The flow of reward information through neuronal ensembles in the accumbens.

The nucleus accumbens shell (NAcSh) integrates reward information through diverse and specialized neuronal ensembles, influencing decision-making. By training rats in a probabilistic choice task and recording NAcSh neuronal activity, we found that rats adapt their choices based solely on the presence or absence of a sucrose reward, suggesting they build an internal representation of reward likelihood. We further demonstrate that NAcSh ensembles dynamically process different aspects of reward-guided behavior, with changes in composition and functional connections observed throughout the reinforcement learning process. The NAcSh forms a highly connected network characterized by a heavy-tailed distribution and the presence of neuronal hubs, facilitating efficient information flow. Reward delivery enhances mutual information, indicating increased communication between ensembles and network synchronization, whereas reward omission decreases it. Our findings reveal how reward information flows through dynamic NAcSh ensembles, whose flexible membership adapts as the rat learns to obtain rewards (energy) in an ever-changing environment.

Sleep debt-induced anxiety and addiction to substances of abuse: A narrative review.

Substance Use Disorder (SUD) has been conceptualized as an outcome of a dysregulated reward system. However, individuals with SUD suffer from anxiety with an intensity depending on the abstinence period length. This review discusses the role of anxiety as a major contributor to the initiation and perpetuation of SUD, and its dependence on an up-regulated defense-antireward system. In addition, it is discussed that sleep debt, and its psychosocial consequences, promote anxiety, contributing to SUD generation and maintenance. Healthy sleep patterns can be disrupted by diverse medical conditions and negative psychosocial interactions, resulting in accumulated sleep debt and anxiety. Within this narrative review, we discuss the interplay between the motivation-reward and defense-antireward systems, framing the progression from recreational drug use to addiction. This interplay is nuanced by sleep debt-induced anxiety and its psychosocial consequences as contributory vulnerability factors in the genesis of addiction.

LEAP2 is associated with impulsivity and reward sensitivity depending on the nutritional status and decreases with protein intake in humans.

AIM: Liver-expressed antimicrobial peptide 2 (LEAP2) dynamics in human plasma and its association with feeding behaviour remain poorly understood. Therefore, this study aims: (a) to investigate fasting LEAP2 in participants with normal weight or with overweight or mild obesity (OW/OB); (b) to study the association between fasting LEAP2 and anthropometric and metabolic traits, feeding behaviour, LEAP2 genetic variants and blood cell DNA methylation status; and (c) to ascertain postprandial changes in LEAP2 after high protein intake and the association with feeding behaviour and food intake. METHODS: Anthropometric and behavioural measures, genotyping, methylation profiling, plasma glucose and LEAP2 concentrations were assessed in 327 females and males. A subgroup of 123 participants received an ad libitum high-protein meal, and postprandial LEAP2 concentration and behavioural measures were assessed. RESULTS: LEAP2 concentration was higher in participants with OW/OB (p < 0.001) and in females (p < 0.001), and was associated with LEAP2 single nucleotide polymorphisms rs765760 (p = 0.012) and rs803223 (p = 0.019), but not with LEAP2 methylation status. LEAP2 concentration was directly related to glycaemia (p = 0.001) and fullness (p = 0.003) in participants with normal weight, whereas it was associated with body mass index (p = 0.018), waist circumference (p = 0.014) and motor impulsivity in participants with OW/OB (p = 0.005). A negative association with reward responsiveness was observed in participants with OW/OB (p = 0.023). LEAP2 concentration was inversely associated with food intake (p = 0.034) and decreased after a high-protein meal (p < 0.001), particularly in women (p = 0.002). CONCLUSION: Increased LEAP2 in participants with OW/OB is associated with behavioural characteristics of obesity. Our results show sexual dimorphism in LEAP2 concentration before and after food intake and highlight the role of LEAP2 in feeding regulation.

Predation risk and floral rewards: How pollinators balance these conflicts and the consequences on plant fitness.

