Ricardo Magalhães - Academia.edu (original) (raw)

Papers by Ricardo Magalhães

Research paper thumbnail of Generation of Synthetic Rat Brain MRI Scans with a 3D Enhanced Alpha Generative Adversarial Network

Applied Sciences

Translational brain research using Magnetic Resonance Imaging (MRI) is becoming increasingly popu... more Translational brain research using Magnetic Resonance Imaging (MRI) is becoming increasingly popular as animal models are an essential part of scientific studies and more ultra-high-field scanners are becoming available. Some disadvantages of MRI are the availability of MRI scanners and the time required for a full scanning session. Privacy laws and the 3Rs ethics rule also make it difficult to create large datasets for training deep learning models. To overcome these challenges, an adaptation of the alpha Generative Adversarial Networks (GANs) architecture was used to test its ability to generate realistic 3D MRI scans of the rat brain in silico. As far as the authors are aware, this was the first time a GAN-based approach was used to generate synthetic MRI data of the rat brain. The generated scans were evaluated using various quantitative metrics, a Turing test, and a segmentation test. The last two tests proved the realism and applicability of the generated scans to real problem...

Research paper thumbnail of Differential patterns of association between resting-state functional connectivity networks and stress in OCD patients

Progress in Neuro-Psychopharmacology and Biological Psychiatry

Research paper thumbnail of Suicidal Ideation Is Associated With Reduced Functional Connectivity and White Matter Integrity in Drug-Naïve Patients With Major Depression

Frontiers in Psychiatry

Depression is a highly prevalent psychiatric disorder affecting millions of people worldwide. Dep... more Depression is a highly prevalent psychiatric disorder affecting millions of people worldwide. Depression is characterized by decreased mood or loss of interest in daily activities, changes in feeding and circadian rhythms and significant impairments in cognitive and executive function. In addition, the occurrence of recurrent thoughts of death and suicidal ideation confers depressed patients a higher risk of suicide than the general population. With this study, we aimed to explore the neural correlates of suicidal ideation in drug-naïve patients diagnosed with depression. Twenty-five patients were scanned using two-different magnetic resonance imaging (MRI) modalities, resting state functional MRI (fMRI) and diffusion tensor imaging (DTI). Resting state allowed the exploration of connectivity patterns in the absence of a specific stimulus and DTI allowed a detailed analysis of structural white matter integrity with measures like fractional anisotropy (FA). Probabilistic independent ...

Research paper thumbnail of A novel method for estimating connectivity‐based parcellation of the human brain from diffusion MRI : Application to an aging cohort

Human Brain Mapping, 2022

Connectivity-based parcellation (CBP) methods are used to define homogenous and biologically mean... more Connectivity-based parcellation (CBP) methods are used to define homogenous and biologically meaningful parcels or nodes-the foundations of brain network fingerprinting-by grouping voxels with similar patterns of brain connectivity. However, we still lack a gold standard method and the use of CBPs to study the aging brain remains scarce. Our study proposes a novel CBP method from diffusion MRI data and shows its potential to produce a more accurate characterization of the longitudinal alterations in brain network topology occurring in aging. For this, we constructed whole-brain connectivity maps from diffusion MRI data of two datasets: an aging cohort evaluated at two timepoints (mean interval time: 52.8 ± 7.24 months) and a normative adult cohort-MGH-HCP. State-of-the-art clustering techniques were used to identify the best performing technique. Furthermore, we developed a new metric (connectivity homogeneity fingerprint [CHF]) to evaluate the success of the final CBP in improving regional/global structural connectivity homogeneity. Our results show that our method successfully generates highly homogeneous parcels, as described by the significantly larger CHF score of the resulting parcellation, when compared to the original. Additionally, we demonstrated that the developed parcellation provides a robust anatomical framework to assess longitudinal changes in the aging brain. Our results reveal that aging is characterized by a reorganization of the brain's structural network involving the decrease of intra-hemispheric, increase of inter-hemispheric connectivity, and topological rearrangement. Overall, this study proposes a new methodology to perform accurate and robust evaluations of CBP of the human brain.

Research paper thumbnail of America: a systematic review

Brain structure across the lifespan: the influence of stress

Research paper thumbnail of Biomarkers of resilience and susceptibility in rodent models of stress

Stress Resilience, 2020

Abstract A major current trend in stress research is to consider both the spectrum of responses b... more Abstract A major current trend in stress research is to consider both the spectrum of responses by different individuals to the same stressful stimulus or environment and the dynamics of the stress response within the individual. The motivation for such an approach is the desire for, and need of, developing methods, which are able to identify individuals susceptible/vulnerable to overall stress or to specific stressors and, in that way, to identify those at risk of developing stress-related disorders. Herein, we briefly review and discuss a number of approaches used in this field of research and describe how they led to our current state of knowledge. We also provide a perspective for the future development of the field to produce relevant findings, while simultaneously generating sensitive and specific predictive biomarkers of stress resilience.

