowest stress level, they were significantly reduced in juvenile males and adult females. These findings offer novel insights into sex-related differences in the persistence of SEFL and introduce new considerations regarding how the timing of developmental stressors influences future threat encoding and fear responses.

Background: ADHD is characterized by inattention and impulsivity. Stimulants such as amphetamine are the first line treatments for ADHD. Amphetamine (AMPH) works by increasing extracellular levels of dopamine and noradrenaline. Such stimulants are used to test predictive validity of animal tasks, where it has been reported that amphetamine improves rat 5-CSRTT accuracy when the session length is increased to 250 trials. This improvement in accuracy was observed later in the session as control performance declined. Proving that amphetamine can improve 5C-CPT task performance adds to the predictive validity of the task. No previous works has demonstrated the pro-attentional effects of amphetamine on sustained attention in rat 5C-CPT. We have previously shown that pharmacological manipulations of dopaminergic system improve waiting impulsivity in a rate dependent manner and the importance of analysing the data using Oldham method. The present study extends this work to investigate the effect of amphetamine on attentional processes. Objective: to investigate effects of amphetamine on attentional processes as measured by 5C-CPT task using correlational analysis and group performance. Methods: Trained female Lister hooded rats were tested with AMPH (0.1, 0.2 and 0.4 mg/kg) under reduced stimulus duration schedule (0.25,0.5,1,1.5 and 2s SD) over normal length session (120 trials). Correlational analysis (Oldham method) was used to understand the relationship between baseline performance measures and the change following administration of AMPH. Results: The highest dose of AMPH impaired attentional performance in the 5C-CPT under reduced SD challenge (0.5s,1s,1.5s and 2s). This impairment was due to increase in FAR. Previous studies in 5-CSRTT suggest that reducing the SD increases attentional demand in the form of reducing accuracy without affecting waiting impulsivity. However, the 5-CSRTT does not include non-target trials, therefore, it cannot be used to measure sustained attention (SI) and responsivity index. The 5C-CPT requires greater attentional resources than the 5-CSRTT.This study is the first to report that reducing the SD changes responsivity index (bias) rather than measures of sustained attention (sensitivity index) in the 5C-CPT. Control sensitivity index did not change until the SD was reduced to less than 0.5s and this change was due to a change in baseline responsivity index (bias). Performance under each reduced SD revealed that the highest dose of AMPH (0.4 mg/kg) showed a tendency toward reducing sensitivity index at 0.5, 1.0 and 1.5s SDs. Under 1.0s SD, the highest dose of AMPH changed sustained attention (SI, HR and FAR) and omission in a rate-dependent manner without changing responsivity index. Performance across the session revealed that the impairment in sustained attention was observed at the beginning of the session. In the third trial block, Oldham method revealed an inverse relationship between baseline accuracy and the change following administration of 0.2 mg/kg AMPH, indicative of a rate-dependent effect. Conclusions: This study successfully demonstrates rate-dependent effects of AMPH on measures of attentional performance in the 5C-CPT. This experiment also demonstrates that responsivity index is sensitive to reduced SD challenge. To our knowledge this is the first study to report the presence of a direct relationship between baseline sustained attention and magnitude of improvement following administration of 0.4 mg/kg AMPH and an inverse relationship between baseline accuracy and the change following administration of 0.2 mg/kg AMPH in 5C-CPT task. Future studies should test lower doses of amphetamine (0.05 and 0.1 mg/kg) over extended session length (250 trials) to reveal the pro-attentional effects of this drug on 5C-CPT performance measures.

