Ibai Diez

• PhD
• PostDoc Position at Massachusetts General Hospital

Background: Neuroimaging studies of functional neurological disorder (FND), a condition at the intersection of psychiatry and neurology, often rely on discrete connections or parcellations that may obscure the brain's functional network architecture. This study applied a gradient-based approach to examine macroscale cortical organization in FND. Me...

Functional neurological disorder (FND) is a neuropsychiatric condition that is framed as a multi-network brain problem. Despite this conceptualization, studies have generally focused on specific regions or connectivity features, under-characterizing the complex and nuanced role of resting-state networks in FND pathophysiology. This study employed t...

Background BrainAge models estimate the biological age of the brain using neuroimaging or clinical features, making them promising tools for studying neurodegenerative diseases like Alzheimers disease (AD). However, the reliance of BrainAge models on neuroimaging features such as gray matter volume and hippocampal atrophy, can introduce biases link...

Background While the precuneus’ role in integrating diverse brain functions and its early involvement in Alzheimer’s Disease (AD) is well established, the differential impact of AD pathology on its subregions is poorly understood. This study aims to delineate the differential involvement and vulnerability of these subdivisions in the early stages o...

INTRODUCTION Global life expectancy has steadily increased in recent decades, resulting in a significant rise in the number of individuals aged 80 years and older. This trend is also evident in Latin America, where life expectancy is improving, though at varying rates across countries and regions. METHODS Partnering with the Neurosciences Group of...

The brain’s modular organization, ranging from microcircuits to large-scale networks, has been extensively studied in terms of its structural and functional properties. Particularly insightful has been the investigation of the coupling between structural connectivity (SC) and functional connectivity (FC), whose analysis has revealed important insig...

Objective Visual disability in Parkinson's disease (PD) is not fully explained by retinal neurodegeneration. We aimed to delineate the brain substrate of visual dysfunction in PD and its association with retinal thickness. Methods Forty‐two PD patients and 29 controls underwent 3‐Tesla MRI, retinal spectral‐domain optical coherence tomography, and...

Background Brain atrophy is a normal part of healthy aging, but it is aggravated by several neurodegenerative diseases. Previous studies have described a large heterogeneity in individual neurodegeneration patterns, but the underlying brain mechanisms are currently not fully understood. From a graph theory‐based framework, the estimation of subject...

Background Brain atrophy is a normal part of healthy aging, but it is aggravated by several neurodegenerative diseases. Previous studies have described a large heterogeneity in individual neurodegeneration patterns, but the underlying brain mechanisms are currently not fully understood. From a graph theory‐based framework, the estimation of subject...

Background A novel method using diffusion‐weighted imaging (DWI) allows for assessing microstructural injury in the gray matter by measuring cortical mean diffusivity (cMD). Previous studies have shown that altered cMD is related to amyloid (Aβ) cross‐sectionally and can predict longitudinal cognitive decline and clinical progression, suggesting ut...

Background The accumulation of misfolded tau proteins, an Alzheimer’s disease (AD) hallmark, starts decades before the emergence of cognitive decline and clinical diagnosis. Autopsy studies support a predictable progression of tau pathology through large‐scale systems. However, less is known about the specific progression patterns. The use of conne...

Background Some individuals can tolerate the presence of Alzheimer disease neuropathologic changes (ADNC) (e.g., plaques and tangles) without developing dementia. A better understanding of the mechanisms underlying this brain resilience to ADNC may inform the development of novel disease biomarkers and therapies. We investigated the differences in...

The human brain is organized as a hierarchical global network. Functional connectivity research reveals that sensory cortices are connected to corresponding association cortices via a series of intermediate nodes linked by synchronous neural activity. These sensory pathways and relay stations converge onto central cortical hubs such as the default‐...

Objective: Research suggests that disrupted interoception contributes to the development and maintenance of functional neurological disorder (FND); however, no functional neuroimaging studies have examined the processing of interoceptive signals in patients with FND. Methods: The authors examined univariate and multivariate functional MRI neural...

Growing evidence suggests that cerebral connectivity changes its network organization by altering modular topology in response to developmental and environmental experience. However, changes in cerebral connectivity associated with visual impairment due to early neurological injury are still not fully understood. Cerebral visual impairment (CVI) is...

Background Brain imaging studies investigating grey matter in functional neurological disorder (FND) have used univariate approaches to report group-level differences compared with healthy controls (HCs). However, these findings have limited translatability because they do not differentiate patients from controls at the individual-level. Methods 1...

