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Luca Passamonti

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10

YNIMG Journal 2021 Journal Article

An in vivo probabilistic atlas of the human locus coeruleus at ultra-high field

  • Rong Ye
  • Catarina Rua
  • Claire O'Callaghan
  • P. Simon Jones
  • Frank H. Hezemans
  • Sanne S. Kaalund
  • Kamen A. Tsvetanov
  • Christopher T. Rodgers

Early and profound pathological changes are evident in the locus coeruleus (LC) in dementia and Parkinson's disease, with effects on arousal, attention, cognitive and motor control. The LC can be identified in vivo using non-invasive magnetic resonance imaging techniques which have potential as biomarkers for detecting and monitoring disease progression. Technical limitations of existing imaging protocols have impaired the sensitivity to regional contrast variance or the spatial variability on the rostrocaudal extent of the LC, with spatial mapping consistent with post mortem findings. The current study employs a sensitive magnetisation transfer sequence using ultrahigh field 7T MRI to investigate the LC structure in vivo at high-resolution (0.4 × 0.4 × 0.5 mm). Magnetisation transfer images from 53 healthy older volunteers (52 - 84 years) clearly revealed the spatial features of the LC and were used to create a probabilistic LC atlas for older adults. This atlas may be especially relevant for studying disorders associated with older age. To use the atlas does not require use of the same MT sequence of 7T MRI, provided good co-registration and normalisation is achieved. Consistent rostrocaudal gradients of slice-wise volume, contrast and variance along the LC were observed, mirroring distinctive ex vivo spatial distributions of LC cells in its subregions. The contrast-to-noise ratios were calculated for the peak voxels, and for the averaged signals within the atlas, to accommodate the volumetric differences in estimated contrast. The probabilistic atlas is freely available, and the MRI dataset will be made available for non-commercial research, for replication or to facilitate accurate LC localisation and unbiased contrast extraction in future studies.

YNICL Journal 2020 Journal Article

Correlation of microglial activation with white matter changes in dementia with Lewy bodies

  • Nicolas Nicastro
  • Elijah Mak
  • Guy B. Williams
  • Ajenthan Surendranathan
  • W Richard Bevan-Jones
  • Luca Passamonti
  • Patricia Vàzquez Rodrìguez
  • Li Su

C]-PK11195 binding in frontal, temporal, and occipital lobes. However, microglial activation was not significantly associated with grey matter changes. Our study suggests that increased microglial activation is associated with a relative preservation of white matter and cognition in DLB, positioning neuroinflammation as a potential early marker of DLB etio-pathogenesis.

YNICL Journal 2020 Journal Article

Reorganization of the structural connectome in primary open angle Glaucoma

  • Francesco Di Ciò
  • Francesco Garaci
  • Silvia Minosse
  • Luca Passamonti
  • Alessio Martucci
  • Simona Lanzafame
  • Francesca Di Giuliano
  • Eliseo Picchi

Primary open angle Glaucoma (POAG) is one of the most common causes of permanent blindness in the world. Recent studies have suggested the hypothesis that POAG is also a central nervous system disorder which may result in additional (i. e. , extra-ocular) involvement. The aim of this study is to assess possible structural, whole-brain connectivity alterations in POAG patients. We evaluated 23 POAG patients and 15 healthy controls by combining multi-shell diffusion weighted imaging, multi-shell, multi-tissue probabilistic tractography, graph theoretical measures and a recently designed ‘disruption index’, which evaluates the global reorganization of brain networks. We also studied the associations between the whole-brain structural connectivity measures and indices of visual acuity including the field index (VFI) and two Optical Coherence Tomography (OCT) parameters, namely the Macula Ganglion Cell Layer (MaculaGCL) and Retinal Nerve Fiber Layer (RNFL) thicknesses. We found both global and local structural connectivity differences between POAG patients and controls, which extended well beyond the primary visual pathway and were localized in the left calcarine gyrus (clustering coefficient p = 0. 036), left lateral occipital cortex (clustering coefficient p = 0. 017, local efficiency p = 0. 035), right lingual gyrus (clustering coefficient p = 0. 009), and right paracentral lobule (clustering coefficient p = 0. 009, local efficiency p = 0. 018). Group-wise (clustering coefficient, p = 6. 59∙10–7 and local efficiency p = 6. 23·10-8) and subject-wise disruption indices (clustering coefficient, p = 0. 018 and local efficiency, p = 0. 01) also differed between POAG patients and controls. In addition, we found negative associations between RNFL thickness and local measures (clustering coefficient, local efficiency and strength) in the right amygdala (local efficiency p = 0. 008, local strength p = 0. 016), right inferior temporal gyrus (clustering coefficient p = 0. 036, local efficiency p = 0. 042), and right temporal pole (local strength p = 0. 008). Overall, we show, in patients with POAG, a whole-brain structural reorganization that spans across a variety of brain regions involved in visual processing, motor control, and emotional/cognitive functions. We also identified a pattern of brain structural changes in relation to POAG clinical severity. Taken together, our findings support the hypothesis that the reduction in visual acuity from POAG can be driven by a combination of local (i. e. , in the eye) and more extended (i. e. , brain) effects.