Research paper thumbnail of Spatial Normalization of MRI Brain Studies Using a U-Net Based Neural Network

Over recent years, Deep Learning has proven to be an excellent technology to solve problems that ... more Over recent years, Deep Learning has proven to be an excellent technology to solve problems that would otherwise be too complex. Furthermore, it has seen great success in the area of medical imaging, especially when applied to the segmentation of brain tissues. As such, this work explores a possible new approach, using Deep Learning to perform spatial normalization on Magnetic Resonance Imaging brain studies. Spatial normalization of Magnetic Resonance images by tools like FSL, or SPM can be inefficient for researches as they require too many resources to achieve good results. These resources include, for example, wasted human and computer time when executing the commands to normalize and waiting for the process to finish. This can take up to several hours just for one study. Therefore, to enable a faster and easier method to normalize the data, a U-Net based Deep Neural Network was developed using Keras and TensorFlow. This approach should free the researchers’ time for other more ...

Research paper thumbnail of Free-Living Physical Activity Measured With a Wearable Device Is Associated With Larger Hippocampus Volume and Greater Functional Connectivity in Healthy Older Adults: An Observational, Cross-Sectional Study in Northern Portugal

Frontiers in Aging Neuroscience, 2021

Several studies using neuroimaging techniques have established a positive relationship between ph... more Several studies using neuroimaging techniques have established a positive relationship between physical activity (PA) and brain structure and function in older populations. However, the use of subjective measures of PA and the lack of multimodal neuroimaging approaches have limited the understanding of this association. This study aims to explore the associations between PA and brain structure and function by objectively evaluating PA. Community-dwelling cognitively healthy older adults (without diagnosed cognitive, neurological or degenerative disease) were recruited from local health centers and local gyms. In a cross-sectional design, participants were evaluated regarding cognitive, clinical, anthropometric, physical performance, and lifestyle characteristics. A 3 T magnetic resonance imaging (MRI) was performed for structural and functional brain measures. PA time and level was assessed via a Xiaomi Mi Band 2® worn for 15 consecutive days. Participants (n = 110, after inclusion/...

Research paper thumbnail of The Association of Metabolic Dysfunction and Mood Across Lifespan Interacts With the Default Mode Network Functional Connectivity

Frontiers in Aging Neuroscience, 2021

Background: Numerous studies suggest a relationship between depression and metabolic syndrome, wh... more Background: Numerous studies suggest a relationship between depression and metabolic syndrome, which is likely influenced by age. Interestingly, functional imaging analysis has shown an association between functional connectivity in the default mode network (DMN-FC) and components of metabolic syndrome, which is explored in this study. Methods: From a larger longitudinal cohort study on healthy aging, 943 individuals were extensively characterized for mood and cognition. Among these, 120 individuals who were selected for displaying extreme cognitive performance within the normal range (good and poor performers) were further studied. Here, in a cross-sectional design, using confirmatory factor analysis (CFA), the association between metabolic dysfunction and depressive mood as a function of age and its relationship with DMN-FC was studied. Results: Metabolic dysfunction was modeled as a second-order latent variable using CFA. First-order latent variables were obesity, glucose dysmeta...

Research paper thumbnail of Frontoparietal hyperconnectivity during cognitive regulation in obsessive-compulsive disorder followed by reward valuation inflexibility

Journal of Psychiatric Research, 2021

Obsessive-compulsive disorder (OCD) is characterized by cognitive deficits and altered reward pro... more Obsessive-compulsive disorder (OCD) is characterized by cognitive deficits and altered reward processing systems. An imbalance between cognitive and reward pathways may explain the lack of control over obsessions followed by rewarding compulsive behaviors. While the processes of emotional cognitive regulation are widely studied in OCD, the mechanisms of cognitive regulation of reward are poorly described. Our goal was to investigate the OCD impact on cognitive regulation of reward at behavioral and neural functioning levels. OCD and control participants performed a functional magnetic resonance imaging task where they cognitively modulated their craving for food pictures under three cognitive regulation conditions: indulge/increase craving, distance/decrease craving, and natural/no regulation of craving. After regulation, the participants gave each picture a monetary value. We found that OCD patients had fixed food valuation scores while the control group modulated these values accordingly to the regulation conditions. Moreover, we observed frontoparietal hyperconnectivity during cognitive regulation. Our results suggest that OCD is characterized by deficits in cognitive regulation of internal states associated with inflexible behavior during reward processing. These findings bring new insights into the nature of compulsive behaviors in OCD.

Research paper thumbnail of Signatures of white-matter microstructure degradation during aging and its association with cognitive status

Scientific Reports, 2021

Previous studies have shown an association between cognitive decline and white matter integrity i... more Previous studies have shown an association between cognitive decline and white matter integrity in aging. This led to the formulation of a “disconnection hypothesis” in the aging-brain, which states that the disruption in cortical network communication may explain the cognitive decline during aging. Although some longitudinal studies have already investigated the changes occurring in white matter microstructure, most focused on specific white matter tracts. Our study aims to characterize the longitudinal whole-brain signatures of white matter microstructural change during aging. Furthermore, we assessed the relationship between distinct longitudinal alterations in white matter integrity and cognition. White matter microstructural properties were estimated from diffusion magnetic resonance imaging, and cognitive status characterized from extensive neurocognitive testing. The same individuals were evaluated at two timepoints, with a mean interval time of 52.8 months (SD = 7.24) betwee...

