Person:
Melero Carrasco, Helena

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First Name
Helena
Last Name
Melero Carrasco
URI
https://hdl.handle.net/20.500.14352/80242
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Psicología
Department
Psicobiología y Metodología en Ciencias del Comportamiento
Area
Psicobiología
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    Grapheme-color synesthetes show peculiarities in their emotional brain: cortical and subcortical evidence from VBM analysis of 3D-T1 and DTI data
    (Experimental Brain Research, 2013) Ríos-Lago, M.; Pajares, G.; Hernández-Tamames, J. A.; Álvarez-Linera, J.; Melero Carrasco, Helena; Peña Melián, Ángel
    Grapheme-color synesthesia is a neurological phenomenon in which viewing achromatic letters/numbers leads to automatic and involuntary color experiences. In this study, voxel-based morphometry analyses were performed on T1 images and fractional anisotropy measures to examine the whole brain in associator grapheme-color synesthetes. These analyses provide new evidence of variations in emotional areas (both at the cortical and subcortical levels), findings that help understand the emotional component as a relevant aspect of the synesthetic experience. Additionally, this study replicates previous findings in the left intraparietal sulcus and, for the first time, reports the existence of anatomical differences in subcortical gray nuclei of developmental grapheme-color synesthetes, providing a link between acquired and developmental synesthesia. This empirical evidence, which goes beyond modality-specific areas, could lead to a better understanding of grapheme-color synesthesia as well as of other modalities of the phenomenon.
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    Variability in the analysis of a single neuroimaging dataset by many teams
    (Nature, 2020) Botvinik-Nezer, R.; Holzmeister, F.; Camerer, C. F.; Dreber, A.; Huber, J.; Johannesson, M.; Kirchler, M.; Iwanir, R.; Mumford, J. A.; Adcock, R. A.; Avesani, P.; Baczkowski, B. M.; Bajracharya, A.; Bakst, L.; Ball, S.; Barilari, M.; Bault, N.; Beaton, D.; Beitner, J.; Benoit, R. G.; Berkers, R. M. W. J.; Bhanji, J. P.; Biswal, B. B.; Bobadilla-Suarez, S.; Bortolini, T.; Bottenhorn, K. L.; Bowring, A.; Braem, S.; Brooks, H. R.; Brudner, E. G.; Calderon, C. B.; Camilleri, J. A.; Castrellon, J. J.; Cecchetti, L.; Cieslik, E. C.; Cole, Z. J.; Collignon, O.; Cox, R. W.; Cunningham, W. A.; Czoschke, S.; Dadi, K.; Davis, C. P.; Luca, A. D.; Delgado, M. R.; Demetriou, L.; Dennison, J. B.; Di, X.; Dickie, E. W.; Dobryakova, E.; Donnat, C. L.; Dukart, J.; Duncan, N. W.; Durnez, J.; Eed, A.; Eickhoff, S. B.; Erhart, A.; Fontanesi, L.; Fricke, G. M.; Fu, S.; Galván, A.; Gau, R.; Genon, S.; Glatard, T.; Glerean, E.; Goeman, J. J.; Golowin, S. A. E.; González-García, C.; Gorgolewski, K. J.; Grady, C. L.; Green, M. A.; Guassi Moreira, J. F.; Guest, O.; Hakimi, S.; Hamilton, J. P.; Hancock, R.; Handjaras, G.; Harry, B.B.; Hawco, C.; Herholz, P.; Herman, G.; Heunis, S.; Hoffstaedter, F.; Hogeveen, J.; Holmes, S.; Hu, C. P.; Huettel, S. A.; Hughes, M. E.; Iacovella, V.; Iordan, A. D.; Isager, P. M.; Isik, A. I.; Jahn, Andrew; Johnson, Matthew R.; Johnstone, Tom; Joseph, Michael J. E.; Juliano, Anthony C.; Kable, Joseph W.; Kassinopoulos, Michalis; Koba, Cemal; Kong, Xiang-Zhen; Koscik, Timothy R.; Kucukboyaci, Nuri Erkut; Kuhl, Brice A.; Kupek, Sebastian; Laird, Angela R.; Lamm, Claus; Langner, Robert; Lauharatanahirun, Nina; Lee, Hongmi; Lee, Sangil; Leemans, Alexander; Leo, Andrea; Lesage, Elise; Li, Flora; Li, Monica Y. C.; Lim, Cheng Phui; Lintz, Evan N.; Liphardt, Schuyler W.; Losecaat Vermeer, Annabel B.; Love, Bradley C.; Mack, Michael L.; Malpica, Norberto; Marins, Theo; Maumet, Camille; McDonald, Kelsey; McGuire, Joseph T.; Méndez Leal, Adriana S.; Meyer, Benjamin; Meyer, Kristin N.; Mihai, Glad; Mitsis, Georgios D.; Moll, Jorge; Nielson, Dylan M.; Nilsonne, Gustav; Notter, Michael