How the human brain introspects about one's own episodes of cognitive control

Available online 8 November 2017.Metacognition refers to our capacity to reflect upon our experiences, thoughts and actions. Metacognition processes are linked to cognitive control functions that allow keeping our actions on-task. But it is unclear how the human brain builds an internal model of one's cognition and behaviour. We conducted two functional magnetic resonance imaging (fMRI) experiments in which brain activity was recorded ‘online’ as participants engaged in a memory-guided search task and then later ‘offline’ when participants introspected about their prior experience and cognitive states during performance. In Experiment 1 the memory cues were task-relevant while in Experiment 2 they were irrelevant. Across Experiments, the patterns of brain activity, including frontoparietal regions, were similar during on-task and introspection states. However the connectivity profile amongst frontoparietal areas was distinct during introspection and modulated by the relevance of the memory cues. Introspection was also characterized by increased temporal correlation between the default-mode network (DMN), frontoparietal and dorsal attention networks and visual cortex. We suggest that memories of one's own experience during task performance are encoded in large-scale patterns of brain activity and that coupling between DMN and frontoparietal control networks may be crucial to build an internal model of one's behavioural performance.D.S. acknowledges support from the Spanish Ministry of Economy and Competitiveness (MINECO), through the ’Severo Ochoa’ Programme for Centres/Units of Excellence in R&D (SEV-2015-490), and project grant PSI2016-76443-P which is also funded by the Agencia Estatal de Investigacion (AEI) and Fondo Europeo de Desarrollo Regional (FEDER)

Memory suppression is an active process that improves over childhood

We all have memories that we prefer not to think about. The ability to suppress retrieval of unwanted memories has been documented in behavioral and neuroimaging research using the Think/No-Think (TNT) paradigm with adults. Attempts to stop memory retrieval are associated with increased activation of lateral prefrontal cortex (PFC) and concomitant reduced activation in medial temporal lobe (MTL) structures. However, the extent to which children have the ability to actively suppress their memories is unknown. This study investigated memory suppression in middle childhood using the TNT paradigm. Forty children aged 8–12 and 30 young adults were instructed either to remember (Think) or suppress (No-Think) the memory of the second word of previously studied word-pairs, when presented with the first member as a reminder. They then performed two different cued recall tasks, testing their memory for the second word in each pair after the TNT phase using the same first studied word within the pair as a cue (intra-list cue) and also an independent cue (extra-list cue). Children exhibited age-related improvements in memory suppression from age 8 to 12 in both memory tests, against a backdrop of overall improvements in declarative memory over this age range. These findings suggest that memory suppression is an active process that develops during late childhood, likely due to an age-related refinement in the ability to engage PFC to down-regulate activity in areas involved in episodic retrieval.Supported by a grant from the Spanish Ministry of Education and Science (Pedro M. Paz-Alonso), and NSF grants 0648564 (Simona Ghetti) and 0448844 (Silvia A. Bunge)

