The researchers combined a mouse nose-poke task with fiber photometry, which used an optical fiber to measure fluorescence from the genetically encoded dopamine sensor GRABDA3m. After individual training in which nose pokes were associated with water, trained animals were paired in adjacent compartments separated by an opaque perforated divider that permitted social communication. A cooperative trial succeeded only when both mice completed sequential nose pokes within a one-second cooperation window. If the interval between their pokes exceeded that window, the trial was counted as a failure and neither mouse received water.

Over seven days of cooperative testing, the mice showed a progressive learning curve. The success rate rose from an extremely low initial level to approximately 15% by the end of training, while the number of successful trials increased to an average of about 23 per day. Latency to the first successful cooperation shortened and stabilized at around 50 seconds. The interval between the two animals’ pokes also became more concentrated within a shorter period, indicating that the improvement was not simply an increase in individual action frequency. The animals learned to arrange their actions into a precise temporal sequence.

Dopamine dynamics in the nucleus accumbens tracked that learning process. On the first day of cooperative training, dopamine transients did not differ significantly between successful and failed trigger actions. As proficiency increased, successful cooperative pokes evoked robust dopamine transients, whereas failed pokes did not produce a significant response. The area under the curve associated with successful pokes increased with training and was positively related to the cooperation success rate, with the reported linear regression accounting for 48.01% of the variation in that measure. Dopamine signals recorded from the two mice also became more synchronized, and this inter-brain correlation was positively associated with behavioral success. Signals associated with reward acquisition changed less over the same period.

Control experiments tested whether the response could instead be explained by the physical nose poke, motor vigor, partner presence or generalized social arousal. In a non-cooperative condition, pairs of mice received water independently for their own pokes while retaining the same broad social exposure to the apparatus and partition. In an independent-action condition, one mouse performed the task while the adjacent compartment remained empty. The non-cooperative and independent groups produced similar numbers of nose pokes. Cooperating mice, by contrast, had longer response latencies because they had to wait for alignment with a partner rather than simply acting as fast as possible. Despite comparable poke behavior and overall locomotor activity, only the cooperative group developed strong poke-locked dopamine transients late in training. In both control groups, little or no enhancement of the poke-stage signal was detected, while dopamine activity was concentrated around reward delivery.

Additional manipulations separated cooperative action from sensory cues and primary reward. During water-reward extinction, successful coordination continued to trigger the success tone, but no water was delivered. Dopamine activity associated with licking declined across the extinction trials, consistent with weakening of the reward response, whereas the dopamine transient following the cooperative poke remained unchanged. In a separate cue-extinction test, the success tone was removed while water reward was retained; both the poke-related and reward-related dopamine signals remained stable. The authors did not retrain the animals between these conditions because restoring the cue-reward association would have weakened the extinction test.

The researchers also introduced a two-second delay between successful coordinated pokes and reward delivery. Cooperating mice showed dopamine peaks both at the coordinated poke and at the later reward, whereas independently acting mice showed a response confined to reward delivery, with little or no significant poke-stage release. At the two-second delay, the poke-stage dopamine area was significantly greater in the cooperative group than in the independent group, while the groups did not differ significantly at the reward stage. Together, the extinction and delay experiments associate the action-linked signal with successful coordination rather than with reward delivery, a success tone or a simple expectation of the upcoming outcome.

These recordings and interventions focused on the medial shell of the nucleus accumbens, a subregion that the study connects with context-dependent motivational processing. The source also notes that this territory receives input from ventral tegmental area dopamine neurons whose response properties are not fully captured by classical reward-prediction-error models. However, the experiments did not directly identify the dopamine neurons or upstream inputs that generated the measured population signal. Fiber photometry cannot resolve individual neurons, projection-defined cell populations or the separate contributions of arousal, attention and other motivational states. The findings therefore support an association between medial-shell dopamine dynamics and successful coordination rather than a complete circuit-level explanation.

Task reversal showed that the learned dopamine pattern could persist after the behavior that first induced it changed. Mice trained to cooperate switched to the independent task and immediately adopted faster, simpler performance, yet their poke-evoked dopamine response remained robust and did not decay to the lower level characteristic of mice trained only to act independently. In the opposite direction, mice moved from independent action to cooperation developed successful-poke dopamine transients progressively as their cooperation success improved. This asymmetry suggested a form of behavioral inertia in the neural representation. The persistence of the signal after reversal may reflect experience-dependent plasticity, but the experiment did not directly distinguish intrinsic-value coding from habit-like stabilization or consolidation.