P.; Olivetti, Emanuele; Onicas, Adrian I.; Papale, Paolo; Patil, Kaustubh R.; Peelle, Jonathan E.; Pérez, Alexandre; Pischedda, Doris; Poline, Jean-Baptiste; Prystauka,Yanina; Ray, Shruti; Reuter-Lorenz, Patricia A.; Reynolds, Richard C.; Ricciardi, Emiliano; Rieck, Jenny R.; Rodriguez-Thompson, Anais M.; Romyn, Anthony; Salo, Taylor; Samanez-Larkin, Gregory R.; Sanz-Morales, Emilio; Schlichting, Margaret L.; Schultz, Douglas H.; Shen, Qiang; Sheridan, Margaret A.; Silvers, Jennifer A.; Skagerlund, Kenny; Smith, Alec; Smith, David V.; Sokol-Hessner, Peter; Steinkamp, Simon R.; Tashjian, Sarah M.; Thirion, Bertrand; Thorp, John N.; Tinghög, Gustav; Tisdall, Loreen; Tompson, Steven H.; Toro-Serey, Claudio; Torre Tresols, Juan Jesus; Tozzi, Leonardo; Truong, Vuong; Turella, Luca; van ‘t Veer, Anna E.; Verguts, Tom; Vettel, Jean M.; Vijayarajah, Sagana; Vo, Khoi; Wall, Matthew B.; Weeda, Wouter D.; Weis, Susanne; White, David J.; Wisniewski, David; Xifra-Porxas, Alba; Yearling, Emily A.; Yoon, Sangsuk; Yuan, Rui; Yuen, Kenneth S. L.; Lei Zhang; Zhang, Xu; Zosky, Joshua E.; Thomas E. Nichols,; Poldrack, Rusell A.; Schonberg, Tom; Melero Carrasco, Helena
    Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses1. The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset2–5. Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed.
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    Abnormal functional connectivity in radiologically isolated syndrome: A resting-state fMRI study
    (Multiple Sclerosis Journal, 2023) Benito León, Julián; Pino, Ana Belén del; Aladro, Yolanda; Cuevas, Constanza; Domingo-Santos, Ángela; Galán Sánchez-Seco, Victoria; Labiano-Fontcuberta, Andrés; Gómez-López, Ana; Salgado-Cámara, Paula; Costa-Frossard, Lucienne; Monreal, Enrique; Sainz de la Maza, Susana; Matías-Guiu, Jordi A; Matías-Guiu Guía, Jorge; Delgado Álvarez, Alfonso; Montero-Escribano, Paloma; Martínez-Ginés, María Luisa; Higueras Hernández, Yolanda; Ayuso-Peralta, Lucía; Malpica, Norberto; Melero Carrasco, Helena
    Background: Radiologically isolated syndrome (RIS) patients might have psychiatric and cognitive deficits, which suggests an involvement of major resting-state functional networks. Notwithstanding, very little is known about the neural networks involved in RIS. Objective: To examine functional connectivity differences between RIS and healthy controls using resting-state functional magnetic resonance imaging (fMRI). Methods: Resting-state fMRI data in 25 RIS patients and 28 healthy controls were analyzed using an independent component analysis; in addition, seed-based correlation analysis was used to obtain more information about specific differences in the functional connectivity of resting-state networks. Participants also underwent neuropsychological testing. Results: RIS patients did not differ from the healthy controls regarding age, sex, and years of education. However, in memory (verbal and visuospatial) and executive functions, RIS patients’ cognitive performance was significantly worse than the healthy controls. In addition, fluid intelligence was also affected. Twelve out of 25 (48%) RIS patients failed at least one cognitive test, and six (24.0%) had cognitive impairment. Compared to healthy controls, RIS patients showed higher functional connectivity between the default mode network and the right middle and superior frontal gyri and between the central executive network and the right thalamus ( pFDR < 0.05; corrected). In addition, the seed-based correlation analysis revealed that RIS patients presented higher functional connectivity between the posterior cingulate cortex, an important hub in neural networks, and the right precuneus. Conclusion: RIS patients had abnormal brain connectivity in major resting-state neural networks and worse performance in neurocognitive tests. This entity should be considered not an “incidental finding” but an exclusively non-motor (neurocognitive) variant of multiple sclerosis.
