Publications by authors named "Richard Edden"

Metabolite concentration estimates from magnetic resonance spectroscopy (MRS) are typically quantified using water referencing, correcting for relaxation-time differences between metabolites and water. One common approach is to correct the reference signal for differential relaxation within three tissue compartments (gray matter, white matter, and cerebrospinal fluid) using fixed literature values. However, water relaxation times (T and T) vary between brain locations and with age.

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Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) has emerged as a powerful imaging technique sensitive to tissue molecular composition, pH, and metabolic processes in situ. CEST MRI uniquely probes the physical exchange of protons between water and specific molecules within tissues, providing a window into physiological phenomena that remain invisible to standard MRI. However, given the very low concentration (millimolar range) of CEST compounds, the effects measured are generally only on the order of a few percent of the water signal.

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Sensory deprivation theory is an important hypothesis involving potential pathways between hearing loss and cognitive impairment in patients with presbycusis. The theory suggests that prolonged auditory deprivation in presbycusis, including neural deafferentation, cortical reallocation, and atrophy, causes long-lasting changes and reorganization in brain structure and function. However, neurophysiological changes underlying the cognition-ear link have not been explored.

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Purpose: Relaxation correction is crucial for accurately estimating metabolite concentrations measured using in vivo MRS. However, the majority of MRS quantification routines assume that relaxation values remain constant across the lifespan, despite prior evidence of T changes with aging for multiple of the major metabolites. Here, we comprehensively investigate correlations between T and age in a large, multi-site cohort.

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Food motivation varies between individuals, affecting body weight and risk for eating disorders. Prior neuroimaging studies in youth and adults have revealed functional and structural alterations in the anterior cingulate cortex [ACC] in those with obesity and disordered eating but have not investigated their neurochemical underpinnings. In a sample of 37 children aged 4 to 13 years old, we used Magnetic Resonance Spectroscopy [MRS] to assess levels of γ-aminobutyric acid [GABA] - the major inhibitory neurotransmitter in the human brain - quantified relative to creatine in a 27-ml voxel including the dorsal ACC.

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The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. The acquisition of multimodal magnetic resonance-based brain development data is central to the study's core protocol. However, application of Magnetic Resonance Imaging (MRI) methods in this population is complicated by technical challenges and difficulties of imaging in early life.

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Purpose: Metabolite amplitude estimates derived from linear combination modeling of MR spectra depend upon the precise list of constituent metabolite basis functions used (the "basis set"). The absence of clear consensus on the "ideal" composition or objective criteria to determine the suitability of a particular basis set contributes to the poor reproducibility of MRS. In this proof-of-concept study, we demonstrate a novel, data-driven approach for deciding the basis-set composition using Bayesian information criteria (BIC).

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Purpose: Relaxometry, specifically and mapping, has become an essential technique for assessing the properties of biological tissues related to various physiological and pathological conditions. Many techniques are being used to estimate and relaxation times, ranging from the traditional inversion or saturation recovery and spin-echo sequences to more advanced methods. Choosing the appropriate method for a specific application is critical since the precision and accuracy of and measurements are influenced by a variety of factors including the pulse sequence and its parameters, the inherent properties of the tissue being examined, the MRI hardware, and the image reconstruction.

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Gamma-aminobutyric acid (GABA), the most important inhibitory neurotransmitter in the human brain, has long been considered essential in human behavior in general and learning in particular. GABA concentration can be quantified using magnetic resonance spectroscopy (MRS). Using this technique, numerous studies have reported associations between baseline GABA levels and various human behaviors.

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Background: The neurobiological underpinnings of Autism Spectrum Disorder (ASD) are diverse and likely multifactorial. One possible mechanism is increased oxidative stress leading to altered neurodevelopment and brain function. However, this hypothesis has mostly been tested in post-mortem studies.

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Cognitive flexibility represents the capacity to switch among different mental schemes, providing an adaptive advantage to a changing environment. The neural underpinnings of this executive function have been deeply studied in humans through fMRI, showing that the left inferior frontal cortex (IFC) and the left inferior parietal lobule (IPL) are crucial. Here, we investigated the inhibitory-excitatory balance in these regions by means of γ-aminobutyric acid (GABA+) and glutamate + glutamine (Glx), measured with magnetic resonance spectroscopy, during a cognitive flexibility task and its relationship with the performance level and the local task-induced blood oxygenation level-dependent (BOLD) response in 40 young (18-35 years; 26 female) and 40 older (18-35 years; 21 female) human adults.

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Cognitive impairment affects 29-67% of patients with neuromyelitis optica spectrum disorder. Previous studies have reported glutamate homeostasis disruptions in astrocytes, leading to imbalances in gamma-aminobutyric acid levels. However, the association between these neurotransmitter changes and cognitive deficits remains inadequately elucidated.

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Purpose: Retrospective frequency-and-phase correction (FPC) methods attempt to remove frequency-and-phase variations between transients to improve the quality of the averaged MR spectrum. However, traditional FPC methods like spectral registration struggle at low SNR. Here, we propose a method that directly integrates FPC into a 2D linear-combination model (2D-LCM) of individual transients ("model-based FPC").