Foraging behavior of pollinators is shaped by, among other factors, the conflict between maximizing resource intake and minimizing predation risk; yet, empirical studies quantifying variation in both forces are rare, compared to those investigating each separately. Here, we discuss the importance of simultaneously assessing bottom-up and top-down forces in the study of plant-pollinator interactions, and propose a conceptual and testable graphical hypothesis for pollinator foraging behavior and plant fitness outcomes as a function of varying floral rewards and predation risk. In low predation risk scenarios, no noticeable changes in pollinator foraging behavior are expected, with reward levels affecting only the activity threshold. However, as predation risk increases we propose that there is a decrease in foraging behavior, with a steeper decline as plants are more rewarding and profitable. Lastly, in high predation risk scenarios, we expect foraging to approach zero, regardless of floral rewards. Thus, we propose that pollinator foraging behavior follows an inverse S-shape curve, with more pronounced changes in foraging activity at intermediate levels of predation risk, especially in high reward systems. We present empirical evidence that is consistent with this hypothesis. In terms of the consequences for plant fitness, we propose that specialized plant-pollinator systems should be more vulnerable to increased predation risk, with a steeper and faster decline in plant fitness, compared with generalist systems, in which pollinator redundancy can delay or buffer the effect of predators. Moreover, whereas we expect that specialist systems follows a similar inverse S-shape curve, in generalist systems we propose three different scenarios as a function not only of reward level but also compatibility, mating-system, and the interplay between growth form and floral display. The incorporation of trade-offs in pollinator behavior balancing the conflicting demands between feeding and predation risk has a promising future as a key feature enabling the development of more complex foraging models.

Baclofen prevents morphine rewarding effects and associated biochemical alterations in male and female mice.

Previous studies from our laboratory have shown sex differences in the behavioral, molecular, and neurochemical manifestations of morphine withdrawal and they were related to an increased sensitivity to morphine effects in males. In addition, we observed an interaction between the GABAergic and opioid systems that could also be sex-dependent. Baclofen, a GABAB receptor agonist, prevented the somatic expression and the molecular and neurochemical changes induced by morphine withdrawal syndrome in mice. On the contrary, little is known about baclofen effects in the rewarding properties of morphine in male and female mice. The present study aimed to explore the effect of baclofen (1, 2 and 3 mg/kg, i.p.) pretreatment in the rewarding effects induced by morphine (7 mg/kg, s.c.) and its effect on c-Fos and brain-derived neurotrophic factor (BDNF) expression induced by the rewarding properties of morphine in prepubertal male and female mice. Baclofen (2 mg/kg) pretreatment prevented the rewarding effects of morphine only in male mice, while baclofen (3 mg/kg) reduced these effects in both sexes. Moreover, the rewarding effects of morphine were associated with a decrease of BDNF and c-Fos expression cingulate cortex, nucleus accumbens shell, cornu ammonis 1 (CA1), and cornu ammonis 3 (CA3) areas of the hippocampus only in male mice. In addition, baclofen pretreatment prevented these changes in BDNF, but not in c-Fos expression. In conclusion, our results show that GABAB receptors have a regulatory role in the rewarding effects of morphine that could be of interest for a potential future therapeutic application in opioid use disorders.

Anticipatory and consummatory neural correlates of monetary and music rewarding stimuli.

Most of the literature on the neural bases of human reward and punishment processing has used monetary gains and losses, but less is known about the neurophysiological mechanisms underlying the anticipation and consumption of other types of rewarding stimuli. In the present study, EEG was recorded from 19 participants who completed a modified version of the Monetary Incentive Delay (MID) task. During the task, cues providing information about potential future outcomes were presented to the participants. Then, they had to respond rapidly to a target stimulus to win money or listening to pleasant music, or to avoid losing money or listening to unpleasant music. Results revealed similar responses for monetary and music cues, with increased activity for cues indicating potential gains compared to losses. However, differences emerged in the outcome phase between money and music. Monetary outcomes showed an interaction between the type of the cue and the outcome in the Feedback Related Negativity and Fb-P3 ERPs and increased theta activity increased for negative feedbacks. In contrast, music outcomes showed significant interactions in the Fb-P3 and theta activities. These findings suggest similar neurophysiological mechanisms in processing cues for potential positive or negative outcomes in these two types of stimuli.

Advancements in addressing drug dependence: A review of promising therapeutic strategies and interventions.

