Biology subjects

Margulies, D. S.

Publications and source records attributed to Margulies, D. S..

52 records · Page 3Linked to original sources

bioRxiv2019

Distinct patterns of thought mediate the link between brain functional connectome and psychological well-being

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 (n = 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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bioRxiv2019

A moment of change: shifts in myeloarchitecture characterise adolescent development of cortical gradients

The biological processes underpinning adolescent brain maturation remain elusive. Expanding on previous work showing age-related changes in cortical morphology, we studied an accelerated longitudinal cohort of adolescents and young adults (n=223, 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) related to overall increases in MT, and ii) showing a 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, and enhanced MT in mid-to-deeper layers was found to spatially co-localise specifically with gene expression markers of oligodendrocytes. Covariance analysis between all pairs of intracortical profiles revealed that these intracortical changes contributed to a gradual and dynamic differentiation from higher-order to 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 organization.\n\neLife digestIntracortical myelin imposes a spatial structure on cortico-cortical connections, yet little is known about how myeloarchitecture develops throughout youth. We formulated a novel approach to study cortical myeloarchitecture in individual humans and leveraged an accelerated longitudinal design to track age-related changes from 14-27 years. We discovered two unique processes: one involving increasing mean myelin and another characterised by the preferential accumulation of myelin in mid-to-deeper cortical layers. Both processes contributed to an increasing segregation of lower-order from higher-order systems along the macroscale cortical hierarchy. These findings illustrate how layer specific microstructural changes contribute to the maturation of cortical organization and suggest adolescent fine tuning of hierarchical gradients of cortical networks.

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bioRxiv2019

Hemispheric asymmetries in resting-state EEG and fMRI are related to approach and avoidance behaviour, but not to eating behaviour or BMI

Much of our behaviour is driven by two motivational dimensions - approach and avoidance. These have been related to frontal hemispheric asymmetries in clinical and resting-state EEG studies: approach was linked to higher activity of the left relative to the right hemisphere, while avoidance was related to the opposite pattern. Increased approach behaviour, specifically towards unhealthy foods, is also observed in obesity and has been linked to asymmetry in the framework of the right-brain hypothesis of obesity. Here, we aimed to replicate previous EEG findings of hemispheric asymmetries for self-reported approach/avoidance behaviour and to relate them to eating behaviour. Further, we assessed whether resting fMRI hemispheric asymmetries can be detected and whether they are related to approach/avoidance, eating behaviour, and BMI. We analysed 3 samples: Sample 1 (n=117) containing EEG and fMRI data from lean participants, and Samples 2 (n=89) and 3 (n=152) containing fMRI data from lean, overweight, and obese participants. While in Sample 1 approach in women was related to EEG and fMRI hemispheric asymmetries, in Samples 2 and 3 this effect was not significant. Here, hemispheric asymmetries were neither related to BMI nor eating behaviour. Our study partly replicates previous EEG findings regarding hemispheric asymmetries and indicates that this relationship could also be captured using fMRI. Our findings suggest that eating behaviour and obesity are likely to be mediated by mechanisms not directly relating to frontal asymmetries in neuronal activation quantified with EEG and fMRI.

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bioRxiv2019

Cross-species Functional Alignment Reveals Evolutionary Hierarchy Within the Connectome

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 demonstrate a function-based method for cross-species cortical alignment that leverages recent advances in understanding cortical organization and that enables the quantification of homologous regions across species, even when their location is decoupled from anatomical landmarks. Critically, our method establishes that cross-species similarity in cortical organization decreases with geodesic distance from unimodal systems, and culminates in the most pronounced changes in posterior regions of the default network (angular gyrus, posterior cingulate and middle temporal cortices). Our findings suggest that the establishment of the default network, as the apex of a cognitive hierarchy, as is seen in humans, is a relatively recent evolutionary adaptation. They also highlight functional changes in regions such as the posterior cingulate cortex and angular gyrus as key influences on uniquely human features of cognition.