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    Real-time fMRI feedback impacts brain activation, results in auditory hallucinations reduction: Part 1: Superior temporal gyrus -Preliminary evidence-
    (Psychiatry Research, 2020) Okano, K.; Bauer, C. C.C.; Ghosh, S.S.; Lee, Y. J.; de los Angeles, C.; Nestor, P. G.; del Re, E. C.; Northoff, G.; Whitfield-Gabrieli, S.; Niznikiewicz, M. A.; Melero Carrasco, Helena
    Auditory hallucinations (AH) are one of the core symptoms of schizophrenia (SZ) and constitute a significant source of suffering and disability. One third of SZ patients experience pharmacology-resistant AH, so an alternative/complementary treatment strategy is needed to alleviate this debilitating condition. In this study, real-time functional Magnetic Resonance Imaging neurofeedback (rt-fMRI NFB), a non-invasive technique, was used to teach 10 SZ patients with pharmacology-resistant AH to modulate their brain activity in the superior temporal gyrus (STG), a key area in the neurophysiology of AH. A functional task was designed in order to provide patients with a specific strategy to help them modify their brain activity in the desired direction. Specifically, they received neurofeedback from their own STG and were trained to upregulate it while listening to their own voice recording and downregulate it while ignoring a stranger's voice recording. This guided performance neurofeedback training resulted in a) a significant reduction in STG activation while ignoring a stranger's voice, and b) reductions in AH scores after the neurofeedback session. A single, 21-minute session of rt-fMRI NFB was enough to produce these effects, suggesting that this approach may be an efficient and clinically viable alternative for the treatment of pharmacology-resistant AH.
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    Sinestesia, bases neuroanatómicas y cognitivas
    (2015) Melero Carrasco, Helena; Peña Melián Lago, Ángel Luis; Ríos Lago, Marcos
    La sinestesia es un fenómeno neurológico de carácter no patológico que aparece cuando la estimulación de una vía sensorial o cognitiva produce una experiencia asociada en una segunda vía que no ha sido estimulada directamente. A pesar de que en los últimos 15 años el estudio de la sinestesia ha dado lugar a más de 500 publicaciones científicas, sus bases neurofisiológicas aún no han sido dilucidadas. Para aportar nuevos datos empíricos sobre esta cuestión, en esta tesis doctoral se ha analizado el fenómeno de la sinestesia investigando la frecuencia relativa de sus diferentes modalidades, así como sus bases neuroanatómicas y cognitivas. La tesis se divide en tres partes. En la primera (Capítulo I), se lleva a cabo una revisión sobre el estado de la cuestión, incluyendo la definición del fenómeno y sus características, los datos de prevalencia, las diferentes modalidades catalogadas, la evidencia experimental acerca de las diferencias estructurales y funcionales del cerebro sinestésico, los hallazgos genéticos y los modelos explicativos. En la segunda parte se presentan tres estudios. En el primero de ellos (Capítulo II) se analiza la presencia de sinestesia en una muestra española para conocer la frecuencia relativa de sus diferentes modalidades. Los resultados han mostrado a) que la representación de la sinestesia en una muestra española de 803 personas es elevada (13,95%); b) que las sinestesias conceptuales son las más frecuentes; c) que la variable sinestesia es independiente de las variables sexo, edad, lateralidad manual y nivel educativo. Estos hallazgos sugieren que la sinestesia está presente en un elevado número de personas, especialmente cuando se trata de modalidades conceptuales, constatando la necesidad de considerar la variable sinestesia como un factor relevante en los diseños experimentales, y de proporcionar a los profesionales del ámbito clínico un adecuado conocimiento del fenómeno y sus características. En el segundo estudio (Capítulo III), se investigan las características estructurales del cerebro sinestésico grafema-color, mediante la combinación del análisis VBM de datos 3D-T1 y DTI, atendiendo