YNIMG Journal 2020 Journal Article

Structural connectome and connectivity lateralization of the multimodal vestibular cortical network

  • Iole Indovina
  • Gianfranco Bosco
  • Roberta Riccelli
  • Vincenzo Maffei
  • Francesco Lacquaniti
  • Luca Passamonti
  • Nicola Toschi

Unlike other sensory systems, the structural connectivity patterns of the human vestibular cortex remain a matter of debate. Based on their functional properties and hypothesized centrality within the vestibular network, the ‘core’ cortical regions of this network are thought to be areas in the posterior peri-sylvian cortex, in particular the retro-insula (previously named the posterior insular cortex-PIC), and the subregion OP2 of the parietal operculum. To study the vestibular network, structural connectivity matrices from n=974 healthy individuals drawn from the public Human Connectome Project (HCP) repository were estimated using multi-shell diffusion-weighted data followed by probabilistic tractography and spherical-deconvolution informed filtering of tractograms in combination with subject-specific grey-matter parcellations. Weighted graph-theoretical measures, modularity, and ‘hubness’ of the multimodal vestibular network were then estimated, and a structural lateralization index was defined in order to assess the difference in fiber density of homonym regions in the right and left hemisphere. Differences in connectivity patterns between OP2 and PIC were also estimated. We found that the bilateral intraparietal sulcus, PIC, and to a lesser degree OP2, are key ‘hub’ regions within the multimodal vestibular network. PIC and OP2 structural connectivity patterns were lateralized to the left hemisphere, while structural connectivity patterns of the posterior peri-sylvian supramarginal and superior temporal gyri were lateralized to the right hemisphere. These lateralization patterns were independent of handedness. We also found that the structural connectivity pattern of PIC is consistent with a key role of PIC in visuo-vestibular processing and that the structural connectivity pattern of OP2 is consistent with integration of mainly vestibular somato-sensory and motor information. These results suggest an analogy between PIC and the simian visual posterior sylvian (VPS) area and OP2 and the simian parieto-insular vestibular cortex (PIVC). Overall, these findings may provide novel insights to the current models of vestibular function, as well as to the understanding of the complexity and lateralized signs of vestibular syndromes.

YNIMG Journal 2019 Journal Article

A parameter-efficient deep learning approach to predict conversion from mild cognitive impairment to Alzheimer's disease

  • Simeon Spasov
  • Luca Passamonti
  • Andrea Duggento
  • Pietro Liò
  • Nicola Toschi

Some forms of mild cognitive impairment (MCI) are the clinical precursors of Alzheimer's disease (AD), while other MCI types tend to remain stable over-time and do not progress to AD. To identify and choose effective and personalized strategies to prevent or slow the progression of AD, we need to develop objective measures that are able to discriminate the MCI patients who are at risk of AD from those MCI patients who have less risk to develop AD. Here, we present a novel deep learning architecture, based on dual learning and an ad hoc layer for 3D separable convolutions, which aims at identifying MCI patients who have a high likelihood of developing AD within 3 years. Our deep learning procedures combine structural magnetic resonance imaging (MRI), demographic, neuropsychological, and APOe4 genetic data as input measures. The most novel characteristics of our machine learning model compared to previous ones are the following: 1) our deep learning model is multi-tasking, in the sense that it jointly learns to simultaneously predict both MCI to AD conversion as well as AD vs. healthy controls classification, which facilitates relevant feature extraction for AD prognostication; 2) the neural network classifier employs fewer parameters than other deep learning architectures which significantly limits data-overfitting (we use ∼550, 000 network parameters, which is orders of magnitude lower than other network designs); 3) both structural MRI images and their warp field characteristics, which quantify local volumetric changes in relation to the MRI template, were used as separate input streams to extract as much information as possible from the MRI data. All analyses were performed on a subset of the database made publicly available via the Alzheimer's Disease Neuroimaging Initiative (ADNI), (n = 785 participants, n = 192 AD patients, n = 409 MCI patients (including both MCI patients who convert to AD and MCI patients who do not covert to AD), and n = 184 healthy controls). The most predictive combination of inputs were the structural MRI images and the demographic, neuropsychological, and APOe4 data. In contrast, the warp field metrics were of little added predictive value. The algorithm was able to distinguish the MCI patients developing AD within 3 years from those patients with stable MCI over the same time-period with an area under the curve (AUC) of 0. 925 and a 10-fold cross-validated accuracy of 86%, a sensitivity of 87. 5%, and specificity of 85%. To our knowledge, this is the highest performance achieved so far using similar datasets. The same network provided an AUC of 1 and 100% accuracy, sensitivity, and specificity when classifying patients with AD from healthy controls. Our classification framework was also robust to the use of different co-registration templates and potentially irrelevant features/image portions. Our approach is flexible and can in principle integrate other imaging modalities, such as PET, and diverse other sets of clinical data. The convolutional framework is potentially applicable to any 3D image dataset and gives the flexibility to design a computer-aided diagnosis system targeting the prediction of several medical conditions and neuropsychiatric disorders via multi-modal imaging and tabular clinical data.