Substance dependence represents a pervasive global concern within the realm of public health. Presently, it is delineated as a persistent and recurrent neurological disorder stemming from drug-triggered neuroadaptations in the brain's reward circuitry. Despite the availability of various therapeutic modalities, there has been a steady escalation in the mortality rate attributed to drug overdoses. Substantial endeavors have been directed towards the exploration of innovative interventions aimed at mitigating cravings and drug-induced repetitive behaviors. Within this review, we encapsulate the most auspicious contemporary treatment methodologies, accentuating meta-analyses of efficacious pharmacological and non-pharmacological approaches: including gabapentin, topiramate, prazosin, physical exercise regimens, and cerebral stimulation techniques.

Foraging task specialization in honey bees (Apis mellifera): the contribution of floral rewards to the learning performance of pollen and nectar foragers.

Social insects live in communities where cooperative actions heavily rely on the individual cognitive abilities of their members. In the honey bee (Apis mellifera), the specialization in nectar or pollen collection is associated with variations in gustatory sensitivity, affecting both associative and non-associative learning. Gustatory sensitivity fluctuates as a function of changes in motivation for the specific floral resource throughout the foraging cycle, yet differences in learning between nectar and pollen foragers at the onset of food collection remain unexplored. Here, we examined nectar and pollen foragers captured upon arrival at food sources. We subjected them to an olfactory proboscis extension reflex (PER) conditioning using a 10% sucrose solution paired (S10%+P) or unpaired (S10%) with pollen as a co-reinforcement. For non-associative learning, we habituated foragers with S10%+P or S10%, followed by dishabituation tests with either a 50% sucrose solution paired (S50%+P) or unpaired (S50%) with pollen. Our results indicate that pollen foragers show lower performance than nectar foragers when conditioned with S10%. Interestingly, performance improves to levels similar to those of nectar foragers when pollen is included as a rewarding stimulus (S10%+P). In non-associative learning, pollen foragers tested with S10%+P displayed a lower degree of habituation than nectar foragers and a higher degree of dishabituation when pollen was used as the dishabituating stimulus (S10%+P). Altogether, our results support the idea that pollen and nectar honey bee foragers differ in their responsiveness to rewards, leading to inter-individual differences in learning that contribute to foraging specialization.

Psychostimulants and social behaviors.

Mounting evidence from animal models and human studies indicates that psychostimulants can significantly affect social behaviors. This is not surprising considering that the neural circuits underlying the regulation and expression of social behaviors are highly overlapped with those targeted by psychostimulants, which in most cases have strong rewarding and, consequently, addictive properties. In the present work, we provide an overview regarding the effects of illicit and prescription psychostimulants, such as cocaine, amphetamine-type stimulants, methylphenidate or modafinil, upon social behaviors such as social play, maternal behavior, aggression, pair bonding and social cognition and how psychostimulants in both animals and humans alter them. Finally, we discuss why these effects can vary depending on numerous variables such as the type of drug considered, acute versus long-term use, clinical versus recreational consumption, or the presence or absence of concomitant risk factors.

Navigating the complex terrain of motivated behavior: a bibliometric and neuroscientific perspective.

Over several decades, motivated behavior has emerged as a crucial study area within neuroscience. Understanding the neural substrates and mechanisms driving behaviors related to reward, addiction, and other motivation forms is pivotal for novel therapeutic interventions. This review provides a bibliometric analysis of the literature, highlighting the main trends, influential authors, and the potential future direction of the field. Utilizing a dataset comprised by 3,150 publications from the Web of Science and Scopus databases ("motivated behavior as query), we delve into key metrics like publication trends, keyword prevalence, author collaborations, citation impacts, and employed an unsupervised natural language processing technique - Latent Dirichlet Allocation - for topic modeling. From early investigations focusing on basic neural mechanism and behaviors in animal models to more recent studies exploring the complex interplay of neurobiological, psychological, and social factors in humans, the field had undergone a remarkable transformation. The last century has seen a proliferation of research dedicated to uncovering the intricacies of motivation, significantly enriching our understanding of its myriad implications for human behavior and mental health. This bibliometric analysis aims to offer comprehensive insights into this dynamic research area, highlighting the field's key contributions and potential future directions, thereby serving as a valuable resource for researchers, and hopefully give a more thorough understanding of the research area.

Changes in ethanol effects in knock-in mice expressing ethanol insensitive alpha1 and alpha2 glycine receptor subunits.

