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Murat Yücel

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12 papers

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YNIMG Journal 2025 Journal Article

Differences in resting state functional connectivity in striatal and frontal networks associated with task-behaviour elicited by gamified two-stage decision task

Maja Brydevall
Chao Suo
Lucy Albertella
Kristian Rotaru
Teresa O’Brien
Murat Yücel
Rico S.C. Lee

This study aims to neurobiologically validate a newly developed gamified version of the modified two-stage task. The two-stage decision-making task is used to measure model-free and model-based decision strategies (commonly considered analogous to habitual and goal-directed decisions, respectively) with a weighting parameter (w) outcome variable indicating to what degree task behaviour is model-free or model-based. Our task is based on the Kool et al. (2016) modified version of the two-stage task, which has a simplified structure and has been designed with animations and narrative structure to improve engagement, understanding, and enjoyment of the task. Using resting state functional connectivity (rsFC) in a community sample of healthy adults (N = 48), we investigated if the weighting parameter (w) is associated with differences in rsFC in networks related to habitual and/or goal-directed decision-making, using seed-based analyses. Lower (w) rates (i.e. more habitual task behaviour) were associated with reduced rsFC between both left and right NAc projections to the left supramarginal gyrus, as well as reduced rsFC between left thalamus and the precuneous. This is consistent with research showing reductions in fronto-striatal network connectivity in obsessive-compulsive disorder, eating disorder, and gaming - conditions commonly assumed to be related to excessive habit-formation. Additionally, increased rsFC projecting from frontal pole to occipital pole was associated with higher (w) (i.e. more goal-directed task behaviour), whereas rsFC connectivity between right inferior frontal gyrus and left superior frontal gyrus as well as between left superior frontal gyrus and right frontal pole were associated with lower (w). These results indicate that task behaviour elicited by our gamified version of the two-stage decision-making task is reflecting differences in functional connectivity in both striatal and frontal networks when the brain is at rest. This is a promising indicator that our gamified two-stage decision task is indeed measuring differences related to neural processes in networks related to habitual and goal-directed decision-making processes.

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YNICL Journal 2021 Journal Article

Gender-related neuroanatomical differences in alcohol dependence: findings from the ENIGMA Addiction Working Group

Maria Gloria Rossetti
Praveetha Patalay
Scott Mackey
Nicholas B. Allen
Albert Batalla
Marcella Bellani
Yann Chye
Janna Cousijn

Gender-related differences in the susceptibility, progression and clinical outcomes of alcohol dependence are well-known. However, the neurobiological substrates underlying such differences remain unclear. Therefore, this study aimed to investigate gender differences in the neuroanatomy (i.e. regional brain volumes) of alcohol dependence. We examined the volume of a priori regions of interest (i.e., orbitofrontal cortex, hippocampus, amygdala, nucleus accumbens, caudate, putamen, pallidum, thalamus, corpus callosum, cerebellum) and global brain measures (i.e., total grey matter (GM), total white matter (WM) and cerebrospinal fluid). Volumes were compared between 660 people with alcohol dependence (228 women) and 326 controls (99 women) recruited from the ENIGMA Addiction Working Group, accounting for intracranial volume, age and education years. Compared to controls, individuals with alcohol dependence on average had (3-9%) smaller volumes of the hippocampus (bilateral), putamen (left), pallidum (left), thalamus (right), corpus callosum, total GM and WM, and cerebellar GM (bilateral), the latter more prominently in women (right). Alcohol-dependent men showed smaller amygdala volume than control men, but this effect was unclear among women. In people with alcohol dependence, more monthly standard drinks predicted smaller amygdala and larger cerebellum GM volumes. The neuroanatomical differences associated with alcohol dependence emerged as gross and widespread, while those associated with a specific gender may be confined to selected brain regions. These findings warrant future neuroscience research to account for gender differences in alcohol dependence to further understand the neurobiological effects of alcohol dependence.