a regiones corticales y subcorticales y explorando las bases neuroanatómicas del componente emocional del fenómeno. Este análisis ha confirmado que las diferencias anatómicas se encuentran distribuidas a nivel cortical y subcortical, incluyendo áreas relacionadas con el procesamiento emocional, lo que ha motivado la propuesta de un nuevo modelo explicativo ¿el Modelo de Integración Emocional. En el tercer estudio (Capítulo IV), se exploran las bases neurofuncionales de las sinestesias acromáticas, siendo esta la primera investigación que se ha centrado en este tipo de experiencias para comprender la sinestesia grafema-color, su dimensión emocional y el efecto de congruencia sinestésica. Los datos obtenidos han permitido confirmar a) que la base funcional de la sinestesia grafema-color se encuentra distribuída en el cerebro y refleja diferentes dimensiones de la experiencia sinestésica: un componente perceptivo, otro atencional/integrador y un componente emocional; b) que el color sinestésico y el color físico no poseen una base neural idéntica; y c) que el efecto de congruencia no debe ser utilizado como criterio para diferenciar la sinestesia congénita de las asociaciones adquiridas mediante aprendizaje asociativo por las personas neurotípicas. En la tercera y última parte Capítulo V, se presenta una discusión general que integra los resultados obtenidos en las tres investigaciones y se discuten las implicaciones que la aparición de este fenómeno tiene sobre el estudio de las diferencias individuales y el conocimiento de la cognición humana en general.
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    Why is the synesthete's “A” red? Using a five-language dataset to disentangle the effects of shape, sound, semantics, and ordinality on inducer–concurrent relationships in grapheme-color synesthesia
    (Cortex, 2018) Root, Nicholas B.; Rouw, Romke; Asano, Michiko; Chai-Youn Kim; Yokosawa, Kazuhiko; Ramachandran, Vilayanur S.; Melero Carrasco, Helena
    Grapheme-color synesthesia is a neurological phenomenon in which viewing a grapheme elicits an additional, automatic, and consistent sensation of color. Color-to-letter associations in synesthesia are interesting in their own right, but also offer an opportunity to examine relationships between visual, acoustic, and semantic aspects of language. Research using large populations of synesthetes has indeed found that grapheme-color pairings can be influenced by numerous properties of graphemes, but the contributions made by each of these explanatory factors are often confounded in a monolingual dataset (i.e., only English-speaking synesthetes). Here, we report the first demonstration of how a multilingual dataset can reveal potentially-universal influences on synesthetic associations, and disentangle previously-confounded hypotheses about the relationship between properties of synesthetic color and properties of the grapheme that induces it. Numerous studies have reported that for English-speaking synesthetes, “A” tends to be colored red more often than predicted by chance, and several explanatory factors have been proposed that could explain this association. Using a five-language dataset (native English, Dutch, Spanish, Japanese, and Korean speakers), we compare the predictions made by each explanatory factor, and show that only an ordinal explanation makes consistent predictions across all five languages, suggesting that the English “A” is red because the first grapheme of a synesthete's alphabet or syllabary tends to be associated with red. We propose that the relationship between the first grapheme and the color red is an association between an unusually-distinct ordinal position (“first”) and an unusually-distinct color (red). We test the predictions made by this theory, and demonstrate that the first grapheme is unusually distinct (has a color that is distant in color space from the other letters' colors). Our results demonstrate the importance of considering cross-linguistic similarities and differences in synesthesia, and suggest that some influences on grapheme-color associations in synesthesia might be universal.
