Lack of effect of citalopram on magnetic resonance spectroscopy measures of glutamate and glutamine in frontal cortex of healthy volunteers

Magnetic resonance spectroscopy (MRS) is a non-invasive imaging technique that can provide localised measures of brain chemistry in vivo. We previously found that healthy volunteers receiving the selective serotonin reuptake inhibitor, citalopram, daily for 1 week showed higher levels of a combined measure of glutamate and glutamine (Glx) in occipital cortex than those receiving placebo. The aim of this study was to assess if a similar effect could be detected in the frontal brain region. Twenty-three healthy volunteers randomised to receive either citalopram 20 mg or a placebo capsule daily for 7–10 days were studied and scanned using a 3T Varian INOVA system before and at the end of treatment. Standard short-TE (echo time) PRESS (Point-resolved spectroscopy) (TE = 26 ms) and PRESS-J spectra were acquired from a single 8-cm3 voxel in a frontal region incorporating anterior cingulate cortex. Glutamate and total Glx levels were quantified both relative to creatine and as absolute levels. Relative to placebo, citalopram produced no change in Glx or glutamate alone at the end of the study. Similarly, no effect was seen on other MRS measures studied: myo-inositol, choline, N-acetylaspartate and creatine. These data suggest that the effects of serotonin reuptake to modify cortical glutamatergic MRS measures may be regionally specific. This supports the potential for MRS in assessing neuroanatomically specific serotonin-glutamate interactions in the human brain

Big GABA II: Water-referenced edited MR spectroscopy at 25 research sites

Accurate and reliable quantification of brain metabolites measured in vivo using 1H magnetic resonance spectroscopy (MRS) is a topic of continued interest. Aside from differences in the basic approach to quantification, the quantification of metabolite data acquired at different sites and on different platforms poses an additional methodological challenge. In this study, spectrally edited γ-aminobutyric acid (GABA) MRS data were analyzed and GABA levels were quantified relative to an internal tissue water reference. Data from 284 volunteers scanned across 25 research sites were collected using GABA+ (GABA + co-edited macromolecules (MM)) and MM-suppressed GABA editing. The unsuppressed water signal from the volume of interest was acquired for concentration referencing. Whole-brain T1-weighted structural images were acquired and segmented to determine gray matter, white matter and cerebrospinal fluid voxel tissue fractions. Water-referenced GABA measurements were fully corrected for tissue-dependent signal relaxation and water visibility effects. The cohort-wide coefficient of variation was 17% for the GABA + data and 29% for the MM-suppressed GABA data. The mean within-site coefficient of variation was 10% for the GABA + data and 19% for the MM-suppressed GABA data. Vendor differences contributed 53% to the total variance in the GABA + data, while the remaining variance was attributed to site- (11%) and participant-level (36%) effects. For the MM-suppressed data, 54% of the variance was attributed to site differences, while the remaining 46% was attributed to participant differences. Results from an exploratory analysis suggested that the vendor differences were related to the unsuppressed water signal acquisition. Discounting the observed vendor-specific effects, water-referenced GABA measurements exhibit similar levels of variance to creatine-referenced GABA measurements. It is concluded that quantification using internal tissue water referencing is a viable and reliable method for the quantification of in vivo GABA levels

Edited magnetic resonance spectroscopy detects an age-related decline in monkey brain GABA levels

Recent research had shown a correlation between aging and decreasing Gamma-aminobutyric acid (GABA) the primary inhibitory neurotransmitter in the brain. However, how GABA level varies with age in the medial portion of the brain has not yet been studied. The purpose of this study was to investigate the GABA level variation with age focusing on posterior cingulate cortex, which is the 'core hub' of the Default mode network. In this study, 14 monkeys between 4 and 21 years were recruited and MEGA-PRESS to measure GABA level in order to explorea potential link between aging and GABA. Our results showed that a correlation between age and GABA+/Creatine ratio was at the edge of significance (r= -0.523, p=0.081). There was also a near-significant trend between grey matter/ white matter ratio and GABA+/Creatine ratio (r = -0.518, p=0.0848). Meanwhile, the correlation between age and grey matter showed no significance (r= -0.028, p = 0.93). Therefore, age and grey matter/ white matter ratio accounts for different part of R-squared as independent variables for predicting GABA levels. These finding suggest that there the internal neurochemical variation of GABA levels in the nonhuman primate is associated with normal aging and brain structural decline

The neurobiological mechanisms of transcranial direct current stimulation: insights from human neuroimaging and psychophysics

The research aimed to investigate the neurobiological basis of transcranial direct current stimulation (tDCS); a neuromodulation technique capable of inducing prolonged changes in behavioural performance. The past 15 years have seen a dramatic increase in tDCS-oriented studies, yet the underpinnings of the method are not completely understood. Consequently, this series of experiments was designed to investigate the mechanisms that contribute to the effects of the method. Focusing on neuroimaging, modulations of excitatory and inhibitory neurochemicals were assessed using Magnetic Resonance Spectroscopy (MRS); incorporating distinct spectral editing sequences to define the precise role of inhibitory neurotransmission. Additionally, concurrent DC stimulation and Magnetoencephalography (MEG) was developed, which permitted the novel investigation of excitatory and inhibitory processes via the influence of tDCS on electrophysiological responses in the motor and visual systems. This simultaneous tDCS-MEG investigation is one of only a few existing studies and was the first such endeavour by a group based in the United Kingdom. Finally, a unique psychophysical approach was adopted whereby variations of a vibrotactile adaptation task were utilised to assess the effects of tDCS on amplitude discrimination ability. The paradigms used were specifically chosen due to their physiological similarity to tDCS, thereby enabling inferences on the underpinnings of the method on the basis of changes in somatosensory task performance. These studies provided varying degrees of support for the neurobiological mechanisms proposed in the existing literature, most likely reflecting the influence of distinctions in stimulation protocols and the presence of individual difference factors thought to modify responses to stimulation. Consequently, in addition to the established insights regarding the underpinnings of tDCS, valuable perspectives on the optimisation of stimulation-based methodology were achieved by conducting the outlined investigations