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YNIMG Journal 2019 Journal Article

Transdiagnostic variations in impulsivity and compulsivity in obsessive-compulsive disorder and gambling disorder correlate with effective connectivity in cortical-striatal-thalamic-cortical circuits

Linden Parkes
Jeggan Tiego
Kevin Aquino
Leah Braganza
Samuel R. Chamberlain
Leonardo F. Fontenelle
Ben J. Harrison
Valentina Lorenzetti

Individual differences in impulsivity and compulsivity is thought to underlie vulnerability to a broad range of disorders and are closely tied to cortical-striatal-thalamic-cortical function. However, whether impulsivity and compulsivity in clinical disorders is continuous with the healthy population and explains cortical-striatal-thalamic-cortical dysfunction across different disorders remains unclear. Here, we characterized the relationship between cortical-striatal-thalamic-cortical effective connectivity, estimated using dynamic causal modelling of resting-state functional magnetic resonance imaging data, and dimensional phenotypes of impulsivity and compulsivity in two symptomatically distinct but phenotypically related disorders, obsessive-compulsive disorder and gambling disorder. 487 online participants provided data for modelling of dimensional phenotypes. These data were combined with 34 obsessive-compulsive disorder patients, 22 gambling disorder patients, and 39 healthy controls, who underwent functional magnetic resonance imaging. Three core dimensions were identified: disinhibition, impulsivity, and compulsivity. Patients’ scores on these dimensions were continuously distributed with the healthy participants, supporting a continuum model of psychopathology. Across all participants, higher disinhibition correlated with lower bottom-up connectivity in the dorsal circuit and greater bottom-up connectivity in the ventral circuit, and higher compulsivity correlated with lower bottom-up connectivity in the dorsal circuit. In patients, higher clinical severity was also linked to lower bottom-up connectivity in the dorsal circuit, but these findings were independent of phenotypic variation, demonstrating convergence towards behaviourally and clinically relevant changes in brain dynamics. Effective connectivity did not differ as a function of traditional diagnostic labels and only weak associations were observed for functional connectivity measures. Together, our results demonstrate that cortical-striatal-thalamic-cortical dysfunction across obsessive-compulsive disorder and gambling disorder may be better characterized by dimensional phenotypes than diagnostic comparisons, supporting investigation of quantitative liability phenotypes.

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YNIMG Journal 2018 Journal Article

An evaluation of the efficacy, reliability, and sensitivity of motion correction strategies for resting-state functional MRI

Linden Parkes
Ben Fulcher
Murat Yücel
Alex Fornito

Estimates of functional connectivity derived from resting-state functional magnetic resonance imaging (rs-fMRI) are sensitive to artefacts caused by in-scanner head motion. This susceptibility has motivated the development of numerous denoising methods designed to mitigate motion-related artefacts. Here, we compare popular retrospective rs-fMRI denoising methods, such as regression of head motion parameters and mean white matter (WM) and cerebrospinal fluid (CSF) (with and without expansion terms), aCompCor, volume censoring (e. g. , scrubbing and spike regression), global signal regression and ICA-AROMA, combined into 19 different pipelines. These pipelines were evaluated across five different quality control benchmarks in four independent datasets associated with varying levels of motion. Pipelines were benchmarked by examining the residual relationship between in-scanner movement and functional connectivity after denoising; the effect of distance on this residual relationship; whole-brain differences in functional connectivity between high- and low-motion healthy controls (HC); the temporal degrees of freedom lost during denoising; and the test-retest reliability of functional connectivity estimates. We also compared the sensitivity of each pipeline to clinical differences in functional connectivity in independent samples of people with schizophrenia and obsessive-compulsive disorder. Our results indicate that (1) simple linear regression of regional fMRI time series against head motion parameters and WM/CSF signals (with or without expansion terms) is not sufficient to remove head motion artefacts; (2) aCompCor pipelines may only be viable in low-motion data; (3) volume censoring performs well at minimising motion-related artefact but a major benefit of this approach derives from the exclusion of high-motion individuals; (4) while not as effective as volume censoring, ICA-AROMA performed well across our benchmarks for relatively low cost in terms of data loss; (5) the addition of global signal regression improved the performance of nearly all pipelines on most benchmarks, but exacerbated the distance-dependence of correlations between motion and functional connectivity; and (6) group comparisons in functional connectivity between healthy controls and schizophrenia patients are highly dependent on preprocessing strategy. We offer some recommendations for best practice and outline simple analyses to facilitate transparent reporting of the degree to which a given set of findings may be affected by motion-related artefact.

