ORCID Profile
0000-0002-7298-2459
Current Organisations
University of York
,
Queen's University
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Publications
Cortical microstructural gradients capture memory network reorganization in temporal lobe epilepsy
Publisher: Cold Spring Harbor Laboratory
Date: 11-2022
DOI: 10.1101/2022.10.31.513891
Abstract: Temporal lobe epilepsy (TLE), one of the most common pharmaco-resistant epilepsies, is associated with pathology of paralimbic brain regions, particularly in the mesiotemporal lobe. Cognitive dysfunction in TLE is frequent, and particularly affects episodic memory. Crucially, these difficulties challenge the quality of life of patients, sometimes more than seizures, underscoring the need to assess neural processes of cognitive dysfunction in TLE to improve patient management. Our work harnessed a novel conceptual and analytical approach to assess spatial gradients of microstructural differentiation between cortical areas based on high-resolution MRI analysis. Gradients track region-to-region variations in intracortical lamination and myeloarchitecture, serving as a system-level measure of structural and functional reorganization. Comparing cortex-wide microstructural gradients between 21 patients and 35 healthy controls, we observed a contracted gradient in TLE driven by reduced microstructural differentiation between paralimbic cortices and the remaining cortex with marked abnormalities in ipsilateral temporopolar and dorsolateral prefrontal regions. Findings were replicated in an independent cohort. Using an independent post mortem dataset, we observed that in vivo findings reflected topographical variations in cortical lamination patterns, confirming that TLE-related changes in the microstructural gradient reflected increased proximity of regions with more dissimilar laminar structure. Disease-related transcriptomics could furthermore show specificity of our findings to TLE over other common epilepsy syndromes. Finally, microstructural dedifferentiation was associated with cognitive network reorganization seen during an episodic memory functional MRI paradigm, and correlated with inter-in idual differences in task accuracy. Collectively, our findings showing a pattern of reduced microarchitectural differentiation between paralimbic regions and the remaining cortex provide a parsimonious explanation for functional network reorganization and cognitive dysfunction characteristic of TLE.
Differences in subcortico-cortical interactions identified from connectome and microcircuit models in autism
Publisher: Springer Science and Business Media LLC
Date: 13-04-2021
DOI: 10.1038/S41467-021-21732-0
Abstract: The pathophysiology of autism has been suggested to involve a combination of both macroscale connectome miswiring and microcircuit anomalies. Here, we combine connectome-wide manifold learning with biophysical simulation models to understand associations between global network perturbations and microcircuit dysfunctions in autism. We studied neuroimaging and phenotypic data in 47 in iduals with autism and 37 typically developing controls obtained from the Autism Brain Imaging Data Exchange initiative. Our analysis establishes significant differences in structural connectome organization in in iduals with autism relative to controls, with strong between-group effects in low-level somatosensory regions and moderate effects in high-level association cortices. Computational models reveal that the degree of macroscale anomalies is related to atypical increases of recurrent excitation/inhibition, as well as subcortical inputs into cortical microcircuits, especially in sensory and motor areas. Transcriptomic association analysis based on postmortem datasets identifies genes expressed in cortical and thalamic areas from childhood to young adulthood. Finally, supervised machine learning finds that the macroscale perturbations are associated with symptom severity scores on the Autism Diagnostic Observation Schedule. Together, our analyses suggest that atypical subcortico-cortical interactions are associated with both microcircuit and macroscale connectome differences in autism.
Genetic and phylogenetic uncoupling of structure and function in human transmodal cortex
Publisher: Cold Spring Harbor Laboratory
Date: 09-06-2021
DOI: 10.1101/2021.06.08.447522
Abstract: Brain structure scaffolds intrinsic function, supporting cognition and ultimately behavioral flexibility. However, it remains unclear how a static, genetically controlled architecture supports flexible cognition and behavior. Here, we synthesize genetic, phylogenetic and cognitive analyses to understand how the macroscale organization of structure-function coupling across the cortex can inform its role in cognition. In humans, structure-function coupling was highest in regions of unimodal cortex and lowest in transmodal cortex, a pattern that was mirrored by a reduced alignment with heritable connectivity profiles. Structure-function uncoupling in non-human primates had a similar spatial distribution, but we observed an increased coupling between structure and function in association regions in macaques relative to humans. Meta-analysis suggested regions with the least genetic control (low heritable correspondence and different across primates) are linked to social cognition and autobiographical memory. Our findings establish the genetic and evolutionary uncoupling of structure and function in different transmodal systems may support the emergence of complex, culturally embedded forms of cognition.
