Publications by authors named "Daniel S Margulies"

132 Publications

Compressed sensorimotor-to-transmodal hierarchical organization in schizophrenia.

Psychol Med 2021 Jun 8:1-14. Epub 2021 Jun 8.

The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation, High-Field Magnetic Resonance Brain Imaging Key Laboratory of Sichuan Province, School of Life Science and Technology, University of Electronic Science and Technology of China, China.

Background: Schizophrenia has been primarily conceptualized as a disorder of high-order cognitive functions with deficits in executive brain regions. Yet due to the increasing reports of early sensory processing deficit, recent models focus more on the developmental effects of impaired sensory process on high-order functions. The present study examined whether this pathological interaction relates to an overarching system-level imbalance, specifically a disruption in macroscale hierarchy affecting integration and segregation of unimodal and transmodal networks.

Methods: We applied a novel combination of connectome gradient and stepwise connectivity analysis to resting-state fMRI to characterize the sensorimotor-to-transmodal cortical hierarchy organization (96 patients v. 122 controls).

Results: We demonstrated compression of the cortical hierarchy organization in schizophrenia, with a prominent compression from the sensorimotor region and a less prominent compression from the frontal-parietal region, resulting in a diminished separation between sensory and fronto-parietal cognitive systems. Further analyses suggested reduced differentiation related to atypical functional connectome transition from unimodal to transmodal brain areas. Specifically, we found hypo-connectivity within unimodal regions and hyper-connectivity between unimodal regions and fronto-parietal and ventral attention regions along the classical sensation-to-cognition continuum (voxel-level corrected, p < 0.05).

Conclusions: The compression of cortical hierarchy organization represents a novel and integrative system-level substrate underlying the pathological interaction of early sensory and cognitive function in schizophrenia. This abnormal cortical hierarchy organization suggests cascading impairments from the disruption of the somatosensory-motor system and inefficient integration of bottom-up sensory information with attentional demands and executive control processes partially account for high-level cognitive deficits characteristic of schizophrenia.
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http://dx.doi.org/10.1017/S0033291721002129DOI Listing
June 2021

The neural correlates of ongoing conscious thought.

iScience 2021 Mar 1;24(3):102132. Epub 2021 Feb 1.

Department of Psychology / York Imaging Centre, University of York, York, England.

A core goal in cognitive neuroscience is identifying the physical substrates of the patterns of thought that occupy our daily lives. Contemporary views suggest that the landscape of ongoing experience is heterogeneous and can be influenced by features of both the person and the context. This perspective piece considers recent work that explicitly accounts for both the heterogeneity of the experience and context dependence of patterns of ongoing thought. These studies reveal that systems linked to attention and control are important for organizing experience in response to changing environmental demands. These studies also establish a role of the default mode network beyond task-negative or purely episodic content, for example, implicating it in the level of vivid detail in experience in both task contexts and in spontaneous self-generated experiential states. Together, this work demonstrates that the landscape of ongoing thought is reflected in the activity of multiple neural systems, and it is important to distinguish between processes contributing to how the experience unfolds from those linked to how these experiences are regulated.
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http://dx.doi.org/10.1016/j.isci.2021.102132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907463PMC
March 2021

Imaging evolution of the primate brain: the next frontier?

Neuroimage 2021 03 5;228:117685. Epub 2021 Jan 5.

Brain Connectivity and Behaviour Laboratory, Sorbonne Universities, Paris, France; Groupe d'Imagerie Neurofonctionnelle, Institut des Maladies Neurodégénératives-UMR 5293, CNRS, CEA, University of Bordeaux, Bordeaux, France. Electronic address:

Evolution, as we currently understand it, strikes a delicate balance between animals' ancestral history and adaptations to their current niche. Similarities between species are generally considered inherited from a common ancestor whereas observed differences are considered as more recent evolution. Hence comparing species can provide insights into the evolutionary history. Comparative neuroimaging has recently emerged as a novel subdiscipline, which uses magnetic resonance imaging (MRI) to identify similarities and differences in brain structure and function across species. Whereas invasive histological and molecular techniques are superior in spatial resolution, they are laborious, post-mortem, and oftentimes limited to specific species. Neuroimaging, by comparison, has the advantages of being applicable across species and allows for fast, whole-brain, repeatable, and multi-modal measurements of the structure and function in living brains and post-mortem tissue. In this review, we summarise the current state of the art in comparative anatomy and function of the brain and gather together the main scientific questions to be explored in the future of the fascinating new field of brain evolution derived from comparative neuroimaging.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116589PMC
March 2021

The psychological correlates of distinct neural states occurring during wakeful rest.

Sci Rep 2020 12 3;10(1):21121. Epub 2020 Dec 3.

Department of Psychology, York Neuroimaging Centre, University of York, York, YO10 5DD, UK.