Highly Superior Autobiographical Memory (HSAM) is a rare form of enhanced memory in which individuals demonstrate an extraordinary ability to remember details of their personal lives with high levels of accuracy and vividness. Neuroimaging studies have identified brain regions - specifically, midline areas within the default network - associated wi...

Background Changes in everyday functioning constitute a clinically meaningful outcome, even in the early stages of Alzheimer's disease. Performance-based assessments of everyday functioning might help uncover these early changes. We aimed to investigate how changes over time in everyday functioning relate to tau and amyloid in cognitively unimpaire...

The direct access of olfactory afferents to memory-related cortical systems has inspired theories about the role of the olfactory pathways in the development of cortical neurodegeneration in Alzheimer’s disease (AD). In this study, we used baseline olfactory identification measures with longitudinal flortaucipir and PiB PET, diffusion MRI of 89 cog...

Autopsy studies indicated that the locus coeruleus (LC) accumulates hyperphosphorylated tau before allocortical regions in Alzheimer’s disease. By combining in vivo longitudinal magnetic resonance imaging measures of LC integrity, tau positron emission tomography imaging and cognition with autopsy data and transcriptomic information, we examined wh...

Background Unawareness is a behavioral condition characterized by a lack of self-awareness of objective memory decline. In the context of Alzheimer’s Disease (AD), unawareness may develop in predementia stages and contributes to disease severity and progression. Here, we use in-vivo multi-modal neuroimaging to profile the brain phenotype of individ...

This multimodal brain imaging study investigated functional MRI (fMRI) neural processing of cardiac interoceptive signals in 38 patients with functional neurological disorder (FND) compared to 38 healthy controls (HCs). Additionally, we characterized how brain fMRI responses during heartbeat counting (interoception) vs. tone counting (exteroception...

The human brain is an extremely complex network of structural and functional connections that operate at multiple spatial and temporal scales. Investigating the relationship between these multi-scale connections is critical to advancing our comprehension of brain function and disorders. However, accurately predicting structural connectivity from it...

Alzheimer’s disease (AD) is a neurodegenerative disorder that is beginning with amyloidosis, followed by neuronal loss and deterioration in structure, function, and cognition. The accumulation of amyloid-\(\beta \) in the brain, measured through 18F-florbetapir (AV45) positron emission tomography (PET) imaging, has been widely used for early diagno...

Background Mnemonic anosognosia (i.e., unawareness) is a behavioral condition characterized by a lack of self‐awareness of objective memory decline. In the context of Alzheimer’s Disease (AD), unawareness may be a sign of predementia stages. It contributes to disease severity, symptomatology worsening, and caregiver burden and is a good predictor o...

Background Patients with Alzheimer’s disease (AD) often demonstrate anosognosia, which is reduced awareness of cognitive decline. Anosognosia has been associated with tau accumulation (d'Oleire Uquillas et al., 2020) and impaired resting‐state functional connectivity (FC) in self‐referential networks (Vannini et al., 2017, Valera‐Bermejo et al., 20...

Background Misfolded tau protein, an Alzheimer’s Disease (AD) hallmark, accumulates decades before the emergence of cognitive decline. Autopsy and neuroimaging studies support the locus coeruleus (LC) as an early site of tau and its contribution to disease progression. However, whether tau in LC precedes cortical tau deposition remains unclear. Und...

It is poorly known how Aβ and tau accumulations associate at the spatiotemporal level in the in vivo human brain to impact cognitive changes in older adults prior to AD symptoms onset. In this study, we used a graph theory-based spatiotemporal analysis to characterize the cortical patterns of Aβ and tau deposits and their relationship with cognitiv...

The neuroscience of creativity seeks to disentangle the complex brain processes that underpin the generation of novel ideas. Neuroimaging studies of functional connectivity, particularly functional magnetic resonance imaging (fMRI), have revealed individual differences in brain network organization associated with creative ability; however, much of...

The human brain is an extremely complex network of structural and functional connections that operate at multiple spatial and temporal scales. Investigating the relationship between these multi-scale connections is critical to advancing our comprehension of brain function and disorders. However, accurately predicting structural connectivity from it...

Introduction Non-invasive diffusion-weighted imaging (DWI) to assess brain microstructural changes via cortical mean diffusivity (cMD) has been shown to be cross-sectionally associated with tau in cognitively normal older adults, suggesting that it might be an early marker of neuronal injury. Here, we investigated how regional cortical microstructu...

Alzheimer's disease (AD) is a neurodegenerative disorder that is beginning with amyloidosis, followed by neuronal loss and deterioration in structure, function, and cognition. The accumulation of amyloid-beta in the brain, measured through 18F-florbetapir (AV45) positron emission tomography (PET) imaging, has been widely used for early diagnosis of...