Background The head-twitch response (HTR) is a serotonin2A receptor (5-HT2AR) dependent behavioral correlate of serotonergic psychedelic action in rodent models. Although cortical 5-HT2ARs have been implicated in HTRs, the contribution of specific cortical circuits to this behavior remains poorly defined, with a few reports implicating the medial prefrontal cortex (mPFC) in the generation of HTRs. Results The serotonergic psychedelic, 2,5-dimethoxy-4-iodoamphetamine (DOI), induced head-twitch responses (HTRs) in male and female rats and mice, with sex differences noted only in mice. DOI also increased ear-scratch responses (ESRs), and reduced digging and grooming behaviors only in mice. While the DOI-evoked HTRs and ESRs were absent in 5-HT2AR knock-out (5-HT2AR KO) mice, reduced digging and grooming occurred in both wild-type and 5-HT2AR KO mice. We assessed the role of 5-HT2ARs in the mPFC in regulating DOI-induced HTRs using pharmacological and genetic approaches. Targeted DOI microinfusion into the mPFC did not induce HTRs in rats, in contrast to the robust increase in HTRs noted following systemic DOI administration. Local delivery of the selective 5-HT2AR antagonist, MDL100907, into the mPFC also had no effect on the systemic DOI-evoked increase in HTRs in rats. Experiments capitalizing on genetic strategies to perturb 5-HT2AR expression in the mPFC, indicated that viral restoration of 5-HT2AR expression in mPFC CaMKII-positive excitatory neurons was not sufficient to reinstate DOI-evoked HTRs or ESRs in 5-HT2AR KO mice. Further, conditional 5-HT2AR deletion in CaMKII-positive excitatory neurons in the mPFC did not alter systemic DOI-induced HTRs and ESRs in mice. Conclusions These findings indicate that the serotonergic psychedelic DOI induces species- and sex-specific behavioral effects in rodent models, with a robust 5-HT2AR dependence noted for DOI-evoked HTRs and ESRs. Further, we show that 5-HT2ARs in the mPFC do not appear to contribute to the enhanced HTRs and ESRs elicited by DOI.

Oxytocin (OT) and vasopressin (AVP) are neuropeptide hormones involved in regulating animal social behavior and a broad spectrum of physiological processes. Although their distributions are well documented in neuroendocrine regions of the forebrain and midbrain, their expression in the hindbrain remains poorly understood. Here, we used immunohistochemistry to quantify OT and AVP immunoreactive puncta within three auditory brainstem nuclei, the lateral superior olive (LSO), the medial superior olive (MSO), and the medial nucleus of the trapezoid body (MNTB) in six wild-caught rodent species differing in sociality. We also quantified the volume of these nuclei and examined variation in total brain volume across species and sociality. OT and AVP puncta count differed among species and social groups. Group-living species exhibited higher OT and AVP puncta counts than monogamous and solitary species in the LSO and MNTB. In the MSO, OT puncta counts did not differ among social groups, whereas AVP puncta counts were higher in group-living than in monogamous and solitary species. Total brain volume and the volumes of the MNTB and MSO differed among species, but not across social groups, whereas LSO volume did not differ among species or sociality. These findings revealed sociality-related variation in OT and AVP immunoreactive puncta within auditory brainstem circuits and suggest that neuropeptide signaling within early auditory brainstem pathways may contribute to the neural integration of social and auditory information.

The hippocampus is particularly vulnerable to hypoxia, yet freedivers, who repeatedly undergo voluntary breath-hold hypoxia, do not appear to show the memory impairments commonly reported after involuntary hypoxic exposure. We investigated whether freediving training is associated with functional connectivity reorganization at the whole-brain and hippocampal levels, and whether hippocampal connectivity relates to preserved episodic memory performance. Seventeen male recreational freedivers underwent fMRI before and after a 7-month standardized training period, and 20 matched aerobic-trained controls were assessed at baseline. Functional connectivity analyses examined (i) whole-brain ROI-to-ROI connectivity, (ii) seed-to-voxel connectivity from the bilateral hippocampus and selected cortical seeds, and (iii) associations between hippocampal connectivity and episodic memory. Compared with controls, freedivers showed distinct connectivity patterns during apnea and rest. After training, whole-brain analyses revealed reorganization involving salience, frontoparietal, sensorimotor, visual, and cerebellar systems. Hippocampal analyses showed reduced connectivity with sensorimotor and default mode regions, alongside increased connectivity with cerebellar and visual areas, with stronger effects after training. In freedivers, specific post-training hippocampal connectivity was associated with episodic memory performance. These findings suggest that repeated voluntary hypoxia during freediving training is associated with selective functional reorganization of hippocampal and large-scale brain networks. This pattern may reflect adaptive neuroplasticity linked to preserved episodic memory under intermittent hypoxic exposure.

