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Preserved social development but impaired executive function in a Shank3-deficient rat model of Phelan-McDermid syndrome

Phelan-McDermid syndrome (PMS) is a genetic neurodevelopmental disorder caused by a microdeletion within chromosome 22q13.3 1-6, and accounts for [~]1-3% of cases of autism spectrum disorders (ASD). Individuals with PMS typically present with neonatal hypotonia, severe speech delay, intellectual disability, motor impairments, and autism-related features, although additional manifestations such as epilepsy, sleep disturbances, and developmental regression are common. As in ASD, there is considerable heterogeneity in cognitive and behavioral impairments in PMS, making it difficult to determine which features arise directly from SHANK3/Shank3 deficiency and how deficits manifest across development. In the present study, we transferred the targeted Shank3 mutation, previously characterized on the Sprague Dawley background, onto the Long-Evans strain and performed a longitudinal behavioral assessment of Shank3-deficient rats from infancy to adulthood. The rats were evaluated for delays in early sensory and motor development, and ultrasonic vocalizations as neonates, social behavior, short term memory and gait as juveniles, and cognitive-executive dysfunction using a touchscreen-based visual discrimination and reversal learning task as adults. Despite profound reductions and/or complete loss of Shank3 protein expression, heterozygous and homozygous male and female rats showed normal physical and neurological reflexes across development, yet female Shank3 knockout pups showed a selective reduction in distress-associated ultrasonic vocalizations. As juveniles, subtle abnormalities emerged in short-term memory and limb coordination, while social preference for novelty and recognition was normal. Prominent behavioral abnormalities were observed in adults characterized by rapid and error-prone responding to visual stimuli during discrimination learning and reversal. These data suggest that rats with complete or partial Shank3 deficiency produce a selective behavioral profile in which high-order cognitive dysfunction is more pronounced than deficits in basic sensorimotor or select social behaviors. More broadly, these findings highlight executive dysfunction as a key consequence of the loss of Shank3. For the first time, we report the loss of Shank3 expression on a Long-Evans background strain as a valuable translational tool for investigating cognitive dysfunction and therapeutic windows in Shank3-associated disorders.

animal behavior and cognition↗

Repeated multi-domain, but not single-domain, cognitive training prevents cognitive decline and amyloid pathology found in the APPNL-G-F mouse model of Alzheimer disease

Education, occupation, and an active lifestyle, comprising enhanced social, physical, and mental components are associated with improved cognitive functions in aged people and may prevent/ or delay the progression of various neurodegenerative diseases including Alzheimers disease (AD). To investigate this protective effect, APPNL-G-F/NL-G-F mice at 3 months of age were exposed to repeated, single- or multi-domain cognitive training. Cognitive training was given at the age of 3, 6, 9 & 12 months of age. Single-domain cognitive training was limited to a spatial navigation task. Multi-domain cognitive training consisted of a spatial navigation task, object recognition, and fear conditioning. At the age of 12 months, behavioral tests were completed for cognitive training groups and control group. After completion of behavioral testing, mice were sacrificed, and their brains were assessed for pathology. AppNL-G-F mice given multi-domain cognitive training compared to APPNL-G-F control group showed an improvement in cognitive functions, reductions in amyloid load and microgliosis, and a preservation of cholinergic function. There were mild reductions in microglosis in the brain of APPNL-G-F mice with singledomain cognitive training. These findings provide causal evidence for the potential of certain forms of cognitive training to mitigate the cognitive deficits in Alzheimer disease.

animal behavior and cognition↗

Maternal choline supplementation: A potential therapy for developmental Manganese exposure?