When unoccupied by an explicit external task, humans engage in a wide range of different types of self-generated thinking. These are often unrelated to the immediate environment and have unique psychological features. Although contemporary perspectives on ongoing thought recognise the heterogeneity of these self-generated states, we lack both a clear understanding of how to classify the specific states, and how they can be mapped empirically. In the current study, we capitalise on advances in machine learning that allow continuous neural data to be divided into a set of distinct temporally re-occurring patterns, or states. We applied this technique to a large set of resting state data in which we also acquired retrospective descriptions of the participants' experiences during the scan. We found that two of the identified states were predictive of patterns of thinking at rest. One state highlighted a pattern of neural activity commonly seen during demanding tasks, and the time individuals spent in this state was associated with descriptions of experience focused on problem solving in the future. A second state was associated with patterns of activity that are commonly seen under less demanding conditions, and the time spent in it was linked to reports of intrusive thoughts about the past. Finally, we found that these two neural states tended to fall at either end of a neural hierarchy that is thought to reflect the brain's response to cognitive demands. Together, these results demonstrate that approaches which take advantage of time-varying changes in neural function can play an important role in understanding the repertoire of self-generated states. Moreover, they establish that important features of self-generated ongoing experience are related to variation along a similar vein to those seen when the brain responds to cognitive task demands.
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http://dx.doi.org/10.1038/s41598-020-77336-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712889PMC
December 2020

A collaborative resource platform for non-human primate neuroimaging.

Neuroimage 2021 02 20;226:117519. Epub 2020 Nov 20.

Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Direction de la Recherche Fondamentale, NeuroSpin Center, Gif-sur-Yvette, France; Cognitive Neuroimaging Unit, Institut National de la Santé et de la Recherche Médicale U992, Gif-sur-Yvette, France.

Neuroimaging non-human primates (NHPs) is a growing, yet highly specialized field of neuroscience. Resources that were primarily developed for human neuroimaging often need to be significantly adapted for use with NHPs or other animals, which has led to an abundance of custom, in-house solutions. In recent years, the global NHP neuroimaging community has made significant efforts to transform the field towards more open and collaborative practices. Here we present the PRIMatE Resource Exchange (PRIME-RE), a new collaborative online platform for NHP neuroimaging. PRIME-RE is a dynamic community-driven hub for the exchange of practical knowledge, specialized analytical tools, and open data repositories, specifically related to NHP neuroimaging. PRIME-RE caters to both researchers and developers who are either new to the field, looking to stay abreast of the latest developments, or seeking to collaboratively advance the field .
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http://dx.doi.org/10.1016/j.neuroimage.2020.117519DOI Listing
February 2021

Toward a hierarchical model of social cognition: A neuroimaging meta-analysis and integrative review of empathy and theory of mind.

Psychol Bull 2021 03 5;147(3):293-327. Epub 2020 Nov 5.

Clinical Psychology and Behavioral Neuroscience, Faculty of Psychology, Technische Universität Dresden.

Along with the increased interest in and volume of social cognition research, there has been higher awareness of a lack of agreement on the concepts and taxonomy used to study social processes. Two central concepts in the field, empathy and Theory of Mind (ToM), have been identified as overlapping umbrella terms for different processes of limited convergence. Here, we review and integrate evidence of brain activation, brain organization, and behavior into a coherent model of social-cognitive processes. We start with a meta-analytic clustering of neuroimaging data across different social-cognitive tasks. Results show that understanding others' mental states can be described by a multilevel model of hierarchical structure, similar to models in intelligence and personality research. A higher level describes more broad and abstract classes of functioning, whereas a lower one explains how functions are applied to concrete contexts given by particular stimulus and task formats. Specifically, the higher level of our model suggests 3 groups of neurocognitive processes: (a) predominantly cognitive processes, which are engaged when mentalizing requires self-generated cognition decoupled from the physical world; (b) more affective processes, which are engaged when we witness emotions in others based on shared emotional, motor, and somatosensory representations; (c) combined processes, which engage cognitive and affective functions in parallel. We discuss how these processes are explained by an underlying principal gradient of structural brain organization. Finally, we validate the model by a review of empathy and ToM task interrelations found in behavioral studies. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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http://dx.doi.org/10.1037/bul0000303DOI Listing
March 2021

Signal diffusion along connectome gradients and inter-hub routing differentially contribute to dynamic human brain function.

Neuroimage 2021 01 7;224:117429. Epub 2020 Oct 7.

Multimodal Imaging and Connectome Analysis Lab, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada. Electronic address:

Human cognition is dynamic, alternating over time between externally-focused states and more abstract, often self-generated, patterns of thought. Although cognitive neuroscience has documented how networks anchor particular modes of brain function, mechanisms that describe transitions between distinct functional states remain poorly understood. Here, we examined how time-varying changes in brain function emerge within the constraints imposed by macroscale structural network organization. Studying a large cohort of healthy adults (n = 326), we capitalized on manifold learning techniques that identify low dimensional representations of structural connectome organization and we decomposed neurophysiological activity into distinct functional states and their transition patterns using Hidden Markov Models. Structural connectome organization predicted dynamic transitions anchored in sensorimotor systems and those between sensorimotor and transmodal states. Connectome topology analyses revealed that transitions involving sensorimotor states traversed short and intermediary distances and adhered strongly to communication mechanisms of network diffusion. Conversely, transitions between transmodal states involved spatially distributed hubs and increasingly engaged long-range routing. These findings establish that the structure of the cortex is optimized to allow neural states the freedom to vary between distinct modes of processing, and so provides a key insight into the neural mechanisms that give rise to the flexibility of human cognition.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117429DOI Listing
January 2021

Network-level causal analysis of set-shifting during trail making test part B: A multimodal analysis of a glioma surgery case.