Objective and efficient methods for investigating animal's mental states are important for advancing animal welfare research. Behavioural observations and physiological measures provide valuable information but may not fully capture affective states. Judgment Bias Tasks (JBTs) offer a promising method to infer affective states from animals' responses to ambiguous stimuli, as distressed individuals show more pessimistic tendencies. However, the application of JBTs outside research settings may be limited due to time-consuming training and methodological or infrastructural requirements. With the present study, we aimed to test the feasibility of a simple and accessible JBT for non-human primates and to investigate its sensitivity to affective states. Eight brown capuchins (Sapajus apella) and eleven Tonkean macaques (Macaca tonkeana) were tested under positive and negative affective conditions. Individuals were trained to discriminate between never rewarded conditioned stimuli and always rewarded ones. They were then presented with ambiguous probes they had never seen before to analyse their responses to ambiguity. The discrimination training required, on average, about 12 sessions lasting a few minutes each to successfully train every individual animal. Both species significantly discriminated between conditioned stimuli and ambiguous probes. Additionally, macaques showed a greater tendency to interact with the never rewarded condition stimuli and the probes under positive conditions during early sessions. In capuchins, however, the affective conditions presented had no significant effect, although the descriptive analysis tended to show that the latency to investigate the probes was greater in the negative condition. This study also highlights key methodological considerations, such as a decrease in ambiguity across sessions. Overall, the present results suggest that, with a few improvements, this method could be effectively implemented to assess affective states of primates under human care, supporting this tool as a valuable candidate for welfare assessment.

Cannabis is one of the most widely consumed substances in the world. Consumers seek out cannabis cultivars with varying levels of phytocannabinoids, primarily delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). The effects of THC, CBD or the combination of THC:CBD have distinct outcomes on cognitive processes, cellular functions, and phytocannabinoid pharmacokinetics. The majority of research on cannabis effects on the brain has focussed on neurons, and few studies have investigated the impact of different cannabis cultivars on glia. In particular, the impact of varying levels of THC:CBD on oligodendrocyte lineage cells, which play numerous support roles in the brain essential to proper neuronal communication, is relatively unknown. This study set out to examine the acute impact of different cultivars of vaporized cannabis on oligodendrocyte lineage cells in the forceps minor of adult male and female mice. Mice were exposed to vapor from cannabis flower high in THC, high in CBD or balanced in THC:CBD over 15 minutes, and brains were fixed 30 minutes post-cannabis onset. Using immunofluorescence microscopy, we observed significant changes to oligodendrocyte progenitor cell (OPC) morphology in mice exposed to balanced cannabis, and, using correlative light and electron microscopy, we observed alterations to OPC mitochondria. The alterations observed (i.e., enlarged soma and nucleus volume, reduced density and increased area of mitochondria in the soma) in OPCs due to balanced cannabis are reminiscent of the very early changes seen during OPC differentiation. This study highlights the differing effects of cannabis cultivars on OPCs and the rapidity of the OPC response to inhaled phytocannabinoids.