To test causality, the researchers locally infused the D1-receptor antagonist SCH-23390 into the nucleus accumbens after the animals had mastered their tasks. A low dose of 0.05 micrograms per side caused a sharp, reversible reduction in cooperative success rate and number of successful trials. Total distance traveled did not differ significantly from the saline condition, arguing against general motor impairment as the explanation. At the same dose, independently acting mice retained their nose-poke performance and movement, while a high dose of 0.5 micrograms per side produced broader behavioral inhibition in both groups. The selective effect of the lower dose provides causal evidence that D1-receptor signaling contributes to maintaining cooperative behavior more strongly than to simple individual reward seeking. It does not reveal whether that contribution operates through motivational value, execution gain, intrinsic-value coding or another process required for coordination.

Several limitations define the study’s scope. It included only two-month-old male mice, so the findings’ generality across sexes is unknown. Cooperation was operationalized as narrowly timed nose pokes in a controlled apparatus, and the findings may not extend to more flexible or ecologically natural social behavior. The investigators did not compare the nucleus accumbens core or lateral shell, so the response may be specific to the medial shell or shared across subregions. The population-level optical measurement also cannot identify the relevant dopamine cell types or inputs. In addition, the resistance of the signal to reward omission could reflect goal-directed valuation, experience-dependent stabilization or habit-like mechanisms, which require dedicated social outcome-devaluation tests to distinguish. The evidence supports the conclusion that accumbal dopamine dynamics track successful coordination and that D1-receptor signaling helps sustain cooperation in this mouse task, while leaving broader interpretations and applications to future research.

Subject of Research: Nucleus accumbens dopamine dynamics during learned cooperation in male mice

Article Title: Dopamine dynamics promote cooperative behavior not just the rewards accompanying cooperation

Article References: Chai, K., Cai, J., Zhuo, Y., Da, N., Wang, W., Liu, H., Yao, D., Xia, Y., Chen, K., & Li, L. (2026). Dopamine dynamics promote cooperative behavior not just the rewards accompanying cooperation. iScience, 29(11), Article 117787. https://doi.org/10.1016/j.isci.2026.117787

Image Credits: AI Generated

DOI: 10.1016/j.isci.2026.117787

Keywords: cooperation, dopamine, nucleus accumbens, D1 receptors, mouse behavior, fiber photometry, social neuroscience, reward processing, motivational signaling, behavioral learning, dynamics, promote

The paper is an expert meeting report rather than a new clinical trial. It followed a meeting organised by GALENOS and the European College of Neuropsychopharmacology, which brought together researchers, clinicians, industry partners and people with lived experience to identify priorities for future research into anhedonia. Lead co-author Brenda Penninx said anhedonia can mean enjoying normally pleasant activities less, anticipating them less or feeling less motivated to make an effort for them. “This distinction is precisely what matters,” Penninx said, because anhedonia is likely to involve different processes surrounding reward and motivation rather than a single phenomenon with one cause.

The meeting was prompted by recent results from the GALENOS living systematic review of drugs that increase dopamine activity. These treatments produced some improvements in anhedonia symptoms, but the effects were relatively small. The review also found that some antidepressants acting through non-dopaminergic mechanisms were associated with bigger reductions in anhedonia than pro-dopaminergic drugs. Lead co-author Andrea Cipriani said the neurobiology of anhedonia in depression likely involves systems that include, but are not limited to, dopaminergic pathways. The report presents these systematic-review observations as the foundation for a research agenda; it does not establish that any medication should be prescribed for anhedonia or that a non-dopaminergic antidepressant is clinically superior for its treatment.

Researchers propose treating anhedonia as an umbrella encompassing several related but distinguishable processes, including reward anticipation, motivation, reward learning and the experience of pleasure itself. Different components may involve different biological systems, among them dopaminergic, glutamatergic, opioid, inflammatory and metabolic pathways. The report therefore supports investigating a broader network of mechanisms rather than assuming that one biological pathway explains every aspect of the symptom. This focus is relevant because anhedonia occurs in depression, schizophrenia, bipolar disorder, Parkinson’s disease and other conditions, and is associated with poorer quality of life, impaired daily functioning and poorer treatment outcomes. The scope of the report is a research strategy informed by evidence and expert discussion, not a comprehensive clinical guideline or proof that the proposed model accounts for every form of anhedonia.

