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Introduction
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Publications
Publications (533)
Childhood exposure to social disadvantage is a major risk factor for psychiatric disorders and poor developmental, educational, and occupational outcomes, presumably because adverse exposures alter the neurodevelopmental processes that contribute to risk trajectories. Yet, given the limited social mobility in the United States and other countries,...
Multiple studies have shown that hyperglycemia increases the cerebral metabolic rate of glucose (CMRglc) in subcortical white matter. This observation remains unexplained. Using positron emission tomography (PET) and euinsulinaemic glucose clamps, we found, for the first time, that acute hyperglycemia increases non-oxidative CMRglc (i.e., aerobic g...
A single dose of psilocybin, a psychedelic that acutely causes distortions of space–time perception and ego dissolution, produces rapid and persistent therapeutic effects in human clinical trials1–4. In animal models, psilocybin induces neuroplasticity in cortex and hippocampus5–8. It remains unclear how human brain network changes relate to subjec...
Background
Functional connectivity (FC) biomarkers play a crucial role in the early diagnosis and mechanistic study of Alzheimer’s disease (AD). However, the identification of effective FC biomarkers remains challenging. In this study, we introduce a novel approach, the spatiotemporal graph convolutional network (ST-GCN) combined with the gradient-...
The red nucleus is a large brainstem structure that coordinates limb movement for locomotion in quadrupedal animals (Basile et al., 2021). The humans red nucleus has a different pattern of anatomical connectivity compared to quadrupeds, suggesting a unique purpose (Hatschek, 1907). Previously the function of the human red nucleus remained unclear a...
Neural activity in awake organisms shows widespread and spatiotemporally diverse correlations with behavioral and physiological measurements. We propose that this covariation reflects in part the dynamics of a unified, arousal-related process that regulates brain-wide physiology on the timescale of seconds. This interpretation motivates a surprisin...
1
Summary
The relationship between the acute effects of psychedelics and their persisting neurobiological and psychological effects is poorly understood. Here, we tracked brain changes with longitudinal precision functional mapping in healthy adults before, during, and for up to 3 weeks after oral psilocybin and methylphenidate (17 MRI visits per...
Major depressive disorder (MDD) is widely hypothesized to result from disordered communication across brain-wide networks. Yet, prior resting-state-functional MRI (rs-fMRI) studies of MDD have studied zero-lag temporal synchrony (functional connectivity) in brain activity absent directional information. We utilize the recent discovery of stereotype...
Motor cortex (M1) has been thought to form a continuous somatotopic homunculus extending down the precentral gyrus from foot to face representations1,2, despite evidence for concentric functional zones³ and maps of complex actions⁴. Here, using precision functional magnetic resonance imaging (fMRI) methods, we find that the classic homunculus is in...
The distribution of brain aerobic glycolysis (AG) in normal young adults correlates spatially with amyloid-beta (Aβ) deposition in individuals with symptomatic and preclinical Alzheimer disease (AD). Brain AG decreases with age, but the functional significance of this decrease with regard to the development of AD symptomatology is poorly understood...
Hippocampal metabolism has been variably reported to be decreased in Alzheimer’s disease (AD), and is less well studied during preclinical stages of AD. Since AD is associated with significant hippocampal atrophy, careful segmentation and partial volume correction methods are necessary. Here we performed manual segmentation of the hippocampus coupl...
White matter lesions in cerebral small vessel disease are related to ischemic injury and increase the risk of stroke and cognitive decline. Pathological changes due to cerebral small vessel disease are increasingly recognized outside of discrete lesions, but the metabolic alterations in nonlesional tissue has not been described. Aerobic glycolysis...
The sleep-wake cycle is a master regulator of metabolic and neuronal activity and when altered, can have profound effects on metabolic health and disease. Although consideration is given to how fluctuations in blood glucose affect peripheral physiology and metabolism, less is known about how glucose dysregulation impacts the intrinsic cooperation b...
Changes in the levels of circulating proteins are associated with Alzheimer’s disease (AD), whereas their pathogenic roles in AD are unclear. Here, we identified soluble ST2 (sST2), a decoy receptor of interleukin-33–ST2 signaling, as a new disease-causing factor in AD. Increased circulating sST2 level is associated with more severe pathological ch...
