Beyond an Intangible Fear: Behavioral Neuroscience for Understanding and Correctly Modulating Anxiety in Complex Diagnoses.

In order to ensure that even the patient with a complex diagnosis can receive deep and caring care on, for example, the issue of anxiety, it is necessary to turn to a branch that can give tangible evidence of what is happening to the person in a bio-psycho-social optics, a concept that many people talk about but in the end few can really apply. The following article will propose the method of behavioural neuroscience.

Is disease a threat to identity? A systematic review of parkinson's disease and personal identity.

Introduction: Parkinson's disease (PD) is a neurological condition that impacts the physical and psychological functioning of the patients. The physical and cognitive changes come with social stigma and threats to roles previously associated with their identities. Objectives: The current paper attempts to study the influence of the disease on the personal identity of the patients. Methods: A systematic review was done on PD and personal identity following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. The Consolidated Criteria for Reporting Qualitative Research checklist was used to assess the quality of the papers. The selected papers were synthesized to understand the relationship between PD and personal identity. Results: The emerging themes were: (1) dissociation of old personal identity: (1.1) Influence of physical symptoms, (1.2) influence of society and stigma, and (1.3) threats to roles associated with identity and (2) changing family dynamics. A Model of Personal, Family, and Disease Dynamics was also developed based on clinical first-hand experience with the patients and the review. Conclusion: The personal identity of the PD patients shifts drastically as a result of their physical and psychosocial experiences. This also results in changed family dynamics, with the patient feeling sidelined due to loss of control and responsibilities in the family.

Neonatal Anoxia Impacts Rats' Maternal Behavior and Offspring Development due to Ultrasonic Vocalization's Impairment.

Hypoxic-ischemic encephalopathy is a severe clinical condition, among others, affecting the brain after offspring exposure to neonatal anoxia, which causes persistent sensorimotor and cognitive deficits. During peripartum, maternal behaviors are crucial for the healthy development of the offspring. In rats, the vocalization of newborns, around 40 kHz, corresponds to separation calls that encourage their mothers to retrieve them. Alterations in this pattern affect the maternal behavior addressed to the offspring. This study aimed to evaluate the maternal behavior of primiparous rats whose offspring were exposed to neonatal anoxia in P2 (postpartum day) during the lactation period, to assess mother-pup interactions through the pups' vocalization from P3 to P18. It also intends to quantify eventual neuronal alterations in the mothers' medial preoptic area after the last weaning (P21) through FOS protein expression. Anoxia offspring were found to reduce maternal behaviors toward them, increased frequency of separation calls in the male anoxia group, and reduced vocalization rate in the female anoxia group compared to their respective controls. Body weight gain reduction of males' and females' anoxia was observed. We concluded that anoxia exerts deleterious effects on the vocalization patterns of the pups, with sex differences that alter maternal behavior toward them. Impaired USV makes an additional negative impact on the already noxious effects of neonatal anoxia. Understanding those phenomena applies/contributes to guiding procedures and strategies to mitigate the deleterious outcomes and orient research concerning the complexity of neonatal anoxia events and the influence of maternal care quality concerning the pups, which should also be considered sex differences.

Model-as-replica, model-as-instrument: Representational power and contextual versatility in animal models.

Existing scholarship on animal models tends to foreground either of the two major roles research organisms play in different epistemic contexts, treating their representational and instrumental roles separately. Based on an empirical case study, this article explores the changing relationship between the two epistemic roles of a research organism over the span of a decade, while the organism was used to achieve various knowledge ends. This rat model was originally intended as a replica of human susceptibility to cardiac arrest. In a fortunate stroke of serendipity, however, the experimenters detected the way mother-infant interactions regulated the pups' resting cardiac rate. This intriguing outcome thus became the model's new representational target and began driving the development of an experimental system. Henceforth, the model acquired an instrumental function, serving to detect and measure system-specific differences. Its subsequent development involved creating stimulus-response measures to explain and theorize those differences. It was this instrumental use of the model that pushed the experimenters into unchartered territory and conferred to the model an ability to adapt to varied epistemic contexts. Despite the prominence of this instrumental role, however, the model's representational power continued to guide research. The model's representational target was widened beyond heart rate to reflect other functional phenomena, such as behavioral activity and sleep/wake rhythm. The rat model was thus transformed from an experimental organism designed to instantiate cardiac regulation to a model organism taken to represent the development of a whole, intact animal under the regulatory influence of maternal care. This article examines this multifaceted transformation within the context of the salient shifts in modeling practice and variations in the model's representational power. It thus explores how the relationship between the representational and instrumental uses of the model changed with respect to the varying exigencies of the investigative context, foregrounding its contextual versatility.