To accelerate progress, the report calls for more precise definitions and measurement tools, greater use of biological markers, and clinical trials that treat anhedonia as a primary outcome rather than only a secondary symptom of depression. The authors also call for studies spanning different disorders and stages of life to clarify how anhedonia develops and responds to treatment. These are proposed priorities and methods, not established therapeutic benefits. By separating the processes that contribute to anhedonia and measuring them more directly, the authors argue, researchers may improve the targeting of future studies and potentially support more effective, personalised approaches. Whether that broader understanding yields clinically useful treatments remains an open question that requires further research and appropriately designed trials.

Subject of Research: Research agenda for anhedonia assessment and treatment across depression and other disorders

Article Title: Dopamine-targeting treatments show only modest benefits for anhedonia, prompting call for new research approaches

Article References: Dopamine-targeting treatments show only modest benefits for anhedonia, prompting call for new research approaches. Original publication (Bibliographic details unavailable.)

Image Credits: AI Generated

DOI: Not provided

Keywords: anhedonia, dopamine, depression, antidepressants, reward processing, GALENOS, systematic review, mental health research, clinical trials, precision psychiatry, Dopamine-targeting, treatments

The trial enrolled 60 participants who were experiencing a current major depressive episode accompanied by clinically significant anhedonia, a symptom domain that has long frustrated psychiatrists. Anhedonia, which involves diminished interest, motivation, and capacity for pleasure, is common in depression, often persists even when other symptoms improve, and is strongly linked to dysfunction in the brain’s reward circuitry. Standard antidepressants such as selective serotonin reuptake inhibitors frequently leave this dimension untouched, which is why the field has been searching for treatments that target reward processing directly rather than mood in general. The researchers designed the study as an experimental medicine trial, a design that uses a neurobiological measure as the primary endpoint to test whether a drug engages its intended brain circuit before committing to larger efficacy trials.

Participants were randomized one to one to receive either azetukalner at a dose of 20 milligrams taken orally once daily with food, or a matching placebo, for eight weeks. The primary endpoint was the change in activity of the bilateral ventral striatum, a key hub of the brain’s reward system, measured with functional magnetic resonance imaging while participants performed a reward task, comparing scans taken at baseline with those taken at week eight. The ventral striatum, which includes the nucleus accumbens, responds robustly to the anticipation and receipt of rewards, and blunted activation in this region has been repeatedly observed in depressed patients, particularly those with prominent anhedonia. The logic of the trial was straightforward: if azetukalner truly modulates reward circuitry, eight weeks of treatment should measurably strengthen the ventral striatum’s response to anticipated rewards.

That primary hypothesis was not borne out. The researchers found no significant difference in the ventral striatum response to reward anticipation between the azetukalner group, which comprised 29 participants, and the placebo group, which comprised 31. In the world of clinical neuroscience, this kind of negative primary endpoint is not unusual, and the authors were careful to report it plainly. Functional MRI measures are noisy, sample sizes in experimental medicine studies are typically modest, and the link between a drug’s molecular mechanism and a hemodynamic imaging signal involves many layers of biology that can dilute an effect. Still, the result means that the most direct test of the drug’s proposed mechanism of action in this study did not find the expected neural signature.

The secondary outcomes told a more encouraging story. Compared with placebo, azetukalner was associated with numerical benefit on the Montgomery-Åsberg Depression Rating Scale, a clinician-administered measure of depression severity, and on the Snaith-Hamilton Pleasure Scale, a widely used self-report instrument for anhedonia. Neither difference reached statistical significance, a critical caveat, but the direction of the effects was consistent with a genuine signal. Perhaps more telling, most of the exploratory endpoints in the trial also numerically favored azetukalner over placebo. When a drug shows a consistent directional trend across many independent measures, even without statistical significance, it can suggest that a real effect exists but that the study was underpowered to detect it, though it can also reflect chance, and the authors acknowledged this ambiguity.

Safety results were a clear positive. Discontinuation rates due to adverse events were low and did not differ between the azetukalner and placebo groups, an important finding for a medication that would need to be taken chronically if it ever reaches the clinic. Kv7 channel openers, which include the anticonvulsant ezogabine that preceded azetukalner in experimental psychiatry research, have generally shown tolerable side effect profiles at the doses used in neuropsychiatric studies. The favorable tolerability observed here matters because depression is a chronic, relapsing condition, and any future treatment must be something patients can sustain over months or years without burdensome side effects driving them off the drug.