Studies in children have reported associations between elevated manganese (Mn) exposure and ADHD-related symptoms of inattention, impulsivity/hyperactivity, and psychomotor impairment. Maternal choline supplementation (MCS) during pregnancy/lactation may hold promise as a protective strategy because it has been shown to lessen cognitive dysfunction caused by numerous early insults. Our objectives were to determine whether (1) developmental Mn exposure alters behavioral reactivity/emotion regulation, in addition to impairing learning, attention, impulse control, and sensorimotor function, and (2) MCS protects against these Mn-induced impairments. Pregnant Long-Evans rats were given standard diet, or a diet supplemented with additional choline throughout gestation and lactation (G3 - PND 21). Male offspring were exposed orally to 0 or 50 mg Mn/kg/day over PND 1-21. In adulthood, animals were tested in a series of learning, attention, impulse control, and sensorimotor tasks. Mn exposure caused lasting dysfunction in attention, reactivity to errors and reward omission, learning, and sensorimotor function, recapitulating the constellation of symptoms seen in ADHD children. MCS lessened Mn-induced attentional dysfunction and partially normalized reactivity to committing an error or not receiving an expected reward but provided no protection against Mn-induced learning or sensorimotor dysfunction. In the absence of Mn exposure, MCS produces lasting offspring benefits in learning, attention, and reactivity to errors. To conclude, developmental Mn exposure produces a constellation of deficits consistent with ADHD symptomology, and MCS offered some protection against the adverse Mn effects, adding to the evidence that maternal choline supplementation is neuroprotective for offspring and improves offspring cognitive functioning. HighlightsO_LIDevelopmental Mn exposure causes lasting dysfunction consistent with ADHD symptomology. C_LIO_LIMaternal choline supplementation (MCS) protects against Mn-induced deficits in attention and behavioral reactivity. C_LIO_LIMCS in control animals produces lasting benefits to offspring in learning, attention, and error reactivity. C_LIO_LIThese data support efforts to increase choline intake during pregnancy, particularly for individuals at risk of neurotoxicant exposure. C_LI

animal behavior and cognition↗

Simulated visual hallucinations in virtual reality enhance cognitive flexibility

Historically, psychedelic drugs are known to modulate cognitive flexibility, a central aspect of cognition permitting adaptation to changing environmental demands. Despite proof suggesting phenomenological similarities between artificially-induced and actual psychedelic altered perception, experimental evidence is still lacking about whether the former is also able to modulate cognitive flexibility. To address this, we measure participants cognitive flexibility through behavioral tasks after the exposure to virtual reality panoramic videos and their hallucinatory-like counterparts generated by the DeepDream algorithm. Results show that the estimated semantic network has a flexible structure when preceded by altered videos. Crucially, following the simulated psychedelic exposure, individuals also show an attenuated contribution of the automatic process and chaotic dynamics underlying the decision process. This suggests that simulated altered perceptual phenomenology enhances cognitive flexibility, presumably due to a reorganization in the cognitive dynamics that facilitates the exploration of uncommon decision strategies and inhibits automated choices.

animal behavior and cognition↗

Ecological Representations

Mainstream cognitive science and neuroscience both rely heavily on the notion of representation in order to explain the full range of our behavioral repertoire. The relevant feature of representation is its ability to designate (stand in for) spatially or temporally distant properties, When we organize our behavior with respect to mental or neural representations, we are (in principle) organizing our behavior with respect to the property it designates. While representational theories are a potentially a powerful foundation for a good cognitive theory, problems such as grounding and system-detectable error remain unsolved. For these and other reasons, ecological explanations reject the need for representations and do not treat the nervous system as doing any mediating work. However, this has left us without a straight-forward vocabulary to engage with so-called representation-hungry problems or the role of the nervous system in cognition. In an effort to develop such a vocabulary, here we show that James J Gibsons ecological information functions to designate the ecologically-scaled dynamical world to an organism. We then show that this designation analysis of information leads to an ecological conceptualization of the neural activity caused by information, which in turn we argue can together support intentional behavior with respect to spatially and temporally distal properties. Problems such as grounding and error detection are solved via law-based specification. This analysis extends the ecological framework into the realm of representation-hungry problems, making it as powerful a potential basis for theories of behavior as traditional cognitive approaches. The resulting analysis does, according to some definitions, allow information and the neural activity to be conceptualized as representations; however, the key work is done by information and the analysis remains true to Gibsons ecological ontology.

