Search

The substantial individual heterogeneity that characterizes people with mental illness is often ignored by classical case-control research, which relies on group mean comparisons. Here we present a comprehensive, multiscale characterization of the heterogeneity of gray matter volume (GMV) differences in 1,294 cases diagnosed with one of six conditions (attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, depression, obsessive-compulsive disorder and schizophrenia) and 1,465 matched controls. Normative models indicated that person-specific deviations from population expectations for regional GMV were highly heterogeneous, affecting the same area in <7% of people with the same diagnosis. However, these deviations were embedded within common functional circuits and networks in up to 56% of cases. The salience-ventral attention system was implicated transdiagnostically, with other systems selectively involved in depression, bipolar disorder, schizophrenia and attention-deficit/hyperactivity disorder. Phenotypic differences between cases assigned the same diagnosis may thus arise from the heterogeneous localization of specific regional deviations, whereas phenotypic similarities may be attributable to the dysfunction of common functional circuits and networks.

IMPORTANCE: Psychotic illness is associated with anatomically distributed gray matter reductions that can worsen with illness progression, but the mechanisms underlying the specific spatial patterning of these changes is unknown. OBJECTIVE: To test the hypothesis that brain network architecture constrains cross-sectional and longitudinal gray matter alterations across different stages of psychotic illness and to identify whether certain brain regions act as putative epicenters from which volume loss spreads. DESIGN, SETTINGS, AND PARTICIPANTS: This case-control study included 534 individuals from 4 cohorts, spanning early and late stages of psychotic illness. Early-stage cohorts included patients with antipsychotic-naive first-episode psychosis (n = 59) and a group of patients receiving medications within 3 years of psychosis onset (n = 121). Late-stage cohorts comprised 2 independent samples of people with established schizophrenia (n = 136). Each patient group had a corresponding matched control group (n = 218). A sample of healthy adults (n = 356) was used to derive representative structural and functional brain networks for modeling of network-based spreading processes. Longitudinal illness-related and antipsychotic-related gray matter changes over 3 and 12 months were examined using a triple-blind randomized placebo-control magnetic resonance imaging study of the antipsychotic-naive patients. All data were collected between April 29, 2008, and January 15, 2020, and analyses were performed between March 1, 2021, and January 14, 2023. MAIN OUTCOMES AND MEASURES: Coordinated deformation models were used to estimate the extent of gray matter volume (GMV) change in each of 332 parcellated areas by the volume changes observed in areas to which they were structurally or functionally coupled. To identify putative epicenters of volume loss, a network diffusion model was used to simulate the spread of pathology from different seed regions. Correlations between estimated

Dysfunction of fronto-striato-thalamic (FST) circuits is thought to contribute to dopaminergic dysfunction and symptom onset in psychosis, but it remains unclear whether this dysfunction is driven by aberrant bottom-up subcortical signalling or impaired top-down cortical regulation. We used spectral dynamic causal modelling of resting-state functional MRI to characterize the effective connectivity of dorsal and ventral FST circuits in a sample of 46 antipsychotic-naïve first-episode psychosis patients and 23 controls and an independent sample of 36 patients with established schizophrenia and 100 controls. We also investigated the association between FST effective connectivity and striatal 18F-DOPA uptake in an independent healthy cohort of 33 individuals who underwent concurrent functional MRI and PET. Using a posterior probability threshold of 0.95, we found that midbrain and thalamic connectivity were implicated as dysfunctional across both patient groups. Dysconnectivity in first-episode psychosis patients was mainly restricted to the subcortex, with positive symptom severity being associated with midbrain connectivity. Dysconnectivity between the cortex and subcortical systems was only apparent in established schizophrenia patients. In the healthy 18F-DOPA cohort, we found that striatal dopamine synthesis capacity was associated with the effective connectivity of nigrostriatal and striatothalamic pathways, implicating similar circuits to those associated with psychotic symptom severity in patients. Overall, our findings indicate that subcortical dysconnectivity is evident in the early stages of psychosis, that cortical dysfunction may emerge later in the illness, and that nigrostriatal and striatothalamic signalling are closely related to striatal dopamine synthesis capacity, which is a robust marker for psychosis.