Functional Dynamics of Dorsal and Ventral Reading Networks in Bilinguals

Published: 06 October 2016In today’s world, bilingualism is increasingly common. However, it is still unclear how left-lateralized dorsal and ventral reading networks are tuned to reading in proficient second-language learners. Here, we investigated differences in functional regional activation and connectivity as a function of L1 and L2 reading, L2 orthographic depth, and task demands. Thirty-seven late bilinguals with the same L1 and either an opaque or transparent L2 performed perceptual and semantic reading tasks in L1 and L2 during functional magnetic resonance imaging (fMRI) scanning. Results revealed stronger regional recruitment for L2 versus L1 reading and stronger connectivity within the dorsal stream during L1 versus L2 reading. Differences in orthographic depth were associated with a segregated profile of left ventral occipitotemporal (vOT) coactivation with dorsal regions for the transparent L2 group and with ventral regions for the opaque L2 group. Finally, semantic versus perceptual demands modulated left vOT engagement, supporting the interactive account of the contribution of vOT to reading, and were associated with stronger coactivation within the ventral network. Our findings support a division of labor between ventral and dorsal reading networks, elucidating the critical role of the language used to read, L2 orthographic depth, and task demands on the functional dynamics of bilingual reading.Supported by a predoctoral grant from the Department of Education, Universities and Research from the Basque Government (M.O.); grants (PSI2015-67353-R) from the Spanish Ministry of Economy and Competitiveness (MINECO), and a grant (ERC-2011-ADG-295362) from the European Research Council (M.C.); grants (RYC-2014-15440, PSI2015-65696) from the MINECO (P.P.), and a grant from the Programa Red guipuzcoana de Ciencia, Tecnología e Innovación (Exp. 65/15) from the Diputación Foral de Gipuzkoa (P.M.P.-A.). BCBL acknowledges funding from Ayuda Centro de Excelencia Severo Ochoa SEV- 2015-0490 from the MINECO

Converging evidence for functional and structural segregation within the left ventral occipitotemporal cortex in reading

Published online September 17, 2018The ventral occipitotemporal cortex (vOTC) is crucial for recognizing visual patterns, and previous evidence suggests that there may be different subregions within the vOTC involved in the rapid identification of word forms. Here, we characterize vOTC reading circuitry using a multimodal approach combining functional, structural, and quantitative MRI and behavioral data. Two main word-responsive vOTC areas emerged: a posterior area involved in visual feature extraction, structurally connected to the intraparietal sulcus via the vertical occipital fasciculus; and an anterior area involved in integrating information with other regions of the language network, structurally connected to the angular gyrus via the posterior arcuate fasciculus. Furthermore, functional activation in these vOTC regions predicted reading behavior outside of the scanner. Differences in the microarchitectonic properties of gray-matter cells in these segregated areas were also observed, in line with earlier cytoarchitectonic evidence. These findings advance our understanding of the vOTC circuitry by linking functional responses to anatomical structure, revealing the pathways of distinct reading-related processes.This work was supported by European Molecular Biology Organization (EMBO, Short-Term Fellowship 158-2015) and Marie Sklodowska-Curie (H2020-MSCA-IF-2017-795807-ReCiModel) grants (to G.L.-U.); Spanish Ministry of Economy and Competitiveness (MINECO, PSI2015- 67353-R, SEV-2015-0490) and European Research Council (ERC, ERC-2011- ADG-295362) grants (to M.C.); and MINECO (RYC-2014-15440, PSI2012- 32093, SEV-2015-0490) and Departamento de Desarrollo Económico y Competitividad, Gobierno Vasco (PI2016-12) grants (to P.M.P.-A.)

Functional characterization of correct and incorrect feature integration

Advance access publication date 30 April 2022Our sensory system constantly receives information from the environment and our own body. Despite our impression to the contrary, we remain largely unaware of this information and often cannot report it correctly. Although perceptual processing does not require conscious effort on the part of the observer, it is often complex, giving rise to errors such as incorrect integration of features (illusory conjunctions). In the present study, we use functional magnetic resonance imaging to study the neural bases of feature integration in a dual task that produced ~30% illusions. A distributed set of regions demonstrated increased activity for correct compared to incorrect (illusory) feature integration, with increased functional coupling between occipital and parietal regions. In contrast, incorrect feature integration (illusions) was associated with increased occipital (V1–V2) responses at early stages, reduced functional connectivity between right occipital regions and the frontal eye field at later stages, and an overall decrease in coactivation between occipital and parietal regions. These results underscore the role of parietal regions in feature integration and highlight the relevance of functional occipito-frontal interactions in perceptual processing.This work was supported by the Spanish Ministry of Science and Innovation research projects PSI2017-88136 and PID2020-119033GB-I00 and the local government of Andalusia (Proyectos de I+D+i en el marco del Programa Operativo FEDER, B-SEJ-570-UGR20) to Ana B. Chica. Pedro M. Paz- Alonso was supported by grants from the Spanish Ministry of Science and Innovation [RYC-2014- 15440 and PGC2018-093408-B-I00], Neuroscience projects from the Fundación Tatiana Pérez de Guzmán el Bueno, Basque Government [PIBA-2021-1-0003], and a grant from “la Caixa” Banking Foundation under the project code LCF/PR/HR19/52160002. BCBL acknowledges support by the Basque Government through the BERC 2022-2025 program and by the Spanish State Research Agency through BCBL Severo Ochoa excellence accreditation CEX2020-001010-S