Animal Behavior and Cognition↗

Boundaries in Spatial Cognition: How They Look is More Important than What They Do

Large walls and other typical boundaries strongly influence neural activity related to navigation and the representations of spatial layouts. They are also major aids to reliable navigation behavior in young children and non-human animals. Is this because they are physical boundaries (barriers to movement), or because they present certain visual features, such as visually extended 3D surfaces? Here, these two factors were dissociated by using immersive virtual reality and real boundaries. Eighty adults recalled target locations in one of four environments: plywood, where a virtual wall coincided with a large piece of real plywood; pass through, where the virtual wall coincided with empty space and participants could pass through it; pass over, where the virtual wall was projected downward to be visible underneath a transparent floor; and cones, where the walls were replaced with traffic cones. One condition had features that were boundaries and looked like boundaries (plywood); two had features that were not boundaries but looked like boundaries (pass over/through); and one had features that were not boundaries and did not look like boundaries (cones). The precision and bias of responses changed only as a function of looking like a boundary. This suggests that variations in spatial coding are more closely linked to the visual properties of environmental layouts than to whether they contain physical boundaries (barriers to movement).

animal behavior and cognition↗

Learning decouples accuracy and reaction time for rapid decisions in a transitive inference task

Transitive inference (TI) is a cognitive process in which decisions are guided by internal representations of abstract relationships. While the mechanisms underlying transitive learning have been well studied, the dynamics of the decision-making process during learning and inference remain less clearly understood. In this study, we investigated whether a modeling framework traditionally applied to perceptual decision-making--the drift diffusion model (DDM)--can account for performance in a TI transfer task involving rapid decisions that deviate from standard accuracy and response time (RT) patterns. We trained six macaque monkeys on a TI transfer task, in which they learned the implied order of a novel list of seven images in each behavioral session, indicating their decisions with saccadic eye movements or reaching movements. Consistent learning of the list structure was achieved within 200-300 trials per session. Behavioral performance exhibited a symbolic distance effect, with accuracy increasing as the ordinal distance between items grew. Notably, RTs remained relatively stable across learning, despite improvements in accuracy. We applied a generalized DDM implementation (PyDDM; Shinn et al., 2020) to jointly fit accuracy and RT data. Model fits were achieved by incorporating both an increasing evidence accumulation rate and a collapsing decision bound, successfully capturing the RT distribution shapes observed during learning. Learning and transfer were fit by varying drift rate with little change in other parameters. Eye and reaching movements showed similar dynamics, with the difference in RT accounted for mainly by non-decision time. Our results highlight a distinct dynamical regime of the DDM framework, extending its applicability to cognitive domains involving symbolic reasoning and serial relational learning.

animal behavior and cognition↗

Testing two competing hypotheses for Eurasian jays' caching for the future: planning versus compensatory caching

Previous research reported that corvids preferentially cache food in a location where no food will be available or cache more of a specific food in a location where this food will not be available. Here, we consider possible explanations for these prospective caching behaviours and directly compare two competing hypotheses. The Compensatory Caching Hypothesis suggests that birds learn to cache more of a particular food in places where that food was less frequently available in the past. In contrast, the Future Planning Hypothesis suggests that birds recall what-when-where features of specific past events to predict the future availability of food. We designed a protocol in which the two hypotheses predict different caching patterns across different caching locations such that the two explanations can be disambiguated. We formalised the hypotheses in a Bayesian model comparison and tested this protocol in two experiments with one of the previously tested species, namely Eurasian jays. Consistently across the two experiments, the observed caching pattern did not support either hypothesis; rather it was best explained by a uniform distribution of caches over the different caching locations. Future research is needed to gain more insight into the cognitive mechanism underpinning corvids caching for the future.

animal behavior and cognition↗

Baby-brain phenomena is a subjective experience: absence of evidence for cognitive deficit in new mothers at one-year postpartum.

The experience and even existence of cognitive deficits in the postpartum period is uncertain, with only a few scientific studies, reporting inconsistent results. Here we investigate cognition in 86 women (43 first-time mothers one year postpartum, and 43 non-mothers). Mothers and non-mothers showed no significant differences on measures of objective cognition (verbal memory, working memory, processing speed or theory of mind). Despite the absence of objective differences, mothers self-reported significantly worse subjective memory than non-mothers. To interpret the difference between objective and subjective measures of memory, we investigated relationships between subjective memory, objective memory, and wellbeing. Mothers, but not non-mothers, showed a positive correlation between subjective and objective measures of memory, indicating mothers are in-tune with their memory performance. Mothers also demonstrated a positive relationship between subjective memory and wellbeing (sleep, anxiety and depression), where better wellbeing correlated with higher subjective memory. This relationship was not apparent in non-mothers. The results suggest that poorer sleep, higher anxiety and higher depression are related to reports of poorer self-reported memory in mothers. Our results add to our growing understanding of maternal cognition at one year postpartum, with no evidence of cognitive differences between mothers and non-mothers.