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YNICL Journal 2018 Journal Article

Decoding moral emotions in obsessive-compulsive disorder

Leonardo F. Fontenelle
Ilana Frydman
Sebastian Hoefle
Ricardo Oliveira-Souza
Paula Vigne
Tiago S. Bortolini
Chao Suo
Murat Yücel

Background: Patients with obsessive-compulsive disorder (OCD) exhibit abnormal neural responses when they experience particular emotions or when they evaluate stimuli with emotional value. Whether these brain responses are sufficiently distinctive to discriminate between OCD patients and healthy controls is unknown. The present study is the first to investigate the discriminative power of multivariate pattern analysis of regional fMRI responses to moral and non-moral emotions. Method: analysis). Results: We found that different frontostriatal regions discriminated OCD patients from controls based on individual emotional experiences. Most notably, the left nucleus accumbens (NAcc) discriminated OCD patients from controls during both disgust and the multiemotion analysis. Among other regions, the angular gyrus responses to anger and the lingual and the middle temporal gyri in the multi-emotion analysis were highly discriminant between samples. Additional BOLD analyses supported the directionality of these findings. Conclusions: In line with previous studies, differential activity in regions beyond the frontostriatal circuitry differentiates OCD from healthy volunteers. The finding that the response of the left NAcc to different basic and moral emotions is highly discriminative for a diagnosis of OCD confirms current pathophysiological models and points to new venues of research.

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YNIMG Journal 2015 Journal Article

Effective connectivity within the frontoparietal control network differentiates cognitive control and working memory

Ian H. Harding
Murat Yücel
Ben J. Harrison
Christos Pantelis
Michael Breakspear

Cognitive control and working memory rely upon a common fronto-parietal network that includes the inferior frontal junction (IFJ), dorsolateral prefrontal cortex (dlPFC), pre-supplementary motor area/dorsal anterior cingulate cortex (pSMA/dACC), and intraparietal sulcus (IPS). This network is able to flexibly adapt its function in response to changing behavioral goals, mediating a wide range of cognitive demands. Here we apply dynamic causal modeling to functional magnetic resonance imaging data to characterize task-related alterations in the strength of network interactions across distinct cognitive processes. Evidence in favor of task-related connectivity dynamics was accrued across a very large space of possible network structures. Cognitive control and working memory demands were manipulated using a factorial combination of the multi-source interference task and a verbal 2-back working memory task, respectively. Both were found to alter the sensitivity of the IFJ to perceptual information, and to increase IFJ-to-pSMA/dACC connectivity. In contrast, increased connectivity from the pSMA/dACC to the IPS, as well as from the dlPFC to the IFJ, was uniquely driven by cognitive control demands; a task-induced negative influence of the dlPFC on the pSMA/dACC was specific to working memory demands. These results reflect a system of both shared and unique context-dependent dynamics within the fronto-parietal network. Mechanisms supporting cognitive engagement, response selection, and action evaluation may be shared across cognitive domains, while dynamic updating of task and context representations within this network are potentially specific to changing demands on cognitive control.

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YNIMG Journal 2012 Journal Article

Successful inhibitory control over an immediate reward is associated with attentional disengagement in visual processing areas

David A. O'Connor
Sarah Rossiter
Murat Yücel
Dan I. Lubman
Robert Hester

We examined the neural basis of the capacity to resist an immediately rewarding stimulus in order to obtain a larger delayed reward. This was investigated with a Go/No-go task employing No-go targets that provided two types of reward outcomes. These were contingent on inhibitory control performance: failure to inhibit Reward No-go targets provided a small monetary reward with immediate feedback; while successful inhibitory control resulted in larger rewards with delayed feedback based on the highest number of consecutive inhibitions. We observed faster Go trial responses with maintained levels of inhibition accuracy during the Reward No-go condition compared to a neutral No-go condition. Comparisons between conditions of BOLD activity showed successful inhibitory control over rewarding No-Go targets was associated with hypoactivity in regions previously associated with regulating emotion and inhibitory control, including insula and right inferior frontal gyrus. In addition, regions previously associated with visual processing centers that are modulated as a function of visual attention, namely the left fusiform and right superior temporal gyri, were hypoactive. These findings suggest a role for attentional disengagement as an aid to withholding response over a rewarding stimulus and are consistent with the notion that gratification can be delayed by directing attention away from immediate rewards.