The Legacy of the Kennard Principle.

Research into neural plasticity has progressed rapidly over the last few decades, but the origins of this field lie in the early 20th century. In 1936, Margaret Kennard introduced the concept of brain plasticity in an animal model by studying the recovery of motor functions after performing brain lesions in infant and adult monkeys. It took until the 1970s for her work to be widely acknowledged. When her work did eventually make it into the limelight, this led to the synthesis of what scientists dubbed the 'Kennard Principle'. The Kennard Principle states that the younger an organism is, the greater and swifter recovery from brain injury will be. This principle itself is subject to controversy and debate; furthermore, it is based on a simplification of Kennard's original results. This article will explore Kennard's original 1936 paper, published in the American Journal of Physiology, and the context in which the Kennard Principle arose. Kennard's paper demonstrates early pioneering work within the field of behavioral neuroscience which provides a historical foundation for psychology and neuroscience undergraduates. Exploring the context in which the Kennard Principle arose also highlights the importance of tracing the origins of scientific principles and theories for students and researchers alike.

Genetic rodent models of brain disorders: Perspectives on experimental approaches and therapeutic strategies.

Neurobehavioral disorders comprised of neurodegenerative, neurodevelopmental, and psychiatric disorders together represent leading causes of morbidity and mortality. Despite significant academic research and industry efforts to elucidate the disease mechanisms operative in these disorders and to develop mechanism-based therapies, our understanding remains incomplete and our access to tractable therapeutic interventions severely limited. The magnitude of these short-comings can be measured by the growing list of disappointing clinical trials based on initially promising compounds identified in genetic animal models. This review and commentary will explore why this may be so, focusing on the central role that genetic models of neurobehavioral disorders have come to occupy in current efforts to identify disease mechanisms and therapies. In particular, we will highlight the unique pitfalls and challenges that have hampered success in these models as compared to genetic models of non-neurological diseases as well as to symptom-based models of the early 20th century that led to the discovery of all major classes of psychoactive pharmaceutical compounds still used today. Using examples from specific genetic rodent models of human neurobehavioral disorders, we will highlight issues of reproducibility, construct validity, and translational relevance in the hopes that these examples will be instructive toward greater success in future endeavors. Lastly, we will champion a two-pronged approach toward identifying novel therapies for neurobehavioral disorders that makes greater use of the historically more successful symptom-based approaches in addition to more mechanism-based approaches.

Immune activation and neuroinflammation in alcohol use and HIV infection: evidence for shared mechanisms.

BACKGROUND: Emerging research points to innate immune mechanisms in the neuropathological and behavioral consequences of heavy alcohol use. Alcohol use is common among people living with HIV infection (PLWH), a chronic condition that carries its own set of long-term effects on brain and behavior. Notably, neurobiological and cognitive profiles associated with heavy alcohol use and HIV infection share several prominent features. This observation raises questions about interacting biological mechanisms as well as compounded impairment when HIV infection and heavy drinking co-occur. OBJECTIVE AND METHOD: This narrative overview discusses peer-reviewed research on specific immune mechanisms of alcohol that exhibit apparent potential to compound the neurobiological and psychiatric sequelae of HIV infection. These include microbial translocation, systemic immune activation, blood-brain barrier compromise, microglial activation, and neuroinflammation. RESULTS: Clinical and preclinical evidence supports overlapping mechanistic actions of HIV and alcohol use on peripheral and neural immune systems. In preclinical studies, innate immune signaling mediates many of the detrimental neurocognitive and behavioral effects of alcohol use. Neuropsychopharmacological research suggests potential for a feed-forward cycle in which heavy drinking induces innate immune signaling, which in turn stimulates subsequent alcohol use behavior. CONCLUSION: Alcohol-induced immune activation and neuroinflammation are a serious health concern for PLWH. Future research to investigate specific immune effects of alcohol in the context of HIV infection has potential to identify novel targets for therapeutic intervention.

Intrahippocampal Anisomycin Impairs Spatial Performance on the Morris Water Maze.

