Roser Sala-Llonch

University of Barcelona | UB · Department of Biomedicine

COVER ILLUSTRATION Larger cohorts of multi‐site MRI data are crucial for neuroimaging research. Harmonization strategies become necessary. The WHARMPA method is user‐friendly and provides a powerful solution to clean the analyses by removing variability associated with the differences between sites. These Weighted HARMonization PArameters encode gl...

Linear Mixed Effects (LME) modelling under both frequentist and Bayesian frameworks have been suggested to study longitudinal trajectories. We studied the performance of both approaches on different dataset configurations using hippocampal volumes from longitudinal MRI data across groups - healthy controls (HC), mild cognitive impairment (MCI) and...

BackgroundMRI atrophy predicts cognitive status in AD. However, this relationship has not been investigated in early-onset AD (EOAD, < 65 years) patients with a biomarker-based diagnosis.Methods Forty eight EOAD (MMSE ≥ 15; A + T + N +) and forty two age-matched healthy controls (HC; A − T − N −) from a prospective cohort underwent full neuropsycho...

Multi-site MRI datasets are crucial for big data research. However, neuroimaging studies must face the batch effect. Here, we propose an approach that uses the predictive probabilities provided by Gaussian processes (GPs) to harmonize clinical-based studies. A multi-site dataset of 216 Parkinson's disease (PD) patients and 87 healthy subjects (HS)...

There is evidence longitudinal atrophy in posterior brain areas in early-onset Alzheimer’s disease (EOAD; aged<65years), but no studies have been conducted in an EOAD cohort with fluid biomarkers characterization. We used 3T-MRI and Freesurfer 6.0 to investigate cortical and subcortical gray matter loss at two years in 12 EOAD patients (A+T+N+) com...

Previous evidence suggests that transcranial direct current stimulation (tDCS) to the left dorsolateral prefrontal cortex (l-DLPFC) can enhance episodic memory in subjects with subjective cognitive decline (SCD), known to be at risk of dementia. Our main goal was to replicate such findings in an independent sample and elucidate if baseline magnetic...

The combination of transcranial direct current stimulation (tDCS) with functional magnetic resonance imaging (fMRI) can provide original data to investigate age-related brain changes. We examined neural activity modulations induced by two multifocal tDCS procedures based on two distinct montages fitting two N-back task-based fMRI patterns (“compens...

Background: Probabilistic tractography, in combination with graph theory, has been used to reconstruct the structural whole-brain connectome. Threshold-free network-based statistics (TFNBS) is a useful technique to study structural connectivity in neurodegenerative disorders; however, there are no previous studies using TFNBS in Parkinson's diseas...

Background Parkinson's disease (PD) is a heterogeneous condition. Cluster analysis based on cortical thickness has been used to define distinct patterns of brain atrophy in PD. However, the potential of other neuroimaging modalities, such as white matter (WM) fractional anisotropy (FA), which has also been demonstrated to be altered in PD, has not...

Changes in functional connectivity (FC) networks have been extensively reported in late onset Alzheimer’s Disease (AD), being the default mode network (DMN) the key system to be affected. However, it remains unclear if FC in early‐onset AD (EOAD) would show a similar pattern than late onset AD. We studied 48 EOAD patients (mean age=57.40±5.53 years...

Structural neuroimaging longitudinal studies in Alzheimer’s disease (AD) have consistently defined a “cortical signature” of gray matter loss. Apparently, early‐onset AD (EOAD) has a greater density of amyloid, a more generalized atrophy and a more aggressive evolution than late‐onset AD (LOAD). We hypothesize EOAD would show pronounced longitudina...

The combination of transcranial direct current stimulation (tDCS) with functional magnetic resonance imaging (fMRI) is able to provide original data about how brain change in aging. Furthermore, tDCS procedures might moderate age‐related brain functional changes associated to cognitive decline. In the present study, we aimed to investigate in which...

Mutations in the granulin gene (GRN) cause familial frontotemporal dementia. Understanding the structural brain changes in presymptomatic GRN carriers would enforce the use of neuroimaging biomarkers for early diagnosis and monitoring. We studied 100 presymptomatic GRN mutation carriers and 94 noncarriers from the Genetic Frontotemporal dementia in...

Brain changes commonly occurring in aging can be indexed by biomarkers. We used cluster analysis to identify sub-groups of individuals with different biomarker profiles. CSF from cognitively unimpaired individuals (n=99, 64-93 years) was analyzed for concentrations of Aβ42, phosphorylated tau (P-tau), and total tau (T-tau), and biomarkers for neuro...

Prior studies have described distinct patterns of brain gray matter and white matter alterations in Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD), as well as differences in their cerebrospinal fluid (CSF) biomarkers profiles. We aim to investigate the relationship between early‐onset AD (EOAD) and FTLD structural alterations...

Background: Walnut consumption counteracts oxidative stress and inflammation, 2 drivers of cognitive decline. Clinical data concerning effects on cognition are lacking. Objectives: The Walnuts And Healthy Aging study is a 2-center (Barcelona, Spain; Loma Linda, CA) randomized controlled trial examining the cognitive effects of a 2-y walnut inter...