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Purpose: Relaxation correction is crucial for accurately estimating metabolite concentrations measured using magnetic resonance spectroscopy (MRS). However, the majority of MRS quantification routines assume that relaxation values remain constant across the lifespan, despite prior evidence of T changes with aging for multiple of the major metabolites. Here, we comprehensively investigate correlations between T and age in a large, multi-site cohort.

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Background: To examine data quality and reproducibility using ISTHMUS, which has been implemented as the standardized MR spectroscopy sequence for the multi-site Healthy Brain and Child Development (HBCD) study.

Methods: ISTHMUS is the consecutive acquisition of short-TE PRESS (32 transients) and long-TE HERCULES (224 transients) data with dual-TE water reference scans. Voxels were positioned in the centrum semiovale, dorsal anterior cingulate cortex, posterior cingulate cortex and bilateral thalamus regions.

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Background: Anorexia nervosa (AN) is a mental and behavioral health condition characterized by an intense fear of weight or fat gain, severe restriction of food intake resulting in low body weight, and distorted self-perception of body shape or weight. While substantial research has focused on general anxiety in AN, less is known about eating-related anxiety and its underlying neural mechanisms. Therefore, we sought to characterize anxiety-to-eat in AN and examine the neurometabolic profile within the dorsal anterior cingulate cortex (dACC), a brain region putatively involved in magnifying the threat response.

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Purpose: The J-difference edited γ-aminobutyric acid (GABA) signal is contaminated by other co-edited signals-the largest of which originates from co-edited macromolecules (MMs)-and is consequently often reported as "GABA+." MM signals are broader and less well-characterized than the metabolites, and are commonly approximated using a Gaussian model parameterization. Experimentally measured MM signals are a consensus-recommended alternative to parameterized modeling; however, they are relatively under-studied in the context of edited MRS.

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Background: Hearing impairment is a common condition in the elderly. However, a comprehensive understanding of its neural correlates is still lacking.

Methods: We recruited 284 elderly adults who underwent structural MRI, magnetic resonance spectroscopy, audiometry, and cognitive assessments.

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Alterations in the structure, function, and microcirculation of the thalamus, a key brain region involved in pain pathways, have previously been demonstrated in patients with painless and painful diabetic peripheral neuropathy (DPN). However, thalamic neurotransmitter levels including γ-aminobutyric acid (GABA) (inhibitory neurotransmitter) and glutamate (excitatory neurotransmitter) in different DPN phenotypes are not known. We performed a magnetic resonance spectroscopy study and quantified GABA and glutamate levels within the thalamus, in a carefully characterized cohort of participants with painless and painful DPN.

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Article Synopsis
  • A new 3D CEST mapping technique, called 3DSOS, was developed and compared with traditional methods to assess its effectiveness in mapping guanidino and amide levels in the human brain.
  • * The method optimized scanning parameters to maximize efficiency and demonstrated superior image quality and reliability compared to segmented 3D EPI techniques.
  • * Results indicated that 3DSOS achieved comparable or better sensitivity for both guanidino and amide markers, along with greater robustness against motion artifacts, making it effective for whole-brain imaging.
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During aging, the brain is subject to greater oxidative stress (OS), which is thought to play a critical role in cognitive impairment. Glutathione (GSH), as a major antioxidant in the brain, can be used to combat OS. However, how brain GSH levels vary with age and their associations with cognitive function is unclear.

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Background: To examine data quality and reproducibility using ISTHMUS, which has been implemented as the standardized MR spectroscopy sequence for the multi-site Healthy Brain and Child Development (HBCD) study.

Methods: ISTHMUS is the consecutive acquisition of short-TE PRESS (32 transients) and long-TE HERCULES (224 transients) data with dual-TE water reference scans. Voxels were positioned in the centrum semiovale, dorsal anterior cingulate cortex, posterior cingulate cortex and bilateral thalamus regions.

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Objective: To compare the GABA+/Glx (glutamate-glutamine) ratio in the prefrontal lobe under non-rapid eye movement sleep between patients with narcolepsy type 1 (NT1) and normal controls and explore the correlation between this difference and abnormal cognitive function, using synchronous electroencephalography-functional magnetic resonance spectroscopy (EEG-fMRS).

Methods: MRS measurements of GABA+ and Glx concentrations as well as synchronous EEG data were obtained from 26 medication-naive patients with NT1 and 29 sex- and age-matched healthy community volunteers. Cognition was appraised with the Beijing version of the Montreal Cognitive Assessment, and daytime sleepiness was measured using the Epworth Sleepiness Scale.

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Purpose: Retrospective frequency-and-phase correction (FPC) methods attempt to remove frequency-and-phase variations between transients to improve the quality of the averaged MR spectrum. However, traditional FPC methods like spectral registration struggle at low SNR. Here, we propose a method that directly integrates FPC into a two-dimensional linear-combination model (2D-LCM) of individual transients ('model-based FPC').

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Relaxation correction is an integral step in quantifying brain metabolite concentrations measured by in vivo magnetic resonance spectroscopy (MRS). While most quantification routines assume constant T relaxation across age, it is possible that aging alters T relaxation rates, as is seen for T relaxation. Here, we investigate the age dependence of metabolite T relaxation times at 3 T in both gray- and white-matter-rich voxels using publicly available metabolite and metabolite-nulled (single inversion recovery TI = 600 ms) spectra acquired at 3 T using Point RESolved Spectroscopy (PRESS) localization.

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