Ethanol occurs naturally in sugar-rich foods used by insects, but its effects in bees have been studied primarily in honeybees. We tested whether dietary ethanol affects survival and locomotor performance in workers of the bumblebee Bombus terrestris (L.). In the survival experiment, workers were fed ethanol (0, 1, or 10%) for 21 days; in the locomotor experiment, they were fed the same doses for one or seven days, after which we measured spontaneous movement using an open-field assay. We measured the proportion of time in movement, speed of movement, path meander (curviness), and arena exploration. The 10% ethanol concentration greatly increased the risk of mortality, whereas the estimated effect of 1% ethanol was smaller and statistically inconclusive. In terms of locomotion, the largest differences occurred after seven days of exposure to 10% ethanol. Workers in this treatment showed greater path meander and lower exploration than control workers. Speed was also lowest in this group. Evidence that exposure for seven days was worse than for one day at the same concentration was detected only for exploration. No clear locomotor effect was detected at 1% ethanol exposure. These findings provide comparative data on sustained ethanol exposure in bumblebees and show a strong concentration-dependent contrast, with substantial effects under high-concentration challenge but no clear effects on the measured endpoints at 1%.

Hypoxia impairs cognitive function, yet its effects on navigation and intrinsic brain activity remain poorly understood. This study investigated whether a continuous exposure to hypoxia (CH) or an intermittent exposure to hypoxia (IH) differentially influence navigation performance and resting-state electroencephalography (EEG) in healthy young adults. Seventy-two participants completed sham (FiO2 = .209) and hypoxia (FiO2 = .13) sessions during either a one hour of CH or IH intervention. Navigation was assessed using the Spatial Performance Assessment for Cognitive Evaluation (SPACE), while resting-state EEG was recorded before and after the intervention in a subset of participants (n = 40). EEG spectra were parameterised into periodic (alpha and beta power and central frequency) and aperiodic (exponent and offset) components. Aligned rank transform (ART) analyses of variance examined effects of hypoxia and intervention group, while linear regression determined whether reductions in peripheral oxygen saturation (SpO2) predicted changes in navigation or EEG. Hypoxia impaired multiple components of navigation, increasing path integration distance error and egocentric pointing angle error irrespective of intervention group, while mapping accuracy was preferentially impaired following IH and perspective taking performance following CH. Hypoxia also reduced alpha and beta power, beta central frequency, and aperiodic exponent, while aperiodic offset and alpha central frequency remained stable. The reduction in aperiodic exponent was primarily evident following IH, suggesting that the temporal pattern of oxygen delivery may influence specific neurophysiological responses. Contrary to our hypothesis, SpO2 reduction did not predict individual differences in navigation performance or EEG activity. These findings demonstrate that brief, moderate hypoxic exposure can disrupt allocentric and egocentric components of spatial navigation while selectively altering periodic and aperiodic features of intrinsic brain activity.

Motor imagery and overt action are proposed to share common planning mechanisms while relying on distinct processes during movement performance. To investigate how repetition affects physical and imagined movements, participants physically or mentally drew paths while avoiding barriers. The barrier orientations were either repeated or different across consecutive trials, and the modality (execution or imagery) of the trials either changed or remained the same for two consecutive trials. Reaction time and movement time were analysed as measures of movement planning and task performance, respectively. Imagined movements produced longer reaction times and movement times than physical movements. Repetition of orientation reduced reaction times in both physical and imagined trials, indicating that trajectory repetition facilitated movement preparation. In contrast, previous trial type influenced reaction times only for physical movements, which were only initiated faster when preceded by another physical trial. Different effects emerged for movement time. Physical movements were faster when the same trajectory was repeated no matter the previous trial type, whereas imagined movements were unaffected by orientation and instead showed shorter durations when preceded by another imagined trial. The findings indicate that physical and imagined movements rely on more similar trajectory representations during the planning stage, but diverge during task performance. While physical movements appear to benefit from the persistence of previously generated movement trajectories, imagined trials seems more influenced by modality-specific cognitive processes. These results provide behavioural support for the Motor-Cognitive model and contribute to understanding how movement repetition influences overt and imagined actions.