The biology behind the approach is worth understanding. Kv7 channels, encoded by the KCNQ gene family, are voltage-gated potassium channels that act as molecular brakes on neuronal firing. By regulating the flow of potassium ions out of neurons, they help stabilize the membrane potential and control how easily a cell fires an action potential. A positive allosteric modulator like azetukalner does not block or activate the channel directly at its main gate; instead, it binds to a site away from the pore and makes the channel easier to open, thereby dampening neuronal excitability. In reward circuits, this dampening is thought to reduce the excessive phasic activity of neurons that project to the ventral striatum, which some theories link to the blunted, dysregulated reward processing seen in depression and anhedonia. Preclinical work and earlier small human studies of ezogabine suggested that enhancing Kv7 activity could normalize reward circuit function, motivating the development of azetukalner as a more refined candidate.

The experimental medicine framework itself is a notable feature of the study. Rather than measuring only symptom scores, the trial put a mechanistic biomarker, reward-related ventral striatum activation, at the center of the design, funded in part by the National Institute of Mental Health under an award supporting this translational strategy. The idea is that demonstrating target engagement in the brain early in development can guide decisions about whether to advance a compound to larger and far more expensive efficacy trials. In this case, the biomarker result argues for caution, while the clinical signal argues for continued interest. The study was registered at ClinicalTrials.gov under identifier NCT04827901, and the investigational product and matching placebo were provided by Xenon Pharmaceuticals under a research agreement with the Icahn School of Medicine at Mount Sinai.

For patients and clinicians, the practical takeaway is that azetukalner remains an unproven but scientifically interesting candidate. The trial was small, with 60 participants, and its primary purpose was to test mechanism rather than to win regulatory approval, so neither a positive nor a negative primary endpoint would have been definitive about clinical efficacy. The consistent numerical trends on depression severity and anhedonia measures, combined with good tolerability, give the researchers grounds to argue that larger trials with adequate statistical power are warranted. At the same time, the failure to shift the ventral striatum imaging signal raises real questions about whether the drug, at this dose and duration, engages the reward circuitry in the way the hypothesis predicted, or whether fMRI measures of reward anticipation are simply too insensitive to capture the effect.

The broader significance of the study lies in what it says about the future of antidepressant development. Depression remains one of the most common and debilitating diseases worldwide, and a substantial fraction of patients do not respond adequately to existing medications, which mostly act on monoamine neurotransmitter systems discovered decades ago. Novel targets such as the Kv7 potassium channels, glutamatergic agents, and psychedelic compounds are all being tested in parallel, reflecting a field-wide effort to find treatments that work through fundamentally different biology. This trial, led by senior author James W. Murrough and first author Rachel Fremont, exemplifies the careful, mechanistically grounded path that new candidates must travel: a clear molecular hypothesis, a measurable brain endpoint, honest reporting of a negative primary result, and a transparent account of the suggestive but unproven clinical signals that remain. Whether azetukalner ultimately helps people with depression and anhedonia will depend on the larger studies that this work now makes easier to design.

Subject of Research: A randomized controlled trial of the Kv7 channel opener azetukalner in major depressive disorder with anhedonia

Article Title: A randomized, controlled experimental medicine study of the novel Kv7 channel opener azetukalner in individuals with major depressive disorder and anhedonia

Article References: Fremont, R., Neukam, P. T., Govindarajulu, U. S., Ables, J. L., Hameed, S., Corwin, M., Hargrove, M. B., Chang, H. L., Boukezzi, S., Kelly, C. A., Swann, A., Salas, R., Amarneh, D., Engelhardt, J., Weyland, A., Bagiella, E., Morris, L., Mathew, S. J., & Murrough, J. W. (2026). A randomized, controlled experimental medicine study of the novel Kv7 channel opener azetukalner in individuals with major depressive disorder and anhedonia. Translational Psychiatry. https://doi.org/10.1038/s41398-026-04431-6

Image Credits: AI Generated

DOI: 10.1038/s41398-026-04431-6

Keywords: azetukalner, Kv7 channels, major depressive disorder, anhedonia, ventral striatum, functional MRI, reward processing, clinical trial, translational psychiatry, potassium channels, antidepressant development, Xenon Pharmaceuticals

The research was led by Kaylin Hill, an assistant professor in Notre Dame’s Department of Psychology and a clinical psychologist who directs the university’s Psychophysiology of Affect across the Lifespan, or PAL, Lab. Hill is also a faculty affiliate of the Shaw Center for Children and Families and the Eck Institute for Global Health, and much of her career has been devoted to a single deceptively simple question: what makes some people vulnerable to depression while others remain resilient? Her team’s latest work addresses that question by connecting two threads that had rarely been woven together in a single longitudinal design, namely observed parenting behavior in toddlerhood and the long-term development of neural reward responsiveness.

