Brain metabolite alterations and cognitive dysfunction in early Huntington's disease.

Huntington's disease (HD) is a neurodegenerative disorder characterized by early cognitive decline that progresses at later stages to dementia and severe movement disorder. HD is caused by a cytosine-adenine-guanine triplet-repeat expansion mutation in the Huntingtin gene, allowing early diagnosis by genetic testing. This study aimed to identify the relationship of N-acetylaspartate and other brain metabolites to cognitive function in HD-mutation carriers by using high-field-strength magnetic resonance spectroscopy (MRS) at 7 Tesla.

Frontal GABA levels change during working memory.

Functional neuroimaging metrics are thought to reflect changes in neurotransmitter flux, but changes in neurotransmitter levels have not been demonstrated in humans during a cognitive task, and the relationship between neurotransmitter dynamics and hemodynamic activity during cognition has not yet been established. We evaluate the concentration of the major inhibitory (GABA) and excitatory (glutamate + glutamine: Glx) neurotransmitters and the cerebral perfusion at rest and during a prolonged delayed match-to-sample working memory task. Resting GABA levels in the dorsolateral prefrontal cortex correlated positively with the resting perfusion and inversely with the change in perfusion during the task.

Altered excitation-inhibition balance in the brain of patients with diabetic neuropathy.

Rationale And Objectives: To assess differences in excitatory (glutamate/glutamine or Glx) and inhibitory (γ-Aminobutyric acid or GABA) neurotransmitter levels using MR spectroscopy in pain processing regions of the brain in patients diabetic neuropathy (DN) and positive sensory symptoms and age-matched healthy control (HC) subjects.

Materials And Methods: Seven diabetic patients (5 males, 2 females, mean age = 57.0 ± 8.

Regionally specific human GABA concentration correlates with tactile discrimination thresholds.

The neural mechanisms underlying variability in human sensory perception remain incompletely understood. In particular, few studies have attempted to investigate the relationship between in vivo measurements of neurochemistry and individuals' behavioral performance. Our previous work found a relationship between GABA concentration in the visual cortex and orientation discrimination thresholds (Edden et al.

Measuring T2 in vivo with J-difference editing: application to GABA at 3 Tesla.

Purpose: To develop an experimental approach for determining in vivo transverse relaxation rates (T(2)) of metabolites that are detected by spectral editing without using simulations, and to demonstrate this approach to measure the T(2) of γ-aminobutyric acid (GABA).

Materials And Methods: The proposed method first determines the TE-dependence of the edited signals using measurements in a pure phantom solution (10 mM γ-aminobutyric acid; GABA); the phantom T(2) is also determined. Once the editing echo time (TE)-modulation pattern is known, it can then be used to determine T(2) in vivo.

Reduced insular γ-aminobutyric acid in fibromyalgia.

Objective: Recent scientific findings have reinvigorated interest in examining the role of γ-aminobutyric acid (GABA), the major inhibitory central nervous system neurotransmitter, in chronic pain conditions. Decreased inhibitory neurotransmission is a proposed mechanism in the pathophysiology of chronic pain syndromes such as fibromyalgia (FM). The purpose of this study was to test the hypothesis that decreased levels of insular and anterior cingulate GABA would be present in FM patients, and that the concentration of this neurotransmitter would be correlated with pressure-pain thresholds.

Spatial and orientational heterogeneity in the statistical sensitivity of skeleton-based analyses of diffusion tensor MR imaging data.

Group comparisons of indices derived from diffusion tensor imaging are common in the literature. An increasingly popular approach to performing such comparisons is the skeleton-projection based approach where, for example, fractional anisotropy (FA) values are projected onto a skeletonized version of the data to minimize differences due to spatial misalignment. In this work, we examine the spatial heterogeneity of the statistical power to detect group differences, and show that there is an intrinsic spatial heterogeneity, with more 'central' structures having less variance within a population.

Dorsolateral prefrontal γ-aminobutyric acid in men predicts individual differences in rash impulsivity.

Background: Impulsivity is a multifaceted personality construct associated with numerous psychiatric disorders. Recent research has characterized four facets of impulsivity: "urgency" (the tendency to act rashly especially in the context of distress or cravings); "lack of premeditation" (not envisaging the consequences of actions); "lack of perseverance" (not staying focused on a task); and "sensation seeking" (engaging in exciting activities). Urgency is particularly associated with clinical populations and problematic disinhibited behavior.