Female-female competition is increasingly recognized as a key driver of female ornamentation, including birdsong, which often functions in intrasexual competition. However, the specific resources females use elaborate traits to compete for remain unclear. In addition, few studies have simultaneously investigated the use of multiple competitive traits in females, despite growing independent interest in these traits (e.g., female song and aggression). We investigated the competitive contexts of female song, aggression and calling behavior in northern house wrens (Troglodytes aedon) to determine which resources females compete for across the breeding season. We simulated conspecific territorial intrusions using female song at three breeding stages representing different contexts: arrival (mate and territory acquisition), nest building (nest site and breeding status defense), and egg laying (brood defense). We tested whether female song and physical aggression varied as reproductive resources shifted across the breeding cycle. Females were significantly more aggressive during nest building, showing 5.8 times greater odds of a higher-intensity aggressive response during nest building compared to arrival. Female song output was similar across early stages but declined during egg laying, though this was not statistically significant after correction for multiple comparisons and individuals varied substantially in overall singing propensity. Non-song vocalizations varied by call type and breeding stage. Calls associated with aggression occurred most frequently during nest building, consistent with peak physical aggression responses. Together, these results identify nest building as the stage of highest female aggression, consistent with heightened competition over nest cavities and associated breeding status in this cavity-nesting species. In contrast, female song occurred across all stages and appears to function in multiple competitive contexts. This study provides evidence for context and mode-specific female signaling in a temperate songbird and highlights that females strategically use aggression, calls, and song to mediate social conflict across breeding contexts.

Following cocaine self-administration, male and female rats received daily semaglutide during a 30-day abstinence period before cue- and cocaine-induced reinstatement tests. Semaglutide attenuated cue-induced reinstatement and cocaine-induced stereotypy, although operant responding was elevated following cocaine priming. These findings support further investigation of semaglutide as a treatment for cocaine use disorder.

Neurofeedback shows promise as a clinical intervention, but its effectiveness is hindered by variability of response across individuals. One factor influencing neurofeedback success may be endogenous brain states, particularly the baseline power within target frequency bands. Transcranial alternating current stimulation (tACS) provides a potential mechanism to modulate these baseline frequency bands. This study explored whether tACS could effectively enhance participants' ability to gain neurofeedback control by increasing lateralised posterior alpha activity prior to engagement in a covert spatial attention-based neurofeedback task. Participants completed three counterbalanced sessions: 1) alpha tACS and active neurofeedback, 2) alpha tACS and sham neurofeedback, 3) gamma (40Hz) tACS and active neurofeedback. Neurofeedback performance was assessed via lateralised posterior alpha power shifts and Posner task reaction times. We identified no difference in reaction times or lateralised alpha power shifts across conditions. While participants reliably demonstrated lateralised posterior alpha patterns, consistent with the covert spatial attention neurofeedback protocol, no advantage of active neurofeedback over sham was observed. The lack of significant effects underscores the need for further rigorous tACS studies to identify the parameters essential for successful neural entrainment, and to evaluate its potential in enhancing neurofeedback efficacy.

Objective. Intermittent theta burst stimulation (iTBS) is a repetitive transcranial magnetic stimulation (rTMS) protocol used in clinical settings to alleviate symptoms of psychiatric disorders. Although the pulse parameters currently used in iTBS have remained unchanged since the first treatments, recent controllable TMS devices allow for the personalization of pulse shape and duration, opening the possibility of testing the efficacy of other pulse parameters in modulating corticospinal excitability (CSE). Methods. In a repeated-measures design, changes in CSE were induced by the administration of iTBS over the left primary motor cortex under three different conditions: long bidirectional pulse (L-Bi), long quasi-unidirectional pulse (L-QU), and a control short quasi-unidirectional pulse (S-QU). We assessed TMS-induced motor evoked potentials before and up to 70 minutes after iTBS. We hypothesized that L-QU pulses would induce greater facilitation than other conditions. Results. A mixed linear model showed that all conditions induced increased MEPs compared to baseline. However, the L-Bi pulse led to a larger and more sustained MEP increase than both unidirectional pulses, while the S-QU pulse appeared less effective in modulating CSE. We observed large within- and between-subject variability in responsiveness to the iTBS protocols. Conclusion. These results suggest that L-Bi pulses in iTBS protocols are more potent than unidirectional pulses in inducing CSE changes in the cortex of healthy adults. The individual variability in response to iTBS and the potential clinical relevance of these findings are discussed.