AIMS: Glycine receptors (GlyRs) are potentiated by physiologically relevant concentrations of ethanol, and mutations in the intracellular loop of α1 and α2 subunits reduced the effect of the drug. Knock-in (KI) mice having these individual mutations revealed that α1 and α2 subunits played a role in ethanol-induced sedation and ethanol intake. In this study, we wanted to examine if the effects of stacking both mutations in a 2xKI mouse model (α1/α2) generated by a selective breeding strategy further impacted cellular and behavioral responses to ethanol. MAIN METHODS: We used electrophysiological recordings to examine ethanol's effect on GlyRs and evaluated ethanol-induced neuronal activation using c-Fos immunoreactivity and the genetically encoded calcium indicator GCaMP6s in the nucleus accumbens (nAc). We also examined ethanol-induced behavior using open field, loss of the righting response, and drinking in the dark (DID) paradigm. KEY FINDINGS: Ethanol did not potentiate GlyRs nor affect neuronal excitability in the nAc from 2xKI. Moreover, ethanol decreased the Ca2+ signal in WT mice, whereas there were no changes in the signal in 2xKI mice. Interestingly, there was an increase in c-Fos baseline in the 2xKI mice in the absence of ethanol. Behavioral assays showed that 2xKI mice recovered faster from a sedative dose of ethanol and had higher ethanol intake on the first test day of the DID test than WT mice. Interestingly, an open-field assay showed that 2xKI mice displayed less anxiety-like behavior than WT mice. SIGNIFICANCE: The results indicate that α1 and α2 subunits are biologically relevant targets for regulating sedative effects and ethanol consumption.

Therapeutic potential of psychedelics: History, advancements, and unexplored frontiers.

Psychedelics (serotonergic hallucinogens) are psychoactive substances that can alter perception and mood, and affect cognitive functions. These substances activate 5-HT2A receptors and may exert therapeutic effects. Some of the disorders for which psychedelic-assisted therapy have been studied include depression, addiction, anxiety and post-traumatic stress disorder. Despite the increasing number of studies reporting clinical effectiveness, with fewer negative symptoms and, additionally, minimal side effects, questions remain to be explored in the field of psychedelic medicine. Although progress has been achieved, there is still little understanding of the relationship among human brain and the modulation induced by these drugs. The present article aimed to describe, review and highlight the most promising findings in the literature regarding the (putative) therapeutic effects of psychedelics.

Effort-reward and overcommitment at work and psychiatric symptoms in healthcare professionals: The mediation role of allostatic load.

Background: Despite decades of advancement to support interventions for managing work-related stress, mental health issues have significantly escalated among healthcare professionals. Effort-reward imbalance (ERI) and overcommitment in the workplace are linked to several psychiatric disorders. However, the underlying biological mechanisms remain unclear. This study investigated whether ERI and overcommitment among healthcare professionals were linked to Allostatic Load (AL) and whether AL mediates the relationship between ERI, overcommitment and mental health issues. Methods: One hundred forty-two nursing workers (n = 142; 90.1 % female, mean age: 39.5 ± 9.6) were randomly recruited from a university hospital in Sao Paulo, Brazil, and applied the ERI scale that assesses work effort, reward, and overcommitment. The Perceived Stress Scale (PSS), The Beck Depression Inventory (BDI), and the Self-Report Questionnaire for psychiatric symptoms (SRQ-20) evaluated the mental health outcomes. Ten neuroendocrine, metabolic, immunologic and cardiovascular biomarkers were analyzed, and values were transformed into an AL index using clinical reference cutoffs. Results: Linear regression adjusted for covariates showed that higher scores for overcommitment were associated with higher AL indexes, which in turn were associated with higher SRQ-20, but not with PSS and DBI scores. As expected, higher scores for effort, lower for reward, and higher ERI were associated with higher scores for PSS, SRQ-20, and DBI, but not with AL index. Direct effect estimates showed that overcommitment was directly associated with higher SRQ-20 scores, and indirectly via AL. Conclusion: Our study reveals that overcommitment, rather than ERI, was linked to increased AL in healthcare workers. Additionally, AL mediates the relationship between overcommitment and higher psychiatric symptoms, highlighting a key mechanism by which work stress can lead to mental health problems. Individual's responses to high work demands need to be considered when designing predictive models and interventions for mental health issues.

Impulsivity and sexual addiction: factor structure and criterion-related validity of the sexual addiction screening test in Mexican adults.