New memories are thought to be solidified (consolidated) by de novo synthesis of proteins in the period subsequent to learning. This view stems from the observation that protein synthesis inhibitors, such as anisomycin (ANI), administered during this consolidation period cause memory impairments. However, in addition to blocking protein synthesis, intrahippocampal infusions of ANI cause the suppression of evoked and spontaneous neural activity, suggesting that ANI could impair memory expression by simply preventing activity-dependent brain functions. Here, we evaluated the influence of intrahippocampal ANI infusions on allocentric spatial navigation using the Morris water maze, a task well known to require dorsal hippocampal integrity. Young, adult male Sprague Dawley rats were implanted with bilateral dorsal hippocampal cannulae, and their ability to learn the location of a hidden platform was assessed before and following infusions of ANI, TTX, or vehicle (PBS). Before infusion, all groups demonstrated normal spatial navigation (training on days 1 and 2), whereas 30 min following infusions (day 3) both the ANI and TTX groups showed significant impairments in allocentric navigation, but not visually cued navigation, when compared with PBS-treated animals. Spatial navigational deficits appeared to resolve on day 4 in the ANI and TTX groups, 24 h following infusion. These results show that ANI and TTX inhibit the on-line function of the dorsal hippocampus in a similar fashion and highlight the importance of neural activity as an intervening factor between molecular and behavioral processes. SIGNIFICANCE STATEMENT: The permanence of memories has long thought to be mediated by the production of new proteins, because protein synthesis inhibitors can block retrieval of recently learned information. However, protein synthesis inhibitors may have additional detrimental effects on neurobiological function. Here we show that anisomycin, a commonly used protein synthesis inhibitor in memory research, impairs on-line brain function in a way similar to an agent that eliminates electrical neural activity. Since disruption of neural activity can also lead to memory loss, it may be that memory permanence is mediated by neural rehearsal following learning.

Effects of transgenic expression of botulinum toxins in Drosophila.

Clostridial neurotoxins (botulinum toxins and tetanus toxin) disrupt neurotransmitter release by cleaving neuronal SNARE proteins. We generated transgenic flies allowing for conditional expression of different botulinum toxins and evaluated their potential as tools for the analysis of synaptic and neuronal network function in Drosophila melanogaster by applying biochemical assays and behavioral analysis. On the biochemical level, cleavage assays in cultured Drosophila S2 cells were performed and the cleavage efficiency was assessed via western blot analysis. We found that each botulinum toxin cleaves its Drosophila SNARE substrate but with variable efficiency. To investigate the cleavage efficiency in vivo, we examined lethality, larval peristaltic movements and vision dependent motion behavior of adult Drosophila after tissue-specific conditional botulinum toxin expression. Our results show that botulinum toxin type B and botulinum toxin type C represent effective alternatives to established transgenic effectors, i.e. tetanus toxin, interfering with neuronal and non-neuronal cell function in Drosophila and constitute valuable tools for the analysis of synaptic and network function.

Students apply research methods to consumer decisions about cognitive enhancing drinks.

The goal of this class project was to provide students with a hands-on research experience that allowed autonomy, but eliminated duplication of effort and could be completed within one semester. Our resources were limited to a small supply budget and an introductory psychology subject pool. Six students from a behavioral neuroscience class tested claims made by a drink company that their product improves cognitive function. The students each chose a cognitive task for their part of the project. The tasks included the Donders Reaction Time Task, the Stroop Task, the Raven's Progressive Matrices, a short-term memory span test, the Rey-Osterrieth Complex Figure Test and a simple measure of prefrontal EEG activity. Participants were randomly assigned to an experimental or control drink. The experimental group received the putative cognitive enhancing drink and the control group received a placebo drink that was very similar in color and taste. The two drinks shared no active ingredients. Results suggest that the putative cognitive enhancing drink did not improve performance on any of the tasks and decreased performance on the short-term memory task. These findings are discussed in regard to implications for consumers as well as further research into supplements and their ability to improve cognitive performance. Each student presented his/her results at a university-wide research conference. This project provided a rich experience in which students had the opportunity to carry out a research project from conception to presentation.

Brain-to-brain coupling forecasts future joint action outcomes.