01 september 2023, Contains fulltext : 296133.pdf (Publisher’s version ) (Open Access), The substantial individual heterogeneity that characterizes people with mental illness is often ignored by classical case-control research, which relies on group mean comparisons. Here we present a comprehensive, multiscale characterization of the heterogeneity of gray matter volume (GMV) differences in 1,294 cases diagnosed with one of six conditions (attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, depression, obsessive-compulsive disorder and schizophrenia) and 1,465 matched controls. Normative models indicated that person-specific deviations from population expectations for regional GMV were highly heterogeneous, affecting the same area in <7% of people with the same diagnosis. However, these deviations were embedded within common functional circuits and networks in up to 56% of cases. The salience-ventral attention system was implicated transdiagnostically, with other systems selectively involved in depression, bipolar disorder, schizophrenia and attention-deficit/hyperactivity disorder. Phenotypic differences between cases assigned the same diagnosis may thus arise from the heterogeneous localization of specific regional deviations, whereas phenotypic similarities may be attributable to the dysfunction of common functional circuits and networks.

Dysfunction of fronto-striato-thalamic (FST) circuits is thought to contribute to dopaminergic dysfunction and symptom onset in psychosis, but it remains unclear whether this dysfunction is driven by aberrant bottom-up subcortical signaling or impaired top-down cortical regulation. We used spectral dynamic causal modelling of resting-state functional magnetic resonance imaging (fMRI) to characterize the effective connectivity of dorsal and ventral FST circuits in a sample of 46 antipsychotic-naive first-episode psychosis patients and 23 controls and an independent sample of 36 patients with established schizophrenia patients and 100 controls. We also investigated the association between FST effective connectivity and striatal [18F]DOPA uptake in an independent healthy cohort of 33 individuals who underwent concurrent fMRI and positron emission tomography. Using a posterior probability threshold of 0.95, we found that midbrain and thalamic connectivity were implicated as dysfunctional across both patient groups. Dysconnectivity in first-episode psychosis patients was mainly restricted to the subcortex, with positive symptom severity being associated with midbrain connectivity. Dysconnectivity between the cortex and subcortical systems was only apparent in established schizophrenia patients. In the healthy [18F]DOPA cohort, we found that striatal dopamine synthesis capacity was associated with the effective connectivity of nigrostriatal and striatothalamic pathways, implicating similar circuits to those associated with psychotic symptom severity in patients. Overall, our findings indicate that subcortical dysconnectivity is evident in the early stages of psychosis, that cortical dysfunction may emerge later in the illness, and that nigrostriatal and striatothalamic signaling are closely related to striatal dopamine synthesis capacity, which is a robust marker for psychosis.Copyright © The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors

New brain atlases with high spatial resolution and whole-brain coverage have rapidly advanced our knowledge of the brain's neural architecture, including the systematic variation of excitatory and inhibitory cell densities across the mammalian cortex. But understanding how the brain's microscale physiology shapes brain dynamics at the macroscale has remained a challenge. While physiologically based mathematical models of brain dynamics are well placed to bridge this explanatory gap, their complexity can form a barrier to providing clear mechanistic interpretation of the dynamics they generate. In this work, we develop a neural-mass model of the mouse cortex and show how bifurcation diagrams, which capture local dynamical responses to inputs and their variation across brain regions, can be used to understand the resulting whole-brain dynamics. We show that strong fits to resting-state functional magnetic resonance imaging (fMRI) data can be found in surprisingly simple dynamical regimes-including where all brain regions are confined to a stable fixed point-in which regions are able to respond strongly to variations in their inputs, consistent with direct structural connections providing a strong constraint on functional connectivity in the anesthetized mouse. We also use bifurcation diagrams to show how perturbations to local excitatory and inhibitory coupling strengths across the cortex, constrained by cell-density data, provide spatially dependent constraints on resulting cortical activity, and support a greater diversity of coincident dynamical regimes. Our work illustrates methods for visualizing and interpreting model performance in terms of underlying dynamical mechanisms, an approach that is crucial for building explanatory and physiologically grounded models of the dynamical principles that underpin large-scale brain activity.

Since race was scientifically invalidated in the aftermath of the Holocaust, there has been extensive academic debate about its conceptual significance particularly in the ‘Global North’ where alternative terms and concepts have been offered up to classify group differences and understand forms of inequality in societies once structured explicitly by racial regimes. In earlier debates, an alternative focus on ethnicity, culture, class, and nationality drew criticism from scholars who saw the abandonment of race discourse as glossing over enduring power structures that perpetuated racism. Today, debates about the salience of race now also grapple with how different kinds of human mobility (and immobility) are further making complex relations of power and inequality especially in diverse immigrant-receiving societies. While older forms of migration, including the forced and violent movements of people in the transatlantic slave trade through to indentured labour migrations, came to underlie a colour-line created by nation-states principally formed around racial logics, newer forms of South to North migrations either forced or voluntary and as well accelerated South to South border crossings, now make even more complex the terms of difference. This chapter locates conceptualisations of race in migration and diversity studies, drawing from intersecting fields of scholarship such as studies of race and ethnicity, critical race theory, comparative migration studies and diversity research. It traces the wider genealogical history of the term in the ‘Global North’ then discusses how race as a concept is applicable to the ‘Global South’ where existing understandings about race are reaffirmed and unsettled. This chapter demonstrates the continued importance of considering race not just as a variable, but a key discursive framework in understandings of migration and diversity.