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bioRxiv2019

Hello, is that me you are looking for? A re-examination of the role of the DMN in off-task thought

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 cognition. 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. 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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bioRxiv2019

Inter-individual Variability of Functional Connectivity in Awake and Anesthetized Rhesus Monkeys

BackgroundNonhuman primate models (NHP) 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 five subjects or fewer. MethodsWe 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 nonhuman primate brain. Specifically, we selected one awake fMRI dataset (Newcastle: n = 10) and two anesthetized fMRI data sets (Oxford: n = 19; UC-Davis: n = 19) to examine individual differences in functional connectivity characteristics across the cortex, as well as potential state dependencies. ResultsWe noted significant individual variations of functional connectivity across the macaque cortex. Similar to the findings in human, 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 T1w/T2w map, the degree of long-distance connectivity, but not short-distance connectivity. However, the inter-individual 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. ConclusionsThis work has implications for our understanding of the evolutionary origins of individual variation in the human brain, as well as methodological implications that must be considered in any pursuit to study individual variation in NHP models.

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bioRxiv2019

Subcortical Anatomy of the Default Mode Network: a functional and structural connectivity study

Most existing research into the default-mode network (DMN) has taken a corticocentric approach. Despite the resemblance of the DMN with the unitary model of the limbic system, the anatomy and contribution of subcortical structures to the network may be underappreciated due to methods limitation. Here, we propose a new and more comprehensive neuroanatomical model of the DMN including the basal forebrain and anterior and mediodorsal thalamic nuclei and cholinergic nuclei. This has been achieved by considering functional territories during interindividual brain alignment. Additionally, tractography of diffusion-weighted imaging was employed to explore the structural connectivity of the DMN and revealed that the thalamus and basal forebrain had high importance in term of values of node degree and centrality in the network. The contribution of these neurochemically diverse brain nuclei reconciles previous neuroimaging with neuropathological findings in diseased brain and offers the potential for identifying a conserved homologue of the DMN in other mammalian species.

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bioRxiv2018

The impact of ischemic stroke on connectivity gradients

Understanding the relationship between localized anatomical damage, reorganization, and functional deficits is a major challenge in stroke research. Previous work has shown that localized lesions cause widespread functional connectivity alterations in structurally intact areas, thereby affecting a whole network of interconnected regions. Recent advances suggest an alternative to discrete functional networks by describing a connectivity space based on a low-dimensional embedding of the full connectivity matrix. The dimensions of this space, described as connectivity gradients, capture the similarity of areas connections along a continuous space. Here, we defined 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 resulted in dimension-specific alterations in functional connectivity over the first week after symptoms onset. Specifically, changes in functional connectivity were captured along connectivity Gradients 1 and 3. The degree of change in functional connectivity was determined by the distance from the lesion along these connectivity gradients regardless of the anatomical distance from the lesion. Together, these results provide a novel framework to study reorganization after stroke and suggest that, rather than only impacting on anatomically proximate areas, the indirect effects of ischemic strokes spread along the brain relative to the space defined by its connectivity.

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bioRxiv2018

Gradients of connectivity distance in the cerebral cortex of the macaque monkey

Cortical connectivity conforms to a series of organizing principles that are common across species. Spatial proximity, similar cortical type, and similar connectional profile all constitute factors for determining the connectivity between cortical regions. We previously demonstrated another principle of connectivity that is closely related to the spatial layout of the cerebral cortex. Using functional connectivity from resting-state fMRI in the human cortex, we found that the further a region is located from primary cortex, the more distant are its functional connections with other areas of the cortex. However, it remains unknown whether this relationship between cortical layout and connectivity extends to other primate species. Here, we investigated this relationship using both resting-state functional connectivity as well as gold-standard tract-tracing connectivity in the macaque monkey cortex. For both measures of connectivity, we found a gradient of connectivity distance extending between primary and frontoparietal regions. As in the human cortex, the further a region is located from primary areas, the stronger its connections to distant portions of the cortex, with connectivity distance highest in frontal and parietal regions. The similarity between the human and macaque findings provide evidence for a phylogenetically conserved relationship between the spatial layout of cortical areas and connectivity.