animal behavior and cognition↗

Fungal States of Minds

Fungal organisms can perceive the outer world in a way similar to what animals sense. Does that mean that they have full awareness of their environment and themselves? Is a fungus a conscious entity? In laboratory experiments we found that fungi produce patterns of electrical activity, similar to neurons. There are low and high frequency oscillations and convoys of spike trains. The neural-like electrical activity is yet another manifestation of the fungal intelligence. In this paper we discuss fungal cognitive capabilities and intelligence in evolutionary perspective, and question whether fungi are conscious and what does fungal consciousness mean, considering their exhibiting of complex behaviours, a wide spectrum of sensory abilities, learning, memory and decision making. We overview experimental evidences of consciousness found in fungi. Our conclusions allow us to give a positive answer to the important research questions of fungal cognition, intelligence and forms of consciousness.

animal behavior and cognition↗

An Evidence-based Cognitive Model of Human Wayfinding under Uncertainty

Existing computational models lack adequate representation of the uncertainty experienced in human wayfinding tasks. They overly rely on optimized pathing algorithms, which reduces realism and limits insights on human responses to architectural designs. To address this, we developed an empirically grounded model that predicts human wayfinding uncertainty experience. Using data from 28 participants navigating an educational building with varying signage, we constructed the model (Study 1), and validated it with data from 11 other participants (Study 2). We found the wayfinding uncertainty correlated with the time elapsed since seeing the last helpful sign. The cognitive agent based on this model closely replicated human-reported uncertainty levels during wayfinding tasks under different signage conditions. Although the model more closely resembled human behavior compared to a shortest-route algorithm, additional environmental variables and heuristics are needed for better human outcome alignment. Our study showcases that evidence-based cognitive agent modeling can provide nuanced, human-like wayfinding behavior, enhancing the potential for effective computational design evaluation.

animal behavior and cognition↗

Examining Anxiety and Risk-taking in Healthy Male and Female Wistar Rats using Spatial and Temporal Analysis of Elevated Plus Maze

The Elevated Plus Maze (EPM) offers a standard set up for understanding anxiety, unconditioned risk-avoidance in rodents. The animal shows a preference for enclosed safe arms and avoids risky, open arms that evoke anxiety due to elevated platform (unconditioned response to elevation). A few rodent studies aiming to understand sex-skewed representation in anxiety disorders use the maze and report that more females compared to males show high levels of anxiety and risk-avoidance on an elevated platform. Ethograms derived from examining animal behaviour in the EPM provide precise measures of behaviour of interest, enabling objective assessment of anxiety and risk behaviour. We report two new parameters that might be critical for quantitative analysis of EPM task as a measure of anxiety with reference to sex-differences in risk-taking: (a) spatial preference for arms (open & closed) (b) temporal shift in arm preference in task trials. We first report results from the conventionally derived measures confirming that males spent more time in the open arms indicating low anxiety and higher risk-taking. Preferences for the two open and two closed arms were non-uniform for males and females; male showed stronger preference for one of the two risky open arms, and females showed a stronger preference for one of the two safe closed arms. Temporal analyses indicated that males spent more time in open arms in 3 out of 6 time bins (time blocks), and females spent more time in the closed arms in 5 out of 6 time bins (time blocks), however, counter-intuitively, females showed larger increase in time spent in open arms in the last phase potentially indicating greater regulation of anxiety and increased risk-taking. Inclusion of spatial and temporal parameters in EPM studies might improve our understanding of cognitive and biological sex-differences pertaining to anxiety, and risky behaviour.

animal behavior and cognition↗

A Multi-task Platform for Profiling Cognitive and Motivational Constructs in Humans and Nonhuman Primates