Categorical rhythmic patterns are fundamental features found in language and music across cultures. In humans, these rhythmic patterns occur in both vocal production and perceptual preference, highlighting a link between rhythmic production and preference. Categorical rhythmic patterns have recently been identified in animal vocalisations too, but whether rhythm production is linked with rhythmic preferences in non-human animals remains unclear. Within this context, zebra finches (Taeniopygia castanotis) are of particular interest, as both sexes develop a song preference, and their song has been suggested to exhibit an isochronous temporal structure. Here, we tested for the first time whether zebra finches prefer songs containing discrete rhythmic patterns, using operant preference tests with either two or four rhythmic patterns. Our results show that no categorical rhythmic pattern was consistently preferred across the population, although responses varied among individuals. These findings indicate that categorical rhythmic patterns are unlikely to be a primary driver of song preference in zebra finches. Together with previous work in other vocal-learning birds, our results suggest that preferences for categorical rhythmic patterns may not be universal and could instead reflect species-specific features of vocal displays rather than the rhythmic categories characteristic of human music.

More than a third of women in the United States are estimated to experience abuse from an intimate partner, in which blows to the head, strangulation, and therefore brain injuries are common. Among 207 survivors of such physical violence, two-thirds reported a partner-inflicted brain injury. These women performed substantially worse than the general population across most cognitive measures, including memory and reaction time. Cognitive performance declined as injury count increased. Translated into cognitive age, survivors with the most partner-inflicted brain injuries performed over two decades older than the general population, and a decade older than survivors with no history of brain injury. Importantly, the cognitive assessment discards scores it judges unreliable, yet these came primarily from the most impaired women, suggesting that the true harm is likely greater than reported here. Such cognitive deficits may limit these women's capacity to live to their potential, including keeping safe from abuse. These findings underscore partner-inflicted brain injury as a major, under-recognized source of cognitive harm, potentially affecting more women than brain injury in professional football or the military while lacking comparable clinical recognition and care.

Resource handling time is an important cost to foraging animals and this is especially true for low-ranking individuals who may be displaced before they acquire rewards. Handling may also require visual attention that can lead to a trade-off between scanning the environment and focusing on food acquisition. We ran a foraging experiment on wild vervet monkeys where we simultaneously offered them three puzzle boxes in a straight-line array that increased sequentially in handling difficulty and reward value. We found that differences in competitive ability had a large impact on access to long-handling time resources and willingness to invest time in costly problem-solving when social interference was possible. Resources with lower handling time and smaller rewards were accessed by individuals of all dominance ranks but only dominant monkeys that did not fear displacement attempted the high handling time puzzle box. Handling time improved with experience at each puzzle box and contrary to predictions, when vigilance rates were higher, monkeys were also faster at solving puzzle boxes. Thus, there is not necessarily a trade-off between attention to foraging tasks that require handling and vigilance, if a high scanning frequency to both can be balanced with limited scanning duration. These results have important implications for understanding the decision-making of foraging animals that live in competitive groups and the diets of individuals, which may vary with dominance when important resources require long handling times.