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YNIMG Journal 2010 Journal Article

Hippocampal pathology in individuals at ultra-high risk for psychosis: A multi-modal magnetic resonance study

Stephen J. Wood
Damien Kennedy
Lisa J. Phillips
Marc L. Seal
Murat Yücel
Barnaby Nelson
Alison R. Yung
Graeme Jackson

Although the hippocampus is a key brain region in the pathophysiology of schizophrenia, it is unclear whether structural or biochemical abnormalities predate illness onset. In this study, we used magnetic resonance imaging and spectroscopy data acquired prior to both the onset of psychosis and treatment with antipsychotics to determine this. Sixty-six young people clinically at ultra high-risk of development of psychosis were recruited, 59 of whom did not later develop a psychotic disorder and 7 who had done so after at least 24months follow-up. These participants were compared with 29 healthy comparison subjects on multiple independent magnetic resonance measures: hippocampal volume, hippocampal T2 relaxation time, and medial temporal lobe metabolite concentrations (including N-acetylaspartate). We found similar reductions in left hippocampal volume in the at-risk group compared to comparison subjects regardless of later transition status; on the right this only reached significance for the at-risk group who did not transition to psychosis. T2 relaxation time in the left hippocampal head was significantly elevated in the later-psychotic group, and this elevation positively correlated with total positive symptoms in the UHR group as a whole. Medial temporal lobe metabolite concentrations did not differ. These findings suggest that there are subtle pathological changes in the hippocampus prior to the development of psychosis, but that they are limited to the left hippocampal head. However, standard measures of neuroanatomical disturbance do not appear to be predictive of later transition, and instead are likely to be non-specific and common in cases that later develop a non-psychotic disorder.

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YNIMG Journal 2010 Journal Article

Whole-brain anatomical networks: Does the choice of nodes matter?

Andrew Zalesky
Alex Fornito
Ian H. Harding
Luca Cocchi
Murat Yücel
Christos Pantelis
Edward T. Bullmore

Whole-brain anatomical connectivity in living humans can be modeled as a network with diffusion-MRI and tractography. Network nodes are associated with distinct grey-matter regions, while white-matter fiber bundles serve as interconnecting network links. However, the lack of a gold standard for regional parcellation in brain MRI makes the definition of nodes arbitrary, meaning that network nodes are defined using templates employing either random or anatomical parcellation criteria. Consequently, the number of nodes included in networks studied by different authors has varied considerably, from less than 100 up to more than 104. Here, we systematically and quantitatively assess the behavior, structure and topological attributes of whole-brain anatomical networks over a wide range of nodal scales, a variety of grey-matter parcellations as well as different diffusion-MRI acquisition protocols. We show that simple binary decisions about network organization, such as whether small-worldness or scale-freeness is evident, are unaffected by spatial scale, and that the estimates of various organizational parameters (e. g. small-worldness, clustering, path length, and efficiency) are consistent across different parcellation scales at the same resolution (i. e. the same number of nodes). However, these parameters vary considerably as a function of spatial scale; for example small-worldness exhibited a difference of 95% between the widely-used automated anatomical labeling (AAL) template (∼100 nodes) and a 4000-node random parcellation (σ AAL =1. 9 vs. σ 4000 =53. 6±2. 2). These findings indicate that any comparison of network parameters across studies must be made with reference to the spatial scale of the nodal parcellation.