Research paper thumbnail of Habitual coffee drinkers display a distinct pattern of brain functional connectivity

Molecular Psychiatry, 2021

Coffee is the most widely consumed source of caffeine worldwide, partly due to the psychoactive e... more Coffee is the most widely consumed source of caffeine worldwide, partly due to the psychoactive effects of this methylxanthine. Interestingly, the effects of its chronic consumption on the brain’s intrinsic functional networks are still largely unknown. This study provides the first extended characterization of the effects of chronic coffee consumption on human brain networks. Subjects were recruited and divided into two groups: habitual coffee drinkers (CD) and non-coffee drinkers (NCD). Resting-state functional magnetic resonance imaging (fMRI) was acquired in these volunteers who were also assessed regarding stress, anxiety, and depression scores. In the neuroimaging evaluation, the CD group showed decreased functional connectivity in the somatosensory and limbic networks during resting state as assessed with independent component analysis. The CD group also showed decreased functional connectivity in a network comprising subcortical and posterior brain regions associated with so...

Research paper thumbnail of Amygdala size varies with stress perception

Neurobiology of Stress, 2021

Stress is inevitably linked to life. It has many and complex facets. Notably, perception of stres... more Stress is inevitably linked to life. It has many and complex facets. Notably, perception of stressful stimuli is an important factor when mounting stress responses and measuring its impact. Indeed, moved by the increasing number of stress-triggered pathologies, several groups drew on advanced neuroimaging techniques to explore stress effects on the brain. From that, several regions and circuits have been linked to stress, and a comprehensive integration of the distinct findings applied to common individuals is being pursued, but with conflicting results. Herein, we performed a volumetric regression analysis using participants' perceived stress as a variable of interest. Data shows that increased levels of perceived stress positively associate with the right amygdala and anterior hippocampal volumes.

Research paper thumbnail of The association of dietary patterns with cognition through the lens of neuroimaging—a Systematic review

Ageing Research Reviews, 2020

Despite the reported benefits of diet on cognition in older adults, randomized controlled trials ... more Despite the reported benefits of diet on cognition in older adults, randomized controlled trials (RCT) testing the impact of dietary interventions on cognitive scores have yielded less promising results when cognition was assessed via neuropsychological tests. More recently, neuroimaging has been used to identify more subtle brainrelated changes associated to cognition. Hence, employing a combination of neuroimaging techniques with neuropsychological tests could clarify this controversy. To determine the effect of diet on cognitive performance, we conducted a systematic review of PubMed and Scopus databases for all studies, on middle-aged and older adults, combining neuroimaging, neuropsychological tests, and data on dietary patterns. The inclusion criteria were met by 14 observational studies and no RCTs. The range of brain measures assessed varied from volumes to white matter integrity, functional connectivity, brain glucose metabolism and beta-amyloid deposition. Given the variability of methods used in assessing cognitive performance, diet and brain correlates, conducting a meta-analysis was not possible. Here the evidence suggests that, in observational studies, dietary patterns may be associated with brain correlates that have been shown to precede cognitive decline. As such, neuroimaging should be included in future RCTs to identify any benefits of diet on brain measures linked with cognitive health.

Research paper thumbnail of Structural neuroimaging biomarkers for obsessive-compulsive disorder in the ENIGMA-OCD consortium: medication matters

ObjectiveNo diagnostic biomarkers are available for obsessive-compulsive disorder (OCD). Magnetic... more ObjectiveNo diagnostic biomarkers are available for obsessive-compulsive disorder (OCD). Magnetic resonance imaging (MRI) studies have provided evidence for structural abnormalities in distinct brain regions, but effect sizes are small and have limited clinical relevance. To investigate whether individual patients can be distinguished from healthy controls, we performed multivariate analysis of structural neuroimaging data from the ENIGMA-OCD consortium.MethodWe included 46 data sets with neuroimaging and clinical data from adult (≥18 years) and pediatric (<18 years) samples. T1 images from 2,304 OCD patients and 2,068 healthy controls were analyzed using standardized processing to extract regional measures of cortical thickness, surface area and subcortical volume. Machine learning classification performance was tested using cross-validation, and possible effects of clinical variables were investigated by stratification.ResultsClassification performance for OCD versus controls u...

Research paper thumbnail of Altered response to risky decisions and reward in patients with obsessive–compulsive disorder

Journal of Psychiatry and Neuroscience, 2020

Background: Patients with obsessive-compulsive disorder (OCD) employ ritualistic behaviours to re... more Background: Patients with obsessive-compulsive disorder (OCD) employ ritualistic behaviours to reduce or even neutralize the anxiety provoked by their obsessions. The presence of excessive rumination and indecision has motivated the view of OCD as a disorder of decision-making. Most studies have focused on the "cold," cognitive aspects of decision-making. This study expands current understanding of OCD by characterizing the abnormalities associated with affective, or "hot" decision-making. Methods: We performed a functional MRI study in a sample of 34 patients with OCD and 33 sex-and age-matched healthy controls, during which participants made 2-choice gambles taking varying levels of risk. Results: During risky decisions, patients showed significantly reduced task-related activation in the posterior cingulum, lingual gyrus and anterior cingulate cortex. We identified significant group × risk interactions in the calcarine cortex, precuneus, amygdala and anterior cingulate cortex. During the outcome phase, patients with OCD showed stronger activation of the orbitofrontal cortex, anterior cingulate cortex and putamen in response to unexpected losses. Limitations: The group of patients not receiving medication was very small (n = 5), which precluded us from assessing the effect of medication on risk-taking behaviour in these patients. Conclusion: Obsessive-compulsive disorder is associated with abnormal brain activity patterns during risky decision-making in a set of brain regions that have been consistently implicated in the processing of reward prediction errors. Alterations in affective "hot" processes implicated in decision-making may contribute to increased indecisiveness and intolerance to uncertainty in patients with OCD.