In this study, we investigated whether brain-to-brain coupling patterns could predict performance in a time-estimation task that requires two players to cooperate. The participant pairs were tasked with synchronizing button presses after converging on a shared representation of "short," "medium," and "long" time intervals while utilizing feedback to adjust responses. We employed electroencephalogram (EEG)-hyperscanning and focused on post-feedback brain activity. We found that negative feedback led to increased frontal mid-line theta activity across individuals. Moreover, a correlation in post-feedback theta power between players forecasted failed joint action, while an anti-correlation forecasted success. These findings suggest that temporally coupled feedback-related brain activity between two individuals serves as an indicator of redundancy in adjustment of a common goal representation. Additionally, the anti-correlation of this activity reflects cognitive strategic mechanisms that ensure optimal joint action outcomes. Rather than a paired overcompensation, successful cooperation requires flexible strategic agility from both partners.

False memories in cuttlefish.

Episodic memory is a reconstructive process per se: during an event, the features composing it are encoded and stored separately in the brain, then reconstructed when the event's memory is retrieved. Even with source monitoring processes (e.g., did I see or did I smell it?), some mistakes can occur. These mnemonic mistakes happen especially when different events share several features, producing overlaps difficult to discriminate, leading to the creation of false memories. The common cuttlefish has the ability to remember specific events about what happened where and when, namely episodic-like memory. In order to investigate whether this memory, such as human episodic memory, is based on reconstructive processes, we elaborated a protocol promoting false memory formation. Our results suggest that cuttlefish do form visual false memories, but not olfactory false memories. These memory errors might be the first indication of the presence of reconstructive processes in the memory of cephalopods.

Spatiotemporal motion features resulting from tactile interface layouts influence tactile speed perception.

Representing tangential motion between objects and the skin using tactile displays enables humans to manipulate virtual objects and recognize their surface properties. To design effective tactile stimuli that accurately represent motion, it is important to understand how humans perceive tactile motion based on spatiotemporal features, an area that remains relatively unexplored. This study elucidates the spatiotemporal features that influence the perceived speed of tactile motion represented by a tactile display with discrete stimulation points. The findings show that the average spatial spacing between stimulation points affects the perceived speed, even though the average spatial spacing does not vary with the speed itself, but rather varies with the stimulation point layout of the tactile display. No significant effects from other features were observed on the perceived speed. The results suggest that perceived speed can be controlled by considering the average spatial spacing during tactile stimulus design.

Functional specialization of medial and lateral orbitofrontal cortex in inferential decision-making.

Inferring prospective outcomes and updating behavior are prerequisites for making flexible decisions in the changing world. These abilities are highly associated with the functions of the orbitofrontal cortex (OFC) in humans and animals. The functional specialization of OFC subregions in decision-making has been established in animals. However, the understanding of how human OFC contributes to decision-making remains limited. Therefore, we studied this issue by examining the information representation and functional interactions of human OFC subregions during inference-based decision-making. We found that the medial OFC (mOFC) and lateral OFC (lOFC) collectively represented the inferred outcomes which, however, were context-general coding in the mOFC and context-specific in the lOFC. Furthermore, the mOFC-motor and lOFC-frontoparietal functional connectivity may indicate the motor execution of mOFC and the cognitive control of lOFC during behavioral updating. In conclusion, our findings support the dissociable functional roles of OFC subregions in decision-making.

Post-interaction neuroplasticity of inter-brain networks underlies the development of social relationship.

Inter-brain coupling has been increasingly recognized for its role in supporting connectedness during social communication. Here we investigate whether inter-brain coupling is plastic and persists beyond the offset of social interaction, facilitating the emergence of social closeness. Dyads were concurrently scanned using functional near infrared spectroscopy (fNIRS) while engaging in a task that involved movement synchronization. To assess post-interaction neuroplasticity, participants performed a baseline condition with no interaction before and after the interaction. The results reveal heightened inter-brain coupling in neural networks comprising the inferior frontal gyrus (IFG) and dorsomedial prefrontal cortex in the post-task compared to the pre-task baseline. Critically, the right IFG emerged as a highly connected hub, with post-task inter-brain coupling in this region predicting the levels of motivation to connect socially. We suggest that post-interactions inter-brain coupling may reflect consolidation of socially related cues, underscoring the role of inter-brain plasticity in fundamental aspects of relationship development.

Identification of a strong genetic risk factor for major depressive disorder in the human virome.