Background: Aberrant dopaminergic activity within fronto-striato-thalamic (FST) circuits is thought to contribute to psychosis onset. It remains unclear whether primary abnormality arises from bottom-up subcortical signaling or impaired top-down cortical regulation. We mapped causal interactions (effective connectivity) of dorsal and ventral FST circuits across the psychosis continuum and identified connections associated with striatal dopamine synthesis. Method(s): Spectral dynamic causal modelling (DCM) for resting-state functional magnetic resonance imaging (fMRI) modelled FST effective connectivity in: (1) 46 antipsychotic-naive first-episode psychosis (FEP) patients and 23 controls; (2) 36 established schizophrenia (SCZ) patients and 100 controls; and (3) 33 healthy individuals assessed for psychosis-like experiences (PLEs) with concurrent [18F]DOPA positron emission tomography. DCM estimated FST connectivity in patients and their respective controls, associations with symptom severity in all cohorts, and with striatal [18F]DOPA uptake in the PLE group. Result(s): Patients commonly showed midbrain disinhibition and reduced top-down influence of thalamus on nucleus accumbens. Cortical dysfunction was only apparent in the SCZ group. Positive symptoms were primarily associated with bottom-up connectivity in FEP and a mixture of bottom-up and top-down connectivity in SCZ and PLE groups, with disinhibition of ventromedial prefrontal cortex and extrinsic connectivity of the midbrain implicated across all cohorts. Thalamic and midbrain connectivity were associated with striatal [18F]DOPA uptake. Conclusion(s): We identified a primary role for subcortical dysconnectivity in psychosis, with cortical dysfunction emerging in established illness. Effective connectivity of the midbrain and thalamus are robustly linked to positive symptom severity and striatal dopamine synthesis capacity, suggesting a central role in the emergence of psychotic symptoms. Supported By: Nationa

Brain network hubs are both highly connected and highly inter-connected, forming a critical communication backbone for coherent neural dynamics. The mechanisms driving this organization are poorly understood. Using diffusion-weighted magnetic resonance imaging in twins, we identify a major role for genes, showing that they preferentially influence connectivity strength between network hubs of the human connectome. Using transcriptomic atlas data, we show that connected hubs demonstrate tight coupling of transcriptional activity related to metabolic and cytoarchitectonic similarity. Finally, comparing over thirteen generative models of network growth, we show that purely stochastic processes cannot explain the precise wiring patterns of hubs, and that model performance can be improved by incorporating genetic constraints. Our findings indicate that genes play a strong and preferential role in shaping the functionally valuable, metabolically costly connections between connectome hubs.

Studies on ‘everyday multiculturalism’ and ‘lived multiculture’ have advanced knowledge on the kinds of inclusive everyday spaces and practices that characterize our culturally complex, mobile and superdiverse cities. This paper expands this agenda by exploring informal sporting and leisure interactions amongst migrant and ethnically diverse urban populations. Embedded in a larger comparative city project that examines how urban environments and wider social structures mediate inclusions and exclusions of urban dwellers, this paper presents a case study of temporary migrant workers in Singapore and their participation in outdoor informal sport. It deploys Lefebvre's notion of ‘Right to the City’ to understand city dwellers’ access to urban resources and their collective ability to democratically inhabit the city. Despite structural constraints imposed on marginalized migrants, the nature of informal sport, the spontaneous coming together to play, creative use of public space and a range of convivial practices, generate a sense of urban belonging.