Converging Evidence for Differential Specialization and Plasticity of Language Systems

First published November 9, 2020.Functional specialization and plasticity are fundamental organizing principles of the brain. Since the mid-1800s, certain cognitive functions have been known to be lateralized, but the provenance and flexibility of hemispheric specialization remain open questions. Language is a uniquely human phenomenon that requires a delicate balance between neural specialization and plasticity, and language learning offers the perfect window to study these principles in the human brain. In the current study, we conducted two separate functional MRI experiments with language learners (male and female), one cross-sectional and one longitudinal, involving distinct populations and languages, and examined hemispheric lateralization and learning-dependent plasticity of the following three language systems: reading, speech comprehension, and verbal production. A multipronged analytic approach revealed a highly consistent pattern of results across the two experiments, showing (1) that in both native and non-native languages, while language production was left lateralized, lateralization for language comprehension was highly variable across individuals; and (2) that with increasing non-native language proficiency, reading and speech comprehension displayed substantial changes in hemispheric dominance, with languages tending to lateralize to opposite hemispheres, while production showed negligible change and remained left lateralized. These convergent results shed light on the long-standing debate of neural organization of language by establishing robust principles of lateralization and plasticity of the main language systems. Findings further suggest involvement of the sensorimotor systems in language lateralization and its plasticity.K.G. eceived support from “la Caixa” Foundation (ID 100010434) through the fellowship LCF/BQ/DI17/11620005 and from the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Grant 713673. J.A.-T. was supported by Basque Government predoctoral Grant PRE_2015_1_028. M.C. was supported by project APCIN-2015-061-MultiLateral, which is funded by the Spanish Ministry of Economy and Competitiveness (MINECO; Grant FLAG-ERA JTC 2015). P.M.P.-A. was supported by MINECO Grants RYC-2014-15440 and PGC2018-093408-B-I00, and the Neuroscience Research Projects program from the Fundacion Tatiana Perez de Guzman el Bueno. The research was also supported by the Basque Government (Grant BERC 2018–2021) and the Spanish State Research Agency through the Basque Center on Cognition, Brain and Language Severo Ochoa excellence accreditation (Grant SEV-2015-0490)

High-Resolution Tractography Protocol to Investigate the Pathways between Human Mediodorsal Thalamic Nucleus and Prefrontal Cortex

