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Michael Breakspear

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30 papers
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30

YNIMG Journal 2023 Journal Article

Functional re-organization of hippocampal-cortical gradients during naturalistic memory processes

  • Léonie Borne
  • Ye Tian
  • Michelle K. Lupton
  • Johan N. van der Meer
  • Jayson Jeganathan
  • Bryan Paton
  • Nikitas Koussis
  • Christine C. Guo

The functional organization of the hippocampus mirrors that of the cortex, changing smoothly along connectivity gradients and abruptly at inter-areal boundaries. Hippocampal-dependent cognitive processes require flexible integration of these hippocampal gradients into functionally related cortical networks. To understand the cognitive relevance of this functional embedding, we acquired fMRI data while participants viewed brief news clips, either containing or lacking recently familiarized cues. Participants were 188 healthy mid-life adults and 31 adults with mild cognitive impairment (MCI) or Alzheimer's disease (AD). We employed a recently developed technique - connectivity gradientography - to study gradually changing patterns of voxel to whole brain functional connectivity and their sudden transitions. We observed that functional connectivity gradients of the anterior hippocampus map onto connectivity gradients across the default mode network during these naturalistic stimuli. The presence of familiar cues in the news clips accentuates a stepwise transition across the boundary from the anterior to the posterior hippocampus. This functional transition is shifted in the posterior direction in the left hippocampus of individuals with MCI or AD. These findings shed new light on the functional integration of hippocampal connectivity gradients into large-scale cortical networks, how these adapt with memory context and how these change in the presence of neurodegenerative disease.

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YNICL Journal 2021 Journal Article

A prospective cohort study of prodromal Alzheimer’s disease: Prospective Imaging Study of Ageing: Genes, Brain and Behaviour (PISA)

  • Michelle K. Lupton
  • Gail A. Robinson
  • Robert J. Adam
  • Stephen Rose
  • Gerard J. Byrne
  • Olivier Salvado
  • Nancy A. Pachana
  • Osvaldo P. Almeida

This prospective cohort study, "Prospective Imaging Study of Ageing: Genes, Brain and Behaviour" (PISA) seeks to characterise the phenotype and natural history of healthy adult Australians at high future risk of Alzheimer's disease (AD). In particular, we are recruiting midlife and older Australians with high and low genetic risk of dementia to discover biological markers of early neuropathology, identify modifiable risk factors, and establish the very earliest phenotypic and neuronal signs of disease onset. PISA utilises genetic prediction to recruit and enrich a prospective cohort and follow them longitudinally. Online surveys and cognitive testing are used to characterise an Australia-wide sample currently totalling over 3800 participants. Participants from a defined at-risk cohort and positive controls (clinical cohort of patients with mild cognitive impairment or early AD) are invited for onsite visits for detailed functional, structural and molecular neuroimaging, lifestyle monitoring, detailed neurocognitive testing, plus blood sample donation. This paper describes recruitment of the PISA cohort, study methodology and baseline demographics.

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YNIMG Journal 2020 Journal Article

Manipulating the structure of natural scenes using wavelets to study the functional architecture of perceptual hierarchies in the brain

  • Alexander M. Puckett
  • Mark M. Schira
  • Zoey J. Isherwood
  • Jonathan D. Victor
  • James A. Roberts
  • Michael Breakspear

Functional neuroimaging experiments that employ naturalistic stimuli (natural scenes, films, spoken narratives) provide insights into cognitive function “in the wild”. Natural stimuli typically possess crowded, spectrally dense, dynamic, and multimodal properties within a rich multiscale structure. However, when using natural stimuli, various challenges exist for creating parametric manipulations with tight experimental control. Here, we revisit the typical spectral composition and statistical dependences of natural scenes, which distinguish them from abstract stimuli. We then demonstrate how to selectively degrade subtle statistical dependences within specific spatial scales using the wavelet transform. Such manipulations leave basic features of the stimuli, such as luminance and contrast, intact. Using functional neuroimaging of human participants viewing degraded natural images, we demonstrate that cortical responses at different levels of the visual hierarchy are differentially sensitive to subtle statistical dependences in natural images. This demonstration supports the notion that perceptual systems in the brain are optimally tuned to the complex statistical properties of the natural world. The code to undertake these stimulus manipulations, and their natural extension to dynamic natural scenes (films), is freely available.

