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November 2016 - September 2017
Publications
Publications (67)
Major Depressive Disorder (MDD) is typically characterized by altered linear functional connectivity (FC) across large-scale brain networks. Yet, it is unclear whether similar alterations are observed when nonlinear FC is examined. This study investigated how antidepressant treatment (i.e., psilocybin and escitalopram) modulates both linear FC and...
In Alzheimer’s disease (AD), disrupted connectivity between medial-parietal cortices and medial-temporal lobes (MTL) is linked with increased MTL local functional connectivity, and parietal atrophy is associated with increased MTL memory activation. We hypothesized that intrinsic activity in MTL subregions is increased and associated with medial-pa...
Background
Autosomal dominant progranulin (GRN) mutations are a common genetic cause of frontotemporal lobar degeneration. Though clinical trials for GRN‐related therapies are underway, there is an unmet need for biomarkers that can predict symptom onset and track disease progression. We previously showed that presymptomatic GRN carriers exhibit th...
Psilocybin has been shown to induce fast and sustained improvements in mental well-being across various populations, yet its long-term mechanisms of action are not fully understood. Initial evidence suggests that longitudinal functional and structural brain changes implicate fronto-striatal-thalamic (FST) circuitry, a broad system involved in goal-...
In frontotemporal lobar degeneration (FTLD), pathological protein aggregation in specific brain regions is associated with declines in human-specialized social-emotional and language functions. In most patients, disease protein aggregates contain either TDP-43 (FTLD-TDP) or tau (FTLD-tau). Here, we explored whether FTLD-associated regional degenera...
Objective
Affective symptoms such as anxiety, low mood, and loneliness are prevalent and highly debilitating symptoms among older adults (OA). Serotonergic psychedelics are currently investigated as novel interventions for affective disorders, yet little is known regarding their effects in OA. We investigated the mental health effects and psycholog...
Affective symptoms such as anxiety, low mood, and loneliness are prevalent and highly debilitating symptoms among older adults (OA). Serotonergic psychedelics are novel experimental interventions for affective disorders, yet little is known regarding their effects in OA. Using a prospective cohort design, we identified 62 OA (age ≥ 60 years) and 62...
N,N-Dimethyltryptamine (DMT) is a serotonergic psychedelic, known to rapidly induce short-lasting alterations in conscious experience, characterized by a profound and immersive sense of physical transcendence alongside rich and vivid auditory distortions and visual imagery. Multimodal neuroimaging data paired with dynamic analysis techniques offer...
Cognitive deficits in Alzheimer's disease (AD) and frontotemporal dementia (FTD) result from atrophy and altered functional connectivity. However, it is unclear how atrophy and functional connectivity disruptions relate across dementia subtypes and stages. We addressed this question using structural and functional MRI from 221 patients with AD (n=8...
In frontotemporal lobar degeneration (FTLD), pathological protein aggregation is associated with a decline in human-specialized social-emotional and language functions. Most disease protein aggregates contain either TDP-43 (FTLD-TDP) or tau (FTLD-tau). Here, we explored whether FTLD targets brain regions that express genes containing human accelera...
Objective:
Microtubule-associated protein tau (MAPT) mutations cause frontotemporal lobar degeneration, and novel biomarkers are urgently needed for early disease detection. We used task-free fMRI mapping, a promising biomarker, to analyze network connectivity in symptomatic and presymptomatic MAPT mutation carriers.
Methods:
We compared cross-s...
Importance:
The neurological substrates of visual artistic creativity (VAC) are unknown. VAC is demonstrated here to occur early in frontotemporal dementia (FTD), and multimodal neuroimaging is used to generate a novel mechanistic hypothesis involving dorsomedial occipital cortex enhancement. These findings may illuminate a novel mechanism underly...
Background:
Emergence of novel visual artistic skills has been described in neurodegenerative disorders, particularly in the frontotemporal dementia - amyotrophic lateral sclerosis (FTD-ALS) spectrum, but associated clinical and genetic features and the underlying neural mechanisms have not been systematically examined. We aimed to address these g...
The outflow of the autonomic nervous system (ANS) is continuous and dynamic, but its functional organization is not well understood. Whether ANS patterns accompany emotions, or arise in basal physiology, remain unsettled questions in the field. Here, we searched for brief ANS patterns amidst continuous, multichannel physiological recordings in 45 h...