Down but not out in posterior cingulate cortex: Deactivation yet functional coupling with prefrontal cortex during demanding semantic cognition
Publisher: Elsevier BV
Date: 11-2016
Meta-awareness, perceptual decoupling and the wandering mind
Publisher: Elsevier BV
Date: 06-2011
DOI: 10.1016/J.TICS.2011.05.006
Abstract: Mind wandering (i.e. engaging in cognitions unrelated to the current demands of the external environment) reflects the cyclic activity of two core processes: the capacity to disengage attention from perception (known as perceptual decoupling) and the ability to take explicit note of the current contents of consciousness (known as meta-awareness). Research on perceptual decoupling demonstrates that mental events that arise without any external precedent (known as stimulus independent thoughts) often interfere with the online processing of sensory information. Findings regarding meta-awareness reveal that the mind is only intermittently aware of engaging in mind wandering. These basic aspects of mind wandering are considered with respect to the activity of the default network, the role of executive processes, the contributions of meta-awareness and the functionality of mind wandering.
The role of mind-wandering in measurements of general aptitude.
Publisher: American Psychological Association (APA)
Date: 11-2012
DOI: 10.1037/A0027968
Abstract: Tests of working memory capacity (WMC) and fluid intelligence (gF) are thought to capture variability in a crucial cognitive capacity that is broadly predictive of success, yet pinpointing the exact nature of this capacity is an area of ongoing controversy. We propose that mind-wandering is associated with performance on tests of WMC and gF, thereby partially explaining both the reliable correlations between these tests and their broad predictive utility. Existing evidence indicates that both WMC and gF are correlated with performance on tasks of attention, yet more decisive evidence requires an assessment of the role of attention and, in particular, mind-wandering during performance of these tests. Four studies employing complementary methodological designs embedded thought s ling into tests of general aptitude and determined that mind-wandering was consistently associated with worse performance on these measures. Collectively, these studies implicate the capacity to avoid mind-wandering during demanding tasks as a potentially important source of success on measures of general aptitude, while also raising important questions about whether the previously documented relationship between WMC and mind-wandering can be exclusively attributed to executive failures preceding mind-wandering (McVay & Kane, 2010b).
Shifting moods, wandering minds: Negative moods lead the mind to wander.
Publisher: American Psychological Association (APA)
Date: 04-2009
DOI: 10.1037/A0014855
Abstract: This study examined the effect of mood states on mind wandering. Positive, neutral, and negative moods were induced in participants prior to them completing a sustained attention task. Mind wandering was measured by using the frequencies of both behavioral lapses and retrospective indices of subjective experience. Relative to a positive mood, induction of a negative mood led participants to make more lapses, report a greater frequency of task irrelevant thoughts, and become less inclined to reengage attentional resources following a lapse. Positive mood, by contrast, was associated with a better ability to adjust performance after a lapse. These results provide further support for the notion that a negative mood reduces the amount of attentional commitment to the task in hand and may do so by enhancing the focus on task irrelevant personal concerns.
An Open MRI Dataset for Multiscale Neuroscience
Publisher: Cold Spring Harbor Laboratory
Date: 05-08-2021
DOI: 10.1101/2021.08.04.454795
Abstract: Multimodal neuroimaging grants a powerful window into the structure and function of the human brain at multiple scales. Recent methodological and conceptual advances have enabled investigations of the interplay between large-scale spatial trends (also referred to as gradients) in brain microstructure and connectivity, offering an integrative framework to study multiscale brain organization. Here, we share a multimodal MRI dataset for Microstructure-Informed Connectomics (MICA-MICs) acquired in 50 healthy adults (23 women 29.54±5.62 years) who underwent high-resolution T1-weighted MRI, myelin-sensitive quantitative T1 relaxometry, diffusion-weighted MRI, and resting-state functional MRI at 3 Tesla. In addition to raw anonymized MRI data, this release includes brain-wide connectomes derived from i) resting-state functional imaging, ii) diffusion tractography, iii) microstructure covariance analysis, and iv) geodesic cortical distance, gathered across multiple parcellation scales. Alongside, we share large-scale gradients estimated from each modality and parcellation scale. Our dataset will facilitate future research examining the coupling between brain microstructure, connectivity, and macroscale function. MICA-MICs is available on the Canadian Open Neuroscience Platform’s data portal ( portal.conp.ca ).
Related Organisations
University Of California Santa Barbara
Location: United States of America
University Of Strathclyde
Location: United Kingdom of Great Britain and Northern Ireland
University Of York
Location: United Kingdom of Great Britain and Northern Ireland
University Of Aberdeen
Location: United Kingdom of Great Britain and Northern Ireland
Glasgow Caledonian University
Location: United Kingdom of Great Britain and Northern Ireland
Related Funding Activities
No related grants have been discovered for Jonathan Smallwood.