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YNIMG Journal 2020 Journal Article

Prediction-error signals to violated expectations about person identity and head orientation are doubly-dissociated across dorsal and ventral visual stream regions

  • Jonathan E. Robinson
  • Will Woods
  • Sumie Leung
  • Jordy Kaufman
  • Michael Breakspear
  • Andrew W. Young
  • Patrick J. Johnston

Predictive coding theories of perception highlight the importance of constantly updated internal models of the world to predict future sensory inputs. Importantly, such theories suggest that prediction-error signalling should be specific to the violation of predictions concerning distinct attributes of the same stimulus. To interrogate this as yet untested prediction, we focused on two different aspects of face perception (identity and orientation) and investigated whether cortical regions which process particular stimulus attributes also signal prediction violations with respect to those same stimulus attributes. We employed a paradigm using sequential trajectories of images to create perceptual expectations about face orientation and identity, and then parametrically violated each attribute. Using MEG data, we identified double dissociations of expectancy violations in the dorsal and ventral visual streams, such that the right fusiform gyrus showed greater prediction-error signals to identity violations than to orientation violations, whereas the left angular gyrus showed the converse pattern of results. Our results suggest that perceptual prediction-error signalling is directly linked to regions associated with the processing of different stimulus properties.

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YNIMG Journal 2020 Journal Article

Subthalamic deep brain stimulation identifies frontal networks supporting initiation, inhibition and strategy use in Parkinson's disease

  • Philip E. Mosley
  • Katherine Robinson
  • Terry Coyne
  • Peter Silburn
  • Megan S. Barker
  • Michael Breakspear
  • Gail A. Robinson
  • Alistair Perry

Initiation and inhibition are executive functions whose disruption in Parkinson's disease impacts substantially on everyday activities. Management of Parkinson's disease with subthalamic deep brain stimulation (DBS) modifies initiation and inhibition, with prior work suggesting that these effects may be mediated via the connectivity of the subthalamic nucleus (STN) with the frontal cortex. Here, we employed high-resolution structural neuroimaging to investigate the variability in initiation, inhibition and strategy use in a cohort of twenty-five (ten females, mean age 62. 5, mean Hoehn and Yahr stage 2. 5) participants undertaking subthalamic DBS for Parkinson's disease. Neuropsychological assessment of initiation and inhibition was performed preoperatively and at six months postoperatively. We first reconstructed the preoperative connectivity of the STN with a frontal network of anterior and superior medial cortical regions. We then modelled the postoperative site of subthalamic stimulation and reconstructed the connectivity of the stimulation field within this same network. We found that, at both pre- and postoperative intervals, inter-individual variability in inhibition and initiation were strongly associated with structural network connectivity. Measures of subcortical atrophy and local stimulation effects did not play a significant role. Preoperatively, we replicated prior work, including a role for the right inferior frontal gyrus in inhibition and strategy use, as well as the left inferior frontal gyrus in tasks requiring selection under conditions of maintained inhibition. Postoperatively, greater connectivity of the stimulation field with right anterior cortical regions was associated with greater rule violations and suppression errors, supporting prior work implicating right-hemispheric STN stimulation in disinhibition. Our findings suggest that, in Parkinson's disease, connectivity of the frontal cortex with the STN is an important mediator of individual variability in initiation and inhibition, . Personalised information on brain network architecture could guide individualised brain circuit manipulation to minimise neuropsychological disruption after STN-DBS.

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YNICL Journal 2018 Journal Article

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

  • Jayson Jeganathan
  • Alistair Perry
  • Danielle S. Bassett
  • Gloria Roberts
  • Philip B. Mitchell
  • Michael Breakspear

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 individuals (n = 84, mean age 22. 4), 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.