Background
Treatment-Resistant Depression (TRD) refers to patients with major depressive disorder who do not remit after two or more antidepressant trials. TRD is common and highly debilitating, but its neurobiological basis remains poorly understood. Recent neuroimaging studies have revealed cortical connectivity gradients that dissociate primary...
The human brain exhibits a diverse yet constrained range of activity states. While these states can be faithfully represented in a low-dimensional latent space, our understanding of the constitutive functional anatomy is still evolving. Here we applied dimensionality reduction to task-free and task fMRI data to address whether latent dimensions ref...
Background
Treatment-Resistant Depression (TRD) refers to patients with major depressive disorder who do not remit after two or more antidepressant trials. TRD is common and highly debilitating, but its neurobiological basis remains poorly understood. Recent neuroimaging studies have revealed cortical connectivity gradients that dissociate primary...
Behavioral-variant frontotemporal dementia (bvFTD) is characterized by neurodegeneration in the frontal and anterior temporal lobes leading to insidious and progressive changes in behavior, personality and social functions. The individual neuroimaging studies in bvFTD point to divergent findings. Thus, quantitative assessment of neural abnormalitie...
IMPORTANCE
The neurological substrates of visual creativity are unknown. We demonstrate the role of dorsomedial visual cortex in emergence of visual artistic creativity (VAC) in the setting of dementia. Our findings illuminate neural substrates of human creativity and suggest that hyperactivation of specific brain areas may manifest as enhanced cog...
Introduction:
Numerous studies have reported brain alterations in behavioral variant frontotemporal dementia (bvFTD). However, they pointed to inconsistent findings.
Methods:
We used a meta-analytic approach to identify the convergent structural and functional brain abnormalities in bvFTD. Following current best-practice neuroimaging meta-analys...
Background
Neurodegenerative diseases involve weakened functional connectivity in disease‐targeted brain areas. Equally important but overlooked is the hyperconnectivity that appears in other brain areas (Hillary and Grafman, TICS 2017). Hyperconnectivity has been attributed to processes like disinhibition, imbalance, compensation, and reserve. It...
Background
Clinical trials for tauopathies require novel biomarkers for disease detection and monitoring. One previous study found functional connectivity (FC) alterations in presymptomatic (preSx) MAPT mutation carriers (Whitwell et al ., 2011), yet studies have not examined FC networks along the MAPT disease continuum. We hypothesized that both s...
Background
Progranulin ( GRN ) mutations cause autosomal dominant frontotemporal lobar degeneration. Clinical trials for GRN ‐targeted therapies are underway, yet reliable biomarkers to predict onset and track disease progression remain elusive. Task‐free functional MRI (tf‐fMRI) connectivity may be more sensitive than structural measures for detec...
Whether activity in the autonomic nervous system differs during distinct emotions remains controversial. We obtained continuous multichannel recordings of autonomic nervous system activity in healthy adults during a video-based emotional reactivity task. Dimensionality reduction revealed five principal components in the autonomic time series data,...
INTRODUCTION: Numerous studies have reported brain alterations in behavioral variant frontotemporal dementia (bvFTD). However, they pointed to inconsistent findings. METHODS: We used a meta-analytic approach to identify the convergent structural and functional brain abnormalities in bvFTD. Following the best-practice neuroimaging meta-analysis guid...
Background
Polymorphisms in TMEM106B, a gene on chromosome 7p21.3 involved in lysosomal trafficking, correlates to worse neuropathological and clinical outcomes in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) with TDP‐43 inclusions. In a small cohort of C9orf72 expansion carriers, we previously found an atypical,...
A central goal of systems neuroscience is to determine the functional-anatomical basis of brain-wide activity dynamics. While brain activity patterns appear to be low-dimensional and guided by spatial gradients, the set of gradients remains provisional and their mode of interaction is unclear. Here we applied deep learning-based dimensionality redu...
Each neurodegenerative syndrome reflects a stereotyped pattern of cellular, regional, and large-scale brain network degeneration. In behavioral variant of frontotemporal dementia (bvFTD), a disorder of social-emotional function, von Economo neurons (VENs), and fork cells are among the initial neuronal targets. These large layer 5 projection neurons...