Research paper thumbnail of Linking sleep quality to brain connectivity: a multimodal MRI approach in normative ageing

Sleep Medicine, 2019

Accumulating evidence suggests that successful OSA treatment with positive airway pressure (PAP) ... more Accumulating evidence suggests that successful OSA treatment with positive airway pressure (PAP) can improve CV outcomes. This study aimed to evaluate the incidence of CV and CeV events and related mortality in 89 males with moderate-to-severe OSA treated with PAP over 10 years, and to assess its relation with PAP adherence. Results: Of the 89 patients included (mean age 53.5±11.7 years, BMI¼33.2±4.9 kg/m 2 , initial AHI¼52.9±20.6 events/h, Epworth scale¼12.2±5.3), 17 were active smokers, 63 had hypertension, 1 hyperuricemia, and 5 had previous CV and/or CeV events. Over follow-up, AHI and Epworth scale decreased significantly (p< 0.001) reaching minimum levels of 2.6±1.8 events/h and 4.2±3.9, respectively. Most of patients were PAP adherent (mean objective com-pliance¼ 93.8±13.9%, with 6.5±1.6 h/use/day). At time of last evaluation, mean adherence rate and hours use/day were, respectively, 98.1±3.1% and 7.0±1.4, being found a progressively strong negative correlation between PAP adherence and CeV/CV events, mostly after the 6 th year. Over this period, 9 patients had CV and 5 CeV events, and 2 experienced both events. Mean survival time was 123.9±25.9 months: lower in those who had CV and/or CeV events (p< 0.001). Ten patients died (3 by CVD complication, 1 myocardial infarction, 2 stroke, and 1 cardiopulmonary arrest). Conclusions: Although AHI presented an immediate and sustained decrease with PAP treatment, only an effective PAP adherence (especially after 24 months) seems to be effective in decreasing CV/CeV events, especially when used for more than 6 years.

Research paper thumbnail of The SIGMA rat brain templates and atlases for multimodal MRI data analysis and visualization

Nature Communications, 2019

Preclinical imaging studies offer a unique access to the rat brain, allowing investigations that ... more Preclinical imaging studies offer a unique access to the rat brain, allowing investigations that go beyond what is possible in human studies. Unfortunately, these techniques still suffer from a lack of dedicated and standardized neuroimaging tools, namely brain templates and descriptive atlases. Here, we present two rat brain MRI templates and their associated gray matter, white matter and cerebrospinal fluid probability maps, generated from ex vivo {\mathrm{T}}_2^ \ast$$T2*-weighted images (90 µm isotropic resolution) and in vivo T2-weighted images (150 µm isotropic resolution). In association with these templates, we also provide both anatomical and functional 3D brain atlases, respectively derived from the merging of the Waxholm and Tohoku atlases, and analysis of resting-state functional MRI data. Finally, we propose a complete set of preclinical MRI reference resources, compatible with common neuroimaging software, for the investigation of rat brain structures and functions.

Research paper thumbnail of Corrigendum: Reduced Hedonic Valuation of Rewards and Unaffected Cognitive Regulation in Chronic Stress

Frontiers in Neuroscience, 2019

Research paper thumbnail of The moderator effect of age in the association between mood and adiposity in the elderly is specific for the subcutaneous adipose compartment: an MRI study

International Journal of Geriatric Psychiatry, 2019

The positive association between obesity and depressive mood in young-and middleage individuals i... more The positive association between obesity and depressive mood in young-and middleage individuals is a phenomenon with major clinical implications in public health. Interestingly, the trend of this association in older individuals is not clear, given the conflicting results of multiple studies. Since aging is accompanied by changes in body fat distribution, we questioned whether age is a modulator of such association. This study explores the role of age in the association between mood and general (body mass index [BMI]) and abdominal adiposity (waist circumference [WC]) in older adults characterizing the different abdominal adipose tissue compartments (subcutaneous adipose tissue [SAT] and visceral adipose tissue [VAT]) with magnetic resonance imaging (MRI) techniques. Methods: One hundred twenty aged community-dwelling individuals (≥50 y of age) were assessed regarding depressive mood (Geriatric Depression Scale) and adiposity (BMI and WC). From these, 96 were assessed for SAT and VAT using MRI. Results: Using multiple linear regression models, depressive mood was positively associated with BMI, WC, and VAT. Age was a significant moderator of the association between depressive mood and BMI, WC, and SAT: positive in younger participants and null or negative in older participants. On the other hand, higher VAT was significantly associated with a more depressive mood, independently of age. Conclusions: This study identifies age as a relevant moderator in the association between depressive mood and adiposity in the elderlies. Furthermore, the body fat compartment analysis revealed that the effect of age is specific for the SAT, suggesting its protective role in depressive mood.