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YNIMG Journal 2007 Journal Article

State, trait and biochemical influences on human anterior cingulate function

Murat Yücel
Ben J. Harrison
Stephen J. Wood
Alex Fornito
Kerrie Clarke
R. Mark Wellard
Sue Cotton
Christos Pantelis

The dorsal part of the human anterior cingulate cortex (dACC) is reliably activated in situations requiring cognitive control, especially during states of conflict. However, little is known about how individual differences in the neural characteristics of the dACC and major dimensions of behavior, affect this brain response. We recruited 28 healthy adults and employed a multi-modal neuroimaging approach combined with a task designed to specifically activate the human dACC and statistical path analysis to demonstrate clear roles for intelligence, personality and concentrations of neuronal N-acetylaspartate in determining dACC activation. These influences were comparable in magnitude to those associated with the experience of conflict. Our findings extend current understandings of the neural substrates of cognitive control by modeling the effect of neuronal viability, intelligence, and personality, on dACC activation. They also highlight the importance of considering enduring personal characteristics when mapping human brain–behavior relationships.

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YNIMG Journal 2006 Journal Article

The influence of sulcal variability on morphometry of the human anterior cingulate and paracingulate cortex

Alex Fornito
Sarah Whittle
Stephen J. Wood
Dennis Velakoulis
Christos Pantelis
Murat Yücel

Human anterior cingulate (ACC) and paracingulate (PaC) cortices play an important role in cognitive and affective regulation and have been implicated in numerous psychiatric and neurological conditions. The region they comprise displays marked inter-individual variability in sulcal and gyral architecture, and although recent evidence suggests that this variability has functional significance, it is often ignored in automated and region-of-interest (ROI) morphometric investigations. This has lead to confounded interpretation of results and inconsistent findings across a number of studies and in a variety of clinical populations. In this paper, we present a reliable method for parcellating the dorsal, ventral, and subcallosal ACC and PaC that accounts for individual variation in the local cortical folding pattern. We also investigated the effect of one well characterized morphological variation, the incidence of the paracingulate sulcus (PCS), on regional volumes in 24 (12 male, 12 female) healthy participants. The presence of a PCS was shown to affect both ACC and PaC volumes, such that it was associated with an 88% increase in paracingulate cortex and a concomitant 39% decrease in cingulate cortex. These findings illustrate the potential confounds inherent in morphometric approaches that ignore or attempt to minimize inter-individual variations in sulcal and gyral anatomy and underscore the need to consider this variability when attempting to understand disease processes or characterize brain structure–function relationships.

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YNIMG Journal 2005 Journal Article

Functional connectivity during Stroop task performance

Ben J. Harrison
Marnie Shaw
Murat Yücel
Rosemary Purcell
Warrick J. Brewer
Stephen C. Strother
Gary F. Egan
James S. Olver

Using covariance-based multivariate analysis, we examined patterns of functional connectivity in rCBF on a practice-extended version of the Stroop color-word paradigm. Color-word congruent and incongruent conditions were presented in six AB trials to healthy subjects during 12 H2 15O PET scans. Analyses identified two reproducible canonical eigenimages (CE) from the PET data, which were converted to a standard Z score scale after cross-validation resampling and correction for random subject effects. The first CE corresponded to practice-dependent changes in covarying rCBF that occurred over early task repetitions and correlated with improved behavioral performance. This included many regions previously implicated by PET and fMRI studies of this task, which we suggest may represent two “parallel” networks: (i) a cingulo-frontal system that was initially engaged in selecting and mapping a task-relevant response (color naming) when the attentional demands of the task were greatest; and (ii) a ventral visual processing stream whose concurrent decrease in activity represented the task-irrelevant inhibition of word reading. The second CE corresponded to a consistent paradigmatic effect of Stroop interference on covarying rCBF. Coactivations were located in dorsal and ventral prefrontal regions as well as frontopolar cortex. This pattern supports existing evidence that prefrontal regions are involved in maintaining attentional control over conflicting response systems. Taken together, these findings may be more in line with theoretical models that emphasize a role for practice in the emergence of Stroop phenomena. These findings may also provide some additional insight into the nature of anterior cingulate- and prefrontal cortical contributions to implementing cognitive control in the brain.

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