Cortex 2020 11 12;132:238-249. Epub 2020 Sep 12.

Frontlab, CNRS UMR 7225, Inserm U1127, Sorbonne Université ICM, Paris, France.

The trail making test part B (TMT-B) is one of the most widely used task for the assessment of set-shifting ability in patients. However, the set of brain regions impacting TMT-B performance when lesioned is still poorly known. In this case report, we provide a multimodal analysis of a patient operated on while awake for a diffuse low-grade glioma located in the right supramarginal gyrus. TMT-B performance was probed intraoperatively. Direct electrical stimulation of the white matter in the depth of the resection generated shifting errors. Using the recent methodology of axono-cortical-evoked potentials (ACEP), we demonstrated that the eloquent fibers were connected to the posterior end of the middle temporal gyrus (MTG). This was further confirmed by a tractography analysis of the postoperative diffusion MRI. Finally, the functional connectivity maps of this MTG seed were assessed in both pre- and post-operative resting state MRI. These maps matched with the Control network B (13th) and Default B (17th) from the 17-networks parcellation of (Yeo et al., 2011). Last but not least, we showed that the dorsal attention B (6th), the control A & B networks (12th and 13th) and the default A (16th) have been preserved here but disconnected after a more extensive resection in a previous glioma case within the same area, and in whom TMT-B was definitively impaired. Taken together, these data support the need of a network-level approach to identify the neural basis of the TMT-B and point to the Control network B as playing an important role in set-shifting.
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http://dx.doi.org/10.1016/j.cortex.2020.08.021DOI Listing
November 2020

Topographic organization of the human subcortex unveiled with functional connectivity gradients.

Nat Neurosci 2020 11 28;23(11):1421-1432. Epub 2020 Sep 28.

Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Parkville, Victoria, Australia.

Brain atlases are fundamental to understanding the topographic organization of the human brain, yet many contemporary human atlases cover only the cerebral cortex, leaving the subcortex a terra incognita. We use functional MRI (fMRI) to map the complex topographic organization of the human subcortex, revealing large-scale connectivity gradients and new areal boundaries. We unveil four scales of subcortical organization that recapitulate well-known anatomical nuclei at the coarsest scale and delineate 27 new bilateral regions at the finest. Ultrahigh field strength fMRI corroborates and extends this organizational structure, enabling the delineation of finer subdivisions of the hippocampus and the amygdala, while task-evoked fMRI reveals a subtle subcortical reorganization in response to changing cognitive demands. A new subcortical atlas is delineated, personalized to represent individual differences and used to uncover reproducible brain-behavior relationships. Linking cortical networks to subcortical regions recapitulates a task-positive to task-negative axis. This new atlas enables holistic connectome mapping and characterization of cortico-subcortical connectivity.
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http://dx.doi.org/10.1038/s41593-020-00711-6DOI Listing
November 2020

Shaping brain structure: Genetic and phylogenetic axes of macroscale organization of cortical thickness.

Sci Adv 2020 Sep 25;6(39). Epub 2020 Sep 25.

Institute of Neuroscience and Medicine (INM-7: Brain and Behavior), Research Centre Jülich, Jülich, Germany.

The topology of the cerebral cortex has been proposed to provide an important source of constraint for the organization of cognition. In a sample of twins ( = 1113), we determined structural covariance of thickness to be organized along both a posterior-to-anterior and an inferior-to-superior axis. Both organizational axes were present when investigating the genetic correlation of cortical thickness, suggesting a strong genetic component in humans, and had a comparable organization in macaques, demonstrating they are phylogenetically conserved in primates. In both species, the inferior-superior dimension of cortical organization aligned with the predictions of dual-origin theory, and in humans, we found that the posterior-to-anterior axis related to a functional topography describing a continuum of functions from basic processes involved in perception and action to more abstract features of human cognition. Together, our study provides important insights into how functional and evolutionary patterns converge at the level of macroscale cortical structural organization.
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http://dx.doi.org/10.1126/sciadv.abb3417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518868PMC
September 2020

Cross-species functional alignment reveals evolutionary hierarchy within the connectome.

Neuroimage 2020 12 9;223:117346. Epub 2020 Sep 9.

Computational Imaging Research Lab, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Austria; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA.

Evolution provides an important window into how cortical organization shapes function and vice versa. The complex mosaic of changes in brain morphology and functional organization that have shaped the mammalian cortex during evolution, complicates attempts to chart cortical differences across species. It limits our ability to fully appreciate how evolution has shaped our brain, especially in systems associated with unique human cognitive capabilities that lack anatomical homologues in other species. Here, we develop a function-based method for cross-species alignment that enables the quantification of homologous regions between humans and rhesus macaques, even when their location is decoupled from anatomical landmarks. Critically, we find cross-species similarity in functional organization reflects a gradient of evolutionary change that decreases from unimodal systems and culminates with the most pronounced changes in posterior regions of the default mode network (angular gyrus, posterior cingulate and middle temporal cortices). Our findings suggest that the establishment of the default mode network, as the apex of a cognitive hierarchy, has changed in a complex manner during human evolution - even within subnetworks.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871099PMC
December 2020

Distinct patterns of thought mediate the link between brain functional connectomes and well-being.