BackgroundUnderstanding the neurobiological substrates of psychiatric disorders requires comprehensive evaluations of cognitive and motivational functions in preclinical research settings. The translational validity of such evaluations will be supported by (1) tasks with high construct validity that are engaging and easy to teach to human and nonhuman participants, (2) software that enables efficient switching between multiple tasks in single sessions, (3) software that supports tasks across a broad range of physical experimental setups, and (4) by platform architectures that are easily extendable and customizable to encourage future optimization and development. New MethodWe describe the Multi-task Universal Suite for Experiments (M-USE), a software platform designed to meet these requirements. It leverages the Unity video game engine and C# programming language to (1) support immersive and engaging tasks for humans and nonhuman primates, (2) allow experimenters or participants to switch between multiple tasks within-session, (3) generate builds that function across computers, tablets, and websites, and (4) is freely available online with documentation and tutorials for users and developers. M-USE includes a task library with seven pre-existing tasks assessing cognitive and motivational constructs of perception, attention, working memory, cognitive flexibility, motivational and affective self-control, relational long-term memory, and visuo-spatial problem solving. ResultsM-USE was used to test NHPs on up to six tasks per session, all available as part of the Task Library, and to extract performance metrics for all major cognitive and motivational constructs spanning the Research Domain Criteria (RDoC) of the National Institutes of Mental Health. Comparison with Existing MethodsOther experiment design and control systems exist, but do not provide the full range of features available in M-USE, including a pre-existing task library for cross-species assessments; the ability to switch seamlessly between tasks in individual sessions; cross-platform build capabilities; license-free availability; and its leveraging of video-engine capabilities used to gamify tasks. ConclusionsThe new multi-task platform facilitates cross-species translational research for understanding the neurobiological substrates of higher cognitive and motivational functions.

animal behavior and cognition↗

Item recognition is associated with gut microbiota composition in healthy humans

Murine studies show that the gut microbiota - the collection of the microbes residing in the large intestine - affects memory performance in the host. However, whether commensal gut bacteria are linked to human episodic memory remains unknown. Here, we investigated whether individual differences in episodic memory performance were associated with differences in the indigenous gut microbiota composition between individuals. We show that greater gut microbiota alpha diversity was associated with better item recognition and that gut microbiota dissimilarity index (beta diversity) between participants was associated with differences in their performance. Finally, our results suggest that Prevotella copri might play a role in the relationship between gut microbiota and human item recognition in healthy individuals. In a sample size larger than previous human studies and examining unmanipulated gut microbiota, we provide evidence that episodic memory in healthy humans is linked to their gut microbiota composition. SIGNIFICANCE STATEMENTUnderstanding the relationship between the gut microbiota - the collective of microbes in our gut - and human cognition represents a pivotal frontier in neuroscience. Our study dives into this quest by exploring the connection between the indigenous gut microbiota and episodic memory in healthy individuals. While prior research has illuminated this relationship in murine models, our study extends these findings to humans, providing compelling evidence that gut microbiota diversity and structural composition are associated with differences in episodic memory performance. By shifting the focus from probiotic-based interventions to the study of our commensal gut microbes, our findings shed light on how the gut microbiota, in its natural state, could be linked to interindividual differences in human cognition.

animal behavior and cognition↗

Low dimensional latent structure underlying the choices of mice

An impressive wealth of cognitive neuroscience tasks involves combining perceptual information with an estimate of the latent state of the environment to make a decision. Such tasks have driven the development of theoretically-motivated cognitive models which offer compactly parameterised, and thereby insightful, accounts of the internal processes by which this might happen. However, the very large amounts of data that can now be collected present a challenge and an opportunity for this frame-work. The challenge is that these models can be shown to underfit the data systematically (Nassar & Frank, 2016; Palminteri, Wyart, & Koechlin, 2017; Wilson & Collins, 2019) - particularly in how they characterise the effect of the latent state estimate. But this opens up the opportunity to extend the framework and employ richer, more highly parameterised and flexible models, in a data-driven manner (Dezfouli, Griffiths, Ramos, Dayan, & Balleine, 2019). Unfortunately, it is tremendously difficult to interpret these models, precisely because of their flexibility. Here, we follow a recent approach (Eckstein, Summerfield, Daw, & Miller, 2024), in which components of compact models are progressively replaced with more flexible homologues, but, where possible, the resulting insights are mapped back into theoretically-transparent forms. We prove the effectiveness of our scheme by applying it to one of the largest available decision-making data sets for mice - more than 300,000 choices from 139 subjects studied by the International Brain Lab (The International Brain Laboratory et al., 2021). We found widely generalisable phenomena such as notable effects of continual fluctuations in task engagement and systematic differences between learning and forgetting of chosen and unchosen options in determining the subjective state estimate. Our results show that combining theory-driven and data-driven methods can reveal cognitive processes that would have been difficult to discover using either method on its own.