YNICL Journal 2015 Journal Article

Cortical thickness, surface area, and folding alterations in male youths with conduct disorder and varying levels of callous–unemotional traits

  • Graeme Fairchild
  • Nicola Toschi
  • Cindy C. Hagan
  • Ian M. Goodyer
  • Andrew J. Calder
  • Luca Passamonti

PURPOSE: Previous studies have reported changes in gray matter volume in youths with conduct disorder (CD), although these differences are difficult to interpret as they may have been driven by alterations in cortical thickness, surface area (SA), or folding. The objective of this study was to use surface-based morphometry (SBM) methods to compare male youths with CD and age and sex-matched healthy controls (HCs) in cortical thickness, SA, and folding. We also tested for structural differences between the childhood-onset and adolescence-onset subtypes of CD and performed regression analyses to assess for relationships between CD symptoms and callous-unemotional (CU) traits and SBM-derived measures. METHODS: We acquired structural neuroimaging data from 20 HCs and 36 CD participants (18 with childhood-onset CD and 18 with adolescence-onset CD) and analyzed the data using FreeSurfer. RESULTS: Relative to HCs, youths with CD showed reduced cortical thickness in the superior temporal gyrus, reduced SA in the orbitofrontal cortex (OFC), and increased cortical folding in the insula. There were no significant differences between the childhood-onset and adolescence-onset CD subgroups in cortical thickness or SA, but several frontal and temporal regions showed increased cortical folding in childhood-onset relative to adolescence-onset CD participants. Both CD subgroups also showed increased cortical folding relative to HCs. CD symptoms were negatively correlated with OFC SA whereas CU traits were positively correlated with insula folding. CONCLUSIONS: Cortical thinning in the superior temporal gyrus may contribute to the social cognitive impairments displayed by youths with CD, whereas reduced OFC SA may lead to impairments in emotion regulation and reward processing in youths with CD. The increased cortical folding observed in the insula may reflect a maturational delay in this region and could mediate the link between CU traits and empathy deficits. Altered cortical folding was observed in childhood-onset and adolescence-onset forms of CD.

YNIMG Journal 2012 Journal Article

5-HTTLPR–environment interplay and its effects on neural reactivity in adolescents

  • Nicholas D. Walsh
  • Tim Dalgleish
  • Valerie J. Dunn
  • Rosemary Abbott
  • Michelle C. St Clair
  • Matthew Owens
  • Graeme Fairchild
  • William S. Kerslake

It is not known how 5-HTTLPR genotype×childhood adversity (CA) interactions that are associated with an increased risk for affective disorders in population studies operate at the neural systems level. We hypothesized that healthy adolescents at increased genetic and environmental risk for developing mood disorders (depression and anxiety) would demonstrate increased amygdala reactivity to emotional stimuli compared to those with only one such risk factor or those with none. Participants (n=67) were classified into one of 4 groups dependent on being homozygous for the long or short alleles within the serotonin-transporter-linked polymorphic region (5-HTTLPR) of the SLC6A4 gene and exposure to CA in the first 11years of life (present or absent). A functional magnetic resonance imaging investigation was undertaken which involved viewing emotionally-salient face stimuli. In addition, we assessed the role of other variables hypothesized to influence amygdala reactivity, namely recent negative life-events (RNLE) assessed at ages 14 and 17, current anxiety symptoms and psychiatric history. We replicated prior findings demonstrating moderation by gene variants in 5-HTTLPR, but found no support for an effect of CA on amygdala reactivity. We also found a significant effect of RNLE aged 17 with amygdala reactivity demonstrating additive, but not interactive effects with 5-HTTLPR. A whole-brain analysis found a 5-HTTLPR×CA interaction in the lingual gyrus whereby CA appears to differentially modify neural reactivity depending on genotype. These results demonstrate that two different forms of environmental adversities interplay with 5-HTTLPR and thereby differentially impact amygdala and cortical reactivity.