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YNICL Journal 2018 Journal Article

The site of stimulation moderates neuropsychiatric symptoms after subthalamic deep brain stimulation for Parkinson's disease

  • Philip E. Mosley
  • David Smith
  • Terry Coyne
  • Peter Silburn
  • Michael Breakspear
  • Alistair Perry

Deep brain stimulation of the subthalamic nucleus for Parkinson's disease is an established advanced therapy that addresses motor symptoms and improves quality of life. However, it has also been associated with neuropsychiatric symptoms such as impulsivity and hypomania. When significant, these symptoms can be distressing, necessitating psychiatric intervention. However, a comprehensive analysis of neurocognitive and neuropsychiatric outcomes with reference to the site of subthalamic stimulation has not been undertaken. We examined this matter in a consecutive sample of 64 persons with Parkinson's disease undertaking subthalamic deep brain stimulation. Participants were assessed with a battery of neuropsychiatric instruments at baseline and at repeated postoperative intervals. A psychiatrist identified patients with emergent, clinically-significant symptoms due to stimulation. The site of the active electrode contact and a simulated volume of activated tissue were evaluated with reference to putative limbic, associative and motor subregions of the subthalamic nucleus. We studied anatomical correlates of longitudinal neuropsychiatric change and delineated specific subthalamic regions associated with neuropsychiatric impairment. We tested the ability of these data to predict clinically-significant symptoms. Subthalamic stimulation within the right associative subregion was associated with inhibitory errors on the Excluded Letter Fluency task at 6-weeks (p = 0. 023) and 13-weeks postoperatively (p = 0. 0017). A cluster of subthalamic voxels associated with inhibitory errors was identified in the right associative and motor subregions. At 6-weeks, clinically-significant neuropsychiatric symptoms were associated with the distance of the active contact to the right associative subregion (p = 0. 0026) and stimulation within the right associative subregion (p = 0. 0009). At 13-weeks, clinically-significant symptoms were associated with the distance to the right (p = 0. 0027) and left (p = 0. 0084) associative subregions and stimulation within the right associative subregion (p = 0. 0026). Discrete clusters of subthalamic voxels associated with high and low likelihood of postoperative neuropsychiatric symptoms were identified in ventromedial and dorsolateral zones, respectively. When a classifier was trained on these data, clinically-significant symptoms were predicted with an accuracy of 79%. These data underscore the importance of accurate electrode targeting, contact selection and device programming to reduce postoperative neuropsychiatric impairment. The ability to predict neuropsychiatric symptoms based on subthalamic data may permit anticipation and prevention of these occurrences, improving safety and tolerability.

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YNICL Journal 2018 Journal Article

Transcranial magnetic stimulation in obsessive-compulsive disorder: A focus on network mechanisms and state dependence

  • Luca Cocchi
  • Andrew Zalesky
  • Zoie Nott
  • Geneviève Whybird
  • Paul B. Fitzgerald
  • Michael Breakspear

Background: Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique that has shown promise as an adjunct treatment for the symptoms of Obsessive-Compulsive Disorder (OCD). Establishing a clear clinical role for TMS in the treatment of OCD is contingent upon evidence of significant efficacy and reliability in reducing symptoms. Objectives: We present the basic principles supporting the effects of TMS on brain activity with a focus on network-based theories of brain function. We discuss the promises and pitfalls of this technique as a means of modulating brain activity and reducing OCD symptoms. Methods: Synthesis of trends and critical perspective on the potential benefits and limitations of TMS interventions in OCD. Findings: Our critical synthesis suggests the need to better quantify the role of TMS in a clinical setting. The context in which the stimulation is performed, the neural principles supporting the effects of local stimulation on brain networks, and the heterogeneity of neuroanatomy are often overlooked in the clinical application of TMS. The lack of consideration of these factors may partly explain the variable efficacy of TMS interventions for OCD symptoms. Conclusions: Results from existing clinical studies and emerging knowledge about the effects of TMS on brain networks are encouraging but also highlight the need for further research into the use of TMS as a means of selectively normalising OCD brain network dynamics and reducing related symptoms. The combination of neuroimaging, computational modelling, and behavioural protocols known to engage brain networks affected by OCD has the potential to improve the precision and therapeutic efficacy of TMS interventions. The efficacy of this multimodal approach remains, however, to be established and its effective translation in clinical contexts presents technical and implementation challenges. Addressing these practical, scientific and technical issues is required to assess whether OCD can take its place alongside major depressive disorder as an indication for the use of TMS.

