{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:09:27Z","timestamp":1785431367198,"version":"3.56.0"},"reference-count":46,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health\u2013Ricerca Corrente program"},{"name":"Italian Minister of Research and University","award":["2022 P2022ST78T"],"award-info":[{"award-number":["2022 P2022ST78T"]}]},{"name":"Ministry of University and Research","award":["PE0000006"],"award-info":[{"award-number":["PE0000006"]}]},{"award":["PE0000006"],"award-info":[{"award-number":["PE0000006"]}],"id":[{"id":"https:\/\/ror.org\/0341vw408","id-type":"ROR","asserted-by":"publisher"}]},{"name":"EMDR Europe Association","award":["1553 11.10.2022"],"award-info":[{"award-number":["1553 11.10.2022"]}]},{"award":["1553 11.10.2022"],"award-info":[{"award-number":["1553 11.10.2022"]}],"id":[{"id":"https:\/\/ror.org\/02etw4c89","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Imaging"],"abstract":"<jats:p>Understanding how to reliably capture neural changes induced by treatments in neurological patients remains a major methodological challenge. This issue is particularly evident in the emotional domain\u2014frequently impaired in conditions such as multiple sclerosis (MS) and a key target of rehabilitation\u2014yet not limited to it. Longitudinal neuroimaging studies predominantly rely on group-level analyses (e.g., General Linear Model, GLM), which assume inter-subject homogeneity and treat inter-subject variability (ISV) as noise. Such assumptions may obscure treatment-related neuroplastic changes, especially in domains like emotion processing, where neural responses are intrinsically variable and highly individualized in clinical populations. This study investigates whether modeling ISV can better capture treatment-related neural changes, using emotion-focused rehabilitation as a representative case. We compared GLM with threshold-weighted overlap maps (OMth\u2212w), which quantify spatial consistency across individuals. Thirty healthy controls (HCs) and thirteen people with MS (pwMS) undergoing EMDR for depression performed an emotional fMRI task (pwMS pre\/post-treatment). GLM revealed no longitudinal effects, whereas OMth\u2212w showed reduced variability in pwMS after treatment, alongside decreased depressive symptoms (p &lt; 0.001). These findings highlight the value of variability-based approaches as a complementary framework to conventional GLM analyses for detecting treatment-related neuroplasticity in neurological populations.<\/jats:p>","DOI":"10.3390\/jimaging12050210","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T14:19:29Z","timestamp":1778854769000},"page":"210","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Beyond GLM: Inter-Subject Variability as a Complementary Approach to Detect Longitudinal Changes in Emotion Processing in Multiple Sclerosis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9474-2344","authenticated-orcid":false,"given":"Alice","family":"Pirastru","sequence":"first","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi ETS, Via Capecelatro 66, 20148 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8395-0452","authenticated-orcid":false,"given":"Valeria","family":"Blasi","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi ETS, Via Capecelatro 66, 20148 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7238-2427","authenticated-orcid":false,"given":"Diego Michael","family":"Cacciatore","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi ETS, Via Capecelatro 66, 20148 Milan, Italy"},{"name":"Department of Psychology, Universit\u00e0 Cattolica del Sacro Cuore, 20123 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9691-1957","authenticated-orcid":false,"given":"Marco","family":"Rovaris","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi ETS, Via Capecelatro 66, 20148 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2927-6657","authenticated-orcid":false,"given":"Elena","family":"Toselli","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi ETS, Via Capecelatro 66, 20148 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Pagnini","sequence":"additional","affiliation":[{"name":"Department of Psychology, Universit\u00e0 Cattolica del Sacro Cuore, 20123 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesare","family":"Cavalera","sequence":"additional","affiliation":[{"name":"Department of Psychology, Universit\u00e0 Cattolica del Sacro Cuore, 20123 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5099-9786","authenticated-orcid":false,"given":"Fabrizio","family":"Esposito","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical and Surgical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2978-1704","authenticated-orcid":false,"given":"Giuseppe","family":"Baselli","sequence":"additional","affiliation":[{"name":"Department of Electronics, Information, and Bioengineering, Politecnico di Milano, 20123 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6145-5274","authenticated-orcid":false,"given":"Francesca","family":"Baglio","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Don Carlo Gnocchi ETS, Via Capecelatro 66, 20148 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.neurol.2017.07.013","article-title":"Theory of mind, empathy and emotion perception in cortical and subcortical neurodegenerative diseases","volume":"174","author":"Fortier","year":"2018","journal-title":"Rev. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.cobeha.2017.05.018","article-title":"Inter- and Intra-Individual Variation in Emotional Complexity: Methodological Considerations and Theoretical Implications","volume":"15","author":"Ong","year":"2017","journal-title":"Curr. Opin. Behav. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1016\/j.neuroimage.2005.12.016","article-title":"A rapid fMRI task battery for mapping of visual, motor, cognitive, and emotional function","volume":"31","author":"Drobyshevsky","year":"2006","journal-title":"Neuroimage"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1177\/0956797620916786","article-title":"What Is the Test-Retest Reliability of Common Task-Functional MRI Measures? New Empirical Evidence and a Meta-Analysis","volume":"31","author":"Elliott","year":"2020","journal-title":"Psychol. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"120503","DOI":"10.1016\/j.neuroimage.2023.120503","article-title":"A precision neuroscience approach to estimating reliability of neural responses during emotion processing: Implications for task-fMRI","volume":"285","author":"Flournoy","year":"2024","journal-title":"Neuroimage"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"411","DOI":"10.3171\/JNS\/2008\/108\/2\/0411","article-title":"Cortical language localization in left, dominant hemisphere. An electrical stimulation mapping investigation in 117 patients. 1989","volume":"108","author":"Ojemann","year":"2008","journal-title":"J. Neurosurg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/(SICI)1097-0193(1999)8:2\/3<73::AID-HBM1>3.0.CO;2-7","article-title":"Creation and use of a Talairach-compatible atlas for accurate, automated, nonlinear intersubject registration, and analysis of functional imaging data","volume":"8","author":"Woods","year":"1999","journal-title":"Hum. Brain Mapp."},{"key":"ref_8","first-page":"83","article-title":"Functional imaging: Heterogeneity in task strategy and functional anatomy and the case for individual analysis","volume":"11","author":"Nadeau","year":"1998","journal-title":"Neuropsychiatry Neuropsychol. Behav. Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Liu, X., and Yang, L. (2023). Individual differences in the language task-evoked and resting-state functional networks. Front. Hum. Neurosci., 17.","DOI":"10.3389\/fnhum.2023.1283069"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1002\/hbm.20053","article-title":"Variability of fMRI activation during a phonological and semantic language task in healthy subjects","volume":"23","author":"Seghier","year":"2004","journal-title":"Hum. Brain Mapp."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1006\/nimg.2000.0621","article-title":"variability in cortical activations during a complex language task","volume":"12","author":"Xiong","year":"2000","journal-title":"Neuroimage"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1162\/089892902760807203","article-title":"Extensive individual differences in brain activations associated with episodic retrieval are reliable over time","volume":"14","author":"Miller","year":"2002","journal-title":"J. Cogn. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5127","DOI":"10.1002\/hbm.22538","article-title":"Same task, different strategies: How brain networks can be influenced by memory strategy","volume":"35","author":"Sanfratello","year":"2014","journal-title":"Hum. Brain Mapp."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1016\/j.neuroimage.2003.10.039","article-title":"Functional MRI of auditory verbal working memory: Long-term reproducibility analysis","volume":"21","author":"Wei","year":"2004","journal-title":"Neuroimage"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1016\/j.neuroimage.2008.05.029","article-title":"Inter-subject variability in the use of two different neuronal networks for reading aloud familiar words","volume":"42","author":"Seghier","year":"2008","journal-title":"Neuroimage"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.tics.2018.03.003","article-title":"Interpreting and Utilising Intersubject Variability in Brain Function","volume":"22","author":"Seghier","year":"2018","journal-title":"Trends Cogn. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.jpsychires.2011.10.013","article-title":"Computational non-linear dynamical psychiatry: A new methodological paradigm for diagnosis and course of illness","volume":"46","author":"Bystritsky","year":"2012","journal-title":"J. Psychiatr. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s12984-016-0148-3","article-title":"Computational neurorehabilitation: Modeling plasticity and learning to predict recovery","volume":"13","author":"Reinkensmeyer","year":"2016","journal-title":"J. Neuroeng. Rehabil."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.neuroimage.2016.06.038","article-title":"Computational neuroimaging strategies for single patient predictions","volume":"145","author":"Stephan","year":"2017","journal-title":"Neuroimage"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1002\/hbm.460020402","article-title":"Statistical parametric maps in functional imaging: A general linear approach","volume":"2","author":"Friston","year":"1994","journal-title":"Hum. Brain Mapp."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.neuroimage.2007.11.048","article-title":"Guidelines for reporting an fMRI study","volume":"40","author":"Poldrack","year":"2008","journal-title":"Neuroimage"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"20170","DOI":"10.1038\/srep20170","article-title":"Visualising inter-subject variability in fMRI using threshold-weighted overlap maps","volume":"6","author":"Seghier","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1177\/13524585241230236","article-title":"Eye movement desensitization and reprocessing for depressed individuals with multiple sclerosis: A pilot study","volume":"30","author":"Rovaris","year":"2024","journal-title":"Mult. Scler."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"120457","DOI":"10.1016\/j.neuroimage.2023.120457","article-title":"The impact of emotional valence and stimulus habituation on fMRI signal reliability during emotion generation","volume":"284","author":"Pirastru","year":"2023","journal-title":"Neuroimage"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/S1474-4422(17)30470-2","article-title":"Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria","volume":"17","author":"Thompson","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_26","unstructured":"Lang, P.J., Bradley, M.M., and Cuthbert, B.N. (2008). International Affective Picture System (IAPS): Affective Ratings of Pictures and Instruction Manual, SCIRP. Technical Report A-8."