The distribution of brain aerobic glycolysis (AG) in normal young adults correlates spatially with amyloid-beta (Aβ) deposition in individuals with dementia of the Alzheimer type (DAT) and asymptomatic individuals with brain amyloid deposition. Brain AG decreases with age but the functional significance of this decrease with regard to the developme...
Exploring individual hallmarks of brain ageing is important. Here, we propose the age-related glucose metabolism pattern (ARGMP) as a potential index to characterize brain ageing in cognitively normal (CN) elderly people. We collected 18F-fluorodeoxyglucose (18F-FDG) PET brain images from two independent cohorts: the Alzheimer’s Disease Neuroimagin...
Background:
Currently, brain tissue atrophy serves as an in vivo MRI biomarker of neurodegeneration in Alzheimer's disease (AD). However, postmortem histopathological studies show that neuronal loss in AD exceeds volumetric loss of tissue and that loss of memory in AD begins when neurons and synapses are lost. Therefore, in vivo detection of neuro...
Background
FDG PET measurements of cerebral glucose hypometabolism in brain regions that are preferentially affected by Alzheimer’s disease (AD) are known to be associated with clinical decline. However, commonly used FDG PET indices such as the standard uptake value ratio (SUVR) lack the sensitivity to detect early metabolic changes associated wit...
Background
Currently, brain tissue atrophy serves as in vivo structural MRI biomarker of neurodegeneration in Alzheimer Disease (AD). However, postmortem histopathological studies show that neuronal loss in AD exceeds volumetric loss of tissue and that AD‐related memory loss begins when neurons are lost. Hence, in vivo detection of neurodegeneratio...
While significant progress has been achieved in studying resting-state functional networks in a healthy human brain and in a wide range of clinical conditions, many questions related to their relationship to the brain’s cellular constituents remain. Here, we use quantitative Gradient-Recalled Echo (qGRE) MRI for mapping the human brain cellular com...
Significance
The finding that human hippocampal-cortical functional connectivity is nonunitary, separated along functional network borders (default mode network [DMN], self-oriented; parietal memory network [PMN], goal-oriented) in the anterior–posterior axis, raises various possibilities as to why this organization might be beneficial and could in...
While significant progress has been achieved in studying resting state functional networks in a healthy human brain and in a wide range of clinical conditions, many questions related to their relationship to the brain's cellular constituents remain open. In this paper we use quantitative Gradient Recalled Echo (qGRE) MRI for in vivo quantitative ma...
We propose and empirically support a parsimonious account of intrinsic, brain-wide spatiotemporal organization arising from traveling waves linked to arousal. We hypothesize that these waves are the predominant physiological process reflected in spontaneous functional magnetic resonance imaging (fMRI) signal fluctuations. The correlation structure...
Background: Currently, brain tissue atrophy serves as in vivo MRI biomarker of neurodegeneration in Alzheimer Disease (AD). However, postmortem histopathological studies show that neuronal loss in AD exceeds volumetric loss of tissue and that loss of memory in AD begins when neurons and synapses are lost. Therefore, in vivo detection of neuronal lo...
Significance
Many studies have examined plasticity in the primary somatosensory and motor cortex during disuse, but little is known about how disuse impacts the brain outside of primary cortical areas. We leveraged the whole-brain coverage of resting-state functional MRI (rs-fMRI) to discover that disuse drives plasticity of distant executive contr...
Significance
Slow waves are the predominant feature of brain activity during sleep and anesthesia. Slow waves are associated with plasticity, memory consolidation, and other brain functions. However, much remains unknown about the brain circuits that coordinate slow wave propagation. Here, we demonstrate that somatosensory stimulation evokes bilate...
The hippocampus is critically important for a diverse range of cognitive processes, such as episodic memory, prospective memory, affective processing, and spatial navigation. The human hippocampus has been thought of as being solely functionally connected to a set of neocortical regions known as the default mode network (DMN), which supports self-r...