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    Achromatic synesthesias - A functional magnetic resonance imaging study
    (NeuroImage, 2014) Melero Carrasco, Helena; Ríos-Lago, M.; Peña Melián, Ángel; Álvarez-Linera, J.
    Grapheme–color synesthetes experience consistent, automatic and idiosyncratic colors associated with specific letters and numbers. Frequently, these specific associations exhibit achromatic synesthetic qualities (e.g. white, black or gray). In this study, we have investigated for the first time the neural basis of achromatic synesthesias, their relationship to chromatic synesthesias and the achromatic congruency effect in order to understand not only synesthetic color but also other components of the synesthetic experience. To achieve this aim, functional magnetic resonance imaging experiments were performed in a group of associator grapheme–color synesthetes and matched controls who were stimulated with real chromatic and achromatic stimuli (Mondrians), and with letters and numbers that elicited different types of grapheme–color synesthesias (i.e. chromatic and achromatic inducers which elicited chromatic but also achromatic synesthesias, as well as congruent and incongruent ones). The information derived from the analysis of Mondrians and chromatic/achromatic synesthesias suggests that real and synesthetic colors/achromaticity do not fully share neural mechanisms. The whole-brain analysis of BOLD signals in response to the complete set of synesthetic inducers revealed that the functional peculiarities of the synesthetic brain are distributed, and reflect different components of the synesthetic experience: a perceptual component, an (attentional) feature binding component, and an emotional component. Additionally, the inclusion of achromatic experiences has provided new evidence in favor of the emotional binding theory, a line of interpretation which constitutes a bridge between grapheme–color synesthesia and other developmental modalities of the phenomenon.
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    Abnormal functional connectivity in radiologically isolated syndrome: A resting-state fMRI study
    (Multiple Sclerosis Journal, 2023) del Pino, Ana Belén; Aladro, Yolanda; Cuevas, Constanza; Domingo-Santos, Ángela; Galán Sánchez-Seco, Victoria; Labiano-Fontcuberta, Andrés; Gómez-López, Ana; Salgado-Cámara, Paula; Costa-Frossard. Lucienne; Monreal. Enrique; Sainz de la Maza, Susana; Montero-Escribano, Paloma; Martínez-Ginés, María Luisa; Higueras, Yolanda; Ayuso-Peralta, Lucía; Malpica, Norberto; Melero Carrasco, Helena; Benito León, Julián; Higueras Hernández, Yolanda; Matías-Guiu Guía, Jorge
    Radiologically isolated syndrome (RIS) patients might have psychiatric and cognitive deficits, which suggests an involvement of major resting-state functional networks. Notwithstanding, very little is known about the neural networks involved in RIS. Objective: To examine functional connectivity differences between RIS and healthy controls using resting-state functional magnetic resonance imaging (fMRI). Methods: Resting-state fMRI data in 25 RIS patients and 28 healthy controls were analyzed using an independent component analysis; in addition, seed-based correlation analysis was used to obtain more information about specific differences in the functional connectivity of resting-state networks. Participants also underwent neuropsychological testing. Results: RIS patients did not differ from the healthy controls regarding age, sex, and years of education. However, in memory (verbal and visuospatial) and executive functions, RIS patients’ cognitive performance was significantly worse than the healthy controls. In addition, fluid intelligence was also affected. Twelve out of 25 (48%) RIS patients failed at least one cognitive test, and six (24.0%) had cognitive impairment. Compared to healthy controls, RIS patients showed higher functional connectivity between the default mode network and the right middle and superior frontal gyri and between the central executive network and the right thalamus (pFDR < 0.05; corrected). In addition, the seed-based correlation analysis revealed that RIS patients presented higher functional connectivity between the posterior cingulate cortex, an important hub in neural networks, and the right precuneus. Conclusion: RIS patients had abnormal brain connectivity in major resting-state neural networks and worse performance in neurocognitive tests. This entity should be considered not an “incidental finding” but an exclusively non-motor (neurocognitive) variant of multiple sclerosis.