animal behavior and cognition↗

Rapid Social Transmission of Predator Location via Gaze Following in Pigeons

Social information transmission is a key advantage of group living, particularly in uncertain or high-stakes contexts. During collective predator vigilance, individuals often initiate evasive action based on social cues--such as the escape behaviour of others--before detecting threats themselves. Yet these cues can be ambiguous or misleading, leading to costly false alarms. Gaze following, a key socio-cognitive skill widespread across species, may reduce this ambiguity by allowing individuals to localize threats with minimal effort and avoid unnecessary escapes. Although this vigilance function has long been hypothesized, direct evidence is lacking. Here we show that pigeons foraging in flocks detect a predator and socially transmit its location rapidly via gaze following, before any escape behaviour occurs. In experiments simulating predator attacks, we reconstructed predator-oriented gaze using high-resolution posture tracking and modelled social transmission with dynamic multi-network Bayesian models. Comparing models based on distinct social cues, we found that pigeons responded selectively to conspecific gaze toward the predator, rather than locomotion, head-up vigilance, or gaze elsewhere. Analyses of network structure further revealed that this transmission occurs through visually connected networks, particularly via peripheral rather than foveal vision. While individuals occasionally followed gaze to non-threatening locations, flocks reliably converged on the actual threat. These findings uncover a previously undocumented, cognition-based mechanism of collective detection. To our knowledge, this is the first evidence that gaze following serves an adaptive function in survival contexts, illustrating how individual-level cognition and group-level dynamics interact to the adaptive value of group living.

animal behavior and cognition↗

Individual differences in Game Transfer Phenomena are associated with creativity and positive schizotypy but not with perceptual priming

Game Transfer Phenomena (GTP) refer to involuntary experience of video-game elements as part of gamers everyday perception, cognition, and behaviour. Although previous research has identified Internet Gaming Disorder (IGD), positive schizotypy, and spontaneous cognitions (e.g., mind-popping, daydreaming) as key predictors of GTP, the role of implicit memory processes and creativity remains unclear. The present study examined whether these cognitive processes are associated with GTP frequency while replicating established predictors such as IGD, involuntary cognitions, and schizotypal traits. A total of 85 video game players (53% males; Mage = 24.89, SD = 5.87) completed a word fragment completion task to assess individual differences in perceptual implicit memory (priming). To measure creativity, participants completed the Alternate Uses Task (AUT) as a measure of divergent thinking, and a free association task to estimate forward flow, a robust predictor of creative cognition. Results showed robust priming effects at the group level (M = .23, SD = .14), however, individual differences in perceptual priming were not associated with GTP frequency. In contrast, AUT scores were positively associated with GTP and contributed uniquely to its prediction. A hierarchical regression model explained 58.2% of the variance in GTP frequency, with IGD, daydreaming, and positive schizotypy as the strongest predictors, alongside hours played per session and AUT scores. These findings suggest that GTP may not be driven by domain-general perceptual implicit memory processes but may be more strongly linked to individual differences in spontaneous cognitions and conceptual associative priming processes.

animal behavior and cognition↗

Complex Dynamics From Simple Cognition: The Primary Ratchet Effect In Animal Culture

AO_SCPLOWBSTRACTC_SCPLOWIt is often observed that human culture, unlike most other animal culture, is cumulative: human technology and behavior is more complex than any individual could invent in their own lifetime. Cumulative culture is often explained by appeal to a combination of high-fidelity social learning and innovation, the \"ratchet effect.\" What is often overlooked is that both human and other animal culture is supported by a more primary ratchet effect that retains and increases the prevalence of adaptive behavior. This primary ratchet can arise without appeal to specialized cognitive adaptations and is plausibly more widespread in animal societies. We use a simple model to highlight how simple forms of contingent social learning can create the primary ratchet effect, dramatically increasing the prevalence of adaptive, hard to invent behavior. We investigate some ways that demography may interact with the primary ratchet to generate patterns of cultural variation. As the primary ratchet may be common to many animal societies, its cognitive components and population dynamics provide a common foundation for the study of animal culture and a necessary foundation for understanding the origins of human cumulative culture.

animal behavior and cognition↗