Whole-brain resting-state functional MRI (rs-fMRI) during two weeks of limb constraint revealed that disused motor regions became more strongly connected to the cingulo-opercular network (CON), an executive control network that includes regions of the dorsal anterior cingulate cortex (dACC) and insula (1). Disuse-driven increases in functional conn...
Patterns of low frequency brain-wide activity have drawn attention across multiple disciplines in neuroscience. Brain-wide activity patterns are often described through correlations, which capture concurrent increases and decreases in neural activity. More recently, several groups have described reproducible temporal sequences across the brain, ill...
In Alzheimer’s disease, brain amyloid deposition has a distinct topography that correlates with aerobic glycolysis (AG), i.e., the use of glucose in the brain beyond that predicted by oxygen consumption. The causes for this relationship remain unclear but might provide critical insight into how and why amyloid deposition begins. Here we develop sta...
Significance
Accumulating evidence suggests that, during task performance, information is encoded at shorter timescales in primary sensory regions as compared to longer timescales in higher-order cortical regions. These encoding timescales correlate with the timescales of activity within these regions. Here, we test the hypothesis that a hierarchy...
To induce brain plasticity in humans, we casted the dominant upper extremity for 2 weeks and tracked changes in functional connectivity using daily 30-min scans of resting-state functional MRI (rs-fMRI). Casting caused cortical and cerebellar regions controlling the disused extremity to functionally disconnect from the rest of the somatomotor syste...
Spontaneous infra-slow brain activity (ISA) exhibits a high degree of temporal synchrony, or correlation, between distant brain regions. The spatial organization of ISA synchrony is not explained by anatomical connections alone, suggesting that active neural processes coordinate spontaneous activity. Inhibitory interneurons (IINs) form electrically...
Electrophysiological recordings have established that GABAergic interneurons regulate excitability, plasticity, and computational function within local neural circuits. Importantly, GABAergic inhibition is focally disrupted around sites of brain injury. However, it remains unclear whether focal imbalances in inhibition/excitation lead to widespread...
Background: Major prevention trials for Alzheimer’s disease (AD) are now focusing on multidomain lifestyle interventions. However, the exact combination of behavioral factors related to AD pathology remains unclear. In 2 cohorts of cognitively unimpaired individuals at risk of AD, we examined which combinations of personality traits, neuropsychiatr...
The amygdala is central to the pathophysiology of many psychiatric illnesses. An imprecise understanding of how the amygdala fits into the larger network organization of the human brain, however, limits our ability to create models of dysfunction in individual patients to guide personalized treatment. Therefore, we investigated the position of the...
OASIS-3 is a compilation of MRI and PET imaging and related clinical data for 1098 participants who were collected across several ongoing studies in the Washington University Knight Alzheimer Disease Research Center over the course of 15 years. Participants include 605 cognitively normal adults and 493 individuals at various stages of cognitive dec...
Experts review the latest research on the neocortex and consider potential directions for future research.
Over the past decade, technological advances have dramatically increased information on the structural and functional organization of the brain, especially the cerebral cortex. This explosion of data has radically expanded our ability to chara...
Spontaneous infra-slow (<0.1 Hz) fluctuations in functional magnetic resonance imaging (fMRI) signals are temporally correlated within large-scale functional brain networks, motivating their use for mapping systems-level brain organization. However, recent electrophysiological and hemodynamic evidence suggest state-dependent propagation of infra-sl...
Tauopathy is a hallmark pathology of Alzheimer's disease with a strong relationship with cognitive impairment. As such, understanding tau may be a key to clinical interventions. In vivo tauopathy has been measured using cerebrospinal fluid assays, but these do not provide information about where pathology is in the brain. The introduction of PET li...
Accumulating evidence indicates that resting-state functional magnetic resonance imaging (rsfMRI) signals correspond to propagating electrophysiological infra-slow activity (<0.1 Hz). Thus, pairwise correlations (zero-lag functional connectivity (FC)) and temporal delays among regional rsfMRI signals provide useful, complementary descriptions of sp...