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YNICL Journal 2016 Journal Article

Whole-brain analytic measures of network communication reveal increased structure-function correlation in right temporal lobe epilepsy

  • Jonathan Wirsich
  • Alistair Perry
  • Ben Ridley
  • Timothée Proix
  • Mathieu Golos
  • Christian Bénar
  • Jean-Philippe Ranjeva
  • Fabrice Bartolomei

The in vivo structure-function relationship is key to understanding brain network reorganization due to pathologies. This relationship is likely to be particularly complex in brain network diseases such as temporal lobe epilepsy, in which disturbed large-scale systems are involved in both transient electrical events and long-lasting functional and structural impairments. Herein, we estimated this relationship by analyzing the correlation between structural connectivity and functional connectivity in terms of analytical network communication parameters. As such, we targeted the gradual topological structure-function reorganization caused by the pathology not only at the whole brain scale but also both in core and peripheral regions of the brain. We acquired diffusion (dMRI) and resting-state fMRI (rsfMRI) data in seven right-lateralized TLE (rTLE) patients and fourteen healthy controls and analyzed the structure-function relationship by using analytical network communication metrics derived from the structural connectome. In rTLE patients, we found a widespread hypercorrelated functional network. Network communication analysis revealed greater unspecific branching of the shortest path (search information) in the structural connectome and a higher global correlation between the structural and functional connectivity for the patient group. We also found evidence for a preserved structural rich-club in the patient group. In sum, global augmentation of structure-function correlation might be linked to a smaller functional repertoire in rTLE patients, while sparing the central core of the brain which may represent a pathway that facilitates the spread of seizures.

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YNICL Journal 2015 Journal Article

Scene unseen: Disrupted neuronal adaptation in melancholia during emotional film viewing

  • Matthew P. Hyett
  • Gordon B. Parker
  • Christine C. Guo
  • Andrew Zalesky
  • Vinh T. Nguyen
  • Tamara Yuen
  • Michael Breakspear

Impairments in attention and concentration are distinctive features of melancholic depression, and may diminish the ability to shift focus away from internal dysphoric states. Disrupted brain networks may underlie the inability to effectively disengage from interoceptive signals in this disorder. This study investigates changes in effective connectivity between cortical systems supporting attention, interoception, and perception in those with melancholic depression when shifting attention from rest to viewing dynamic film stimuli. We hypothesised that those with melancholia would show impaired attentional shifting from rest to emotional film viewing, captured in neuronal states that differed little across conditions. Functional magnetic resonance imaging (fMRI) data were acquired from 48 participants (16 melancholic depressed, 16 non-melancholic depressed, and 16 healthy controls) at rest and whilst viewing emotionally salient movies. Using independent component analysis, we identified 8 cortical modes (default mode, executive control, left/right frontoparietal attention, left/right insula, visual and auditory) and studied their dynamics using dynamic causal modelling. Engagement with dynamic emotional material diminished in melancholia and was associated with network-wide increases in effective connectivity. Melancholia was also characterised by an increase in effective connectivity amongst cortical regions involved in attention and interoception when shifting from rest to negative film viewing, with the converse pattern in control participants. The observed involvement of attention- and insula-based cortical systems highlights a potential neurobiological mechanism for disrupted attentional resource allocation, particularly in switching between interoceptive and exteroceptive signals, in melancholia.

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