Sexual addiction is associated with serious health problems. Due to that fact, it is quite important to perform a comprehensive assessment. The Sex Addiction Screening Test (SAST-R) is a self-administered questionnaire with good psychometric properties used in several countries. Our study conducts a cross-cultural adaptation of the SAST-R on the Mexican population. The original version of the SAST-R was translated into Mexican Spanish, and we performed a pilot with 23 participants to be sure that the participants understood the meaning of the items. The final version was administered to 370 adults who completed the SAST-R, and measures of impulsivity (the Kirby questionnaire), reward/punishment responsivity (BIS-BAS scale), personality (BIG-Five), and psychological distress (SCL-90). The confirmatory factor analysis (CFA) with a five-factor model with one second-order factor model had the best fit. Reliability analysis suggests acceptable internal consistency (α = 0.80). The SAST-R scores exhibited significant correlations with several variables. Specifically, they showed a positive correlation with the neuroticism scale (r = 0.11, p < 0.05), a negative correlation with the conscientiousness scale (r = -0.21, p < 0.01), a negative correlation with the BIS scale (r = -0.11, p < 0.05), and a positive correlation with psychological distress (r = 0.34, p < 0.01). Notably, there were no significant correlations observed with variables that we initially expected to have a substantial association, such as impulsivity (r = -0.004, p > 0.05) and the three BAS subscales (p > 0.05). We found with an algorithm that psychological distress, impulsivity, neuroticism, and agreeableness were the good predictors to identify high scores of hypersexuality. Our results confirmed that the Mexican Spanish version of the SAST-R has good psychometric properties to be used in future research.

Exploratory study of the prevalence of food addiction and its relationship with executive functioning, depression, and reinforcement sensitivity in a sample of Mexican adults.

Introduction: The study of food addiction (FA) has become relevant due to its high prevalence, the negative impact on quality of life, and its association with neuropsychological and psychiatric symptoms. Several studies have provided scientific support for these associations, however, the results are contradictory. Additionally, studies have unsuccessfully elucidated the true nature of the failures in executive functioning in people with FA symptomatology, particularly when it comes to executive deficits. Therefore, the purpose of this research was to establish whether the presence of executive dysfunction, depressive symptoms and binge eating problems, as well as high reward sensitivity entails a greater severity in FA traits and high body mass index (BMI) in a sample of Mexican adults. Methods: The sample consisted of Mexican men and women between 21-59 years (n = 36); who completed self-report questionnaires and performance tests to measure the study variables. Additionally, BMI was estimated with self-reported height and weight. Results: Our results showed that a high number of FA symptoms were associated with higher executive dysfunction scores, greater reward sensitivity, and more severe depressive and binge eating problems. Furthermore, factors that are more strongly associated with higher scores of FA include severe executive deficits, greater activation of the punishment avoidance system, and persistence in the search for reward when the depressive symptoms increased. The factors that best explained changes in the estimated BMI of women were a decreased crystallized intellectual capacity and the inability to control food intake as the number of FA symptoms increased. Discussion: In summary, the cognitive functioning profile characterized by general failure of the executive functioning, as well as a greater activation of the Punishment Avoidance System and persistence in the search for reward, were associated with greater severity of FA symptoms, especially when the depressive symptomatology was severe. In parallel, the psychopathology in participants associated with FA confirms the contribution of anxious and depressive symptomatology and borderline personality traits which could facilitate the expression of clinically relevant FA symptoms in women. Finally, we found that decreased crystallized intellectual capacity and inability to control food intake were linked to higher BMI when the number of FA symptoms increased.

Being friendly: paced mating for the study of physiological, behavioral, and neuroplastic changes induced by sexual behavior in females.

Paced mating in rats is an experimental condition that allows the evaluation of sexual behavior in a way that closely resembles what occurs in seminatural and natural conditions enabling the female to control the rate of the sexual interaction. In conventional non-paced mating tests, females cannot escape from male approaches, which may lead to an unrewarding overstimulation. Paced mating is an alternative laboratory procedure that improves animal welfare and has a higher ethological relevance. The use of this procedure contributed to the identification of physiological and behavioral factors that favor reproduction. Paced mating includes motivational and behavioral components differentiating quantitative and qualitative characteristics that are critical for the induction of the rewarding properties of mating. These positive consequences ensure that the behavior will be repeated, favoring the species' survival. Sexual reward is an immediate consequence of paced mating, mediated mainly by the endogenous opioid system. Paced mating also induces long-lasting neuroplastic changes, including gene expression, synthesis of proteins, and neurogenesis in sex-relevant brain areas. The interest in paced mating is growing since the complexity of its elements and consequences at different levels in a laboratory setting resembles what occurs in natural conditions. In this review, we analyze the classic studies and recent publications demonstrating the advantages of using paced mating to evaluate different aspects of sexual behavior in females.