Research paper thumbnail of Generation of Synthetic Rat Brain MRI Scans with a 3D Enhanced Alpha Generative Adversarial Network

Applied Sciences

Translational brain research using Magnetic Resonance Imaging (MRI) is becoming increasingly popu... more Translational brain research using Magnetic Resonance Imaging (MRI) is becoming increasingly popular as animal models are an essential part of scientific studies and more ultra-high-field scanners are becoming available. Some disadvantages of MRI are the availability of MRI scanners and the time required for a full scanning session. Privacy laws and the 3Rs ethics rule also make it difficult to create large datasets for training deep learning models. To overcome these challenges, an adaptation of the alpha Generative Adversarial Networks (GANs) architecture was used to test its ability to generate realistic 3D MRI scans of the rat brain in silico. As far as the authors are aware, this was the first time a GAN-based approach was used to generate synthetic MRI data of the rat brain. The generated scans were evaluated using various quantitative metrics, a Turing test, and a segmentation test. The last two tests proved the realism and applicability of the generated scans to real problem...

Research paper thumbnail of Differential patterns of association between resting-state functional connectivity networks and stress in OCD patients

Progress in Neuro-Psychopharmacology and Biological Psychiatry

Research paper thumbnail of Suicidal Ideation Is Associated With Reduced Functional Connectivity and White Matter Integrity in Drug-Naïve Patients With Major Depression

Frontiers in Psychiatry

Depression is a highly prevalent psychiatric disorder affecting millions of people worldwide. Dep... more Depression is a highly prevalent psychiatric disorder affecting millions of people worldwide. Depression is characterized by decreased mood or loss of interest in daily activities, changes in feeding and circadian rhythms and significant impairments in cognitive and executive function. In addition, the occurrence of recurrent thoughts of death and suicidal ideation confers depressed patients a higher risk of suicide than the general population. With this study, we aimed to explore the neural correlates of suicidal ideation in drug-naïve patients diagnosed with depression. Twenty-five patients were scanned using two-different magnetic resonance imaging (MRI) modalities, resting state functional MRI (fMRI) and diffusion tensor imaging (DTI). Resting state allowed the exploration of connectivity patterns in the absence of a specific stimulus and DTI allowed a detailed analysis of structural white matter integrity with measures like fractional anisotropy (FA). Probabilistic independent ...

Research paper thumbnail of A novel method for estimating connectivity‐based parcellation of the human brain from diffusion MRI : Application to an aging cohort

Human Brain Mapping, 2022

Connectivity-based parcellation (CBP) methods are used to define homogenous and biologically mean... more Connectivity-based parcellation (CBP) methods are used to define homogenous and biologically meaningful parcels or nodes-the foundations of brain network fingerprinting-by grouping voxels with similar patterns of brain connectivity. However, we still lack a gold standard method and the use of CBPs to study the aging brain remains scarce. Our study proposes a novel CBP method from diffusion MRI data and shows its potential to produce a more accurate characterization of the longitudinal alterations in brain network topology occurring in aging. For this, we constructed whole-brain connectivity maps from diffusion MRI data of two datasets: an aging cohort evaluated at two timepoints (mean interval time: 52.8 ± 7.24 months) and a normative adult cohort-MGH-HCP. State-of-the-art clustering techniques were used to identify the best performing technique. Furthermore, we developed a new metric (connectivity homogeneity fingerprint [CHF]) to evaluate the success of the final CBP in improving regional/global structural connectivity homogeneity. Our results show that our method successfully generates highly homogeneous parcels, as described by the significantly larger CHF score of the resulting parcellation, when compared to the original. Additionally, we demonstrated that the developed parcellation provides a robust anatomical framework to assess longitudinal changes in the aging brain. Our results reveal that aging is characterized by a reorganization of the brain's structural network involving the decrease of intra-hemispheric, increase of inter-hemispheric connectivity, and topological rearrangement. Overall, this study proposes a new methodology to perform accurate and robust evaluations of CBP of the human brain.

Research paper thumbnail of America: a systematic review

Brain structure across the lifespan: the influence of stress

Research paper thumbnail of Biomarkers of resilience and susceptibility in rodent models of stress

Stress Resilience, 2020

Abstract A major current trend in stress research is to consider both the spectrum of responses b... more Abstract A major current trend in stress research is to consider both the spectrum of responses by different individuals to the same stressful stimulus or environment and the dynamics of the stress response within the individual. The motivation for such an approach is the desire for, and need of, developing methods, which are able to identify individuals susceptible/vulnerable to overall stress or to specific stressors and, in that way, to identify those at risk of developing stress-related disorders. Herein, we briefly review and discuss a number of approaches used in this field of research and describe how they led to our current state of knowledge. We also provide a perspective for the future development of the field to produce relevant findings, while simultaneously generating sensitive and specific predictive biomarkers of stress resilience.