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    The interplay between functioning problems and symptoms in first episode of psychosis: An approach from network analysis
    (Journal of Psychiatric Research, 2021) Ana Izquierdo; María Cabello; Itziar Leal; Blanca Mellor-Marsá; Miriam Ayora; María-Fe Bravo-Ortiz; Ángela Ibáñez; Karina S. MacDowell; Norberto Malpica; Enrique Baca-García; Natalia E. Fares-Otero; Helena Melero; Pilar López-García; Covadonga M. Díaz-Caneja; Jose Luis Ayuso-Mateos; Manuel Durán-Cutilla; Jessica Merchán-Naranjo; Roberto Mediavilla-Torres; Ainoa Muñoz-Sanjosé; Luis Sanchez-Pastor; Monica Dompablo; Patricia Fernández-Martín; Pablo Puras-Rico; Lucía Albarracin-García; Melero Carrasco, Helena; Rodríguez Jiménez, Roberto; Díaz Marsa, Marina Francisca; Arango López, Celso; García-Albea Martín, Julia Isabel; Leza Cerro, Juan Carlos; Leticia León Quismondo
    The relationship between psychotic symptoms and global measures of functioning has been widely studied. No previous study has assessed so far the interplay between specific clinical symptoms and particular areas of functioning in first-episode psychosis (FEP) using network analysis methods. A total of 191 patients with FEP (age 24.45 ± 6.28 years, 64.9% male) participating in an observational and longitudinal study (AGES-CM) comprised the study sample. Functioning problems were assessed with the WHO Disability Assessment Schedule (WHODAS), whereas the Positive and Negative Syndrome Scale (PANSS) was used to assess symptom severity. Network analysis were conducted with the aim of analysing the patterns of relationships between the different dimensions of functioning and PANSS symptoms and factors at baseline. According to our results, the most important nodes were “conceptual disorganization”, “emotional withdrawal”, “lack of spontaneity and flow of conversation”, “delusions”, “unusual thought content”, “dealing with strangers” and “poor rapport”. Our findings suggest that these symptoms and functioning dimensions should be prioritized in the clinical assessment and management of patients with FEP. These areas may also become targets of future early intervention strategies, so as to improve quality of life in this population.
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    Tractography dissection variability: What happens when 42 groups dissect 14 white matter bundles on the same dataset?
    (Neuroimage, 2021) Schilling, Kurt G.; Rheault, François; Petit, Laurent; Hansen, Colin B.; Nath, Vishwesh; Yeh, Fang-Cheng; Girard, Gabriel; Barakovic, Muhamed; Rafael-Patino, Jonathan; Yu, Thomas; Fischi-Gomez, Elda; Pizzolato, Marco; Ocampo-Pineda, Mario; Schiavi, Simona; Canales-Rodríguez, Erick J.; Daducci, Alessandro; Granziera, Cristina; Innocenti, Giorgio; Thiran, Jean-Philippe; Mancini, Laura; Wastling, Stephen; Cocozza, Sirio; Petracca, Maria; Pontillo, Giuseppe; Mancini, Matteo; Vos, Sjoerd B.; Vakharia, Vejay N.; Duncan, John S.; Melero Carrasco, Helena; Manzanedo, Lidia; Sanz-Morales, Emilio; Peña-Melián, Ángel; Calamante, Fernando; Attyé, Arnaud; Cabeen, Ryan P.; Korobova, Laura; Toga, Arthur W.; Vijayakumari, Anupa Ambili; Parker, Drew; Verma, Ragini; Radwan, Ahmed; Sunaert, Stefan; Emsell, Louise; De Luca, Alberto; Leemans, Alexander; Bajada, Claude J.; Haroon, Hamied; Azadbakht, Hojjatollah; Chamberland, Maxime; Genc, Sila; Tax, Chantal M.W.; Yeh, Ping-Hong; Srikanchana, Rujirutana; Mcknight, Colin D.; Yang, Joseph