The stakes of the question are considerable. Data from the National Alliance on Mental Illness indicate that more than one in five adults in the United States experiences mental illness in any given year, and that more than one in seven young people between the ages of six and seventeen lives with a mental health disorder. The timing of onset is striking: half of all lifetime mental illness begins by age fourteen, and three quarters by age twenty-four. Any factor that can be identified early, and potentially modified, therefore carries enormous public health significance. Parenting behavior, unlike genetic inheritance, is something that can in principle be changed, which is precisely why Hill and her colleagues consider the new findings so promising.

To trace the connection between early experience and later brain function, the researchers relied on a longitudinal study spanning fifteen years and involving 465 young people and their parents, carried out at Stony Brook University in New York and supported by a grant from the National Institute of Mental Health. When the children were three years old, trained observers watched one-on-one interactions between each child and parent in a laboratory setting and systematically coded what they saw. Positive parenting behaviors included displays of warmth, support, and encouragement, while negative parenting behaviors included harshness, heavy-handedness, and excessive intrusiveness. These coded observations then became the baseline against which each child’s later brain development was measured.

The measurement tool was the electroencephalogram, or EEG, a noninvasive technique in which small electrodes attached to the scalp through a cap record the brain’s electrical activity with millisecond-level precision. Beginning at age nine, and again at ages twelve, fifteen, and eighteen, each participant completed a reward task while EEG data were collected. The task was a guessing game in which winning was rewarded with money, allowing the researchers to compare the brain’s electrical signals immediately after a win with those after a loss. The difference between those two signals provides an index of reward responsiveness, one of the largest neural indicators of risk for mental health concerns currently known, as Hill describes it. Because the EEG paradigm is adaptable across a wide range of abilities and cognitive stages, the same measure could be tracked repeatedly across the entire arc of adolescence.

Reward processing, the brain’s capacity to register and respond to positive stimuli, is not a luxury of experience. Previous research has shown that adequate reward processing is necessary for adolescents and adults to feel joy, excitement, and pleasure, and that the foundations of this capacity are visible even in early childhood. When reward responsiveness is blunted, a condition researchers describe as blunted reward sensitivity, individuals tend to experience less pleasure from everyday positive events, a hallmark feature associated with depression. Hill emphasized that reward processing appears to be one piece of the puzzle of what may put a person at risk for developing mental disorders, and that being able to observe how it develops from ages nine to eighteen is genuinely informative for understanding depression risk.

The results of the fifteen-year follow-up were strikingly consistent. Children whose parents had displayed higher levels of positive parenting at age three showed larger neural reward responses to winning the guessing game across adolescence, in effect getting more excited, at the level of brain electrical activity, about positive outcomes. Children raised with more negative parenting styles showed the opposite pattern, responding with less enthusiasm to the same rewards. In Hill’s summary, the more positive and the less negative the parenting behaviors observed at age three, the larger the brain’s reward response seemed to be for individuals across adolescence. The study is, according to the researchers, the first of its kind to measure which early life experiences are associated with reward processing from childhood through late adolescence and early adulthood.

The interpretation Hill and her team offer is that positive parenting in the early years may function as a kind of instruction manual for the developing brain, teaching it how to respond to good things such as fun activities, friendships, success, and well-being. Praise and affirmation from parents, delivered consistently during the preschool period, appear to help children become better at recognizing the joyful elements of life. Conversely, when a parent is particularly harsh or intrusive, the child’s brain may develop a low reward response, a diminished capacity to experience pleasure and happiness that can subsequently open the door to sadness and despondency. Experiencing positive parenting, Hill noted, seems to help facilitate reward processing, which is important for promoting both physical and mental health.

It is important to note that the study was observational, meaning it documents associations between parenting behavior and brain development rather than proving direct causation. Hill acknowledges this limitation but argues that the design still yields important clues about how experiences and development may unfold over time. Current research indicates that the most reliable and prominent predictor of depression is a family history of the disorder combined with the experience of a stressful life event. What the new findings add is a plausible mechanism, rooted in observable behavior and measurable brain function, by which risk might be transmitted within families, and one that is far more open to modification than genetics.