Research paper thumbnail of Spatial Normalization of MRI Brain Studies Using a U-Net Based Neural Network

Over recent years, Deep Learning has proven to be an excellent technology to solve problems that ... more Over recent years, Deep Learning has proven to be an excellent technology to solve problems that would otherwise be too complex. Furthermore, it has seen great success in the area of medical imaging, especially when applied to the segmentation of brain tissues. As such, this work explores a possible new approach, using Deep Learning to perform spatial normalization on Magnetic Resonance Imaging brain studies. Spatial normalization of Magnetic Resonance images by tools like FSL, or SPM can be inefficient for researches as they require too many resources to achieve good results. These resources include, for example, wasted human and computer time when executing the commands to normalize and waiting for the process to finish. This can take up to several hours just for one study. Therefore, to enable a faster and easier method to normalize the data, a U-Net based Deep Neural Network was developed using Keras and TensorFlow. This approach should free the researchers’ time for other more ...

Research paper thumbnail of Free-Living Physical Activity Measured With a Wearable Device Is Associated With Larger Hippocampus Volume and Greater Functional Connectivity in Healthy Older Adults: An Observational, Cross-Sectional Study in Northern Portugal

Frontiers in Aging Neuroscience, 2021

Several studies using neuroimaging techniques have established a positive relationship between ph... more Several studies using neuroimaging techniques have established a positive relationship between physical activity (PA) and brain structure and function in older populations. However, the use of subjective measures of PA and the lack of multimodal neuroimaging approaches have limited the understanding of this association. This study aims to explore the associations between PA and brain structure and function by objectively evaluating PA. Community-dwelling cognitively healthy older adults (without diagnosed cognitive, neurological or degenerative disease) were recruited from local health centers and local gyms. In a cross-sectional design, participants were evaluated regarding cognitive, clinical, anthropometric, physical performance, and lifestyle characteristics. A 3 T magnetic resonance imaging (MRI) was performed for structural and functional brain measures. PA time and level was assessed via a Xiaomi Mi Band 2® worn for 15 consecutive days. Participants (n = 110, after inclusion/...

Research paper thumbnail of The Association of Metabolic Dysfunction and Mood Across Lifespan Interacts With the Default Mode Network Functional Connectivity

Frontiers in Aging Neuroscience, 2021

Background: Numerous studies suggest a relationship between depression and metabolic syndrome, wh... more Background: Numerous studies suggest a relationship between depression and metabolic syndrome, which is likely influenced by age. Interestingly, functional imaging analysis has shown an association between functional connectivity in the default mode network (DMN-FC) and components of metabolic syndrome, which is explored in this study. Methods: From a larger longitudinal cohort study on healthy aging, 943 individuals were extensively characterized for mood and cognition. Among these, 120 individuals who were selected for displaying extreme cognitive performance within the normal range (good and poor performers) were further studied. Here, in a cross-sectional design, using confirmatory factor analysis (CFA), the association between metabolic dysfunction and depressive mood as a function of age and its relationship with DMN-FC was studied. Results: Metabolic dysfunction was modeled as a second-order latent variable using CFA. First-order latent variables were obesity, glucose dysmeta...

Research paper thumbnail of Frontoparietal hyperconnectivity during cognitive regulation in obsessive-compulsive disorder followed by reward valuation inflexibility

Journal of Psychiatric Research, 2021

Obsessive-compulsive disorder (OCD) is characterized by cognitive deficits and altered reward pro... more Obsessive-compulsive disorder (OCD) is characterized by cognitive deficits and altered reward processing systems. An imbalance between cognitive and reward pathways may explain the lack of control over obsessions followed by rewarding compulsive behaviors. While the processes of emotional cognitive regulation are widely studied in OCD, the mechanisms of cognitive regulation of reward are poorly described. Our goal was to investigate the OCD impact on cognitive regulation of reward at behavioral and neural functioning levels. OCD and control participants performed a functional magnetic resonance imaging task where they cognitively modulated their craving for food pictures under three cognitive regulation conditions: indulge/increase craving, distance/decrease craving, and natural/no regulation of craving. After regulation, the participants gave each picture a monetary value. We found that OCD patients had fixed food valuation scores while the control group modulated these values accordingly to the regulation conditions. Moreover, we observed frontoparietal hyperconnectivity during cognitive regulation. Our results suggest that OCD is characterized by deficits in cognitive regulation of internal states associated with inflexible behavior during reward processing. These findings bring new insights into the nature of compulsive behaviors in OCD.

Research paper thumbnail of Signatures of white-matter microstructure degradation during aging and its association with cognitive status

Scientific Reports, 2021

Previous studies have shown an association between cognitive decline and white matter integrity i... more Previous studies have shown an association between cognitive decline and white matter integrity in aging. This led to the formulation of a “disconnection hypothesis” in the aging-brain, which states that the disruption in cortical network communication may explain the cognitive decline during aging. Although some longitudinal studies have already investigated the changes occurring in white matter microstructure, most focused on specific white matter tracts. Our study aims to characterize the longitudinal whole-brain signatures of white matter microstructural change during aging. Furthermore, we assessed the relationship between distinct longitudinal alterations in white matter integrity and cognition. White matter microstructural properties were estimated from diffusion magnetic resonance imaging, and cognitive status characterized from extensive neurocognitive testing. The same individuals were evaluated at two timepoints, with a mean interval time of 52.8 months (SD = 7.24) betwee...