Background Neuroimaging studies have found dysconnectivity of frontostriatal circuits across a broad spectrum of psychotic symptoms. However, it is unknown whether dysconnectivity within frontostriatal circuits originates from disrupted bottom-up or top-down control signaling within these systems. Here, we used dynamic causal modelling (DCM) to examine the effective connectivity of frontostriatal systems in first-episode psychosis (FEP). Methods A total of 55 FEP patients (26 males; mean [SD] age = 19.24 [2.89]) and 24 healthy controls (15 males; mean [SD] age = 21.83 [1.93]) underwent a resting-state functional magnetic resonance imaging protocol. Biologically plausible connections between eight left hemisphere regions encompassing the dorsal and ventral frontostriatal systems were modelled using spectral DCM. The regions comprise dorsolateral prefrontal cortex, ventromedial prefrontal cortex, anterior hippocampus, amygdala, dorsal caudate, nucleus accumbens, thalamus, and the midbrain. Effective connectivity between groups were assessed using a parametric Bayesian model. Associations between effective connectivity parameters and positive symptoms, measured by the Brief Psychiatric Rating Scale positive subscale, was assessed in the patient group in a separate Bayesian general linear model. Results DCM shows evidence for differences in effective connectivity between patients and healthy controls, namely in the bottom-down connections distributed in the frontostriatal system encompassing the hippocampus, amygdala, striatum, and midbrain. Compared to healthy controls, patients also demonstrated increased disinhibition of the midbrain. In patients, positive symptoms are associated with increased top-down connections to the midbrain. Outgoing connection from the midbrain to the nucleus accumbens is also increased in association with positive symptoms. Discussion Aberrant top-down connectivity in the frontostriatal system in patients is consistent with top-down

The term ‘everyday anti-racism’ is employed across varied studies to refer to the ways in which individuals respond to racism in their day-to-day lives. This can include the actions of victims confronting perpetrators, witnesses speaking out against racism, practices that bridge cultural difference, material and subjective strategies deployed by those on the receiving end of racism to repair stigmatized identities, and aestheticized expressions through popular culture such as forms of music, youth cultures and media that challenge racism. This chapter reviews selected works examining anti-racism in everyday life and draws out its key tenets as an area of study, with the aim of highlighting how it contributes to broader anti-racism theory and praxis. It summaries the notable areas that make up literature on everyday anti-racism: the ‘micro’ dimensions of historical social movements and epochs; ‘doing’ anti-racism in organizational/institutional contexts; negotiating cultural difference and countering racism in spaces of ‘encounter’; and victims developing ‘cultural repertoires’ to cope with racism. The chapter highlights some of the central objectives of this scholarship which involve enhancing understandings of how the everyday is an integral part of processes that configure and challenge racism.

2018 Elsevier B.V. Background: Functional magnetic resonance imaging (fMRI) is commonly used to infer hemodynamic changes in the brain after increased neural activity, measuring the blood oxygen level-dependent (BOLD) signal. An important challenge in the analyses of fMRI data is to develop methods that can accurately deconvolve the BOLD signal to extract the driving neural activity and the underlying cerebrovascular effects. New method: A biophysically based method is developed, which combines an extensively verified physiological hemodynamic model with a Wiener filter, to deconvolve the BOLD signal. Results: The method is able to simultaneously obtain spatiotemporal images of underlying neurovascular signals, including neural activity, cerebral blood flow, cerebral blood volume, and deoxygenated hemoglobin concentration. The method is tested on simulated data and applied to various experimental data to demonstrate its stability, accuracy, and utility. Comparison with existing methods: The resulting profiles of the deconvolved signals are consistent with measurements reported in the literature, obtained via multiple neuroimaging modalities. Conclusions: The method provides new testable predictions of the spatiotemporal relations of the deconvolved signals for future studies. This demonstrates the ability of the method to quantify and analyze the neurovascular mechanisms that underlie fMRI, thereby expanding its potential uses.

© 2018 Kristine Aquino. All Rights Reserved. Filipino migrants constitute one of the largest global diasporas today. In Australia, Filipino settlement is markedly framed by the country's on-going nation-building project that continues to racialise immigrants and delineate the possibilities and limits of belonging to the national community. This book explores the ways in which Filipino migrants in Australia experience, understand and negotiate racism in their everyday lives. In particular, it explores the notion of everyday anti-racism - the strategies individuals deploy to manage racism in their day to day lives. Through case studies based on extensive fieldwork the author shares ethnographic observation and interview material that demonstrate the ways in which Filipinos are racially constituted in Australian society and are subject to everyday racisms that criss-cross different modes of power and domination. Drawing on theoretical approaches in critical race scholarship and the sociology of everyday life, this book illuminates the operation of racism in a multicultural society that persists insidiously in exchanges across a range of public and private spaces. More importantly, it explores the quotidian ways in which 'victims' of racism cope with routine racialised domination, an area underdeveloped in anti-racism research that has tended to focus on institutional anti-racism politics. Shedding light on a neglected corner of the global Filipino diaspora and highlighting the complexity of lived experiences in translocal and transnational social fields, this book will be of interest to academics in the field of diaspora and migration studies, the study of race and racism and ethnic minorities, with particular reference to the Asian diaspora.

