Biology subjects

McIntosh, A. R.

Publications and source records attributed to McIntosh, A. R..

8 recordsLinked to original sources

bioRxiv2018

Exploring the limits of network topology estimation using diffusion-based tractography and tracer studies in the macaque cortex

Reconstructing the anatomical pathways of the brain to study the human connectome has become an important endeavour for understanding brain function and dynamics. Reconstruction of the cortico-cortical connectivity matrix in vivo often relies on noninvasive diffusion-weighted imaging (DWI) techniques but the extent to which they can accurately represent the topological characteristics of structural connectomes remains unknown. We explored this question by constructing connectomes using DWI data collected from macaque monkeys in vivo and with data from published invasive tracer studies. We found the strength of fiber tracts was well estimated from DWI and topological properties like degree and modularity were captured by tractography-based connectomes. Rich-club/core-periphery type architecture could also be detected but the classification of hubs using betweenness centrality, participation coefficient and core-periphery identification techniques was inaccurate. Our findings indicate that certain aspects of cortical topology can be faithfully represented in noninvasively-obtained connectomes while other network analytic measures warrant cautionary interpretations.

neuroscience↗

bioRxiv2018

Mechanisms of trophic niche compression: evidence from landscape disturbance

O_LINatural and anthropogenic disturbances commonly alter patterns of biodiversity and ecosystem functioning. However, how food webs respond to these changes remains poorly understood. Here, we have described aquatic food webs using invertebrate and fish community composition, functional traits, and stable isotopes from twelve agricultural streams along a landscape disturbance gradient.\nC_LIO_LIWe predicted that excessive inputs of fine inorganic sediment (sedimentation) associated with agricultural land uses would negatively influence stream trophic diversity (e.g., reduced vertical and horizontal trophic niche breadths).\nC_LIO_LIFood-web properties based on Bayesian analyses of stable isotope data ({delta}13C and {delta}15N) from consumers showed that increasing sediment disturbance was associated with reduced trophic diversity, indicated by the whole community (fish and invertebrates combined) occupying a smaller area in isotopic niche space. Reductions in trophic diversity were best explained by a narrowing of the consumer {delta}13C range, and to a lesser extent, consumer {delta}15N range along the sedimentation gradient.\nC_LIO_LIWe hypothesized that multiple mechanisms associated with sedimentation may have caused trophic niche compression. Decreased niche partitioning, driven by increasing habitat homogeneity, environmental filtering, and resource scarcity seemingly lead to a greater similarity in trophic roles. These pathways may have contributed to a reduction in trophic diversity, whereas increased resource homogeneity was seemingly less important.\nC_LIO_LIOur results also indicate downward shifts in the vertical trophic position of benthic meospredators and invertebrate prey relative to higher consumers. This trophic decoupling suggests that terrestrial resource subsidies may offset reductions of aquatic prey for larger stream fishes.\nC_LIO_LISedimentation was associated with reduced trophic diversity, which may affect the functioning and stability of stream ecosystems. Our study helps explain how multiple mechanisms can influence food-web properties in response to this type of disturbance.\nC_LI

ecology↗

bioRxiv2018

Unique mapping of structural and functional connectivity on cognition

The unique mapping of structural and functional brain connectivity (SC, FC) on cognition is currently not well understood. It is not clear whether cognition is mapped via a global connectome pattern or instead is underpinned by several sets of distributed connectivity patterns. Moreover, we also do not know whether the pattern of SC and of FC that underlie cognition are overlapping or distinct. Here, we study the relationship between SC and FC and an array of psychological tasks in 609 subjects from the Human Connectome Project (HCP). We identified several sets of connections that each uniquely map onto different aspects of cognitive function. We found a small number of distributed SC and a larger set of cortico-cortical and cortico-subcortical FC that express this association. Importantly, SC and FC each show unique and distinct patterns of variance across subjects and differential relationships to cognition. The results suggest that a complete understanding of connectome underpinnings of cognition calls for a combination of the two modalities.\n\nSignificance StatementStructural connectivity (SC), the physical white-matter inter-regional pathways in the brain, and functional connectivity (FC), the temporal co-activations between activity of brain regions, have each been studied extensively. Little is known, however, about the distribution of variance in connections as they relate to cognition. Here, in a large sample of subjects (N = 609), we showed that two sets of brain-behavioural patterns capture the correlations between SC, and FC with a wide range of cognitive tasks, respectively. These brain-behavioural patterns reveal distinct sets of connections within the SC and the FC network and provide new evidence that SC and FC each provide unique information for cognition.

neuroscience↗

bioRxiv2018

Differentiation of Alzheimer’s disease based on local and global parameters in personalized Virtual Brain models

Alzheimers disease (AD) is marked by cognitive dysfunction emerging from neuropathological processes impacting brain function. AD affects brain dynamics at the local level, such as changes in the balance of inhibitory and excitatory neuronal populations, as well as long-range changes to the global network. Individual differences in these changes as they relate to behaviour are poorly understood. Here, we use a multi-scale neurophysiological model, \"The Virtual Brain (TVB)\", based on empirical multi-modal neuroimaging data, to study how local and global dynamics correlate with individual differences in cognition. In particular, we modeled individual resting-state functional activity of 124 individuals across the behavioral spectrum from healthy aging, to amnesic Mild Cognitive Impairment (MCI), to AD. The model parameters required to accurately simulate empirical functional brain imaging data correlated significantly with cognition, and exceeded the predictive capacity of empirical connectomes.