Research paper thumbnail of Habitual coffee drinkers display a distinct pattern of brain functional connectivity

Molecular Psychiatry, 2021

Coffee is the most widely consumed source of caffeine worldwide, partly due to the psychoactive e... more Coffee is the most widely consumed source of caffeine worldwide, partly due to the psychoactive effects of this methylxanthine. Interestingly, the effects of its chronic consumption on the brain’s intrinsic functional networks are still largely unknown. This study provides the first extended characterization of the effects of chronic coffee consumption on human brain networks. Subjects were recruited and divided into two groups: habitual coffee drinkers (CD) and non-coffee drinkers (NCD). Resting-state functional magnetic resonance imaging (fMRI) was acquired in these volunteers who were also assessed regarding stress, anxiety, and depression scores. In the neuroimaging evaluation, the CD group showed decreased functional connectivity in the somatosensory and limbic networks during resting state as assessed with independent component analysis. The CD group also showed decreased functional connectivity in a network comprising subcortical and posterior brain regions associated with so...

Research paper thumbnail of Amygdala size varies with stress perception

Neurobiology of Stress, 2021

Stress is inevitably linked to life. It has many and complex facets. Notably, perception of stres... more Stress is inevitably linked to life. It has many and complex facets. Notably, perception of stressful stimuli is an important factor when mounting stress responses and measuring its impact. Indeed, moved by the increasing number of stress-triggered pathologies, several groups drew on advanced neuroimaging techniques to explore stress effects on the brain. From that, several regions and circuits have been linked to stress, and a comprehensive integration of the distinct findings applied to common individuals is being pursued, but with conflicting results. Herein, we performed a volumetric regression analysis using participants' perceived stress as a variable of interest. Data shows that increased levels of perceived stress positively associate with the right amygdala and anterior hippocampal volumes.

Research paper thumbnail of The association of dietary patterns with cognition through the lens of neuroimaging—a Systematic review

Ageing Research Reviews, 2020

Despite the reported benefits of diet on cognition in older adults, randomized controlled trials ... more Despite the reported benefits of diet on cognition in older adults, randomized controlled trials (RCT) testing the impact of dietary interventions on cognitive scores have yielded less promising results when cognition was assessed via neuropsychological tests. More recently, neuroimaging has been used to identify more subtle brainrelated changes associated to cognition. Hence, employing a combination of neuroimaging techniques with neuropsychological tests could clarify this controversy. To determine the effect of diet on cognitive performance, we conducted a systematic review of PubMed and Scopus databases for all studies, on middle-aged and older adults, combining neuroimaging, neuropsychological tests, and data on dietary patterns. The inclusion criteria were met by 14 observational studies and no RCTs. The range of brain measures assessed varied from volumes to white matter integrity, functional connectivity, brain glucose metabolism and beta-amyloid deposition. Given the variability of methods used in assessing cognitive performance, diet and brain correlates, conducting a meta-analysis was not possible. Here the evidence suggests that, in observational studies, dietary patterns may be associated with brain correlates that have been shown to precede cognitive decline. As such, neuroimaging should be included in future RCTs to identify any benefits of diet on brain measures linked with cognitive health.

Research paper thumbnail of Structural neuroimaging biomarkers for obsessive-compulsive disorder in the ENIGMA-OCD consortium: medication matters

ObjectiveNo diagnostic biomarkers are available for obsessive-compulsive disorder (OCD). Magnetic... more ObjectiveNo diagnostic biomarkers are available for obsessive-compulsive disorder (OCD). Magnetic resonance imaging (MRI) studies have provided evidence for structural abnormalities in distinct brain regions, but effect sizes are small and have limited clinical relevance. To investigate whether individual patients can be distinguished from healthy controls, we performed multivariate analysis of structural neuroimaging data from the ENIGMA-OCD consortium.MethodWe included 46 data sets with neuroimaging and clinical data from adult (≥18 years) and pediatric (<18 years) samples. T1 images from 2,304 OCD patients and 2,068 healthy controls were analyzed using standardized processing to extract regional measures of cortical thickness, surface area and subcortical volume. Machine learning classification performance was tested using cross-validation, and possible effects of clinical variables were investigated by stratification.ResultsClassification performance for OCD versus controls u...

Research paper thumbnail of Altered response to risky decisions and reward in patients with obsessive–compulsive disorder

Journal of Psychiatry and Neuroscience, 2020

Background: Patients with obsessive-compulsive disorder (OCD) employ ritualistic behaviours to re... more Background: Patients with obsessive-compulsive disorder (OCD) employ ritualistic behaviours to reduce or even neutralize the anxiety provoked by their obsessions. The presence of excessive rumination and indecision has motivated the view of OCD as a disorder of decision-making. Most studies have focused on the "cold," cognitive aspects of decision-making. This study expands current understanding of OCD by characterizing the abnormalities associated with affective, or "hot" decision-making. Methods: We performed a functional MRI study in a sample of 34 patients with OCD and 33 sex-and age-matched healthy controls, during which participants made 2-choice gambles taking varying levels of risk. Results: During risky decisions, patients showed significantly reduced task-related activation in the posterior cingulum, lingual gyrus and anterior cingulate cortex. We identified significant group × risk interactions in the calcarine cortex, precuneus, amygdala and anterior cingulate cortex. During the outcome phase, patients with OCD showed stronger activation of the orbitofrontal cortex, anterior cingulate cortex and putamen in response to unexpected losses. Limitations: The group of patients not receiving medication was very small (n = 5), which precluded us from assessing the effect of medication on risk-taking behaviour in these patients. Conclusion: Obsessive-compulsive disorder is associated with abnormal brain activity patterns during risky decision-making in a set of brain regions that have been consistently implicated in the processing of reward prediction errors. Alterations in affective "hot" processes implicated in decision-making may contribute to increased indecisiveness and intolerance to uncertainty in patients with OCD.