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bioRxiv2018

Neural dynamics at rest associated with patterns of ongoing thought

Conscious experience is dynamic, and its fluidity is particularly marked when attention is not occupied by events in the external world and our minds are free to wander. Our study used measures of neural function, and advanced analyses techniques to examine how unconstrained neural state transitions relate to patterns of ongoing experience. Neural activity was recorded during wakeful rest using functional magnetic resonance imaging and Hidden Markov modelling identified recurrent patterns of brain activity constituting functional dynamic brain states. Individuals making more frequent transitions between states subsequently described experiences highlighting problem solving and lacking unpleasant intrusive features. Frequent switching between states also predicted better health and well-being as assessed by questionnaire. These data provide evidence that the fluidity with which individuals shift through dynamic neural states has an impact on the nature of ongoing thought, and suggest that greater flexibility at rest is an important indicator of a healthy mind.

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bioRxiv2018

Macroscale Cortical Organization and a Default-Like Transmodal Apex Network in the Marmoset Monkey

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 were explored to determine if a homologue exists in marmoset. Results revealed that a gradient of networks extend outward from primary cortex to progressively higher-order transmodal association cortex in both frontal and temporal cortex. The transmodal apex 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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bioRxiv2018

Individual differences in reading comprehension and off-task thought relate to perceptually-coupled and decoupled cognition

Although the default mode network (DMN) is associated with off-task states, recent evidence shows it can support tasks. This raises the question of how DMN activity can be both beneficial and detrimental to task performance. The decoupling hypothesis proposes that these opposing states occur because DMN supports modes of cognition driven by external input, as well as retrieval states unrelated to input. To test this account, we capitalised on the fact that during reading, regions in DMN are thought to represent the meaning of words through their coupling with visual cortex; the absence of visual coupling should occur when the attention drifts off from the text. We examined individual differences in reading comprehension and off-task thought while participants read an expository text in the laboratory, and related variation in these measures to (i) the neural response during reading in the scanner (Experiment 1), and (ii) patterns of intrinsic connectivity measured in the absence of a task (Experiment 2). The responsiveness of a region of DMN in middle temporal gyrus (MTG) to orthographic inputs during reading predicted good comprehension, while intrinsic decoupling of the same site from visual cortex at rest predicted more frequent off-task thought. In addition, good comprehension was associated with greater intrinsic connectivity between MTG and medial prefrontal regions also within DMN, demonstrating that DMN coupling can support task performance, not only off-task states. These findings indicate that the opposing roles of DMN in cognition reflect its capacity to support both perceptually-coupled and decoupled cognition.

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bioRxiv2017

Association of Peripheral Blood Pressure with Grey Matter Volume in 19- to 40-Year-Old Adults

ObjectiveTo test whether elevated blood pressure (BP) relates to grey matter volume (GMV) changes in young adults who had not previously been diagnosed as hypertensive (systolic BP (SBP)/diastolic BP (DBP)[≥]140/90 mmHg).\n\nMethodsWe associated BP with GMV from structural 3 Tesla T1-weighted MRI of 423 healthy adults between 19-40 years (mean age=27.7{+/-}5.3 years, 177 women, SBP/DBP=123.2/73.4{+/-}12.2/8.5 mmHg). Data originated from four previously unpublished cross-sectional studies conducted in Leipzig, Germany. We performed voxel-based morphometry on each study separately and combined results in image-based meta-analyses (IBMA) to assess cumulative effects across studies. Resting BP was assigned to one of four categories: (1) SBP<120 and DBP<80 mmHg, (2) SBP 120-129 or DBP 80-84 mmHg, (3) SBP 130-139 or DBP 85-89 mmHg, (4) SBP[≥]140 or DBP[≥]90 mmHg.\n\nResultsIBMA yielded: (a) lower regional GMV was correlated with higher peripheral BP; (b) lower GMV with higher BP when comparing individuals in sub-hypertensive categories 3 and 2, respectively, to those in category 1; (c) lower BP-related GMV was found in regions including hippocampus, amygdala, thalamus, frontal and parietal structures (e.g. precuneus).\n\nConclusionsBP[≥]120/80 mmHg was associated with lower GMV in regions that have previously been related to GM decline in older individuals with manifest hypertension. Our study shows that BP-associated GM alterations emerge continuously across the range of BP and earlier in adulthood than previously assumed. This suggests that treating hypertension or maintaining lower BP in early adulthood might be essential for preventing the pathophysiological cascade of asymptomatic cerebrovascular disease to symptomatic end-organ damage, such as stroke or dementia.