Significance
Prior work has identified many sex differences in the brain, including during brain aging and in neurodegenerative diseases. Notably, many of these studies are performed by comparing age-matched females and males. Evolutionary theorists have predicted that females might have more youthful brains (neoteny) as compared with males, but un...
The cerebellum contains the majority of neurons in the human brain and is unique for its uniform cytoarchitecture, absence of aerobic glycolysis, and role in adaptive plasticity. Despite anatomical and physiological differences between the cerebellum and cerebral cortex, group-average functional connectivity studies have identified networks related...
Significance
Understanding the structure and function of the human brain at a cellular level is a fundamental aim of neuroscience. Tremendous progress has been made in recent years based on different in vivo and ex vivo approaches, including major advances in brain MRI. However, uncertainties remain in determining how brain MRI measurements relate...
Glucose is the predominant fuel supporting brain function. If the brain’s entire glucose supply is consumed by oxidative phosphorylation, the molar ratio of oxygen to glucose consumption (OGI) is equal to 6. An OGI of less than 6 is evidence of non-oxidative glucose metabolism. Several studies have reported that the OGI in the resting human brain i...
Papers excluded after a full-text review.
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Assessment of bias within studies.
(NA = Not Applicable; NS = Not stated).
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Summary characteristics of included studies.
Studies that were found only through searching the first authors records are indicated by a *. (NA = Not Applicable).
(DOCX)
Appraising success in meeting the world's nutritional needs has largely focused on infant mortality and anthropometric measurements with an emphasis on the first 1,000 days (conception to approximately age 2 years). This ignores the unique nutritional needs of the human brain. Although the intrauterine environment and the early postnatal years are...
A hallmark of non-rapid eye movement (REM) sleep is the decreased brain activity as measured by global reductions in cerebral blood flow, oxygen metabolism, and glucose metabolism. It is unknown whether the blood oxygen level dependent (BOLD) signal undergoes similar changes. Here we show that, in contrast to the decreases in blood flow and metabol...
https://deepblue.lib.umich.edu/bitstream/2027.42/153153/1/alzjjalz2018062845.pdf
Adequate nutrition is critical for human brain development, which depends particularly upon glucose. The adult human brain accounts for 20% to 25% of total body resting glucose consumption, and studies indicate that the developing brain requires an even greater percentage of glucose. Here we critically review the currently available data on glucose...
Purpose:
Temporal lobe epilepsy (TLE) affects resting state brain networks in adults. This study aims to correlate resting state functional MRI (rsMRI) signal latency in pediatric TLE patients with their laterality.
Methods:
From 2006 to 2016, 26 surgical TLE patients (12 left, 14 right) with a mean age of 10.7 years (range 0.9-18) were prospect...
Glucose and oxygen metabolism are tightly coupled in the human brain, with the preponderance of the brain’s glucose supply used to generate ATP via oxidative phosphorylation. A fraction of glucose is consumed outside of oxidative phosphorylation despite the presence of sufficient oxygen to do so. We refer to this process as aerobic glycolysis. A re...
Research of the human brain metabolism in vivo has largely focused on total glucose use (via FDG PET) and, until recently, did not examine the use of glucose outside oxidative phosphorylation which is known as aerobic glycolysis (AG). AG supports important functions including biosynthesis and neuroprotection but decreases dramatically with aging. T...
Systems-level organization in spontaneous infra-slow (<0.1Hz) brain activity, measured using blood oxygen signals in fMRI and optical imaging, has become a major theme in the study of neural function in both humans and animal models. Yet the neurophysiological basis of infra-slow activity (ISA) remains unresolved. In particular, is ISA a distinct p...
Directed signaling among and within the large-scale networks of the human brain is functionally critical. Recent advances in our understanding of spontaneous fluctuations of the fMRI BOLD signal have provided strategies to study the spatial-temporal properties of directed signaling at infra-slow frequencies. Herein we explore the relationship betwe...
Background:
Models of Alzheimer's disease propose a sequence of amyloid β (Aβ) accumulation, hypometabolism, and structural decline that precedes the onset of clinical dementia. These pathological features evolve both temporally and spatially in the brain. In this study, we aimed to characterise where in the brain and when in the course of the dis...