Published: November 15, 2023Animal studies have established that the mediodorsal nucleus (MD) of the thalamus is heavily and reciprocally connected with all areas of the prefrontal cortex (PFC). In humans, however, these connections are difficult to investigate. High-resolution imaging protocols capable of reliably tracing the axonal tracts linking the human MD with each of the PFC areas may thus be key to advance our understanding of the variation, development, and plastic changes of these important circuits, in health and disease. Here, we tested in adult female and male humans the reliability of a new reconstruction protocol based on in vivo diffusion MRI to trace, measure, and characterize the fiber tracts interconnecting the MD with 39 human PFC areas per hemisphere. Our protocol comprised the following three components: (1) defining regions of interest; (2) preprocessing diffusion data; and, (3) modeling white matter tracts and tractometry. This analysis revealed largely separate PFC territories of reciprocal MD–PFC tracts bearing striking resemblance with the topographic layout observed in macaque connection-tracing studies. We then examined whether our protocol could reliably reconstruct each of these MD–PFC tracts and their profiles across test and retest sessions. Results revealed that this protocol was able to trace and measure, in both left and right hemispheres, the trajectories of these 39 area-specific axon bundles with good-to-excellent test-retest reproducibility. This protocol, which has been made publicly available, may be relevant for cognitive neuroscience and clinical studies of normal and abnormal PFC function, development, and plasticity.L.M. was supported by Horizon 2020 the European Union’s research and innovation program under Marie Skłodowska-Curie Grant 713673 and from “la Caixa” Foundation (Grants 11660016 and 100010434 under Agreement HR18-00178-DYSTHAL). G.L-U. was supported by the Spanish Ministry of Science and Innovation (Grants IJC2020-042887-I and PID2021-123577NA-I00) and the Basque Government (Grant PIBA-2022-1- 0014). F.C. was supported by the Spanish Ministry of Science and Innovation (Grants MICINN-AEI PCI2019- 111900-2 and PID2020-115780GB-I00). P.M.P-A. was supported by the Spanish Ministry of Science and Innovation (Grant PID2021-123574NB-I00), the Basque Government (Grant PIBA-2021-1-0003), and the Red guipuzcoana de Ciencia, Tecnología e Innovación of the Diputación Foral de Gipuzkoa (Grant FA/OF 422/2022), and “la Caixa” Foundation (Grant 100010434 under Agreement HR18-00178-DYSTHAL). The Basque Center on Cognition, Brain and Language (BCBL) acknowledges funding from the Basque Government through the BERC 2022-2025 program and by the Spanish State Research Agency through BCBL Severo Ochoa Excellence Accreditation CEX2020-001010-S

Reproducible protocol to obtain and measure first-order relay human thalamic white-matter tracts

Available online 13 August 2022The “primary ”or “first-order relay ”nuclei of the thalamus feed the cerebral cortex with information about on- going activity in the environment or the subcortical motor systems. Because of the small size of these nuclei and the high specificity of their input and output pathways, new imaging protocols are required to investigate thala- mocortical interactions in human perception, cognition and language. The goal of the present study was twofold: I) to develop a reconstruction protocol based on in vivo diffusion MRI to extract and measure the axonal fiber tracts that originate or terminate specifically in individual first-order relay nuclei; and, II) to test the reliability of this reconstruction protocol. In left and right hemispheres, we investigated the thalamocortical/corticothalamic axon bundles linking each of the first-order relay nuclei and their main cortical target areas, namely, the lateral geniculate nucleus (optic radiation), the medial geniculate nucleus (acoustic radiation), the ventral posterior nu- cleus (somatosensory radiation) and the ventral lateral nucleus (motor radiation). In addition, we examined the main subcortical input pathway to the ventral lateral posterior nucleus, which originates in the dentate nucleus of the cerebellum. Our protocol comprised three components: defining regions-of-interest; preprocessing diffu- sion data; and modeling white-matter tracts and tractometry. We then used computation and test-retest methods to check whether our protocol could reliably reconstruct these tracts of interest and their profiles. Our results demonstrated that the protocol had nearly perfect computational reproducibility and good-to-excellent test-retest reproducibility. This new protocol may be of interest for both basic human brain neuroscience and clinical studies and has been made publicly available to the scientific community.This work was supported by grants from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie (grant agreement No. 713673 ), and from “la Caixa ”Foundation (grant No. 11660016 ) to M.L.; grants from the Span- ish Ministerio de Ciencia e Innovación ( IJC2020-042887-I ; PID2021- 123577NA-I00 ) to G.L.-U.; grants from the European Union ’s Horizon 2020 Research and Innovation Program, European Commission (grant agreement No. 945539 - HBP SGA3 ) and from the Ministerio de Ciencia e Innovación FLAG-ERA grant NeuronsReunited ( MICINN-AEI PCI2019-111900-2 ) to F.C.; and grants from the Ministerio de Ciencia e Innovación ( PGC2018-093408-B-I00 ; PID2021-123574NB-I00 ), Neuro- science projects from the Fundación Tatiana Pérez de Guzmán el Bueno , Basque Government ( PIBA-2021-1-0003 ), and a grant from “la Caixa ”Banking Foundation under the project code LCF/PR/HR19/52160002 to P.M.P.-A. BCBL acknowledges support by the Basque Government through the BERC 2022-2025 program and by the S panish State Re- search Agency through BCBL Severo Ochoa excellence accreditation CEX2020-001010-S