Background: There is little consensus and controversial evidence on anatomical alterations in the brain of patients with autism spectrum disorder (ASD), due in part to the large heterogeneity present in ASD, which in turn is a major drawback for developing therapies. One strategy to characterize this heterogeneity in ASD is to cluster large-scale...

Background: We aimed to characterize subtypes of synucleinopathies using a clustering approach based on cognitive and other nonmotor data and to explore structural and functional magnetic resonance imaging (MRI) brain differences between identified clusters. Methods: Sixty-two patients (n = 6 E46K-SNCA, n = 8 dementia with Lewy bodies (DLB) and...

Non‐invasive diffusion‐weighted imaging (DWI) to assess brain microstructural changes via cortical mean diffusivity (cMD) was recently shown to be cross‐sectionally associated with tau in cognitively‐normal older adults (Rodriguez‐Vieitez et al., Mol. Psych. 2021), suggesting that it might be an early marker of neuronal injury. However, the impact...

Studies suggest that internally oriented cognitive processes are central to creativity. Here, we distinguish between intentional and unintentional forms of mind wandering and explore their behavioral and neural correlates. We used a sample of 155 healthy adults from the mind-brain-body dataset, all of whom completed resting-state fMRI scans and tra...

The human brain generates a rich repertoire of spatio-temporal activity patterns, which support a wide variety of motor and cognitive functions. These patterns of activity change with age in a multi-factorial manner. One of these factors is the variations in the brain’s connectomics that occurs along the lifespan. However, the precise relationship...

Cognitive impairment, and working memory deficits in particular, are debilitating, treatment-resistant aspects of schizophrenia. Dysfunction of brain network hubs, putatively related to altered neurodevelopment, is thought to underlie the cognitive symptoms associated with this illness. Here, we used weighted degree, a robust graph theory metric re...

Within stress-diathesis models, adverse life experiences (ALEs) increase the susceptibility to functional neurological symptoms through neuroplasticity effects. We aimed to characterize potential genetic influences on this relationship in 20 patients with functional seizures. Questionnaires, structural MRIs and Allen Human Brain Atlas gene expressi...

A key hallmark of Alzheimer’s disease (AD) pathology is the intracellular accumulation of tau protein in the form of neurofibrillary tangles across large-scale networks of the human brain cortex. Currently, it is still unclear how tau accumulates within specific cortical systems and whether in situ genetic traits play a role in this circuit-based p...

The large heterogeneity in autism spectrum disorder (ASD) is a major drawback for the development of therapies. Here, we apply consensus-subtyping strategies based on functional connectivity patterns to a population of N=657 quality-assured autistic subjects. We found two major subtypes (each divided hierarchically into several minor subtypes): Sub...

Objective: This study aimed to illuminate potential gene expression influences in neuroanatomical variation related to adverse life experiences (ALEs) and functional neurological symptom severity in patients with functional seizures. Background: ALEs increase the susceptibility to psychopathologies, likely through neurodevelopmental and genetic eff...

SIGNIFICANCE Amyloid-β and tau, hallmark pathologies of Alzheimer’s disease (AD), are hypothesized to spread through brain functional networks that are critical for neural communication. Using high-resolution network analyses and positron emission tomography, we showed that greater tau burden was related to functional dysconnectivity of regions ass...

Understanding the architectural principle that shapes the topology of the human connectome at its multiple spatial scales is a major challenge for systems neuroscience. This would provide key fundamental principles and a theory for browsing brain’s networks, to ultimately generate hypothesis and approach to which extent key structures might impact...

Background: Dissociative seizures (DS) are a common subtype of functional neurological disorder (FND) with an incompletely understood pathophysiology. Here, gray matter variations and their relationship to clinical features were investigated. Methods: Forty-eight patients with DS without neurological comorbidities and 43 matched clinical control...

Small vessel disease (SVD) is a disorder that causes vascular lesions in the entire parenchyma of the human brain. At present, it is not well known how primary and secondary damage interact to give rise to the complex scenario of white matter (WM) and grey matter (GM) lesions. Using novel cross-sectional and longitudinal connectomic approaches, we...

The genetic traits that underlie vulnerability to neuronal damage across specific brain circuits in Parkinson’s disease (PD) remain to be elucidated. In this study, we characterized the brain topological intersection between propagating connectivity networks in controls and PD participants and gene expression patterns across the human cortex – such...

Objective: Adverse life experiences (ALEs) increase the susceptibility to functional (somatoform/dissociative) symptoms, likely through neurodevelopmental effects. This analysis aimed to illuminate potential genetic influences in neuroanatomical variation related to functional symptoms and ALEs in patients with functional seizures. Methods: Questio...