Netw Neurosci 2020 1;4(3):637-657. Epub 2020 Jul 1.

Department of Psychology, University of York, York, United Kingdom.

Ongoing thought patterns constitute important aspects of both healthy and abnormal human cognition. However, the neural mechanisms behind these daily experiences and their contribution to well-being remain a matter of debate. Here, using resting-state fMRI and retrospective thought sampling in a large neurotypical cohort ( = 211), we identified two distinct patterns of thought, broadly describing the participants' current concerns and future plans, that significantly explained variability in the individual functional connectomes. Consistent with the view that ongoing thoughts are an emergent property of multiple neural systems, network-based analysis highlighted the central importance of both unimodal and transmodal cortices in the generation of these experiences. Importantly, while state-dependent current concerns predicted better psychological health, mediating the effect of functional connectomes, trait-level future plans were related to better social health, yet with no mediatory influence. Collectively, we show that ongoing thoughts can influence the link between brain physiology and well-being.
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http://dx.doi.org/10.1162/netn_a_00137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462429PMC
July 2020

Toward a connectivity gradient-based framework for reproducible biomarker discovery.

Neuroimage 2020 12 1;223:117322. Epub 2020 Sep 1.

Center for Biomedical Imaging and Neuromodulation, Nathan Kline Institute, NY, USA. Electronic address:

Despite myriad demonstrations of feasibility, the high dimensionality of fMRI data remains a critical barrier to its utility for reproducible biomarker discovery. Recent efforts to address this challenge have capitalized on dimensionality reduction techniques applied to resting-state fMRI, identifying principal components of intrinsic connectivity which describe smooth transitions across different cortical systems, so called "connectivity gradients". These gradients recapitulate neurocognitively meaningful organizational principles that are present in both human and primate brains, and also appear to differ among individuals and clinical populations. Here, we provide a critical assessment of the suitability of connectivity gradients for biomarker discovery. Using the Human Connectome Project (discovery subsample=209; two replication subsamples= 209 × 2) and the Midnight scan club (n = 9), we tested the following key biomarker traits - reliability, reproducibility and predictive validity - of functional gradients. In doing so, we systematically assessed the effects of three analytical settings, including i) dimensionality reduction algorithms (i.e., linear vs. non-linear methods), ii) input data types (i.e., raw time series, [un-]thresholded functional connectivity), and iii) amount of the data (resting-state fMRI time-series lengths). We found that the reproducibility of functional gradients across algorithms and subsamples is generally higher for those explaining more variances of whole-brain connectivity data, as well as those having higher reliability. Notably, among different analytical settings, a linear dimensionality reduction (principal component analysis in our study), more conservatively thresholded functional connectivity (e.g., 95-97%) and longer time-series data (at least ≥20mins) was found to be preferential conditions to obtain higher reliability. Those gradients with higher reliability were able to predict unseen phenotypic scores with a higher accuracy, highlighting reliability as a critical prerequisite for validity. Importantly, prediction accuracy with connectivity gradients exceeded that observed with more traditional edge-based connectivity measures, suggesting the added value of a low-dimensional and multivariate gradient approach. Finally, the present work highlights the importance and benefits of systematically exploring the parameter space for new imaging methods before widespread deployment.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117322DOI Listing
December 2020

Joint embedding: A scalable alignment to compare individuals in a connectivity space.

Neuroimage 2020 11 7;222:117232. Epub 2020 Aug 7.

Computational Imaging Research Lab, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address:

A common coordinate space enabling comparison across individuals is vital to understanding human brain organization and individual differences. By leveraging dimensionality reduction algorithms, high-dimensional fMRI data can be represented in a low-dimensional space to characterize individual features. Such a representative space encodes the functional architecture of individuals and enables the observation of functional changes across time. However, determining comparable functional features across individuals in resting-state fMRI in a way that simultaneously preserves individual-specific connectivity structure can be challenging. In this work we propose scalable joint embedding to simultaneously embed multiple individual brain connectomes within a common space that allows individual representations across datasets to be aligned. Using Human Connectome Project data, we evaluated the joint embedding approach by comparing it to the previously established orthonormal alignment model. Alignment using joint embedding substantially increased the similarity of functional representations across individuals while simultaneously capturing their distinct profiles, allowing individuals to be more discriminable from each other. Additionally, we demonstrated that the common space established using resting-state fMRI provides a better overlap of task-activation across participants. Finally, in a more challenging scenario - alignment across a lifespan cohort aged from 6 to 85 - joint embedding provided a better prediction of age (r2 = 0.65) than the prior alignment model. It facilitated the characterization of functional trajectories across lifespan. Overall, these analyses establish that joint embedding can simultaneously capture individual neural representations in a common connectivity space aligning functional data across participants and populations and preserve individual specificity.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779372PMC
November 2020

Neurocognitive patterns dissociating semantic processing from executive control are linked to more detailed off-task mental time travel.