Background
Neuroimaging studies have just begun to explore the acute effects of psychedelics on large-scale brain networks’ functional organization. Even less is known about the neural correlates of subacute effects taking place days after the psychedelic experience. This study explores the subacute changes of primary sensory brain networks and net...
The brain is a complex, multiscale dynamical system composed of many interacting regions. Knowledge of the spatiotemporal organization of these interactions is critical for establishing a solid understanding of the brain’s functional architecture and the relationship between neural dynamics and cognition in health and disease. The possibility of st...
The human anterior insula (aINS) is a topographically organized brain region, in which ventral portions contribute to socio-emotional function through limbic and autonomic connections, whereas the dorsal aINS contributes to cognitive processes through frontal and parietal connections. Open questions remain, however, regarding how aINS connectivity...
In mammals, the hippocampus, entorhinal, perirhinal, and parahippocampal cortices (i.e., core regions of the human medial temporal lobes, MTL) are locally interlaced with the adjacent amygdala nuclei at the structural and functional levels. At the global brain level, the human MTL has been described as part of the default mode network and amygdala...
Background
Neuroimaging studies have just begun to explore the acute effects of psychedelics on large-scale brain networks’ functional organization. Even less is known on the neural correlates of subacute effects taking place days after the psychedelic experience. This study explores the subacute changes of primary sensory brain networks and networ...
The human anterior insula (aINS) is a topographically organized brain region, in which ventral portions contribute to socio-emotional function through limbic and autonomic connections, whereas the dorsal aINS contributes to cognitive processes through frontal and parietal connections. Open questions remain, however, regarding how aINS connectivity...
Each neurodegenerative syndrome presents with characteristic symptoms that reflect the specific pattern of cellular, regional, and large-scale network vulnerability. In behavioral variant frontotemporal dementia (bvFTD), a disorder of social-emotional function, von Economo neurons (VENs) and fork cells are among the initial cellular targets. These...
Introduction:
Heterogeneity of segmentation protocols for medial temporal lobe regions and hippocampal subfields on in vivo magnetic resonance imaging hinders the ability to integrate findings across studies. We aim to develop a harmonized protocol based on expert consensus and histological evidence.
Methods:
Our international working group, fun...
In mammals, the hippocampus, entorhinal, perirhinal, and parahippocampal cortices (i.e., core regions of the human medial temporal lobes, MTL) are locally interlaced with the adjacent amygdala nuclei at the structural and functional levels. At the global brain level, the human MTL has been described as part of the default mode network whereas amygd...
The posteromedial cortex (PMC) and medial temporal lobes (MTL) are two brain regions particularly vulnerable in Alzheimer’s disease (AD). We have reviewed the spatiotemporal patterns of amyloid-β and tau accumulation, local MTL functional alterations and MTL-PMC network reconfiguration, and propose a model to relate these elements to each other. Fu...
Objective:
We aimed to understand the impact of dopamine receptor D4 (DRD4) polymorphisms on neurodegeneration in patients with dementia. We hypothesized that DRD4dampened-variants with reduced functional potency would be associated with greater atrophy in regions with higher receptor density. Given that DRD4 is concentrated in anterior regions of...
For over two decades, the field of neuroimaging hosted a vigorous debate regarding the neural origin, functional significance, and clinical potential of resting functional MRI (rfMRI). While some issues remain unresolved, a large body of work has now established the reliability, neural origins, behavioral relevance, and sensitivity to pathology of...
A prominent finding of postmortem and molecular imaging studies on Alzheimer's disease (AD) is the accumulation of neuropathological proteins in brain regions of the default mode network (DMN). Molecular models suggest that the progression of disease proteins depends on the directionality of signaling pathways. At network level, effective connectiv...
TAR DNA-binding protein 43 (TDP-43) aggregation is the most common pathological hallmark in frontotemporal dementia (FTD) and characterizes nearly all patients with motor neuron disease (MND). The earliest stages of TDP-43 pathobiology are not well-characterized, and whether neurodegeneration results from TDP-43 loss-of-function or aggregation rema...
For over two decades, the field of neuroimaging hosted a vigorous debate regarding the neural origin, functional significance, and clinical potential of resting functional MRI (rfMRI). While some issues remain unresolved, a large body of work has now established the reliability, neural origins, behavioral relevance, and sensitivity to pathology of...
