Cross-species comparison of rodent and human decision-making in the Iowa Gambling Task in select neurological and psychiatric disorders: translational approach to examine age- and sex-specific effects of stress and corticolimbic perturbations
IntroductionRodent models are widely used to understand brain pathologies and address cognitive deficits experienced by humans diagnosed with clinical disorders. However, stark differences in the nervous system and in the environmental demands of rodents and humans make it difficult to translate ins...
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Frontiers Media S.A.
2025-07-01
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| author | Varsha Singh Manjari Tripathi Sarat P. Chandra Rohit Verma Sushil Kumar Jha Harvinder Singh Chhabra Mrinmoy Chakravarty Mrinmoy Chakravarty Shambhovi Mitra Indupriya B Ankit Jha Sakshi Sharma Jyotsna Pandey Divyanshi Pandey Insha Shamshad Ekta Ahlawat Titli Saha Chloé César Suman Jain |
| author_facet | Varsha Singh Manjari Tripathi Sarat P. Chandra Rohit Verma Sushil Kumar Jha Harvinder Singh Chhabra Mrinmoy Chakravarty Mrinmoy Chakravarty Shambhovi Mitra Indupriya B Ankit Jha Sakshi Sharma Jyotsna Pandey Divyanshi Pandey Insha Shamshad Ekta Ahlawat Titli Saha Chloé César Suman Jain |
| author_sort | Varsha Singh |
| collection | DOAJ |
| description | IntroductionRodent models are widely used to understand brain pathologies and address cognitive deficits experienced by humans diagnosed with clinical disorders. However, stark differences in the nervous system and in the environmental demands of rodents and humans make it difficult to translate insights from rodents to humans. Age and sex further increase vulnerability to disorders via experiences marked by neglect, deprivation, threat, and constraining environments instead of care, nutrition, safety, and enriching environment. These differences impact cognitive processing of rewards, risks, and decision-making. Although rodent models allow for investigations of precise brain regions critical for decision-making, such as the prefrontal cortex (PFC), and enable controlled exposure to stress and disorder trajectories, the prefrontal cortex of rodents and humans differ in size, cytoarchitecture, and anatomical–functional organization. This non-analogous structural–functional mapping of brain regions and cognitive deficits result in rodent models that fail to establish causal links of brain pathophysiology and clinical conditions, and the model remains a poor depiction of cognitive deficits experienced by humans. We argue that the Iowa Gambling Task (IGT) is characterized by molecules to behavior, relies on intact cognitive, affective, and motivational systems of inhibitive control involving cortico-limbic circuitry in both humans and rodents.MethodWe conducted a rodent–human task comparison under stress and disruption in the central nervous system (CNS) to link cognitive deficits in poor decision-making with disruptions in brain architecture. A cross-species comparison, accounting for age and sex, was performed on pooled data from human and rodent IGT studies (N = 892; humans = 722; rodents = 170) to examine organism-, age-, and sex-specific decision-making under three levels of stress—psychological stress, CNS perturbation, and limbic perturbation—that can impair decision-making.ResultsThe results from four mixed-factor analyses of variances corrected for multiple group comparison showed that stress, CNS perturbation, and limbic perturbations impaired decision making. The adverse effects of psychological stress and CNS perturbations were unique to human task performance, while the adverse effect of limbic perturbations was age-specific in humans and sex-specific in rodents. Infrequent punishment choice was prominent in humans (women), and the healthy group compared to rodents (males) and the CNS perturbed group.DiscussionFindings suggest that the task might be useful for producing reliable cross-species comparisons of causal mechanisms underlying cognitive deficits in clinical disorders. Preclinical and clinical studies could use the task to reduce the translational gap in neurobiological and clinical neuroscience in ways that might be useful in improving human health. |
| format | Article |
| id | doaj-art-7a18ca9e2f5842849e90a127885f4ec8 |
| institution | Kabale University |
| issn | 1664-0640 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Psychiatry |
| spelling | doaj-art-7a18ca9e2f5842849e90a127885f4ec82025-08-20T03:31:27ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402025-07-011610.3389/fpsyt.2025.15514771551477Cross-species comparison of rodent and human decision-making in the Iowa Gambling Task in select neurological and psychiatric disorders: translational approach to examine age- and sex-specific effects of stress and corticolimbic perturbationsVarsha Singh0Manjari Tripathi1Sarat P. Chandra2Rohit Verma3Sushil Kumar Jha4Harvinder Singh Chhabra5Mrinmoy Chakravarty6Mrinmoy Chakravarty7Shambhovi Mitra8Indupriya B9Ankit Jha10Sakshi Sharma11Jyotsna Pandey12Divyanshi Pandey13Insha Shamshad14Ekta Ahlawat15Titli Saha16Chloé César17Suman Jain18Department of Humanities and Social Sciences, Indian Institute of Technology Delhi (IIT), New Delhi, IndiaDepartment of Neurology, All India Institute of Medical Sciences (AIIMS), New Delhi, IndiaDepartment of Neurology, All India Institute of Medical Sciences (AIIMS), New Delhi, IndiaDepartment of Psychiatry, All India Institute of Medical Sciences (AIIMS), New Delhi, IndiaSchool of Life Sciences, Jawaharlal Nehru University (JNU), New Delhi, IndiaDepartment of Spine and Rehabilitation, Sri Balaji Action Medical Institute, New Delhi, IndiaDepartment of Social Sciences and Humanities, Indraprastha Institute of Information Technology Delhi (IIIT), New Delhi, IndiaCentre for Design and New Media, Indraprastha Institute of Information Technology Delhi (IIIT), New Delhi, IndiaIndian Spinal Injuries Centre (ISIC), New Delhi, IndiaUniversity of Queensland – IIT Delhi Academy of Research (UQIDAR), Indian Institute of Technology, New Delhi, IndiaUniversity of Queensland – IIT Delhi Academy of Research (UQIDAR), Indian Institute of Technology, New Delhi, India0School of Interdisciplinary Research (SIRe), Indian Institute of Technology, New Delhi, India0School of Interdisciplinary Research (SIRe), Indian Institute of Technology, New Delhi, IndiaDepartment of Humanities and Social Sciences, Indian Institute of Technology Delhi (IIT), New Delhi, IndiaDepartment of Humanities and Social Sciences, Indian Institute of Technology Delhi (IIT), New Delhi, IndiaDepartment of Spine and Rehabilitation, Sri Balaji Action Medical Institute, New Delhi, India0School of Interdisciplinary Research (SIRe), Indian Institute of Technology, New Delhi, India1Master’s Program, Sorbonne Université, Département du Master Biologie Intégrative et Physiologie (BIP), Paris, France2Department of Physiology, All India Institute of Medical Sciences, New Delhi, IndiaIntroductionRodent models are widely used to understand brain pathologies and address cognitive deficits experienced by humans diagnosed with clinical disorders. However, stark differences in the nervous system and in the environmental demands of rodents and humans make it difficult to translate insights from rodents to humans. Age and sex further increase vulnerability to disorders via experiences marked by neglect, deprivation, threat, and constraining environments instead of care, nutrition, safety, and enriching environment. These differences impact cognitive processing of rewards, risks, and decision-making. Although rodent models allow for investigations of precise brain regions critical for decision-making, such as the prefrontal cortex (PFC), and enable controlled exposure to stress and disorder trajectories, the prefrontal cortex of rodents and humans differ in size, cytoarchitecture, and anatomical–functional organization. This non-analogous structural–functional mapping of brain regions and cognitive deficits result in rodent models that fail to establish causal links of brain pathophysiology and clinical conditions, and the model remains a poor depiction of cognitive deficits experienced by humans. We argue that the Iowa Gambling Task (IGT) is characterized by molecules to behavior, relies on intact cognitive, affective, and motivational systems of inhibitive control involving cortico-limbic circuitry in both humans and rodents.MethodWe conducted a rodent–human task comparison under stress and disruption in the central nervous system (CNS) to link cognitive deficits in poor decision-making with disruptions in brain architecture. A cross-species comparison, accounting for age and sex, was performed on pooled data from human and rodent IGT studies (N = 892; humans = 722; rodents = 170) to examine organism-, age-, and sex-specific decision-making under three levels of stress—psychological stress, CNS perturbation, and limbic perturbation—that can impair decision-making.ResultsThe results from four mixed-factor analyses of variances corrected for multiple group comparison showed that stress, CNS perturbation, and limbic perturbations impaired decision making. The adverse effects of psychological stress and CNS perturbations were unique to human task performance, while the adverse effect of limbic perturbations was age-specific in humans and sex-specific in rodents. Infrequent punishment choice was prominent in humans (women), and the healthy group compared to rodents (males) and the CNS perturbed group.DiscussionFindings suggest that the task might be useful for producing reliable cross-species comparisons of causal mechanisms underlying cognitive deficits in clinical disorders. Preclinical and clinical studies could use the task to reduce the translational gap in neurobiological and clinical neuroscience in ways that might be useful in improving human health.https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1551477/fullIowa Gambling Task (IGT)decision makinganimal cognitionrodent modelsrisk–rewardstress |
| spellingShingle | Varsha Singh Manjari Tripathi Sarat P. Chandra Rohit Verma Sushil Kumar Jha Harvinder Singh Chhabra Mrinmoy Chakravarty Mrinmoy Chakravarty Shambhovi Mitra Indupriya B Ankit Jha Sakshi Sharma Jyotsna Pandey Divyanshi Pandey Insha Shamshad Ekta Ahlawat Titli Saha Chloé César Suman Jain Cross-species comparison of rodent and human decision-making in the Iowa Gambling Task in select neurological and psychiatric disorders: translational approach to examine age- and sex-specific effects of stress and corticolimbic perturbations Frontiers in Psychiatry Iowa Gambling Task (IGT) decision making animal cognition rodent models risk–reward stress |
| title | Cross-species comparison of rodent and human decision-making in the Iowa Gambling Task in select neurological and psychiatric disorders: translational approach to examine age- and sex-specific effects of stress and corticolimbic perturbations |
| title_full | Cross-species comparison of rodent and human decision-making in the Iowa Gambling Task in select neurological and psychiatric disorders: translational approach to examine age- and sex-specific effects of stress and corticolimbic perturbations |
| title_fullStr | Cross-species comparison of rodent and human decision-making in the Iowa Gambling Task in select neurological and psychiatric disorders: translational approach to examine age- and sex-specific effects of stress and corticolimbic perturbations |
| title_full_unstemmed | Cross-species comparison of rodent and human decision-making in the Iowa Gambling Task in select neurological and psychiatric disorders: translational approach to examine age- and sex-specific effects of stress and corticolimbic perturbations |
| title_short | Cross-species comparison of rodent and human decision-making in the Iowa Gambling Task in select neurological and psychiatric disorders: translational approach to examine age- and sex-specific effects of stress and corticolimbic perturbations |
| title_sort | cross species comparison of rodent and human decision making in the iowa gambling task in select neurological and psychiatric disorders translational approach to examine age and sex specific effects of stress and corticolimbic perturbations |
| topic | Iowa Gambling Task (IGT) decision making animal cognition rodent models risk–reward stress |
| url | https://www.frontiersin.org/articles/10.3389/fpsyt.2025.1551477/full |
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