Yuan-Mou; Chen, Jian; Kelly, Claire E.; Yeh, Chun-Hung; Cochereau, Jerome; Maller, Jerome J.; Welton, Thomas; Almairac, Fabien; Seunarine, Kiran K; Clark, Chris A.; Zhang, Fan; Makris, Nikos; Golby, Alexandra; Rathi, Yogesh; O'Donnell, Lauren J.; Xia, Yihao; Aydogan, Dogu Baran; Shi, Yonggang; Guerreiro Fernandes, Francisco; Raemaekers, Mathijs; Warrington, Shaun; Michielse, Stijn; Ramírez-Manzanares, Alonso; Concha, Luis; Aranda, Ramón; Rivera Meraz, Mariano; Lerma-Usabiaga, Garikoitz; Roitman, Lucas; Fekonja, Lucius S.; Calarco, Navona; Joseph, Michael; Nakua, Hajer; Voineskos, Aristotle N.; Karan, Philippe; Grenier, Gabrielle; Legarreta, Jon Haitz; Adluru, Nagesh; Nair, Veena A.; Prabhakaran, Vivek; Alexander, Andrew L.; Kamagata, Koji; Saito, Yuya; Uchida, Wataru; Andica, Christina; Abe, Masahiro; Bayrak, Roza G.; Gandini Wheeler-Kingshott, Claudia A.M.; D'Angelo, Egidio; Palesi, Fulvia; Savini, Giovanni; Rolandi, Nicolò; Guevara, Pamela; Houenou, Josselin; López-López, Narciso; Mangin, Jean-François; Poupon, Cyril; Claudio Román, Claudio; Vázquez, Andrea; Maffei, Chiara; Arantes, Mavilde; Andrade, José Paulo; Silva, Susana Maria; Calhoun, Vince D.; Caverzasi, Eduardo; Sacco, Simone; Lauricella, Michael; Pestilli, Franco; Daniel Bullock, Daniel; Zhan, Yang; Brignoni-Perez, Edith; Lebel, Catherine; Reynolds, Jess E; Nestrasil, Igor; Labounek, René; Lenglet, Christophe; Paulson, Amy; Aulicka, Stefania; Heilbronner, Sarah R.; Heuer, Katja; Chandio, Bramsh Qamar; Guaje, Javier; Tang, Wei; Garyfallidis, Eleftherios; Raja, Rajikha; Anderson, Adam W.; Landman, Bennett A.; Descoteaux, Maxime
    White matter bundle segmentation using diffusion MRI fiber tractography has become the method of choice to identify white matter fiber pathways in vivo in human brains. However, like other analyses of complex data, there is considerable variability in segmentation protocols and techniques. This can result in different reconstructions of the same intended white matter pathways, which directly affects tractography results, quantification, and interpretation. In this study, we aim to evaluate and quantify the variability that arises from different protocols for bundle segmentation. Through an open call to users of fiber tractography, including anatomists, clinicians, and algorithm developers, 42 independent teams were given processed sets of human whole-brain streamlines and asked to segment 14 white matter fascicles on six subjects. In total, we received 57 different bundle segmentation protocols, which enabled detailed volume-based and streamline-based analyses of agreement and disagreement among protocols for each fiber pathway. Results show that even when given the exact same sets of underlying streamlines, the variability across protocols for bundle segmentation is greater than all other sources of variability in the virtual dissection process, including variability within protocols and variability across subjects. In order to foster the use of tractography bundle dissection in routine clinical settings, and as a fundamental analytical tool, future endeavors must aim to resolve and reduce this heterogeneity. Although external validation is needed to verify the anatomical accuracy of bundle dissections, reducing heterogeneity is a step towards reproducible research and may be achieved through the use of standard nomenclature and definitions of white matter bundles and well-chosen constraints and decisions in the dissection process