If J doesn't evolve, it won't J-resolve: J-PRESS with bandwidth-limited refocusing pulses.

There is increasing interest in the J-PRESS technique, an in vivo implementation of two-dimensional J-spectroscopy combined with PRESS localization, for high-field spectroscopy studies of the human brain. The experiment is designed to resolve scalar couplings in the second, indirectly detected dimension, but will only do so if the slice-selective refocusing pulses in the PRESS sequence affect all coupled spins equally. At high magnet field strengths, due to limited RF pulse bandwidth, PRESS-based localization results in spatially dependent evolution of coupling.

In vivo detection of GABA and glutamate with MEGA-PRESS: reproducibility and gender effects.

Purpose: To evaluate the reproducibility of γ-amino-butyric acid (GABA) and glutamate concentrations derived using three different spectral fitting methods, and to investigate gender-related differences in neurotransmitter levels.

Materials And Methods: Single voxel MEGA-edited PRESS MR spectra were acquired from a 30-mL voxel in the dorso-lateral prefrontal cortex in 14 adult volunteers (7 female) at 3 Tesla (3T). For each participant, four consecutive resting spectra were acquired within the same scanning session.

Individual variability in the shape and amplitude of the BOLD-HRF correlates with endogenous GABAergic inhibition.

It has previously been demonstrated that there is a negative correlation between the amplitude of the BOLD response and resting γ amino-butyric acid (GABA) concentration in visual cortex. The work here is the first to empirically characterize individual variability in the haemodynamic response functions (HRFs) in response to a simple visual stimulus and baseline GABA concentration in a population of young adult males (n = 15, aged 20-28 years). The results demonstrate that GABA concentration is negatively correlated with BOLD response amplitude (r = -0.

High resolution spectroscopic imaging of GABA at 3 Tesla.

A spin echo-based MRSI sequence was developed to acquire edited spectra of γ-aminobutyric acid in an entire slice. Water and lipid signals were suppressed by a dual-band presaturation sequence, which included integrated outer volume suppression pulses for additional lipid suppression. Experiments in three normal volunteers were performed at 3 T using a 32-channel head coil.

Individual differences in subconscious motor control predicted by GABA concentration in SMA.

Subliminal visual stimuli affect motor planning, but the size of such effects differs greatly between individuals. Here, we investigated whether such variation may be related to neurochemical differences between people. Cortical responsiveness is expected to be lower under the influence of more of the main inhibitory neurotransmitter, GABA.

Longitudinal and multi-echo transverse relaxation times of normal breast tissue at 3 Tesla.

Purpose: To measure longitudinal (T(1)) and multi-echo transverse (T(2)) relaxation times of healthy breast tissue at 3 Tesla (T).

Materials And Methods: High-resolution relaxation time measurements were made in six healthy female subjects. Inversion recovery images were acquired at 10 inversion times between 100 ms and 4000 ms, and multiple spin echo images were acquired at 16 echo times between 10 ms and 160 ms.

In vivo measurement of brain GABA concentrations by magnetic resonance spectroscopy in smelters occupationally exposed to manganese.

Background: Exposure to excessive levels of manganese (Mn) is known to induce psychiatric and motor disorders, including parkinsonian symptoms. Therefore, finding a reliable means for early detection of Mn neurotoxicity is desirable.

Objectives: Our goal was to determine whether in vivo brain levels of γ-aminobutyric acid (GABA), N-acetylaspartate (NAA), and other brain metabolites in male smelters were altered as a consequence of Mn exposure.

Edited MRS is sensitive to changes in lactate concentration during inspiratory hypoxia.

Purpose: To demonstrate the application of Mescher-Garwood (MEGA) point-resolved spectroscopy sequence (PRESS) editing to the detection of lactate in the brain at 3T and to investigate changes in lactate concentration associated with inspiratory gas challenges.

Materials And Methods: Edited lactate measurements were made in six healthy volunteers while the subjects breathed normoxic (21% O(2)), hypoxic (12% O(2)), and hyperoxic (40% O(2)) gas mixtures. Lactate concentration was quantified relative to the unsuppressed water signal from the same volume.

More GABA, less distraction: a neurochemical predictor of motor decision speed.

People vary markedly in the efficiency with which they can resolve competitive action decisions, even simple ones such as shifting gaze to one stimulus rather than another. We found that an individual's ability to rapidly resolve such competition is predicted by the concentration of GABA, the main inhibitory neurotransmitter, in a region of frontal cortex that is relevant for eye movements, but not in a control region (occipital cortex).

