Logo of the Gun and Bertil Stohne’s Foundation. (Image from the Foundation’s website.)
Yu-Wei Chang received one of the Gun and Bertil Stohnes Foundation Prizes for PhD students, with his recent research focusing on deep learning analysis of longitudinal tau pathology. The price consists in 100000 SEK given to one – or shared between two – student(s) at a Swedish university.
The Gun and Bertil Stohnes Foundation awards this prize to research projects in geriatrics that the Board deems of exceptional interest and value.
Anna Canal Garcia, from Karolinska Institutet and supervised by Prof. Joana B. Pereira, is the other recipient of this award. Anna’s research focuses on the intricate multilayer network analysis of brain neuroimaging data.
Average functional gradients of the locus coeruleus in the CamCAN 3T dataset. (Image from the publication.)Age-related differences in the functional topography of the locus coeruleus and their implications for cognitive and affective functions
Dániel Veréb, Mite Mijalkov, Anna Canal-Garcia, Yu-Wei Chang, Emiliano Gomez-Ruiz, Blanca Zufiria Gerboles, Miia Kivipelto, Per Svenningsson, Henrik Zetterberg, Giovanni Volpe, Matthew Betts, Heidi IL Jacobs, Joana B Pereira
eLife 12, RP87188 (2023)
doi: 10.7554/eLife.87188.3
The locus coeruleus (LC) is an important noradrenergic nucleus that has recently attracted a lot of attention because of its emerging role in cognitive and psychiatric disorders. Although previous histological studies have shown that the LC has heterogeneous connections and cellular features, no studies have yet assessed its functional topography in vivo, how this heterogeneity changes over aging, and whether it is associated with cognition and mood. Here, we employ a gradient-based approach to characterize the functional heterogeneity in the organization of the LC over aging using 3T resting-state fMRI in a population-based cohort aged from 18 to 88 years of age (Cambridge Centre for Ageing and Neuroscience cohort, n=618). We show that the LC exhibits a rostro-caudal functional gradient along its longitudinal axis, which was replicated in an independent dataset (Human Connectome Project [HCP] 7T dataset, n=184). Although the main rostro-caudal direction of this gradient was consistent across age groups, its spatial features varied with increasing age, emotional memory, and emotion regulation. More specifically, a loss of rostral-like connectivity, more clustered functional topography, and greater asymmetry between right and left LC gradients was associated with higher age and worse behavioral performance. Furthermore, participants with higher-than-normal Hospital Anxiety and Depression Scale (HADS) ratings exhibited alterations in the gradient as well, which manifested in greater asymmetry. These results provide an in vivo account of how the functional topography of the LC changes over aging, and imply that spatial features of this organization are relevant markers of LC-related behavioral measures and psychopathology.
Spatial maps depicting the strongest connections from the medial parietal cortex to other cortical and subcortical areas in the PREVENT-AD cohort. (Reproduced from the publication.)Functional gradients of the medial parietal cortex in a healthy cohort with family history of sporadic Alzheimer’s disease
Dániel Veréb, Mite Mijalkov, Yu-Wei Chang, Anna Canal-Garcia, Emiliano Gomez-Ruis, Anne Maass, Sylvia Villeneuve, Giovanni Volpe Joana B. Pereira
Alzheimer’s Research & Therapy 15, 82 (2023)
doi: 10.1186/s13195-023-01228-3
Background
The medial parietal cortex is an early site of pathological protein deposition in Alzheimer’s disease (AD). Previous studies have identified different subregions within this area; however, these subregions are often heterogeneous and disregard individual differences or subtle pathological alterations in the underlying functional architecture. To address this limitation, here we measured the continuous connectivity gradients of the medial parietal cortex and assessed their relationship with cerebrospinal fluid (CSF) biomarkers, ApoE ε4 carriership and memory in asymptomatic individuals at risk to develop AD.
Methods
Two hundred sixty-three cognitively normal participants with a family history of sporadic AD who underwent resting-state and task-based functional MRI using encoding and retrieval tasks were included from the PREVENT-AD cohort. A novel method for characterizing spatially continuous patterns of functional connectivity was applied to estimate functional gradients in the medial parietal cortex during the resting-state and task-based conditions. This resulted in a set of nine parameters that described the appearance of the gradient across different spatial directions. We performed correlation analyses to assess whether these parameters were associated with CSF biomarkers of phosphorylated tau181 (p-tau), total tau (t-tau), and amyloid-ß1-42 (Aß). Then, we compared the spatial parameters between ApoE ε4 carriers and noncarriers, and evaluated the relationship between these parameters and memory.
Results
Alterations involving the superior part of the medial parietal cortex, which was connected to regions of the default mode network, were associated with higher p-tau, t-tau levels as well as lower Aß/p-tau levels during the resting-state condition (p < 0.01). Similar alterations were found in ApoE ε4 carriers compared to non-carriers (p < 0.003). In contrast, lower immediate memory scores were associated with changes in the middle part of the medial parietal cortex, which was connected to inferior temporal and posterior parietal regions, during the encoding task (p = 0.001). No results were found when using conventional connectivity measures.