Sci Rep 2020 07 17;10(1):11904. Epub 2020 Jul 17.

Department of Psychology, University of York, York, UK.

Features of ongoing experience are common across individuals and cultures. However, certain people express specific patterns of thought to a greater extent than others. Contemporary psychological theory assumes that individual differences in thought patterns occur because different types of experience depend on the expression of different neurocognitive processes. Consequently, individual variation in the underlying neurocognitive architecture is hypothesised to determine the ease with which certain thought patterns are generated or maintained. Our study (N = 178) tested this hypothesis using multivariate pattern analysis to infer shared variance among measures of cognitive function and neural organisation and examined whether these latent variables explained reports of the patterns of on-going thoughts people experienced in the lab. We found that relatively better performance on tasks relying primarily on semantic knowledge, rather than executive control, was linked to a neural functional organisation associated, via meta-analysis, with task labels related to semantic associations (sentence processing, reading and verbal semantics). Variability of this functional mode predicted significant individual variation in the types of thoughts that individuals experienced in the laboratory: neurocognitive patterns linked to better performance at tasks that required guidance from semantic representation, rather than those dependent on executive control, were associated with patterns of thought characterised by greater subjective detail and a focus on time periods other than the here and now. These relationships were consistent across different days and did not vary with level of task demands, indicating they are relatively stable features of an individual's cognitive profile. Together these data confirm that individual variation in aspects of ongoing experience can be inferred from hidden neurocognitive architecture and demonstrate that performance trade-offs between executive control and long-term semantic knowledge are linked to a person's tendency to imagine situations that transcend the here and now.
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http://dx.doi.org/10.1038/s41598-020-67605-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368037PMC
July 2020

Intrinsic network architecture predicts the effects elicited by intracranial electrical stimulation of the human brain.

Nat Hum Behav 2020 10 6;4(10):1039-1052. Epub 2020 Jul 6.

Stanford Human Intracranial Cognitive Electrophysiology Program, Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.

Intracranial electrical stimulation (iES) of the human brain has long been known to elicit a remarkable variety of perceptual, motor and cognitive effects, but the functional-anatomical basis of this heterogeneity remains poorly understood. We conducted a whole-brain mapping of iES-elicited effects, collecting first-person reports following iES at 1,537 cortical sites in 67 participants implanted with intracranial electrodes. We found that intrinsic network membership and the principal gradient of functional connectivity strongly predicted the type and frequency of iES-elicited effects in a given brain region. While iES in unimodal brain networks at the base of the cortical hierarchy elicited frequent and simple effects, effects became increasingly rare, heterogeneous and complex in heteromodal and transmodal networks higher in the hierarchy. Our study provides a comprehensive exploration of the relationship between the hierarchical organization of intrinsic functional networks and the causal modulation of human behaviour and experience with iES.
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http://dx.doi.org/10.1038/s41562-020-0910-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572705PMC
October 2020

A gradient from long-term memory to novel cognition: Transitions through default mode and executive cortex.

Neuroimage 2020 10 20;220:117074. Epub 2020 Jun 20.

Department of Psychology, University of York, Heslington, York, YO10 5DD, United Kingdom. Electronic address:

Human cognition flexibly guides decision-making in familiar and novel situations. Although these decisions are often treated as dichotomous, in reality, situations are neither completely familiar, nor entirely new. Contemporary accounts of brain organization suggest that neural function is organized along a connectivity gradient from unimodal regions of sensorimotor cortex, through executive regions to transmodal default mode network. We examined whether this graded view of neural organization helps to explain how decision-making changes across situations that vary in their alignment with long-term knowledge. We used a semantic judgment task, which parametrically varied the global semantic similarity of items within a feature matching task to create a 'task gradient', from conceptual combinations that were highly overlapping in long-term memory to trials that only shared the goal-relevant feature. We found the brain's response to the task gradient varied systematically along the connectivity gradient, with the strongest response in default mode network when the probe and target items were highly overlapping conceptually. This graded functional change was seen in multiple brain regions and within individual brains, and was not readily explained by task difficulty. Moreover, the gradient captured the spatial layout of networks involved in semantic processing, providing an organizational principle for controlled semantic cognition across the cortex. In this way, the cortex is organized to support semantic decision-making in both highly familiar and less familiar situations.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573535PMC
October 2020

Network convergence zones in the anterior midcingulate cortex.

Handb Clin Neurol 2019 ;166:103-111

Department of Psychology, University of Miami, Coral Gables, FL, United States; Neuroscience Program, University of Miami Miller School of Medicine, Miami, FL, United States. Electronic address:

Situated medially and centrally in the brain, the anterior midcingulate cortex (aMCC) is a nexus of control. This specialized neocortical brain region participates in large-scale brain networks underlying attention, motor, and limbic processes. The functional diversity and proximity of cognitive and affective subdivisions within this region are its distinguishing features, rendering it an effective site for integration across domains. Here we review comparative neuroanatomic, meta-analytic, and connectomic analyses contributing to the emerging picture of the aMCC as comprising functionally diverse, flexible network nodes involved in multiple regulatory behaviors. We further present data providing evidence for an organizing gradient along the anterior and midcingulate cortex and explore the implications of these findings for understanding the functional role of the anterior midcingulate within this spectrum. We conclude by highlighting open questions and proposing future directions for investigations into the functional role of this important network convergence zone.
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http://dx.doi.org/10.1016/B978-0-444-64196-0.00007-8DOI Listing
April 2020

Shifts in myeloarchitecture characterise adolescent development of cortical gradients.