Despite the well-described deleterious effects of aging on cognition, some individuals are able to show stability. Here, we aimed to describe the functional and structural brain characteristics of older individuals, particularly focusing on those with stable working memory (WM) performance, as measured with a verbal N-back task across a 2-year foll...

A better and non-invasive characterization of the preclinical phases of Alzheimer’s disease (AD) is important to advance its diagnosis and obtain more effective benefits from potential treatments. The TgF344-AD rat model has been well characterized and shows molecular, behavioral and brain connectivity alterations that resemble the silent period of...

Individuals with autosomal dominant Alzheimer's disease (ADAD) present amyloid deposits before symptoms onset. We aimed to investigate efficacy and safety of 18F-florbetaben (FBB) for assessing amyloid deposition in ADAD. We acquired FBB positron emission tomography and magnetic resonance imaging of 25 individuals from PSEN1 families (NCT02362880)....

Introduction: [¹⁸F]fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET) is part of the regular preoperative work-up in medically refractory epilepsy. As a complement to visual evaluation of PET, statistical parametric maps can help in the detection of the epileptogenic zone (EZ). However, software packages currently available are time-co...

Appendix S1: Supporting Information.

The analysis of Functional Connectivity (FC) is a key technique of fMRI, having been used to distinguish brain states and conditions. While many approaches to calculating FC are available, there have been few assessments of their differences, making it difficult to choose approaches, and compare results. Here, we assess the impact of methodological...

Sleep problems relate to brain changes in aging and disease, but the mechanisms are unknown. Studies suggest a relationship between β-amyloid (Aβ) accumulation and sleep, which is likely augmented by interactions with multiple variables. Here, we tested how different cerebrospinal fluid (CSF) biomarkers for brain pathophysiology, brain atrophy, mem...

Amyloid deposition occurs in aging, even in individuals free from cognitive symptoms, and is often interpreted as preclinical Alzheimer's disease (AD) pathophysiology. YKL-40 is a marker of neuroinflammation, being increased in AD, and hypothesized to interact with amyloid-β (Aβ) in causing cognitive decline early in the cascade of AD pathophysiolo...

High education, as a proxy of cognitive reserve (CR), has been associated with cognitive advantage amongst old adults and may operate through neuroprotective and/or compensation mechanisms. In neuromaging studies, indirect evidences of neuroprotection can be inferred from positive relationships between CR and brain integrity measures. In contrast,...

Cerebrospinal fluid (CSF) neurofilament light (NFL) is a marker of axonal degeneration. We tested whether CSF NFL levels predict hippocampal atrophy rate in cognitively healthy older adults independently of the established CSF Alzheimer’s disease (AD) biomarkers, β-amyloid 1-42 (Aβ42) and phosphorylated tau (P-tau). We included 144 participants in...

Cognitive reserve (CR) models posit that lifestyle factors such as education modulate the relationship between brain damage and cognition. However, the functional correlates of CR in healthy aging are still under investigation. White matter hyperintensities (WMH) are a common age-associated finding that impacts cognition. In this study, we used fMR...

Transcranial Magnetic Stimulation (TMS) was proposed as a neurophysiological tool almost three decades ago. It now encompasses a very wide range of applications including clinical research and the treatment of psychiatric, neurologic and medical conditions such as depression, schizophrenia, addictions, post-traumatic stress disorders, pain, migrain...

PSEN1 mutations are the most frequent cause of autosomal dominant Alzheimer's disease (ADAD), and show nearly full penetrance. There is presently increasing interest in the study of biomarkers that track disease progression in order to test therapeutic interventions in ADAD. We used white mater (WM) volumetric characteristics and diffusion tensor i...

There is a growing realization that early life influences have lasting impact on brain function and structure. Recent research has demonstrated that genetic relationships in adults can be used to parcellate the cortex into regions of maximal shared genetic influence, and a major hypothesis is that genetically programmed neurodevelopmental events ca...

To date, limited data are available regarding the inter-site consistency of test-retest reproducibility of functional connectivity measurements, in particular with regard to integrity of the Default Mode Network (DMN) in elderly participants. We implemented a harmonized resting-state fMRI protocol on 13 clinical scanners at 3.0T using vendor-provid...

Neural correlates of working memory (WM) in healthy subjects have been extensively investigated using functional MRI (fMRI). However it still remains unclear how cortical areas forming part of functional WM networks are also connected by white matter fiber bundles, and whether DTI measures, used as indices of microstructural properties and directio...

Healthy aging (HA) is associated with certain declines in cognitive functions, even in individuals that are free of any process of degenerative illness. Functional magnetic resonance imaging (fMRI) has been widely used in order to link this age-related cognitive decline with patterns of altered brain function. A consistent finding in the fMRI liter...

The human brain is a complex network that has been noted to contain a group of densely interconnected hub regions. With a putative "rich club" of hubs hypothesized to play a central role in global integrative brain functioning, we assessed whether hub and rich club organizations are associated with cognitive performance in healthy participants and...