Encoding and inhibition of arbitrary episodic context with abstract concepts

Published online: 18 August 2021Context is critical for conceptual processing, but the mechanism underpinning its encoding and reinstantiation during abstract concept processing is unclear. Context may be especially important for abstract concepts—we investigated whether episodic context is recruited differently when processing abstract compared with concrete concepts. Experiments 1 and 2 presented abstract and concrete words in arbitrary contexts at encoding (Experiment 1: red/green colored frames; Experiment 2: male/female voices). Recognition memory for these contexts was worse for abstract concepts. Again using frame color and voice as arbitrary contexts, respectively, Experiments 3 and 4 presented words from encoding in the same or different context at test to determine whether there was a greater recognition memory benefit for abstract versus concrete concepts when the context was unchanged between encoding and test. Instead, abstract concepts were less likely to be remembered when context was retained. This suggests that at least some types of episodic context—when arbitrary—are attended less, and may even be inhibited, when processing abstract concepts. In Experiment 5, we utilized a context—spatial location—which (as we show) tends to be relevant during real-world processing of abstract concepts.We presented words in different locations, preserving or changing location at test. Location retention conferred a recognitionmemory advantage for abstract concepts. Thus, episodic context may be encoded with abstract concepts when context is relevant to real-world processing. The systematic contexts necessary for understanding abstract concepts may lead to arbitrary context inhibition, but greater attention to contexts that tend to be more relevant during real-world processing

Reproducible Tract Profiles 2 (RTP2) suite, from diffusion MRI acquisition to clinical practice and research

Published: 2023 Apr 12Diffusion MRI is a complex technique, where new discoveries and implementations occur at a fast pace. The expertise needed for data analyses and accurate and reproducible results is increasingly demanding and requires multidisciplinary collaborations. In the present work we introduce Reproducible Tract Profiles 2 (RTP2), a set of flexible and automated methods to analyze anatomical MRI and diffusion weighted imaging (DWI) data for reproducible tractography. RTP2 reads structural MRI data and processes them through a succession of serialized containerized analyses. We describe the DWI algorithms used to identify white-matter tracts and their summary metrics, the flexible architecture of the platform, and the tools to programmatically access and control the computations. The combination of these three components provides an easy-to-use automatized tool developed and tested over 20 years, to obtain usable and reliable state-of-the-art diffusion metrics at the individual and group levels for basic research and clinical practice.G. L-U. was supported by grants from the Spanish Ministry of Science and Innovation (IJC2020-042887-I and PID2021-123577NA-I00) and Basque Government (PIBA-2022-1-0014); M.L. was supported by grants from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie (grant agreement No. 713673), and from “la Caixa” Foundation (grant No. 11660016); P.M.P.-A. was supported by grants from the Spanish Ministry of Science and Innovation (PID2021-123574NB-I00), from the Basque Government (PIBA-2021-1-0003), from the Red guipuzcoana de Ciencia, Tecnología e Innovación of the Diputación Foral de Gipuzkoa (FA/OF 422/2022), from “la Caixa” Foundation (ID 100010434) under the agreement HR18-00178-DYSTHAL. BCBL acknowledges support by the Basque Government through the BERC 2022–2025 program and by the Spanish State Research Agency through BCBL Severo Ochoa excellence accreditation CEX2020-001010-S