That openness to intervention is where Hill sees the greatest promise. She argues that support may need to include parents and children together, and that it is critical to support parents, perhaps even before a child is born, as well as children and adolescents, in order to address the full sequence running from parent behaviors observed at age three to child development through age eighteen. Behaviors, she points out, are far more open to intervention than a genetic explanation of what drives risk within families. She and her team hope the work can inform a broader conversation about preventing depression, one of the most prevalent and debilitating mental disorders, by pulling together a single strand, one explanation among likely many, of what puts someone at risk and how that risk might be interrupted before it takes hold.

Subject of Research: The association between early parenting behaviors and the development of neural reward responsiveness in children and adolescents

Article Title: Study finds positive parenting teaches children how to experience joy—and could lead to better mental health

Article References: Study finds positive parenting teaches children how to experience joy—and could lead to better mental health. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: positive parenting, reward processing, adolescence, depression risk, EEG, neural reward responsiveness, child development, mental health, longitudinal study, parent-child interaction, Communications Psychology, early intervention

The research team, led by Alexandra Rich and Ifat Levy, recruited 415 participants online through the Prolific platform across two independent cohorts, with 279 participants ultimately included in the final analysis. Rather than using neutral shapes or abstract symbols, as most value-learning studies do, the researchers personalized the experiment to each individual. Participants first rated 65 snack images from the Food Folio database, ranging from granola bars to croissants, on a four-point scale from strongly dislike to strongly like. From these ratings, the researchers built a personalized set of four foods for each participant: one strongly liked, one liked, one disliked, and one strongly disliked. Importantly, the team verified that these preference ratings did not track the foods’ caloric or nutritional content, confirming that the experiment captured genuinely subjective values rather than objective properties of the snacks.

Participants then completed a probabilistic reversal-learning task. On each trial, one of their four personal foods appeared on screen, and they had three seconds to predict whether it would be followed by a positive outcome of plus five points or a negative outcome of minus five points. The task unfolded in six blocks of 32 to 36 trials each. In Congruent blocks, the outcomes aligned with participants’ existing preferences 90 percent of the time: liked foods usually predicted rewards and disliked foods usually predicted punishments. In Incongruent blocks, the relationship flipped, forcing participants to learn associations that ran directly against their priors. Crucially, participants knew the task involved switching relationships, but they were never told when reversals would occur or that the block structure was tied to their own ratings.

The results revealed a surprising order effect. Participants who began the task with a Congruent block—meaning their priors were initially reinforced—showed greater overall accuracy than those who began with an Incongruent block. More tellingly, the Congruent-start group achieved exceptionally high accuracy on later Congruent blocks, averaging 0.73, while performing far worse on Incongruent blocks, averaging 0.59. In contrast, participants who started with a block that challenged their priors performed similarly across both block types, around 0.62. This interaction between starting condition and block type was replicated in both independent cohorts. In other words, the first reinforcement of one’s food preferences appeared to potentiate rigidity: once the brain’s existing associations were validated, they became harder to overturn later, even though participants explicitly knew the rules would change.

The researchers propose several cognitive mechanisms that could explain this anchoring-like effect. Participants likely entered the experiment with the plausible hypothesis that outcomes would follow their personal preferences. For those who started with a Congruent block, that hypothesis was immediately confirmed, strengthening the anchor linking liked foods to rewards and disliked foods to punishments. Associative priming, confirmation bias, increased confidence, and egocentric discounting may all have compounded the effect. Conversely, participants whose initial evidence contradicted their priors may have been less biased in subsequent judgments, which is consistent with their more uniform performance across block types.

An equally important finding concerned an asymmetry between liked and disliked foods. For liked items, prediction accuracy was consistently higher in Congruent blocks than in Incongruent blocks, regardless of which block type participants started with—positive priors made these associations stubbornly inflexible. Disliked foods behaved differently: participants performed better in whichever condition they started in, suggesting that associations with non-preferred foods were far more suggestible to the surrounding task environment. The authors interpret this as an asymmetry in food-value plasticity. It may be considerably easier to add a disliked food to one’s diet than to remove a liked one, a conclusion that challenges the optimism of earlier training studies that modestly devalued highly preferred foods through cued-approach paradigms.