Research paper thumbnail of Linking sleep quality to brain connectivity: a multimodal MRI approach in normative ageing

Sleep Medicine, 2019

Accumulating evidence suggests that successful OSA treatment with positive airway pressure (PAP) ... more Accumulating evidence suggests that successful OSA treatment with positive airway pressure (PAP) can improve CV outcomes. This study aimed to evaluate the incidence of CV and CeV events and related mortality in 89 males with moderate-to-severe OSA treated with PAP over 10 years, and to assess its relation with PAP adherence. Results: Of the 89 patients included (mean age 53.5±11.7 years, BMI¼33.2±4.9 kg/m 2 , initial AHI¼52.9±20.6 events/h, Epworth scale¼12.2±5.3), 17 were active smokers, 63 had hypertension, 1 hyperuricemia, and 5 had previous CV and/or CeV events. Over follow-up, AHI and Epworth scale decreased significantly (p< 0.001) reaching minimum levels of 2.6±1.8 events/h and 4.2±3.9, respectively. Most of patients were PAP adherent (mean objective com-pliance¼ 93.8±13.9%, with 6.5±1.6 h/use/day). At time of last evaluation, mean adherence rate and hours use/day were, respectively, 98.1±3.1% and 7.0±1.4, being found a progressively strong negative correlation between PAP adherence and CeV/CV events, mostly after the 6 th year. Over this period, 9 patients had CV and 5 CeV events, and 2 experienced both events. Mean survival time was 123.9±25.9 months: lower in those who had CV and/or CeV events (p< 0.001). Ten patients died (3 by CVD complication, 1 myocardial infarction, 2 stroke, and 1 cardiopulmonary arrest). Conclusions: Although AHI presented an immediate and sustained decrease with PAP treatment, only an effective PAP adherence (especially after 24 months) seems to be effective in decreasing CV/CeV events, especially when used for more than 6 years.

Research paper thumbnail of The SIGMA rat brain templates and atlases for multimodal MRI data analysis and visualization

Nature Communications, 2019

Preclinical imaging studies offer a unique access to the rat brain, allowing investigations that ... more Preclinical imaging studies offer a unique access to the rat brain, allowing investigations that go beyond what is possible in human studies. Unfortunately, these techniques still suffer from a lack of dedicated and standardized neuroimaging tools, namely brain templates and descriptive atlases. Here, we present two rat brain MRI templates and their associated gray matter, white matter and cerebrospinal fluid probability maps, generated from ex vivo {\mathrm{T}}_2^ \ast$$T2*-weighted images (90 µm isotropic resolution) and in vivo T2-weighted images (150 µm isotropic resolution). In association with these templates, we also provide both anatomical and functional 3D brain atlases, respectively derived from the merging of the Waxholm and Tohoku atlases, and analysis of resting-state functional MRI data. Finally, we propose a complete set of preclinical MRI reference resources, compatible with common neuroimaging software, for the investigation of rat brain structures and functions.

Research paper thumbnail of Corrigendum: Reduced Hedonic Valuation of Rewards and Unaffected Cognitive Regulation in Chronic Stress

Frontiers in Neuroscience, 2019

Research paper thumbnail of The moderator effect of age in the association between mood and adiposity in the elderly is specific for the subcutaneous adipose compartment: an MRI study

International Journal of Geriatric Psychiatry, 2019

The positive association between obesity and depressive mood in young-and middleage individuals i... more The positive association between obesity and depressive mood in young-and middleage individuals is a phenomenon with major clinical implications in public health. Interestingly, the trend of this association in older individuals is not clear, given the conflicting results of multiple studies. Since aging is accompanied by changes in body fat distribution, we questioned whether age is a modulator of such association. This study explores the role of age in the association between mood and general (body mass index [BMI]) and abdominal adiposity (waist circumference [WC]) in older adults characterizing the different abdominal adipose tissue compartments (subcutaneous adipose tissue [SAT] and visceral adipose tissue [VAT]) with magnetic resonance imaging (MRI) techniques. Methods: One hundred twenty aged community-dwelling individuals (≥50 y of age) were assessed regarding depressive mood (Geriatric Depression Scale) and adiposity (BMI and WC). From these, 96 were assessed for SAT and VAT using MRI. Results: Using multiple linear regression models, depressive mood was positively associated with BMI, WC, and VAT. Age was a significant moderator of the association between depressive mood and BMI, WC, and SAT: positive in younger participants and null or negative in older participants. On the other hand, higher VAT was significantly associated with a more depressive mood, independently of age. Conclusions: This study identifies age as a relevant moderator in the association between depressive mood and adiposity in the elderlies. Furthermore, the body fat compartment analysis revealed that the effect of age is specific for the SAT, suggesting its protective role in depressive mood.