Elife 2019 11 14;8. Epub 2019 Nov 14.

Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.

We studied an accelerated longitudinal cohort of adolescents and young adults (n = 234, two time points) to investigate dynamic reconfigurations in myeloarchitecture. Intracortical profiles were generated using magnetization transfer (MT) data, a myelin-sensitive magnetic resonance imaging contrast. Mixed-effect models of depth specific intracortical profiles demonstrated two separate processes i) overall increases in MT, and ii) flattening of the MT profile related to enhanced signal in mid-to-deeper layers, especially in heteromodal and unimodal association cortices. This development was independent of morphological changes. Enhanced MT in mid-to-deeper layers was found to spatially co-localise specifically with gene expression markers of oligodendrocytes. Interregional covariance analysis revealed that these intracortical changes contributed to a gradual differentiation of higher-order from lower-order systems. Depth-dependent trajectories of intracortical myeloarchitectural development contribute to the maturation of structural hierarchies in the human neocortex, providing a model for adolescent development that bridges microstructural and macroscopic scales of brain organisation.
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http://dx.doi.org/10.7554/eLife.50482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6855802PMC
November 2019

Distinct individual differences in default mode network connectivity relate to off-task thought and text memory during reading.

Sci Rep 2019 11 7;9(1):16220. Epub 2019 Nov 7.

Department of Psychology, University of York, Heslington, York, YO10 5DD, UK.

Often, as we read, we find ourselves thinking about something other than the text; this tendency to mind-wander is linked to poor comprehension and reduced subsequent memory for texts. Contemporary accounts argue that periods of off-task thought are related to the tendency for attention to be decoupled from external input. We used fMRI to understand the neural processes that underpin this phenomenon. First, we found that individuals with poorer text-based memory tend to show reduced recruitment of left middle temporal gyrus in response to orthographic input, within a region located at the intersection of default mode, dorsal attention and frontoparietal networks. Voxels within these networks were taken as seeds in a subsequent resting-state study. The default mode network region (i) had greater connectivity with medial prefrontal cortex, falling within the same network, for individuals with better text-based memory, and (ii) was more decoupled from medial visual regions in participants who mind-wandered more frequently. These findings suggest that stronger intrinsic connectivity within the default mode network is linked to better text processing, while reductions in default mode network coupling to the visual system may underpin individual variation in the tendency for our attention to become disengaged from what we are reading.
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http://dx.doi.org/10.1038/s41598-019-52674-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838089PMC
November 2019

Hello, is that me you are looking for? A re-examination of the role of the DMN in social and self relevant aspects of off-task thought.

PLoS One 2019 7;14(11):e0216182. Epub 2019 Nov 7.

Department of Psychology, University of York, York England, United Kingdom.

Neural activity within the default mode network (DMN) is widely assumed to relate to processing during off-task states, however it remains unclear whether this association emerges from a shared role in self or social content that is common in these conditions. In the current study, we examine the possibility that the role of the DMN in ongoing thought emerges from contributions to specific features of off-task experience such as self-relevant or social content. A group of participants described their experiences while performing a laboratory task over a period of days. In a different session, neural activity was measured while participants performed Self/Other judgements (e.g., Does the word 'Honest' apply to you (Self condition) or Barack Obama (Other condition)). Despite the prominence of social and personal content in off-task reports, there was no association with neural activity during off-task trait adjective judgements. Instead, during both Self and Other judgements we found recruitment of caudal posterior cingulate cortex-a core DMN hub-was above baseline for individuals whose laboratory experiences were characterised as detailed. These data provide little support for a role of the DMN in self or other content in the off-task state and instead suggest a role in how on-going thought is represented.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0216182PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6837379PMC
March 2020

An improved neuroanatomical model of the default-mode network reconciles previous neuroimaging and neuropathological findings.

Commun Biol 2019 10;2:370. Epub 2019 Oct 10.

1Brain Connectivity and Behaviour Laboratory, BCBlab, Sorbonne Universities, Paris, France.

The brain is constituted of multiple networks of functionally correlated brain areas, out of which the default-mode network (DMN) is the largest. Most existing research into the DMN has taken a corticocentric approach. Despite its resemblance with the unitary model of the limbic system, the contribution of subcortical structures to the DMN may be underappreciated. Here, we propose a more comprehensive neuroanatomical model of the DMN including subcortical structures such as the basal forebrain, cholinergic nuclei, anterior and mediodorsal thalamic nuclei. Additionally, tractography of diffusion-weighted imaging was employed to explore the structural connectivity, which revealed that the thalamus and basal forebrain are of central importance for the functioning of the DMN. The contribution of these neurochemically diverse brain nuclei reconciles previous neuroimaging with neuropathological findings in diseased brains and offers the potential for identifying a conserved homologue of the DMN in other mammalian species.
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http://dx.doi.org/10.1038/s42003-019-0611-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787009PMC
May 2020

The impact of ischemic stroke on connectivity gradients.