The study also uncovered a robust positivity bias. Across all conditions, participants predicted reward-associated outcomes more accurately than punishment-associated outcomes, with average accuracy of 0.69 for rewards versus 0.61 for punishments. This held regardless of block type, food preference, or starting condition—even though the point outcomes were arbitrary and carried no real-world value beyond a bonus payment tied to overall accuracy. Translated to the dinner table, the finding hints that emphasizing the rewarding aspects of healthy foods, such as their benefits, may influence associative learning more effectively than warnings about negative health consequences. Carrots, in this sense, may genuinely work better than sticks.

Behavioral measures collected before and after the task reinforced the plasticity story. Participants who began with an Incongruent block showed significant increases in their willingness to pay, enjoyment, and expected satisfaction for disliked foods after the task, along with a decrease in satisfaction for liked foods. Congruent-start participants showed almost no such changes. This suggests that beginning with experiences that challenge one’s priors may promote broader updating of item value rather than mere trial-by-trial adaptation—a cumulative shift in valuation that could be harnessed in interventions aimed at reshaping eating habits.

Exploratory analyses added a clinical dimension. Among Congruent-start participants, higher scores on the Binge Eating Scale were associated with lower accuracy when learning that disliked foods predicted rewards, a relationship that remained significant in a regression controlling for age, gender, and body mass index. This finding aligns with prior evidence that reward processing and cognitive flexibility are altered in binge eating, and it hints that impaired updating of non-preferred stimuli’s values may be a cognitive feature of obesity with comorbid binge eating—a population for whom dietary interventions already show reduced efficacy. The authors caution, however, that this effect was weak and emerged from multiple comparisons, warranting further study.

The study’s limitations invite follow-up work. The outcomes were arbitrary points rather than motivationally salient rewards, and the researchers cannot yet say whether the findings generalize to other valued items, such as sports teams or politicians, or how neutral stimuli would perform in the same paradigm. Still, the central message is clear and ecologically important: we rarely learn about value in a naive environment, and our prior preferences confound the process from the very first trial. For public health, that means the sequencing of experiences matters. Interventions that begin by challenging existing food preferences, rather than reinforcing them, may stand a better chance of building the flexible food-value learning that healthier eating requires.

Subject of Research: How prior food preferences interfere with the flexible associative learning of food values in humans

Article Title: Prior preferences interfere with the associative learning of food values

Article References: Rich, A., Kapadia, S., Henry, R., Dan, O. J., & Levy, I. (2026). Prior preferences interfere with the associative learning of food values. Communications Psychology, 4(1), Article 132. https://doi.org/10.1038/s44271-026-00533-5

Image Credits: AI Generated

DOI: 10.1038/s44271-026-00533-5

Keywords: food value learning, associative learning, reversal learning, prior preferences, reinforcement learning, positivity bias, dietary interventions, binge eating, cognitive flexibility, decision making, reward processing, behavioral neuroscience

Bulimia nervosa is a serious psychiatric condition characterized by recurrent episodes of binge eating followed by compensatory behaviors such as purging, along with intense preoccupation with body shape and weight. The disorder carries substantial medical and psychological burden, and while enhanced cognitive behavioral therapy, known as CBT-E, remains the first-line intervention, remission rates remain stubbornly modest. This treatment gap has driven researchers to ask a fundamental question: what changes in the brain when therapy succeeds, and can those changes, or the brain’s starting configuration, tell us who is likely to respond?

To investigate, researchers affiliated with the Eating Disorder Neuroimaging Initiative recruited thirty Japanese women with bulimia nervosa, with an average age of 33.6 years. The participants received one of three CBT-based treatments delivered across multiple sites: twenty-four received enhanced CBT in person, four received CBT via videoconference, and two completed guided internet-based CBT. Each woman underwent resting-state functional magnetic resonance imaging and completed symptom assessments, including the Eating Disorder Examination Questionnaire, both before and after treatment, with an average interval of 5.6 months between scans.

Resting-state functional connectivity, the technique at the heart of the study, measures how spontaneously synchronized activity is between brain regions when a person is simply lying still in the scanner. Rather than probing task-driven brain responses, it captures the intrinsic wiring diagram of the brain, offering a window into the circuit organization that persists across mental states. The researchers computed connectivity between pairs of predefined regions of interest across the whole brain and used statistical harmonization procedures to remove site-specific differences introduced by the multi-center design, a critical step for ensuring that scanner effects did not masquerade as clinical findings.