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bioRxiv2017

An open resource for nonhuman primate imaging

Non-human primate neuroimaging is a rapidly growing area of research that promises to transform and scale translational and cross-species comparative neuroscience.\n\nUnfortunately, the technological and methodological advances of the past two decades have outpaced the accrual of data, which is particularly challenging given the relatively few centers that have the necessary facilities and capabilities. The PRIMate Data Exchange (PRIME-DE) addresses this challenge by aggregating independently acquired non-human primate magnetic resonance imaging (MRI) datasets and openly sharing them via the International Neuroimaging Data-sharing Initiative (INDI). Here, we present the rationale, design and procedures for the PRIME-DE consortium, as well as the initial release, consisting of 13 independent data collections aggregated across 11 sites (total = 98 macaque monkeys). We also outline the unique pitfalls and challenges that should be considered in the analysis of the non-human primate MRI datasets, including providing automated quality assessment of the contributed datasets.

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bioRxiv2017

A functional connectome phenotyping dataset including cognitive state and personality measures

The dataset enables exploration of higher-order cognitive faculties, self-generated mental experience, and personality features in relation to the intrinsic functional architecture of the brain. We provide multimodal magnetic resonance imaging (MRI) data and a broad set of state and trait phenotypic assessments: mind-wandering, personality traits, and cognitive abilities. Specifically, 194 healthy participants (between 20 and 75 years of age) filled out 31 questionnaires, performed 7 tasks, and reported 4 probes of in-scanner mind-wandering. The scanning session included four 15.5-min resting-state functional MRI runs using a multiband EPI sequence and a high-resolution structural scan using a 3D MP2RAGE sequence. This dataset constitutes one part of the MPI-Leipzig Mind-Brain-Body database.

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bioRxiv2016

Predicting brain-age from multimodal imaging data captures cognitive impairment

The disparity between the chronological age of an individual and their brain-age measured based on biological information has the potential to offer clinically-relevant biomarkers of neurological syndromes that emerge late in the lifespan. While prior brain-age prediction studies have relied exclusively on either structural or functional brain data, here we investigate how multimodal brainimaging data improves age prediction. Using cortical anatomy and whole-brain functional connectivity on a large adult lifespan sample (N = 2354, age 19-82), we found that multimodal data improves brain-based age prediction, resulting in a mean absolute prediction error of 4.29 years. Furthermore, we found that the discrepancy between predicted age and chronological age captures cognitive impairment. Importantly, the brain-age measure was robust to confounding effects: head motion did not drive brain-based age prediction and our models generalized reasonably to an independent dataset acquired at a different site (N = 475). Generalization performance was increased by training models on a larger and more heterogeneous dataset. The robustness of multimodal brain-age prediction to confounds, generalizability across sites, and sensitivity to clinically-relevant impairments, suggests promising future application to the early prediction of neurocognitive disorders.\n\nHighlightsO_LIBrain-based age prediction is improved with multimodal neuroimaging data.\nC_LIO_LIParticipants with cognitive impairment show increased brain aging.\nC_LIO_LIAge prediction models are robust to motion and generalize to independent datasets from other sites.\nC_LI

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