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Perry, A.

Publications and source records attributed to Perry, A..

4 recordsLinked to original sources
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

Fronto-limbic dysconnectivity leads to impaired brain network controllability in young people with bipolar disorder and those at high genetic risk

Recent investigations have used diffusion-weighted imaging to reveal disturbances in the neurocircuitry that underlie cognitive-emotional control in bipolar disorder (BD) and in unaffected siblings or children at high genetic risk (HR). It has been difficult to quantify the mechanism by which structural changes disrupt the superimposed brain dynamics, leading to the emotional lability that is characteristic of BD. Average controllability is a concept from network control theory that extends structural connectivity data to estimate the manner in which local neuronal fluctuations spread from a node or subnetwork to alter the state of the rest of the brain. We used this theory to ask whether structural connectivity deficits previously observed in HR (n=84, mean age 22.4) individuals, patients with BD (n=38, mean age 23.9), and age- and gender-matched controls (n=96, mean age 22.6) translate to differences in the ability of brain systems to be manipulated between states. Localized impairments in network controllability were seen in the left parahippocampal, left middle occipital, left superior frontal, right inferior frontal, and right precentral gyri in BD and HR groups. Subjects with BD had distributed deficits in a subnetwork containing the left superior and inferior frontal gyri, postcentral gyrus, and insula (p=0.004). HR participants had controllability deficits in a right-lateralized subnetwork involving connections between the dorsomedial and ventrolateral prefrontal cortex, the superior temporal pole, putamen, and caudate nucleus (p=0.008). Between-group controllability differences were attenuated after removal of topological factors by network randomization. Some previously reported differences in network connectivity were not associated with controllability-differences, likely reflecting the contribution of more complex brain network properties. These analyses highlight the potential functional consequences of altered brain networks in BD, and may guide future clinical interventions.\n\nHighlightsO_LIControl theory estimates how neuronal fluctuations spread from local networks.\nC_LIO_LIWe compare brain controllability in bipolar disorder and their high-risk relatives.\nC_LIO_LIThese groups have impaired controllability in networks supporting cognitive and emotional control.\nC_LIO_LIWeaker connectivity as well as topological alterations contribute to these changes.\nC_LI

neuroscience↗
bioRxiv2017

Brain-behavior patterns define a dimensional biotype in medication-naïve adults with attention-deficit hyperactivity disorder

BackgroundChildhood-onset attention-deficit hyperactivity disorder (ADHD) in adults is clinically heterogeneous and commonly presents with different patterns of cognitive deficits. It is unclear if this clinical heterogeneity expresses a dimensional or categorical difference in ADHD.\n\nMethodsWe first studied differences in functional connectivity in multi-echo resting-state functional magnetic resonance imaging (rs-fMRI) acquired from 80 medication-naive adults with ADHD and 123 matched healthy controls. We then used canonical correlation analysis (CCA) to identify latent relationships between symptoms and patterns of altered functional connectivity (dimensional biotype) in patients. Clustering methods were implemented to test if the individual associations between resting-state brain connectivity and symptoms reflected a non-overlapping categorical biotype.\n\nResultsAdults with ADHD showed stronger functional connectivity compared to healthy controls, predominantly between the default-mode, cingulo-opercular and subcortical networks. CCA identified a single mode of brain-symptom co-variation, corresponding to an ADHD dimensional biotype. This dimensional biotype is characterized by a unique combination of altered connectivity correlating with symptoms of hyperactivity-impulsivity, inattention, and intelligence. Clustering analyses did not support the existence of distinct categorical biotypes of adult ADHD.\n\nConclusionsOverall, our data advance a novel finding that the reduced functional segregation between default-mode and cognitive control networks supports a clinically important dimensional biotype of childhood-onset adult ADHD. Despite the heterogeneity of its presentation, our work suggests that childhood-onset adult ADHD is a single disorder characterized by dimensional brain-symptom mediators.

neuroscience↗
bioRxiv2017

The independent influences of age and education on functional brain networks and cognition in healthy older adults

Healthy ageing is accompanied by a constellation of changes in cognitive processes and alterations in functional brain networks. The relationships between brain networks and cognition during ageing in later life are moderated by demographic and environmental factors, such as prior education, in a poorly understood manner. Using multivariate analyses, we identify three latent patterns (or modes) linking resting-state functional connectivity to demographic and cognitive measures in 101 cognitively-normal elders. The first mode (p=0.00043) captures an opposing association between age and core cognitive processes such as attention and processing speed on functional connectivity patterns. The functional subnetwork expressed by this mode links bilateral sensorimotor and visual regions through key areas such as the parietal operculum. A strong, independent association between years of education and functional connectivity loads onto a second mode (p=0.012), characterised by the involvement of key hub-regions. A third mode (p=0.041) captures weak, residual brain-behaviour relations. Our findings suggest that circuits supporting lower-level cognitive processes are most sensitive to the influence of age in healthy older adults. Education, and to a lesser extent, executive functions, load independently onto functional networks - suggesting that the moderating effect of education acts upon networks distinct from those vulnerable with ageing. This has important implications in understanding the contribution of education to cognitive reserve during healthy ageing.

neuroscience↗