The heritability of major depressive disorder (MDD) is reportedly 30-50%. However, the genetic basis of its heritability remains unknown. Within SITH-1, a risk factor for MDD in human herpesvirus 6B (HHV-6B), we discovered a gene polymorphism with a large odds ratio for an association with MDD. It was a sequence whose number of repeats was inversely correlated with SITH-1 expression. This number was significantly lower in MDD patients. Rates for 17 or fewer repeats of the sequence were 67.9% for MDD and 28.6% for normal controls, with an odds ratio of 5.28. For patients with 17 or less repeats, the rate for presence of another MDD patient in their families was 47.4%, whereas there were no MDD patients in the families of patients with more than 17 repeats. Since HHV-6B is transmitted primarily mother to child and within families and persists for life, this gene polymorphism could potentially influence heritability of MDD.

Oxytocin-induced birth causes sex-specific behavioral and brain connectivity changes in developing rat offspring.

Despite six decades of the use of exogenous oxytocin for management of labor, little is known about its effects on the developing brain. Motivated by controversial reports suggesting a link between oxytocin use during labor and autism spectrum disorders (ASDs), we employed our recently validated rat model for labor induction with oxytocin to address this important concern. Using a combination of molecular biological, behavioral, and neuroimaging assays, we show that induced birth with oxytocin leads to sex-specific disruption of oxytocinergic signaling in the developing brain, decreased communicative ability of pups, reduced empathy-like behaviors especially in male offspring, and widespread sex-dependent changes in functional cortical connectivity. Contrary to our hypothesis, social behavior, typically impaired in ASDs, was largely preserved. Collectively, our foundational studies provide nuanced insights into the neurodevelopmental impact of birth induction with oxytocin and set the stage for mechanistic investigations in animal models and prospective longitudinal clinical studies.

Growth-suppressor microRNAs mediate synaptic overgrowth and behavioral deficits in Fragile X mental retardation protein deficiency.

Abnormal neuronal and synapse growth is a core pathology resulting from deficiency of the Fragile X mental retardation protein (FMRP), but molecular links underlying the excessive synthesis of key synaptic proteins remain incompletely defined. We find that basal brain levels of the growth suppressor let-7 microRNA (miRNA) family are selectively lowered in FMRP-deficient mice and activity-dependent let-7 downregulation is abrogated. Primary let-7 miRNA transcripts are not altered in FMRP-deficiency and posttranscriptional misregulation occurs downstream of MAPK pathway induction and elevation of Lin28a, a let-7 biogenesis inhibitor. Neonatal restoration of brain let-7 miRNAs corrects hallmarks of FMRP-deficiency, including dendritic spine overgrowth and social and cognitive behavioral deficits, in adult mice. Blockade of MAPK hyperactivation normalizes let-7 miRNA levels in both brain and peripheral blood plasma from Fmr1 KO mice. These results implicate dysregulated let-7 miRNA biogenesis in the pathogenesis of FMRP-deficiency, and highlight let-7 miRNA-based strategies for future biomarker and therapeutic development.

Prior knowledge biases the visual memory of body postures.

Body postures provide information about others' actions, intentions, and emotions. Little is known about how postures are represented in the visual system. Considering our extensive visual and motor experience with body postures, we hypothesized that priors derived from this experience may systematically bias visual body posture representations. We examined two priors: gravity and biomechanical constraints. Gravity pushes body parts downward, while biomechanical constraints limit the range of possible postures (e.g., an arm raised far behind the head cannot go down further). Across three experiments (N = 246), we probed participants' visual memory of briefly presented postures using change discrimination and adjustment tasks. Results showed that lifted arms were misremembered as lower and as more similar to the nearest biomechanically plausible postures. Inverting the body stimuli eliminated both biases, ruling out visual confounds. These findings show that visual memory representations of body postures are modulated by a combination of category-general and category-specific priors.

Opposing serial effects of stimulus and choice in speech perception scale with context variability.

In this study, we investigated serial effects on the perception of auditory vowel stimuli across three experimental setups with different degrees of context variability. Aligning with recent findings in visual perception, our results confirm the existence of two distinct processes in serial dependence: a repulsive sensory effect coupled with an attractive decisional effect. Importantly, our study extends these observations to the auditory domain, demonstrating parallel serial effects in audition. Furthermore, we uncover context variability effects, revealing a linear pattern for the repulsive perceptual effect and a quadratic pattern for the attractive decisional effect. These findings support the presence of adaptive sensory mechanisms underlying the repulsive effects, while higher-level mechanisms appear to govern the attractive decisional effect. The study provides valuable insights into the interplay of attractive and repulsive serial effects in auditory perception and contributes to our understanding of the underlying mechanisms.