Background:
Neurodegenerative processes in the elderly damage the brain, leading to progressive, incapacitating cognitive, behavioral, and motor dysfunctions which culminate in dementia. Fully manifest dementia is likely to be preceded by the presence of neurological signs, which could serve as early determinants of dementia and predictors of mort...
Background
Both ongoing local metabolic activity (LMA) and corresponding functional connectivity (FC) with remote brain regions are progressively impaired in Alzheimer’s disease (AD), particularly in the posterior default mode network (pDMN); however, it is unknown how these impairments interact. It is well known that decreasing mean synaptic activ...
Functional connectivity of blood oxygenation level dependent signal fluctuations (BOLD-FC) is decreased in Alzheimer’s disease (AD), and suggested to reflect reduced coherence in neural population activity; however, as both neuronal and vascular-hemodynamic processes underlie BOLD signals, impaired perfusion might also contribute to reduced BOLD-FC...
In Alzheimer’s disease (AD), amyloid-β (Aβ) pathology and intrinsic functional connectivity (iFC) interact. Across stages of AD, we expected individual spatial correspondence of Aβ and iFC to reveal both Aβ accumulation and its detrimental effects on iFC. We used resting-state functional magnetic imaging and Aβ imaging in a cross-sectional sample o...
Introduction
Changes in intrinsic functional connectivity (iFC) have been reported at various stages of the Alzheimer's disease (AD) spectrum. We aimed to investigate such alterations over a variety of large-scale intrinsic brain networks (iBNs) across the spectrum of amyloid β positivity and uncover their relation to cognitive impairment.
Methods...
Very early Alzheimer’s disease (AD) – i.e., AD at stages of mild cognitive impairment (MCI) and mild dementia – is characterized by progressive structural and neuropathologic changes, such as atrophy or tangle deposition in medial temporal lobes, including hippocampus and entorhinal cortex and also adjacent amygdala. While progressively disrupted i...
Objectives: Based on the hippocampus disconnection hypothesis in Alzheimer disease (AD), which postulates that uncoupling from cortical inputs contributes to disinhibition-like changes in hippocampus activity, we suggested that in patients with AD, the more the intrinsic functional connectivity between hippocampus and precuneus is decreased, the hi...
Background / Purpose:
The purpose of this study was to investigate the link between ongoing activity in hippocampal subfields and structural degradation of medial parietal areas, within a distributed memory network in Alzheimer's disease.
Main conclusion:
Ongoing activity of hippocampal subfields were increased in Alzheimer's disease and negat...
Background
The hippocampus (HP) is part of the default mode network (DMN), and both are key targets of Alzheimer's disease (AD). Because of widespread network degeneration, it has been suggested that increasing HP disconnection from the DMN may lead to progressive disinhibition of intra-HP synchronized activity.
Methods
To analyze HP local (i.e.,...
Amyloid-β pathology (Aβ) and impaired cognition characterize Alzheimer's disease (AD); however, neural mechanisms that link Aβ-pathology with impaired cognition are incompletely understood. Large-scale intrinsic connectivity networks (ICNs) are potential candidates for this link: Aβ-pathology affects specific networks in early AD, these networks sh...
There is striking overlap between the spatial distribution of amyloid-β pathology in patients with Alzheimer's disease and the spatial distribution of high intrinsic functional connectivity in healthy persons. This overlap suggests a mechanistic link between amyloid-β and intrinsic connectivity, and indeed there is evidence in patients for the detr...
In Alzheimer's disease (AD), recent findings suggest that amyloid-ß-pathology (Aß) might start 20-30 years before first cognitive symptoms arise. To account for age as most relevant risk factor for sporadic AD, it has been hypothesized that lifespan intrinsic (i.e. ongoing) activity of hetero-modal brain areas with highest levels of functional conn...
Disruption of intrinsic functional connectivity (iFC) between hippocampus (HP) and retrosplenial cortex (RSC) is a stable feature of Alzheimer’s disease (AD) and mild cognitive impairment (MCI). Both regions are further characterized by hypometabolism, mainly in the RSC and atrophy, mainly in the HP in early AD. However, little is known about the a...