Background Subjective perception of cognitive decline is identified as an important marker related to the risk of progression to Alzheimer's disease. However, loss of awareness has also been observed in predementia stages, potentially reducing the validity of the subjective experience. The aim of this study was to characterize the trajectories of c...

Background Alzheimer’s disease (AD)‐related pathology (i.e., amyloid‐β and neurofibrillary tangles) disrupts functional networks that support higher‐order cognitive functions. Yet, it is not well known how the brain’s functional architecture is differentially associated with in vivo pathology in preclinical AD, which is critical for predicting dise...

Background Obsessive-Compulsive Symptoms (OCS) during childhood predispose to Obsessive-Compulsive Disorder (OCD) and have been associated with changes in brain circuits altered in OCD samples. OCS may arise from disturbed glutamatergic neurotransmission, impairing cognitive oscillations and promoting over-stable functional states. Methods 227 hea...

The relationship between human brain connectomics and genetic evolutionary traits remains elusive due to the inherent challenges in combining complex associations within cerebral tissue. In this study, insights are provided about the relationship between connectomics, gene expression and divergent evolutionary pathways from non-human primates to hu...

The human brain generates a rich repertoire of spatio-temporal activity patterns, which support a wide variety of motor and cognitive functions. These patterns of activity change with age in a multi-factorial manner. One of these factors is the variations in the brain’s connectomics that occurs along the lifespan. However, the precise relationship...

Functional neurological (conversion) disorder (FND) is a neuropsychiatric condition whereby individuals present with sensorimotor symptoms incompatible with other neurological disorders. Early-life maltreatment (ELM) is a risk factor for developing FND, yet few studies have investigated brain network–trauma relationships in this population. In this...

The ability to produce novel ideas is central to societal progress and innovation; however, little is known about the biological basis of creativity. Here, we investigate the organization of brain networks that support creativity by combining functional neuroimaging data with gene expression information. Given the multifaceted nature of creative th...

The human brain is composed of functional networks that have a modular topology, where brain regions are organized into communities that form internally dense (segregated) and externally sparse (integrated) subnetworks that underlie higher-order cognitive functioning. It is hypothesized that amyloid-β and tau pathology in preclinical Alzheimer’s di...

Investment decisions rely on perceptions from external stimuli along with the integration of inner brain-body signals, all of which are shaped by experience. As experience is capable of molding both the structure and function of the human brain, we have used a novel neuroimaging connectomic-genetic approach to investigate the influence of investmen...

Objective: To discover new physiological markers of pains perception by reading out the brains electrical activity and its interaction with hemodynamics. Methods: We present a prototype consisting of a compact setup that on one hand generates well-controlled thermal stimuli produced by a Peltier cell controlled by a computer, and on the other ha...

Purpose of review: The prevalence of new public datasets of brain-wide and single-cell transcriptome data has created new opportunities to link neuroimaging findings with genetic data. The aim of this study is to present the different methodological approaches that have been used to combine this data. Recent findings: Drawing from various source...

Amyloid‐beta (Aβ) plaques and tau neurofibrillary tangles are pathological hallmarks of Alzheimer's disease (AD); their contribution to neurodegeneration and clinical manifestations are critical in understanding preclinical AD. At present, the mechanisms related to Aβ and tau pathogenesis leading to cognitive decline in older adults remain largely...

Aim To delineate the neurogenetic profiles of brain degeneration patterns in Myotonic Dystrophy Type I (DM1). Methods In two cohorts of DM1 patients, brain maps of volume loss (VL) and neuropsychological deficits (ND) were intersected to large‐scale transcriptome maps provided by the Allen Human Brain Atlas (AHBA). For validation, neuropathologica...

Functional networks provide a topological description of activity patterns in the brain, as they stem from the propagation of neural activity on the underlying anatomical or structural network of synaptic connections. This latter is well known to be organized in hierarchical and modular way. While it is assumed that structural networks shape their...

Brain networks can be defined and explored through their connectivity. Here, we analyzed the relationship between structural connectivity (SC) across 2,514 regions that cover the entire brain and brainstem, and their dynamic functional connectivity (DFC). To do so, we focused on a combination of two metrics: the first assesses the degree of SC-DFC...

Background: Brain interdependencies can be studied from either a structural/anatomical perspective ("structural connectivity") or by considering statistical interdependencies ("functional connectivity" [FC]). Interestingly, while structural connectivity is by definition pairwise (white-matter fibers project from one region to another), FC is not. H...