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1109\/TMI.2010.2046908","article-title":"N4ITK: Improved N3 bias correction","volume":"29","author":"Tustison","year":"2010","journal-title":"IEEE Trans. Med. Imaging"},{"key":"ref_28","unstructured":"Jenkinson, M., Pechaud, M., and Smith, S. (2005). BET2: MR-based estimation of brain, skull and scalp surfaces. Eleventh Annual Meeting of the Organization for Human Brain Mapping, Elsevier."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1002\/hbm.10062","article-title":"Fast robust automated brain extraction","volume":"17","author":"Smith","year":"2002","journal-title":"Hum. Brain Mapp."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2062","DOI":"10.1002\/hbm.21344","article-title":"Evaluating and reducing the impact of white matter lesions on brain volume measurements","volume":"33","author":"Battaglini","year":"2012","journal-title":"Hum. Brain Mapp."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"116189","DOI":"10.1016\/j.neuroimage.2019.116189","article-title":"Automated anatomical labelling atlas 3","volume":"206","author":"Rolls","year":"2020","journal-title":"Neuroimage"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1037\/1040-3590.6.4.284","article-title":"Guidelines, criteria, and rules of thumb for evaluating normed and standardized assessment instruments in psychology","volume":"6","author":"Cicchetti","year":"1994","journal-title":"Psychol. Assess."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.neubiorev.2020.07.001","article-title":"Multiple large-scale neural networks underlying emotion regulation","volume":"116","author":"Morawetz","year":"2020","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.brainresrev.2004.02.004","article-title":"Lateralization of amygdala activation: A systematic review of functional neuroimaging studies","volume":"45","author":"Baas","year":"2004","journal-title":"Brain Res. Brain Res. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/S1053-8119(03)00078-8","article-title":"Valence, gender, and lateralization of functional brain anatomy in emotion: A meta-analysis of findings from neuroimaging","volume":"19","author":"Wager","year":"2003","journal-title":"Neuroimage"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"117917","DOI":"10.1016\/j.neuroimage.2021.117917","article-title":"Test-retest reliability of emotion regulation networks using fMRI at ultra-high magnetic field","volume":"232","author":"Berboth","year":"2021","journal-title":"Neuroimage"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.1016\/j.neuroimage.2012.01.129","article-title":"Test-retest reliability of evoked BOLD signals from a cognitive-emotive fMRI test battery","volume":"60","author":"Plichta","year":"2012","journal-title":"Neuroimage"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1111\/psyp.12129","article-title":"Test-retest reliability of amygdala response to emotional faces","volume":"50","author":"Sauder","year":"2013","journal-title":"Psychophysiology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1176\/appi.ajp.2007.07040609","article-title":"Temporal stability of individual differences in amygdala reactivity","volume":"164","author":"Manuck","year":"2007","journal-title":"Am. J. Psychiatry"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/nrn3256","article-title":"The cognitive neuroscience of ageing","volume":"13","author":"Grady","year":"2012","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.cortex.2019.02.017","article-title":"Emotional disturbances in multiple sclerosis: A neuropsychological and fMRI study","volume":"117","author":"Pfaff","year":"2019","journal-title":"Cortex"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Landin-Romero, R., Moreno-Alcazar, A., Pagani, M., and Amann, B.L. (2018). How Does Eye Movement Desensitization and Reprocessing Therapy Work? A Systematic Review on Suggested Mechanisms of Action. Front. Psychol., 9.","DOI":"10.3389\/fpsyg.2018.01395"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.neuroimage.2019.01.014","article-title":"Qoala-T: A supervised-learning tool for quality control of FreeSurfer segmented MRI data","volume":"189","author":"Klapwijk","year":"2019","journal-title":"Neuroimage"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.dcn.2017.11.006","article-title":"Current methods and limitations for longitudinal fMRI analysis across development","volume":"33","author":"Madhyastha","year":"2018","journal-title":"Dev. Cogn. Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"235","DOI":"10.3758\/CABN.5.2.235","article-title":"Understanding the effects of task-specific practice in the brain: Insights from individual-differences analyses","volume":"5","author":"Ganis","year":"2005","journal-title":"Cogn. Affect. Behav. Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/S0924-9338(00)00517-4","article-title":"Interindividual variation of cerebral activation during encoding and retrieval of words","volume":"15","author":"Heun","year":"2000","journal-title":"Eur. Psychiatry"}],"container-title":["Journal of Imaging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2313-433X\/12\/5\/210\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T10:53:33Z","timestamp":1779447213000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2313-433X\/12\/5\/210"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,15]]},"references-count":46,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["jimaging12050210"],"URL":"https:\/\/doi.org\/10.3390\/jimaging12050210","relation":{},"ISSN":["2313-433X"],"issn-type":[{"value":"2313-433X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,15]]}}}