Depth recordings of the mouse homologue of the Reward Positivity.

We recently advanced a rodent homologue for the reward-specific, event-related potential component observed in humans known as the Reward Positivity. We sought to determine the cortical source of this signal in mice to further test the nature of this homology. While similar reward-related cortical signals have been identified in rats, these recordings were all performed in cingulate gyrus. Given the value-dependent nature of this event, we hypothesized that more ventral prelimbic and infralimbic areas also contribute important variance to this signal. Depth probes assessed local field activity in 29 mice (15 males) while they completed multiple sessions of a probabilistic reinforcement learning task. Using a priori regions of interest, we demonstrated that the depth of recording in the cortical midline significantly correlated with the size of reward-evoked delta band spectral activity as well as the single trial correlation between delta power and reward prediction error. These findings provide important verification of the validity of this translational biomarker of reward responsiveness, learning, and valuation.

Habit-, reward- and fear-related motivations in alcohol use disorder: A one-year prospective study.

OBJECTIVE: Cross-sectional studies show that habitual use of alcohol is associated with severity of alcohol dependence reflected across a range of domains and lower number of detoxifications in multiple settings. In this study, we investigated whether alcohol use disorder (AUD) patients with greater habitual use of alcohol at baseline showed worse outcomes after one year of follow-up. METHODS: A sample of inpatients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) alcohol use disorder (AUD) was assessed at baseline (n = 50) and after one year (n = 30). The Habit, Reward, and Fear Scale (HRFS) was employed to quantify affective (fear or reward) and non-affective (habitual) drives for alcohol use, the Alcohol Dependence Scale (ADS) was used to assess clinical outcomes, and the Depression, Anxiety and Stress Scale (DASS-21) was used to quantify and control for associated affective symptoms. RESULTS: There was a significant reduction in the three HRFS scores at the follow-up. Regression analyses demonstrated that greater habit- and fear-related drives at baseline predicted greater decreases in the ADS scores at the endpoint. However, after controlling for age, sex and affective symptoms, only reward and fear were associated with reductions in ADS scores at the end of one year. Prescriptions of naltrexone and antidepressants/benzodiazepines did not predict decreases in reward and fear-related motivations. CONCLUSION: Although we were unable to confirm that habitual subscores at baseline predict worse long-term outcomes among inpatients with AUD, we found that a greater fear and reward motives for the use of alcohol predicted a greater magnitude of improvement in the AUD symptoms after one year. We hope that these findings will help develop new approaches toward AUD treatment and inform models of addiction research.

Obesity-mediated Lipoinflammation Modulates Food Reward Responses.

Accumulation of white adipose tissue (WAT) during obesity is associated with the development of chronic low-grade inflammation, a biological process known as lipoinflammation. Systemic and central lipoinflammation accumulates pro-inflammatory cytokines including IL-6, IL-1ß and TNF-α in plasma and also in brain, disrupting neurometabolism and cognitive behavior. Obesity-mediated lipoinflammation has been reported in brain regions of the mesocorticolimbic reward circuit leading to alterations in the perception and consumption of ultra-processed foods. While still under investigation, lipoinflammation targets two major outcomes of the mesocorticolimbic circuit during food reward: perception and motivation ("Wanting") and the pleasurable feeling of feeding ("Liking"). This review will provide experimental and clinical evidence supporting the contribution of obesity- or overnutrition-related lipoinflammation affecting the mesocorticolimbic reward circuit and enhancing food reward responses. We will also address neuroanatomical targets of inflammatory profiles that modulate food reward responses during obesity and describe potential cellular and molecular mechanisms of overnutrition linked to addiction-like behavior favored by brain lipoinflammation.

Studying behavior under constrained movement.

A new platform for studying how brain activity is linked to behavior enables researchers to perform diverse experiments on mice that have their heads immobilized.