It is claimed that investment decision-making should rely on rational analyses based on facts and not emotions. However, trying to make money out of market forecasts can trigger all types of emotional responses. As the question on how investors decide remains controversial, we carried out an activation likelihood estimation (ALE) meta-analysis usin...

Recent studies of creative cognition have revealed interactions between functional brain networks involved in the generation of novel ideas; however, the neural basis of creativity is highly complex and presents a great challenge in the field of cognitive neuroscience, partly because of ambiguity around how to assess creativity. We applied a novel...

Functional neurological (conversion) disorder (FND) was of great interest to early clinical neuroscience leaders. During the 20th century, neurology and psychiatry grew apart - leaving FND a borderland condition. Fortunately, a renaissance has occurred in the last two decades, fostered by increased recognition that FND is prevalent and diagnosed us...

In motor functional neurological disorders (mFND), relationships between inter-oception (a construct of high theoretical relevance to its pathophysiology) and neuro-anatomy have not been previously investigated. This study characterized white matter in mFND patients compared to healthy controls (HCs), and investigated associations between fiber bun...

Brain networks can be defined and explored through their connectivity. Here, we analyzed the relationship between structural connectivity (SC) across 2,514 regions that cover the entire brain and brainstem, and their dynamic functional connectivity (DFC). To do so, we focused on a combination of two metrics: the first assesses the degree of SC-DFC...

The authors have withdrawn their manuscript because after a peer-review process of four different reviewers, several important points were raised, which made us go over all concerns. One major concern involved a gene-wise statistical control for multiple testing, which, after implementation, changed the main conclusion of the study. Other points in...

Objective To characterize the progression of brain structural abnormalities in adults with pediatric and adult/late onset DM1, as well as to examine the potential predictive markers of such progression. Methods 21 DM1 patients (pediatric onset: N = 9; adult/late onset: N = 12) and 18 healthy controls (HC) were assessed longitudinally over 9.17 yea...

Despite significant research, the biological mechanisms underlying the brain degeneration in Myotonic Dystrophy Type I (DM1) remain largely unknown. Here we have assessed brain degeneration by measuring the volume loss (VL) and cognitive deficits (CD) in two cohorts of DM1 patients, and associating them to the large-scale brain transcriptome maps p...

Objective To develop a new device that will help identify physiological markers of pain perception by reading the brain’s electrical activity and the bodies hemodynamic interactions while applying thermoalgesic stimulation. Methods: We designed a compact prototype that generates well-controlled thermal stimuli using a computer driven Peltier cell w...

Neuroimaging studies describing brain circuits’ alterations in cobalamin (vitamin B12)-deficient patients are limited and have not been carried out in patients with inborn errors of cobalamin metabolism. The objective of this study was to assess brain functionality and brain circuit alterations in a patient with an ultra-rare inborn error of cobala...

Brain interdependencies can be studied either from a structural/anatomical perspective ("structural connectivity", SC) or by considering statistical interdependencies ("functional connectivity", FC). Interestingly, while SC is typically pairwise (white-matter fibers start in a certain region and arrive at another), FC is not; however, most FC analy...

Brain networks can be defined and explored using different types of connectivity. Here, we studied P=48 healthy participants with neuroimaging state-of-the-art techniques and analyzed the relationship between the actual structural connectivity (SC) networks (between 2514 regions of interest covering the entire brain and brainstem) and the dynamical...

Functional networks provide a topological description of activity patterns in the brain, as they stem from the propagation of activity on the anatomical, or structural network of synaptic connections, which possess a hierarchical organization. While it is assumed that structural networks shape their functional counterparts, it is also hypothesized...

Significance Previous research has explored the association between behavioral disorders and dysfunction in corresponding neural networks. For example, autism spectrum disorder, Prader–Willi syndrome, and Dravet syndrome are characterized by behavioral deficits in the visuomotor integration system. To date, few investigations have combined brain co...

Alzheimer's disease (AD) is associated with brain network dysfunction. Network-based investigations of brain connectivity have mainly focused on alterations in the strength of connectivity; however, the network breakdown in AD spectrum is a complex scenario in which multiple pathways of connectivity are affected. To integrate connectivity changes t...

Multiorgan failure (MOF) is a life-threating condition that affects two or more systems of organs not involved in the disorder that motivates admission to an Intensive Care Unit (ICU). Patients who survive MOF frequently present long-term functional, neurological, cognitive, and psychiatric sequelae. However, the changes to the brain that explain s...

Background Functional neurological disorder (FND) is a condition at the intersection of neurology and psychiatry. Individuals with FND exhibit corticolimbic abnormalities, yet little is known about the role of white matter tracts in the pathophysiology of FND. This study characterized between-group differences in microstructural integrity, and corr...