neuroscience↗

bioRxiv2017

Defining subtypes of autism spectrum disorder using static and dynamic functional connectivity

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder, characterized by impairments in social communication and restricted, repetitive behaviours. Neuroimaging studies have shown complex patterns of functional connectivity (FC) in ASD, with no clear consensus on brain-behaviour relationships or shared patterns of FC with typically developing controls. Here, we used k-means clustering and multivariate statistical analyses to characterize distinct FC patterns and FC-behaviour relationships in participants with and without ASD. Two FC subtypes were identified by the clustering analysis. One subtype was defined by increased FC within resting-state networks and decreased FC across networks compared to the other subtype. A separate FC pattern distinguished ASD from controls, particularly within default mode, cingulo-opercular, sensorimotor, and occipital networks. There was no significant interaction between subtypes and diagnostic groups. Finally, analysis of FC patterns with behavioural measures of IQ, social responsiveness and ASD severity showed unique brain-behaviour relations in each subtype, and a continuum of brain-behavior relations from ASD to controls within one subtype. These results demonstrate that distinct clusters of FC patterns exist in both ASD and controls, and that FC subtypes can reveal unique information about brain-behaviour relationships.\n\nAuthor SummaryAutism spectrum disorder (ASD) is a neurodevelopmental disorder, with high variation in the types of severity of impairments in social communication and restricted, repetitive behaviours. Neuroimaging studies have shown complex patterns of communication between brain regions, or functional connectivity (FC), in ASD. Here, we defined two distinct FC patterns and relationships between FC and behaviour in participants with and without ASD. One subtype was defined by increased FC within distinct networks of brain regions, and decreased FC between networks compared to the other subtype. A separate FC pattern distinguished ASD from controls. The interaction between subtypes and diagnostic groups was not significant. Analysis of FC patterns with behavioural measures revealed unique information about brain-behaviour relations in each subtype.

neuroscience↗

bioRxiv2017

Inferring multi-scale neural mechanisms with brain network modelling

The neurophysiological processes underlying non-invasive brain activity measurements are not well understood. Here, we developed a novel connectome-based brain network model that integrates individual structural and functional data with neural population dynamics to support multi-scale neurophysiological inference. Simulated populations were linked by structural connectivity and, as a novelty, driven by electroencephalography (EEG) source activity. Simulations not only predicted subjects individual resting-state functional magnetic resonance imaging (fMRI) time series and spatial network topologies over 20 minutes of activity, but more importantly, they also revealed precise neurophysiological mechanisms that underlie and link six empirical observations from different scales and modalities: (1) slow resting-state fMRI oscillations, (2) spatial topologies of functional connectivity networks, (3) excitation-inhibition balance, (4, 5) pulsed inhibition on short and long time scales, and (6) fMRI power-law scaling. These findings underscore the potential of this new modelling framework for general inference and integration of neurophysiological knowledge to complement empirical studies.

bioinformatics↗

bioRxiv2017

Functional Connectivity Dynamics of the Resting State across the Human Adult Lifespan

Functional Connectivity (FC) during resting-state or task conditions is not fixed but inherently dynamic. Yet, there is no consensus on whether fluctuations in FC may resemble isolated transitions between discrete FC states rather than continuous changes. This quarrel hampers advancing the study of dynamic FC. This is unfortunate as the structure of fluctuations in FC can certainly provide more information about developmental changes, aging, and progression of pathologies. We merge the two perspectives and consider dynamic FC as an ongoing network reconfiguration, including a stochastic exploration of the space of possible steady FC states. The statistical properties of this random walk deviate both from a purely "order-driven" dynamics, in which the mean FC is preserved, and from a purely "randomness-driven" scenario, in which fluctuations of FC remain uncorrelated over time. Instead, dynamic FC has a complex structure endowed with long-range sequential correlations that give rise to transient slowing and acceleration epochs in the continuous flow of reconfiguration. Our analysis for fMRI data in healthy elderly revealed that dynamic FC tends to slow down and becomes less complex as well as more random with increasing age. These effects appear to be strongly associated with age-related changes in behavioural and cognitive performance. HighlightsO_LIDynamic Functional Connectivity (dFC) at rest and during cognitive task performs a "complex" (anomalous) random walk. C_LIO_LISpeed of dFC slows down with aging. C_LIO_LIResting dFC replaces complexity by randomness with aging. C_LIO_LITask performance correlates with the speed and complexity of dFC. C_LI

neuroscience↗

bioRxiv2016

Bridging multiple scales in the human brain using computational modelling

Brain dynamics span multiple spatial and temporal scales, from fast spiking neurons to slow fluctuations over distributed areas. No single experimental method links data across scales. Here, we bridge this gap using The Virtual Brain connectome-based modelling platform to integrate multimodal data with biophysical models and support neurophysiological inference. Simulated cell populations were linked with subject-specific white-matter connectivity estimates and driven by electroencephalography-derived electric source activity. The models were fit to subject-specific resting-state functional magnetic resonance imaging data, and overfitting was excluded using 5-fold cross-validation. Further evaluation of the models show how balancing excitation with feedback inhibition generates an inverse relationship between -rhythms and population firing on a faster time scale and resting-state network oscillations on a slower time scale. Lastly, large-scale interactions in the model lead to the emergence of scale-free power-law spectra. Our novel findings underscore the integrative role for computational modelling to complement empirical studies.

neuroscience↗