© 2015 Taylor & Francis. ABSTRACT: While a focus on institutional anti-racism challenges structural formations of racialized inequality, the inattention to quotidian resistance misses the complex manner in which racism is negotiated in everyday life. Examining ‘everyday anti-racism’ can better identify the cultural repertoires that frame how individuals deal with racism across different contexts. This paper shares findings from ethnographic research with Filipino migrants living in Sydney. Specifically, it focuses on middle-class Filipino migrants and their use of social mobility to manage routine racism. The experience of middle-class racial minorities presents distinct perspectives as their strategies do not sit comfortably with anti-racism ideals of ‘equality for all’. I advance the concept of everyday anti-racism to argue for a broader anti-racism politics that captures situated approaches to combating racism. Furthermore, I propose that the identity repair in middle-class contexts offer a chance to build anti-racism praxis that cuts across traditional solidarities.

It is shown that recently discovered haemodynamic waves can form shock-like fronts when driven by stimuli that excite the cortex in a patch that moves faster than the haemodynamic wave velocity. If stimuli are chosen in order to induce shock-like behaviour, the resulting blood oxygen level-dependent (BOLD) response is enhanced, thereby improving the signal to noise ratio of measurements made with functional magnetic resonance imaging. A spatio-temporal haemodynamic model is extended to calculate the BOLD response and determine the main properties of waves induced by moving stimuli. From this, the optimal conditions for stimulating shock-like responses are determined, and ways of inducing these responses in experiments are demonstrated in a pilot study.

The gray matter of human cortex is characterized by depth-dependent differences in neuronal activity and connections (Shipp, 2007) as well as in the associated vasculature (Duvernoy et al., 1981). The resolution limit of functional magnetic resonance imaging (fMRI) measurements is now below a millimeter, promising the non-invasive measurement of these properties in awake and behaving humans (Muckli et al., 2015; Olman et al., 2012; Ress et al., 2007). To advance this endeavor, we present a detailed spatiotemporal hemodynamic response function (HRF) reconstructed through the use of high-resolution, submillimeter fMRI. We decomposed the HRF into directions tangential and perpendicular to the cortical surface and found that key spatial properties of the HRF change significantly with depth from the cortical surface. Notably, we found that the spatial spread of the HRF increases linearly from 4.8mm at the gray/white matter boundary to 6.6mm near the cortical surface. Using a hemodynamic model, we posit that this effect can be explained by the depth profile of the cortical vasculature, and as such, must be taken into account to properly estimate the underlying neuronal responses at different cortical depths.

© 2015, © 2015 Taylor & Francis. This paper explores marginalisation experienced in mainstream basketball by young Filipino-Australian men from Sydney's western suburbs. Sharing findings from a larger ethnographic study undertaken with Filipino immigrants in Sydney on experiences of everyday racism and resistance, this paper uses a biographical account to examine intricate connections between lives and racialising social processes. In sporting contexts, the body and its comportment provide the sites for domination and resistance. The analysis applies Bourdieu's concept of habitus to examine how broad racial formations are embodied in mainstream basketball. Furthermore, this paper examines the ways in which the playing style of ‘street ball’ is used to engage with corporeality as a mode of everyday anti-racism.

Functional magnetic resonance imaging (fMRI) is a powerful and broadly used means of non-invasively mapping human brain activity. However fMRI is an indirect measure that rests upon a mapping from neuronal activity to the blood oxygen level dependent (BOLD) signal via hemodynamic effects. The quality of estimated neuronal activity hinges on the validity of the hemodynamic model employed. Recent work has demonstrated that the hemodynamic response has non-separable spatiotemporal dynamics, a key property that is not implemented in existing fMRI analysis frameworks. Here both simulated and empirical data are used to demonstrate that using a physiologically based model of the spatiotemporal hemodynamic response function (stHRF) results in a quantitative improvement of the estimated neuronal response relative to unphysical space-time separable forms. To achieve this, an integrated spatial and temporal deconvolution is established using a recently developed stHRF. Simulated data allows the variation of key parameters such as noise and the spatial complexity of the neuronal drive, while knowing the neuronal input. The results demonstrate that the use of a spatiotemporally integrated HRF can avoid "ghost" neuronal responses that can otherwise be falsely inferred. Applying the spatiotemporal deconvolution to high resolution fMRI data allows the recovery of neuronal responses that are consistent with independent electrophysiological measures. 2014 Elsevier Inc.

presented at the Australian Neuroscience Society Inc 33rd Annual Meeting, 3-6 Feb 2013, Melbourne, Australia

presented at the Australian Neuroscience Society Inc 33rd Annual Meeting, 3-6 Feb 2013, Melbourne, Australia