Neuroimage Clin 2019 19;24:101947. Epub 2019 Jul 19.

Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin, Germany; Department of Neurology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Berlin, Germany. Electronic address:

The functional organization of the brain can be represented as a low-dimensional space that reflects its macroscale hierarchy. The dimensions of this space, described as connectivity gradients, capture the similarity of areas' connections along a continuous space. Studying how pathological perturbations with known effects on functional connectivity affect these connectivity gradients provides support for their biological relevance. Previous work has shown that localized lesions cause widespread functional connectivity alterations in structurally intact areas, affecting a network of interconnected regions. By using acute stroke as a model of the effects of focal lesions on the connectome, we apply the connectivity gradient framework to depict how functional reorganization occurs throughout the brain, unrestricted by traditional definitions of functional network boundaries. We define a three-dimensional connectivity space template based on functional connectivity data from healthy controls. By projecting lesion locations into this space, we demonstrate that ischemic strokes result in dimension-specific alterations in functional connectivity over the first week after symptom onset. Specifically, changes in functional connectivity were captured along connectivity Gradients 1 and 3. The degree of functional connectivity change was associated with the distance from the lesion along these connectivity gradients (a measure of functional similarity) regardless of the anatomical distance from the lesion. Together, these results provide support for the biological validity of connectivity gradients and suggest a novel framework to characterize connectivity alterations after stroke.
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http://dx.doi.org/10.1016/j.nicl.2019.101947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6676042PMC
September 2020

Individual variation in patterns of task focused, and detailed, thought are uniquely associated within the architecture of the medial temporal lobe.

Neuroimage 2019 11 23;202:116045. Epub 2019 Jul 23.

Department of Psychology, University of York, England, UK.

Understanding the neural processes that support different patterns of ongoing thought is an important goal of contemporary cognitive neuroscience. Early accounts assumed the default mode network (DMN) was especially important for conscious attention to task-irrelevant/personally relevant materials. However, simple task-negative accounts of the DMN are incompatible with more recent evidence that neural patterns within the system can be related to ongoing processing during active task states. To better characterise the contribution of the DMN to ongoing thought, we conducted a cross-sectional analysis of the relationship between the structural organisation of the brain, as indexed by cortical thickness, and patterns of experience, identified using experience sampling in the cognitive laboratory. In a sample of 181 healthy individuals (mean age 20 years, 117 females) we identified an association between cortical thickness in the anterior parahippocampus and patterns of task focused thought, as well as an adjacent posterior region in which cortical thickness was associated with experiences with higher levels of subjective detail. Both regions fell within regions of medial temporal lobe associated with the DMN, yet varied in their functional connectivity: the time series of signals in the 'on-task' region were more correlated with systems important for external task-relevant processing (as determined by meta-analysis) including the dorsal and ventral attention, and fronto-parietal networks. In contrast, connectivity within the region linked to subjective 'detail' was more correlated with the medial core of the DMN (posterior cingulate and the medial pre-frontal cortex) and regions of primary visual cortex. These results provide cross-sectional evidence that confirms a role of the DMN in how detailed experiences are and so provide further evidence that the role of this system in experience is not simply task-irrelevant. Our results also highlight processes within the medial temporal lobe, and their interactions with other regions of cortex, as important in determining multiple aspects of how human cognition unfolds.
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http://dx.doi.org/10.1016/j.neuroimage.2019.116045DOI Listing
November 2019

10Kin1day: A Bottom-Up Neuroimaging Initiative.

Front Neurol 2019 9;10:425. Epub 2019 May 9.

Department of Psychiatry, Stellenbosch University, Cape Town, South Africa.

We organized 10Kin1day, a pop-up scientific event with the goal to bring together neuroimaging groups from around the world to jointly analyze 10,000+ existing MRI connectivity datasets during a 3-day workshop. In this report, we describe the motivation and principles of 10Kin1day, together with a public release of 8,000+ MRI connectome maps of the human brain.
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http://dx.doi.org/10.3389/fneur.2019.00425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524614PMC
May 2019

Microstructural and functional gradients are increasingly dissociated in transmodal cortices.

PLoS Biol 2019 05 20;17(5):e3000284. Epub 2019 May 20.

McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada.