Ageing entails cognitive and motor decline as well as brain changes such as loss of gray (GM) and white matter (WM) integrity, neurovascular and functional connectivity alterations. Regarding connectivity, reduced resting-state fMRI connectivity between anterior and posterior nodes of the Default Mode Network (DMN) relates to cognitive function and...

Graph-theoretical analyses of functional networks obtained with resting-state functional magnetic resonance imaging (fMRI) have recently proven to be a useful approach for the study of the substrates underlying cognitive deficits in different diseases. We used this technique to investigate whether cognitive deficits in Parkinson's disease (PD) are...

The purpose of this work was to evaluate changes in the connectivity patterns of a set of cognitively relevant, dynamically interrelated brain networks in association with cognitive deficits in Parkinson's disease (PD) using resting-state functional MRI. Sixty-five nondemented PD patients and 36 matched healthy controls were included. Thirty-four p...

We used resting-functional magnetic resonance imaging data from 98 healthy older adults to analyze how local and global measures of functional brain connectivity are affected by age, and whether they are related to differences in memory performance. Whole-brain networks were created individually by parcellating the brain into 90 cerebral regions an...

Background Transcranial Magnetic Stimulation (TMS) can affect episodic memory, one of the main cognitive hallmarks of aging, but the mechanisms of action remain unclear. Objectives: To evaluate the behavioral and functional impact of excitatory TMS in a group of healthy elders. Methods We applied a paradigm of repetitive TMS -intermittent theta-bu...

Large-scale longitudinal multi-site MRI brain morphometry studies are becoming increasingly crucial to characterize both normal and clinical population groups using fully automated segmentation tools. The test–retest reproducibility of morphometry data acquired across multiple scanning sessions, and for different MR vendors, is an important reliabi...

Obesity is a major health problem in modern societies. It has been related to abnormal functional organization of brain networks believed to process homeostatic (internal) and/or salience (external) information. This study used resting-state functional magnetic resonance imaging analysis to delineate possible functional changes in brain networks re...

Signal intensity contrast of T1-weighted MRI scans has been associated with tissue integrity and reported as a sign of neurodegenerative changes in diseases such as AD. After severe traumatic brain injury (TBI), progressive structural changes occur in white and gray matter. In the current study, we assessed the signal intensity contrast of gray mat...

Importance: The study of brain activity and connectivity at rest provides a unique opportunity for the investigation of the brain substrates of cognitive outcome after traumatic axonal injury. This knowledge may contribute to improve clinical management and rehabilitation programs. Objective: To study functional magnetic resonance imaging abnorm...

PSEN1 mutations are the most frequent cause of familial Alzheimer's disease and show nearly full penetrance. Here we studied alterations in brain function in a cohort of 19 PSEN1 mutation carriers: 8 symptomatic (SMC) and 11 asymptomatic (AMC). Asymptomatic carriers were, on average, 12 years younger than the predicted age of disease onset. Thirtee...

Cognitive reserve capacity may increase tolerance of neurodegenerative processes. However, its role regarding amyloid-β (Aβ42) deposition in cognitively normal subjects is not well understood. We aimed to investigate the association between areas showing Aβ42-related structural changes and cognitive reserve proxies in cognitively intact subjects sh...

Studies in asymptomatic granulin gene (GRN) mutation carriers are essential to improve our understanding of the pattern and timing of early morphologic brain changes in frontotemporal lobar degeneration. The main objectives of this study were to assess the effect of age in cortical thickness changes (CTh) in preclinical GRN mutation carriers and to...

Obesity is a health problem that has become a major focus of attention in recent years. There is growing evidence of an association between obesity and differences in reward processing. However, it is not known at present whether these differences are linked exclusively to food, or whether they can be detected in other rewarding stimuli. We compare...

Background: In a previous functional MRI (fMRI) study, we found that patients with Parkinson's disease (PD) presented with dysfunctions in the recruitment of recognition memory networks. We aimed to investigate the changes in these networks over time. Methods: We studied 17 PD patients and 13 age and sex matched healthy subjects. In both groups...

Obesity is a health problem that has become a major focus of attention in recent years. There is growing evidence of an association between obesity and differences in reward processing. However, it is not known at present whether these differences are linked exclusively to food, or whether they can be detected in other rewarding stimuli. We compare...

To identify long-term effects of preterm birth and of periventricular leukomalacia (PVL) on cortical thickness (CTh). To study the relationship between CTh and cognitive-behavioral abnormalities. We performed brain magnetic resonance imaging on 22 preterm children with PVL, 14 preterm children with no evidence of PVL and 22 full-term peers. T1-weig...

In recent years, several theories have been proposed in attempts to identify the neural mechanisms underlying successful cognitive aging. Old subjects show increased neural activity during the performance of tasks, mainly in prefrontal areas, which is interpreted as a compensatory mechanism linked to functional brain efficiency. Moreover, resting-s...

In this study functional magnetic resonance imaging (fMRI) is used to investigate the functional brain activation pattern in the preclinical stage of AD (pre-AD) subjects during a visual encoding memory task. Thirty subjects, eleven in the pre-AD stage, with decreased cerebrospinal fluid levels of Aβ42 (<500 pg/ml), and 19 controls with normal Aβ42...