Courtship is an essential component of reproductive success for many species and many courtship behaviors, such as vocalization, are energetically demanding. In order to successfully balance investment in courtship with feeding and foraging, individuals must be aware of their current energy balance, and hormonal signals of energetic state have been found to influence social signal effort across a variety of species. Ghrelin is one hormone that plays an important role in regulating energy balance by signaling hunger and promoting feeding. Previous studies have investigated the role of ghrelin in courtship, aggression, and mating behavior. In this study, we build on prior work by investigating the effects of ghrelin on ultrasonic vocalizations (USV) and other courtship behaviors of male mice. We expand on previous research by observing ghrelin's effects over longer interactions, allowing us to understand how ghrelin impacts the dynamics of USV production over time. Our results show that while males initially vocally court females at a high rate regardless of treatment, ghrelin reduces overall USV production by increasing the rate of decline of vocalization. Surprisingly, despite its effects on vocal courtship, we found no significant differences in the production or timing of other, non-vocal, courtship behaviors. This study deepens our understanding of the role of hormones traditionally associated with controlling hunger and feeding in regulating social behaviors.

Reward operates as a cycle in which a stimulus produces a pleasure response, and the degree of pleasure experienced reinforces the behaviours that lead back to it. Music provides a useful model for examining this cycle because it is intrinsically pleasurable, can be learned, and engages reward-related frontostriatal circuitry that overlaps with circuitry involved in primary and secondary rewards, such as food, sex, and money. Transcranial magnetic stimulation (TMS), a non-invasive stimulation method, has been shown to produce bidirectional effects on music-evoked pleasure by increasing or decreasing activity in cortical regions, such as the left dorsolateral prefrontal cortex (DLPFC), that are functionally connected to subcortical regions, including the striatum. Here, we further characterize the reward cycle by incorporating TMS into a paradigm that combines musical pleasure ratings with an early musical skill acquisition task. In a within-subjects, counterbalanced crossover design, 23 participants with 2-10 years of musical experience received intermittent TBS (iTBS; excitatory) and continuous TBS (cTBS; inhibitory) over the left DLPFC in separate sessions. Participants rated the pleasantness of short piano melodies before stimulation (T0), immediately afterwards (T1), and 24 hours later (T2). After stimulation, they learned to play the melodies, and pitch and rhythm accuracy were assessed during three performance phases, namely acquisition, immediately after acquisition, and 24 hours later. Liking did not differ between conditions at T1; however, the increase in liking from baseline (T0) to T2 was significantly larger following iTBS than cTBS, a divergence that emerged across the 24-hour interval spanning both learning and sleep. Pitch and rhythm accuracy did not differ between conditions at any phase, despite improvement across trials in both. These results indicate that TMS to the left DLPFC can produce delayed, condition-dependent shifts in musical liking without a parallel change in early skill acquisition.

Sleep disturbances compromise cognition, and overall physical and mental health; however, animal models of these effects remain limited, and typically impose more extreme disturbances than those experienced by humans. Here, we use behavioural interventions in mice to model two common types of sleep disruption: (1) sleep displacement associated with shiftwork and (2) sleep fragmentation associated with aging and disease. C57BL6/J mice were subjected to either a sleep deprivation protocol (n = 8, females = 4) or a fragmentation protocol (n = 8, females = 4), in which they were completely deprived of sleep or awoken every 2 min respectively, for 12 hours during their typical rest phase (lights-on) across 7 consecutive days. Age-matched control mice (n = 14, females = 7) remained undisturbed in their home cages. Activity during the 12-hour active phase was recorded via infrared motion sensors. After protocol completion, mice were injected with bromodeoxyuridine (BrdU, 200mg/kg) 2 hours prior to brain and blood collection; hippocampal neurogenesis and plasma corticosterone were then assessed. Results show that the sleep deprivation and fragmentation protocols had different, dynamic effects on behaviour; sleep deprivation was associated with an accumulating sleep need, operationalized as progressively reduced locomotor activity across the week, whereas fragmentation produced only an acute reduction of locomotor activity. Cell proliferation rates and corticosterone did not differ from controls. These protocols provide a foundation for future research into the mechanistic links between shiftwork and sleep fragmentation on health and cognition.