Flexible Goal-directed Cognition and Inner-Speech in Schizophrenia Spectrum Disorders: from clinical data to computational modeling, and backward.

Flexible Goal-directed Cognition and Inner-Speech in Schizophrenia Spectrum Disorders: from clinical data to computational modeling, and backward. | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Flexible Goal-directed Cognition and Inner-Speech in Schizophrenia Spectrum Disorders: from clinical data to computational modeling, and backward. Giovanni Granato, Raffaele Costanzo, Anna Borghi, Andrea Mattera, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3611379/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Flexible goal-directed human cognition is supported by many forms of self-directed manipulation of representations. Among them, Inner-Speech (IS; covert self-directed speech) acts on second-order representations (e.g., goals/sub-goals), empowering attention and feedback processing. Interestingly, patients with Schizophrenia Spectrum Disorders (SSD) show impaired Executive Functions (EF; e.g., cognitive flexibility) and, probably, a related IS alteration. However, fragmentary evidence and no computational modeling prevent a clear assessment of these processes and focused therapeutic interventions. Here, we address these issues by exploiting a translational approach that integrates experimental clinical data, machine learning, and computational modeling. First, we administered the Wisconsin Cards Sorting Test (WCST; a neuropsychological test probing cognitive flexibility) to SSD patients and computed the behavioural data with a data-driven clustering algorithm. Second, we extracted the cluster neuropsychological profiles with our theory-based validated computational model of the WCST. Finally, we exploited our model to emulate an IS-based psychotherapeutic intervention for SSD subpopulations. We identified different SSD sub-populations and global trends (e.g., a descending feedback sensitivity); however, extremely different neuropsychological profiles emerged. In particular, `Relatively Intact' patients showed an unexpected profile (distraction/reasoning failures), quite divergent from the perseverative/rigid profile of the others. Importantly, the former showed no impact of Interfering-IS, while the others showed increased Interfering-IS strongly affecting their cognition. These differences highlight that SSD populations require a cluster-dependent individualisation of the intervention to achieve adequate cognitive performance. Overall, these results support a clear definition of neuropsychological profiles and the related Interfering-IS impact in SSD subpopulations, thus showing important implications for basic research (e.g., cognitive neuroscience) and clinical fields (clinical psychology and psychiatry). Biological sciences/Neuroscience/Computational neuroscience/Network models Biological sciences/Psychology/Human behaviour Health sciences/Diseases/Psychiatric disorders/Schizophrenia Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryMaterials.pdf Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3611379","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":251393021,"identity":"d694366a-4c86-4e61-b599-56a34dae3a8b","order_by":0,"name":"Giovanni Granato","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0003-3050-0287","institution":"National Research Council of Italy","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Giovanni","middleName":"","lastName":"Granato","suffix":""},{"id":251393022,"identity":"911cb914-7aad-47d0-ac2c-96e6eb857b8f","order_by":1,"name":"Raffaele Costanzo","email":"","orcid":"https://orcid.org/0009-0001-1572-404X","institution":"\"Foro Italico\" University of Rome, Department of Movement, Human and Health Sciences; National Research Council of Italy, Institute of Cognitive Sciences and Technologies","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Raffaele","middleName":"","lastName":"Costanzo","suffix":""},{"id":251393023,"identity":"aaeef941-2e8e-4320-933c-8c9039a8bad1","order_by":2,"name":"Anna Borghi","email":"","orcid":"https://orcid.org/0000-0001-9455-8408","institution":"Sapienza University of Rome, Department of Dynamic and Clinical Psychology, and Health Studies; National Research Council of Italy, Institute of Cognitive Sciences and Technologies","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Anna","middleName":"","lastName":"Borghi","suffix":""},{"id":251393024,"identity":"5e70f09a-0b88-4485-82c6-8114dd5bb0e7","order_by":3,"name":"Andrea Mattera","email":"","orcid":"","institution":"National Research Council of Italy, Institute of Cognitive Sciences and Technologies","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Andrea","middleName":"","lastName":"Mattera","suffix":""},{"id":251393025,"identity":"bcf08d5c-c963-41b5-b1c3-b07ef24fb637","order_by":4,"name":"Sean Carruthers","email":"","orcid":"","institution":"Faculty of Health, Arts and Design, School of Health Sciences; Centre for Mental Health and Brain Sciences, Swinburne University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Sean","middleName":"","lastName":"Carruthers","suffix":""},{"id":251393026,"identity":"c4f4b98e-70c6-4003-af0e-6686f2a1463d","order_by":5,"name":"Susan