While the role of cortical microstructure in organising neural function is well established, it remains unclear how structural constraints can give rise to more flexible elements of cognition. While nonhuman primate research has demonstrated a close structure-function correspondence, the relationship between microstructure and function remains poorly understood in humans, in part because of the reliance on post mortem analyses, which cannot be directly related to functional data. To overcome this barrier, we developed a novel approach to model the similarity of microstructural profiles sampled in the direction of cortical columns. Our approach was initially formulated based on an ultra-high-resolution 3D histological reconstruction of an entire human brain and then translated to myelin-sensitive magnetic resonance imaging (MRI) data in a large cohort of healthy adults. This novel method identified a system-level gradient of microstructural differentiation traversing from primary sensory to limbic regions that followed shifts in laminar differentiation and cytoarchitectural complexity. Importantly, while microstructural and functional gradients described a similar hierarchy, they became increasingly dissociated in transmodal default mode and fronto-parietal networks. Meta-analytic decoding of these topographic dissociations highlighted involvement in higher-level aspects of cognition, such as cognitive control and social cognition. Our findings demonstrate a relative decoupling of macroscale functional from microstructural gradients in transmodal regions, which likely contributes to the flexible role these regions play in human cognition.
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http://dx.doi.org/10.1371/journal.pbio.3000284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544318PMC
May 2019

Interindividual Variability of Functional Connectivity in Awake and Anesthetized Rhesus Macaque Monkeys.

Biol Psychiatry Cogn Neurosci Neuroimaging 2019 06 11;4(6):543-553. Epub 2019 Mar 11.

Center for the Developing Brain, Child Mind Institute, New York, New York; Center for Biomedical Imaging and Neuromodulation, Nathan Kline Institute for Psychiatric Research, Orangeburg, New York.

Background: Nonhuman primate (NHP) models are commonly used to advance our understanding of brain function and organization. However, to date, they have offered few insights into individual differences among NHPs. In large part, this is due to the logistical challenges of NHP research, which limit most studies to 5 subjects or fewer.

Methods: We leveraged the availability of a large-scale open NHP imaging resource to provide an initial examination of individual differences in the functional organization of the NHP brain. Specifically, we selected one awake functional magnetic resonance imaging dataset (Newcastle University: n = 10) and two anesthetized functional magnetic resonance imaging datasets (Oxford University: n = 19; University of California, Davis: n = 19) to examine individual differences in functional connectivity characteristics across the cortex as well as potential state dependencies.

Results: We noted significant individual variations of functional connectivity across the macaque cortex. Similar to the findings in humans, during the awake state, the primary sensory and motor cortices showed lower variability than the high-order association regions. This variability pattern was significantly correlated with T1-weighted and T2-weighted mapping and degree of long-distance connectivity, but not short-distance connectivity. The interindividual variability under anesthesia exhibited a very distinct pattern, with lower variability in medial frontal cortex, precuneus, and somatomotor regions and higher variability in the lateral ventral frontal and insular cortices.

Conclusions: This work has implications for our understanding of the evolutionary origins of individual variation in the human brain and methodological implications that must be considered in any pursuit to study individual variation in NHP models.
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http://dx.doi.org/10.1016/j.bpsc.2019.02.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063583PMC
June 2019

Macroscale cortical organization and a default-like apex transmodal network in the marmoset monkey.

Nat Commun 2019 04 29;10(1):1976. Epub 2019 Apr 29.

Centre National de la Recherche Scientifique, CNRS UMR 7225, Institut du Cerveau et de la Moelle épinière, Paris, 75013, France.

Networks of widely distributed regions populate human association cortex. One network, often called the default network, is positioned at the apex of a gradient of sequential networks that radiate outward from primary cortex. Here, extensive anatomical data made available through the Marmoset Brain Architecture Project are explored to show a homologue exists in marmoset. Results reveal that a gradient of networks extend outward from primary cortex to progressively higher-order transmodal association cortex in both frontal and temporal cortex. The apex transmodal network comprises frontopolar and rostral temporal association cortex, parahippocampal areas TH / TF, the ventral posterior midline, and lateral parietal association cortex. The positioning of this network in the gradient and its composition of areas make it a candidate homologue to the human default network. That the marmoset, a physiologically- and genetically-accessible primate, might possess a default-network-like candidate creates opportunities for study of higher cognitive and social functions.
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http://dx.doi.org/10.1038/s41467-019-09812-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488644PMC
April 2019

The architecture of mammalian cortical connectomes in light of the theory of the dual origin of the cerebral cortex.

Cortex 2019 09 13;118:244-261. Epub 2019 Mar 13.

Institute of Computational Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg University, Hamburg, Germany; Department of Health Sciences, Boston University, Boston, MA, USA.

Uncovering organizational principles of the cerebral cortex is essential for proper understanding of this prominent structure of the mammalian brain. The theory of the dual origin of the cerebral cortex offers such organizational principle. Here, we demonstrate that a duality pertains to the connectional architecture of the cerebral cortex of different mammals. This dual structure also constitutes a major axis of organization of the transcriptional architecture of the cortex and reflects the expression of different morphogens stemming from distinct patterning centers in the developing pallium. The duality of the cortex is also reflected in its spatial dimension, highlighting cortical areas as spatially ordered constellations that are centered around the paleocortex and archicortex, with the later primordial moieties reminiscent of antipodal points in the cortical sheet. The ontogeny of the uncovered dual connectional structure might be rooted in heterochronous neurodevelopmental gradients in the developing pallium, a suggestion corroborated by computational modeling. In all, the current results exemplify the duality of the cerebral cortex as an overarching organizational principle, reflected across the different levels of cortical architecture of different mammalian species, defining a natural axis of mammalian cortical organization.
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http://dx.doi.org/10.1016/j.cortex.2019.03.002DOI Listing
September 2019