YNIMG Journal 2009 Journal Article

Anxiety predicts a differential neural response to attended and unattended facial signals of anger and fear

  • Michael P. Ewbank
  • Andrew D. Lawrence
  • Luca Passamonti
  • Jill Keane
  • Polly V. Peers
  • Andrew J. Calder

Behavioural evidence indicates that individual differences in anxiety influence the response to facial signals of threat. Angry and fearful faces represent qualitatively different forms of threat. Fearful faces are thought to signal the presence of a significant, yet undetermined source of danger within the environment, referred to as ‘ambiguous threat’. In contrast, angry faces represent a more direct form of threat, often used in face-to-face encounters to exert dominance. Given the inherent differences between anger and fear, we hypothesised that anxiety would modulate the amygdala response to angry faces to a greater extent when attended. Following previous research, we expected anxiety to show a stronger relationship with the amygdala response to unattended fearful faces. In an event-related fMRI study, we presented images of two houses and two faces (consisting of fearful, angry or neutral expressions) in horizontal and vertical pairs around a central fixation cross, with participants instructed to attend to either the face or house stimuli. The results showed that higher anxiety levels produced an increased right amygdala response to viewer directed angry facial expressions (versus neutral or fearful faces) only when attended. By contrast, increased anxiety was associated with a greater left amygdala response to fearful faces (versus neutral or angry faces) in the unattended condition, with only borderline evidence for attended fear (relative to neutral). Our findings demonstrate the striking effects of personality in a non-clinical population, and show how this can distinguish the neural coding of anger and fear faces.

YNIMG Journal 2008 Journal Article

Connectivity from the ventral anterior cingulate to the amygdala is modulated by appetitive motivation in response to facial signals of aggression

  • Luca Passamonti
  • James B. Rowe
  • Michael Ewbank
  • Adam Hampshire
  • Jill Keane
  • Andrew J. Calder

For some people facial expressions of aggression are intimidating, for others they are perceived as provocative, evoking an aggressive response. Identifying the key neurobiological factors that underlie this variation is fundamental to our understanding of aggressive behaviour. The amygdala and the ventral anterior cingulate cortex (ACC) have been implicated in aggression. Using functional magnetic resonance imaging (fMRI), we studied how the interaction between these regions is influenced by the drive to obtain reward (reward–drive or appetitive motivation), a personality trait consistently associated with aggression. Two distinct techniques showed that the connectivity between the ventral ACC and the amygdala was strongly correlated with personality, with high reward–drive participants displaying reduced negative connectivity. Furthermore, the direction of this effect was restricted from ventral ACC to the amygdala but not vice versa. The personality-mediated variation in the pathway from the ventral anterior cingulate cortex to the amygdala provides an account of why signals of aggression are interpreted as provocative by some individuals more than others.

YNIMG Journal 2008 Journal Article

Genetically dependent modulation of serotonergic inactivation in the human prefrontal cortex

  • Luca Passamonti
  • Antonio Cerasa
  • Maria Cecilia Gioia
  • Angela Magariello
  • Maria Muglia
  • Aldo Quattrone
  • Francesco Fera

Previous research suggests that genetic variations regulating serotonergic neurotransmission mediate individual differences in the neural network underlying impulsive and aggressive behaviour. Although with conflicting findings, the monoamine oxidase-A (MAOA) and the serotonin transporter (5HTT) gene polymorphisms have been associated with an increased risk to develop impulsive and aggressive behaviour. Double knock-out mice studies have also demonstrated that MAOA and 5HTT genes strongly interact in the metabolic pathway leading to the serotonergic inactivation; however, their potential interactive effect in human brain remains uninvestigated. We used blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to assess the independent and interactive effects of both MAOA and 5HTT polymorphisms on the brain activity elicited by a response inhibition task in healthy volunteers. Multivariate analysis demonstrated an individual effect of both MAOA and 5HTT polymorphisms and a strong allele–allele interaction in the anterior cingulate cortex (ACC), a key region implicated in cognitive control and in the pathophysiology of impulsive and aggressive behaviour. These findings suggest that the MAOA×5HTT allelic interaction exerts a significant modulation on the BOLD response associated with response inhibition and contribute to validate haplotype models as useful tools for a better understanding of the neurobiology underlying complex cognitive functions.

v2026.09.13