Diurnal stability of gamma-aminobutyric acid concentration in visual and sensorimotor cortex.

Purpose: To establish the diurnal stability of edited magnetic resonance spectroscopy measurements of gamma-aminobutyric acid (GABA) in visual and sensorimotor regions of the brain.

Materials And Methods: GABA measurements were made in two regions of the brain (an occipital, "visual" region and a "sensorimotor" region centered on the precentral gyrus) using the MEGA-PRESS editing method, scanning eight healthy adults at five timepoints during a single day. GABA concentration was quantified from the ratio of the GABA integral to the unsuppressed water signal.

Orientation discrimination performance is predicted by GABA concentration and gamma oscillation frequency in human primary visual cortex.

Neuronal orientation selectivity has been shown in animal models to require corticocortical network cooperation and to be dependent on the presence of GABAergic inhibition. However, it is not known whether variability in these fundamental neurophysiological parameters leads to variability in behavioral performance. Here, using a combination of magnetic resonance spectroscopy, magnetoencephalography, and visual psychophysics, we show that individual performance on a visual orientation discrimination task is correlated with both the resting concentration of GABA and the frequency of stimulus-induced gamma oscillations in human visual cortex.

Resting GABA concentration predicts peak gamma frequency and fMRI amplitude in response to visual stimulation in humans.

Functional imaging of the human brain is an increasingly important technique for clinical and cognitive neuroscience research, with functional MRI (fMRI) of the blood oxygen level-dependent (BOLD) response and electroencephalography or magnetoencephalography (MEG) recordings of neural oscillations being 2 of the most popular approaches. However, the neural and physiological mechanisms that generate these responses are only partially understood and sources of interparticipant variability in these measures are rarely investigated. Here, we test the hypothesis that the properties of these neuroimaging metrics are related to individual levels of cortical inhibition by combining magnetic resonance spectroscopy to quantify resting GABA concentration in the visual cortex, MEG to measure stimulus-induced visual gamma oscillations and fMRI to measure the BOLD response to a simple visual grating stimulus.

Measurement of T1 and T2 in the cervical spinal cord at 3 tesla.

T(1) and T(2) were measured for white matter (WM) and gray matter (GM) in the human cervical spinal cord at 3T. T(1) values were calculated using an inversion-recovery (IR) and B(1)-corrected double flip angle gradient echo (GRE) and show significant differences (p = 0.002) between WM (IR = 876 +/- 27 ms, GRE = 838 +/- 54 ms) and GM (IR = 973 +/- 33 ms, GRE = 994 +/- 54 ms).

Spatial effects in the detection of gamma-aminobutyric acid: improved sensitivity at high fields using inner volume saturation.

The MEGA-PRESS-IVS method has been developed, which combines MEGA (a frequency-selective editing technique) editing with the point-resolved spectroscopy sequence (PRESS) and inner volume saturation (IVS) localization, reducing the deleterious effects of spatial variation in coupling evolution. The IVS method has been previously described for improved efficiency of lactate detection. The current study demonstrates that the combination of MEGA-PRESS with IVS results in increased sensitivity for edited single-voxel measurements of glutamate and gamma-aminobutyric acid (GABA).

Proton MR spectroscopic imaging of the medulla and cervical spinal cord.

Purpose: To demonstrate the feasibility of quantitative, one-dimensional proton MR spectroscopic imaging (1D-MRSI) of the upper cervical spine and medulla at 3.0 Tesla.

Materials And Methods: A method was developed for 1D-point-resolved spectroscopy sequence (PRESS)-MRSI, exciting signal in five voxels extending from the pontomedullary junction to the level of the C3 vertebra, and performed in 10 healthy volunteers to generate control data.

In vivo differentiation of N-acetyl aspartyl glutamate from N-acetyl aspartate at 3 Tesla.

A method is described that allows the in vivo differentiation of N-acetyl aspartate (NAA) from N-acetyl aspartyl glutamate (NAAG) by in vivo MR spectroscopy (MRS) at 3 Tesla (3T). The method, which is based on MEGA-point-resolved spectroscopy (PRESS) editing, selectively targets the aspartyl spin system of one species while deliberately removing the other species from the spectrum. This allows quantitative measurements of NAA and NAAG without the need for fitting of unresolved peaks.