Rossell","email":"","orcid":"","institution":"Faculty of Health, Arts and Design, School of Health Sciences; Centre for Mental Health and Brain Sciences, Swinburne University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Susan","middleName":"","lastName":"Rossell","suffix":""},{"id":251393027,"identity":"b4d7764c-e0f1-4ce3-940a-e1370cabeedb","order_by":6,"name":"Gianluca Baldassarre","email":"","orcid":"","institution":"National Research Council of Italy, Institute of Cognitive Sciences and Technologies","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Gianluca","middleName":"","lastName":"Baldassarre","suffix":""}],"badges":[],"createdAt":"2023-11-14 16:50:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3611379/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3611379/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":46889027,"identity":"d5dd5c86-996d-4645-8836-41448094cfe9","added_by":"auto","created_at":"2023-11-22 02:36:10","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1548705,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3611379/v1_covered_94478e45-3d1d-4410-8971-e16f7be93e6a.pdf"},{"id":46888539,"identity":"bfc69bcb-996b-43e2-8449-a22a1f4326f2","added_by":"auto","created_at":"2023-11-22 02:28:03","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":212790,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"SupplementaryMaterials.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3611379/v1/92107b2a010bd19a018e6687.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Flexible Goal-directed Cognition and Inner-Speech in Schizophrenia Spectrum Disorders: from clinical data to computational modeling, and backward.","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-3611379/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3611379/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Flexible goal-directed human cognition is supported by many forms of self-directed manipulation of representations. Among them, Inner-Speech (IS; covert self-directed speech) acts on second-order representations (e.g., goals/sub-goals), empowering attention and feedback processing. Interestingly, patients with Schizophrenia Spectrum Disorders (SSD) show impaired Executive Functions (EF; e.g., cognitive flexibility) and, probably, a related IS alteration. However, fragmentary evidence and no computational modeling prevent a clear assessment of these processes and focused therapeutic interventions. Here, we address these issues by exploiting a translational approach that integrates experimental clinical data, machine learning, and computational modeling. First, we administered the Wisconsin Cards Sorting Test (WCST; a neuropsychological test probing cognitive flexibility) to SSD patients and computed the behavioural data with a data-driven clustering algorithm. Second, we extracted the cluster neuropsychological profiles with our theory-based validated computational model of the WCST.\r\nFinally, we exploited our model to emulate an IS-based psychotherapeutic intervention for SSD subpopulations. We identified different SSD sub-populations and global trends (e.g., a descending feedback sensitivity); however, extremely different neuropsychological profiles emerged. In particular, `Relatively Intact' patients showed an unexpected profile (distraction/reasoning failures), quite divergent from the perseverative/rigid profile of the others. Importantly, the former showed no impact of Interfering-IS, while the others showed increased Interfering-IS strongly affecting their cognition. These differences highlight that SSD populations require a cluster-dependent individualisation of the intervention to achieve adequate cognitive performance. Overall, these results support a clear definition of neuropsychological profiles and the related Interfering-IS impact in SSD subpopulations, thus showing important implications for basic research (e.g., cognitive neuroscience) and clinical fields (clinical psychology and psychiatry).","manuscriptTitle":"Flexible Goal-directed Cognition and Inner-Speech in Schizophrenia Spectrum Disorders: from clinical data to computational modeling, and backward.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-11-22 02:27:59","doi":"10.21203/rs.3.rs-3611379/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"13f3cebe-f1c7-4490-932d-6bf855b70bca","owner":[],"postedDate":"November 22nd, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":26537817,"name":"Biological sciences/Neuroscience/Computational neuroscience/Network models"},{"id":26537818,"name":"Biological sciences/Psychology/Human behaviour"},{"id":26537819,"name":"Health sciences/Diseases/Psychiatric disorders/Schizophrenia"}],"tags":[],"updatedAt":"2023-11-23T09:52:02+00:00","versionOfRecord":[],"versionCreatedAt":"2023-11-22 02:27:59","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3611379","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3611379","identity":"rs-3611379","version":["v1"]},"buildId":"FbvkV6FR0MCFSLy54lSbu","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}