Conclusions
Functional alterations in the medial parietal gradients are associated with CSF AD biomarkers, ApoE e4 carriership, and lower memory in an asymptomatic cohort with a family history of sporadic AD, suggesting that functional gradients are sensitive to subtle changes associated with early AD stages.
Example of the 21 resting-state networks used as nodes and their positive (red) and negative connections (blue) for one of 140 the subjects included in the analyses. (Image by the Authors of the manuscript.)Sex differences in multilayer functional network topology over the course of aging in 37543 UK Biobank participants
Mite Mijalkov, Dániel Veréb, Oveis Jamialahmadi, Anna Canal-Garcia, Emiliano Gómez-Ruiz, Didac Vidal-Piñeiro, Stefano Romeo, Giovanni Volpe, Joana B. Pereira
Network Neuroscience 1-40 (2022)
doi: 10.1162/netn_a_00286
medRxiv: 10.1101/2022.03.08.22272089
Aging is a major risk factor for cardiovascular and neurodegenerative disorders, with considerable societal and economic implications. Healthy aging is accompanied by changes in functional connectivity between and within resting-state functional networks, which have been associated with cognitive decline. However, there is no consensus on the impact of sex on these age-related functional trajectories. Here, we show that multilayer measures provide crucial information on the interaction between sex and age on network topology, allowing for better assessment of cognitive, structural, and cardiovascular risk factors that have been shown to differ between men and women, as well as providing additional insights into the genetic influences on changes in functional connectivity that occur during aging. In a large cross-sectional sample of 37543 individuals from the UK Biobank cohort, we demonstrate that such multilayer measures that capture the relationship between positive and negative connections are more sensitive to sex-related changes in the whole-brain connectivity patterns and their topological architecture throughout aging, when compared to standard connectivity and topological measures. Our findings indicate that multilayer measures contain previously unknown information on the relationship between sex and age, which opens up new avenues for research into functional brain connectivity in aging.
The Soft Matter Lab participates to the SPIE Optics+Photonics conference in San Diego, CA, USA, 21-25 August 2022, with the presentations listed below.
Martin Selin: Scalable construction of quantum dot arrays using optical tweezers and deep learning (@SPIE)
22 August 2022 • 11:05 AM – 11:25 AM PDT | Conv. Ctr. Room 5A
Jesus Pineda: Revealing the spatiotemporal fingerprint of microscopic motion using geometric deep learning (@SPIE)
23 August 2022 • 11:05 AM – 11:25 AM PDT | Conv. Ctr. Room 5A
Anna Canal Garcia: Multilayer brain connectivity analysis in Alzheimer’s disease using functional MRI data (@SPIE)
24 August 2022 • 2:25 PM – 2:45 PM PDT | Conv. Ctr. Room 5A
Mite Mijalkov: A novel method for quantifying men and women-like features in brain structure and function (@SPIE)
24 August 2022 • 3:05 PM – 3:25 PM PDT | Conv. Ctr. Room 5A
Brain nodes. (Image taken from the article.)Multiplex Connectome Changes across the Alzheimer’s Disease Spectrum Using Gray Matter and Amyloid Data
Mite Mijalkov, Giovanni Volpe, Joana B Pereira
Anna Canal-Garcia, Emiliano Gómez-Ruiz, Mite Mijalkov, Yu-Wei Chang, Giovanni Volpe, Joana B Pereira, Alzheimer’s Disease Neuroimaging Initiative
Cerebral Cortex, bhab429 (2022)
doi: 10.1093/cercor/bhab429
The organization of the Alzheimer’s disease (AD) connectome has been studied using graph theory using single neuroimaging modalities such as positron emission tomography (PET) or structural magnetic resonance imaging (MRI). Although these modalities measure distinct pathological processes that occur in different stages in AD, there is evidence that they are not independent from each other. Therefore, to capture their interaction, in this study we integrated amyloid PET and gray matter MRI data into a multiplex connectome and assessed the changes across different AD stages. We included 135 cognitively normal (CN) individuals without amyloid-β pathology (Aβ−) in addition to 67 CN, 179 patients with mild cognitive impairment (MCI) and 132 patients with AD dementia who all had Aβ pathology (Aβ+) from the Alzheimer’s Disease Neuroimaging Initiative. We found widespread changes in the overlapping connectivity strength and the overlapping connections across Aβ-positive groups. Moreover, there was a reorganization of the multiplex communities in MCI Aβ + patients and changes in multiplex brain hubs in both MCI Aβ + and AD Aβ + groups. These findings offer a new insight into the interplay between amyloid-β pathology and brain atrophy over the course of AD that moves beyond traditional graph theory analyses based on single brain networks.