The analysis then asked two complementary questions. First, did changes in connectivity between the pre- and post-treatment scans track the degree of symptom improvement measured by the questionnaire? Second, did the strength of specific connections before treatment predict how much a patient would improve? The team used multiple regression models that adjusted for age and pretreatment psychotropic medication, and they applied false discovery rate correction at two levels: a seed-level correction across all connections emanating from each region, and a stricter analysis-level correction across every tested connection in the study.

Under the most conservative statistical threshold, no individual connection survived correction, a sobering but honest result that the authors emphasize throughout. However, at the exploratory seed level, a coherent pattern emerged. Greater improvement in eating disorder symptoms was associated with decreased connectivity between the right orbitofrontal cortex, a region central to reward valuation and decision-making, and the right posterior supramarginal gyrus, which participates in integrating sensory and bodily information. Improvement was also linked to increased connectivity between the right anterior temporal fusiform cortex and cerebellar regions, and between the right caudate nucleus, a key node of the basal ganglia reward system, and the right cerebellar hemisphere IX.

These circuits are not random. The orbitofrontal cortex and caudate nucleus have long been implicated in the aberrant reward processing thought to drive binge eating and purging, while the cerebellum is increasingly recognized as far more than a motor structure, contributing to cognitive and affective regulation. The finding that symptom improvement accompanied a loosening of orbitofrontal connections and a strengthening of striatal-cerebellar coupling suggests that successful therapy may reorganize how reward signals are computed and propagated through the brain, potentially dampening the pathological valuation of food and body shape that sustains the disorder.

Equally intriguing were the pretreatment predictors. Women who improved more showed stronger baseline connectivity between the right superior parietal lobule and inferior frontal and temporo-occipital regions, as well as between the left postcentral gyrus and bilateral inferior temporal gyri. The postcentral gyrus houses the primary somatosensory cortex, which represents the body’s physical form, while the superior parietal lobule supports spatial attention and cognitive control. Stronger connectivity in these networks before therapy may reflect a neural readiness, a capacity for body-awareness integration and self-regulation that allows patients to engage more fully with the cognitive restructuring work that CBT demands.

The researchers are careful to frame these results as preliminary. The sample of thirty participants is small, there was no healthy control group, and the findings did not survive the strictest multiple-comparison correction. Resting-state connectivity measures are also sensitive to head motion and physiological noise, and the mixed treatment modalities, while all CBT-based, introduce heterogeneity. Replication in larger, controlled cohorts is essential before these connectivity signatures could inform clinical practice. Still, the study’s multi-site harmonized design and longitudinal structure represent methodological advances over the cross-sectional snapshots that have dominated the field.

The broader significance lies in what this line of research could eventually deliver: biomarkers that identify patients at risk of treatment failure before therapy begins, and mechanistic targets for interventions that directly modulate the circuits involved. Brain stimulation techniques, neurofeedback, and digitally delivered therapies could all be refined by a clearer map of the neural substrate of recovery. For now, the study offers a cautious but compelling glimpse of the brain rewiring itself as patients heal, suggesting that the path out of bulimia nervosa may be written, in part, in the changing conversation between the reward system, the body’s sensory maps, and the mind’s capacity for control.

Subject of Research: Resting-state functional connectivity changes and pretreatment predictors of cognitive behavioral therapy response in bulimia nervosa

Article Title: Resting-state functional connectivity changes and pretreatment features associated with symptom improvement after cognitive behavioral therapy for bulimia nervosa

Article References: Sudo, Y., Chhatkuli, R. B., Takamura, T., Kamashita, R., Matsumoto, K., Numata, N., Hamatani, S., Moriguchi, Y., Ino, K., Ando, T., Ohara, C., Funaba, M., Isobe, M., Noda, T., Tose, K., Murai, T., Sunada, M., Morimoto, K., Taniguchi, M., … Futatsuya, K. (2026). Resting-state functional connectivity changes and pretreatment features associated with symptom improvement after cognitive behavioral therapy for bulimia nervosa. Journal of Eating Disorders. https://doi.org/10.1186/s40337-026-01754-z

Image Credits: AI Generated

DOI: 10.1186/s40337-026-01754-z

Keywords: bulimia nervosa, cognitive behavioral therapy, resting-state functional connectivity, fMRI, reward processing, somatosensory cortex, orbitofrontal cortex, cerebellum, treatment response, eating disorders, neuroimaging, predictive biomarkers