Showing papers by "Jamie Near published in 2011"
TL;DR: A relationship was found between MRS‐assessed GABA and a TMS protocol with less clearly understood physiological underpinnings that may reflect extrasynaptic GABA tone, suggesting that MRS measures of glutamate do reflect glutamatergic activity.
Abstract: Magnetic resonance spectroscopy (MRS) allows measurement of neurotransmitter concentrations within a region of interest in the brain. Inter-individual variation in MRS-measured GABA levels have been related to variation in task performance in a number of regions. However, it is not clear how MRS-assessed measures of GABA relate to cortical excitability or GABAergic synaptic activity. We therefore performed two studies investigating the relationship between neurotransmitter levels as assessed by MRS and transcranial magnetic stimulation (TMS) measures of cortical excitability and GABA synaptic activity in the primary motor cortex. We present uncorrected correlations, where the P value should therefore be considered with caution. We demonstrated a correlation between cortical excitability, as assessed by the slope of the TMS input-output curve and MRS-assessed glutamate levels (r = 0.803, P = 0.015) but no clear relationship between MRS-assessed GABA levels and TMS-assessed synaptic GABA(A) activity (2.5 ms inter-stimulus interval (ISI) short-interval intracortical inhibition (SICI); Experiment 1: r = 0.33, P = 0.31; Experiment 2: r = -0.23, P = 0.46) or GABA(B) activity (long-interval intracortical inhibition (LICI); Experiment 1: r = -0.47, P = 0.51; Experiment 2: r = 0.23, P = 0.47). We demonstrated a significant correlation between MRS-assessed GABA levels and an inhibitory TMS protocol (1 ms ISI SICI) with distinct physiological underpinnings from the 2.5 ms ISI SICI (r = -0.79, P = 0.018). Interpretation of this finding is challenging as the mechanisms of 1 ms ISI SICI are not well understood, but we speculate that our results support the possibility that 1 ms ISI SICI reflects a distinct GABAergic inhibitory process, possibly that of extrasynaptic GABA tone.
321 citations
TL;DR: Simulations and phantom experiments indicate that this new approach provides improved GABA editing efficiency relative to MEGA‐PRESS, and in vivo results demonstrate effective removal of macromolecule contamination.
Abstract: One of the most commonly used methods for in vivo MRS detection of γ-aminobutyric acid (GABA) is the MEGA-point-resolved spectroscopy (MEGA-PRESS) technique. However, accurate quantification of GABA using MEGA-PRESS is complicated by spectral co-editing of macromolecular resonances. In this article, a new pulse sequence is presented which enables GABA editing at 3T with the removal of macromolecule contamination. This sequence combines the conventional MEGA editing scheme with the SPECIAL localisation technique, and is therefore named MEGA-SPECIAL. Simulations and phantom experiments indicate that this new approach provides improved GABA editing efficiency relative to MEGA-PRESS, and in vivo results demonstrate effective removal of macromolecule contamination. In a study of the occipital lobe of five healthy volunteers, the macromolecule-corrected GABA/creatine ratio was found to be 0.093 ± 0.007 (mean ± standard deviation), whereas prior to macromolecule correction, the ratio was found to be 0.173 ± 0.013. Copyright © 2011 John Wiley & Sons, Ltd.
77 citations
TL;DR: Findings suggest that abnormalities in glutamate neurotransmission may reflect a trait marker of vulnerability to depression, as demonstrated in medication-free recovered depressed patients.
Abstract: Using proton magnetic resonance spectroscopy (MRS), we have demonstrated regional abnormalities in cortical γ-aminobutyric acid (GABA) and glutamate in medication-free recovered depressed patients. It is unclear whether these changes represent an underlying trait vulnerability to depression, or an after-effect of episodes of illness or its treatment. We sought to examine this question by examining a group of high-risk, never-depressed, individuals. We used MRS to measure GABA and glutamate in parieto-occipital cortex in young people (ages 16-21 yr) with a family history of parental depression (n=24) but no personal history of illness and a control group without a history of depression in any first-degree relative (n=28). Participants with a parental history of depression had significantly higher levels of glutamate than controls in parieto-occipital cortex (F₁,₄₇=5.5, p=0.02). These findings suggest that abnormalities in glutamate neurotransmission may reflect a trait marker of vulnerability to depression.
35 citations