GABA-edited Magnetic Resonance Spectroscopy Research Articles

Spectro-ViT: A vision transformer model for GABA-edited MEGA-PRESS reconstruction using spectrograms

This study investigated the use of a Vision Transformer (ViT) for reconstructing GABA-edited Magnetic Resonance Spectroscopy (MRS) data from a reduced number of transients. Transients refer to the samples collected during an MRS acquisition by repeating the experiment to generate a signal of sufficient quality. Specifically, 80 transients were used instead of the typical 320 transients, aiming to reduce scan time. The 80 transients were pre-processed and converted into a spectrogram image representation using the Short-Time Fourier Transform (STFT). A pre-trained ViT, named Spectro-ViT, was fine-tuned and then tested using in-vivo GABA-edited MEGA-PRESS data. Its performance was compared against other pipelines in the literature using quantitative quality metrics and estimated metabolite concentration values, with the typical 320-transient scans serving as the reference for comparison. The Spectro-ViT model exhibited the best overall quality metrics among all other pipelines against which it was compared. The metabolite concentrations from Spectro-ViT's reconstructions for GABA+ achieved the best average R2 value of 0.67 and the best average Mean Absolute Percentage Error (MAPE) value of 9.68%, with no significant statistical differences found compared to the 320-transient reference. The code to reproduce this research is available at https://github.com/MICLab-Unicamp/Spectro-ViT

Frequency and phase correction of GABA-edited magnetic resonance spectroscopy using complex-valued convolutional neural networks

PurposeTo determine the significance of complex-valued inputs and complex-valued convolutions compared to real-valued inputs and real-valued convolutions in convolutional neural networks (CNNs) for frequency and phase correction (FPC) of GABA-edited magnetic resonance spectroscopy (MRS) data. MethodsAn ablation study using simulated data was performed to determine the most effective input (real or complex) and convolution type (real or complex) to predict frequency and phase shifts in GABA-edited MEGA-PRESS data using CNNs. The best CNN model was subsequently compared using both simulated and in vivo data to two recently proposed deep learning (DL) methods for FPC of GABA-edited MRS. All methods were trained using the same experimental setup and evaluated using the signal-to-noise ratio (SNR) and linewidth of the GABA peak, choline artifact, and by visually assessing the reconstructed final difference spectrum. Statistical significance was assessed using the Wilcoxon signed rank test. ResultsThe ablation study showed that using complex values for the input represented by real and imaginary channels in our model input tensor, with complex convolutions was most effective for FPC. Overall, in the comparative study using simulated data, our CC-CNN model (that received complex-valued inputs with complex convolutions) outperformed the other models as evaluated by the mean absolute error. ConclusionOur results indicate that the optimal CNN configuration for GABA-edited MRS FPC uses a complex-valued input and complex convolutions. Overall, this model outperformed existing DL models.

Results of the 2023 ISBI challenge to reduce GABA-edited MRS acquisition time.

Use a conference challenge format to compare machine learning-based gamma-aminobutyric acid (GABA)-edited magnetic resonance spectroscopy (MRS) reconstruction models using one-quarter of the transients typically acquired during a complete scan. There were three tracks: Track 1: simulated data, Track 2: identical acquisition parameters with in vivo data, and Track 3: different acquisition parameters with in vivo data. The mean squared error, signal-to-noise ratio, linewidth, and a proposed shape score metric were used to quantify model performance. Challenge organizers provided open access to a baseline model, simulated noise-free data, guides for adding synthetic noise, and in vivo data. Three submissions were compared. A covariance matrix convolutional neural network model was most successful for Track 1. A vision transformer model operating on a spectrogram data representation was most successful for Tracks 2 and 3. Deep learning (DL) reconstructions with 80 transients achieved equivalent or better SNR, linewidth and fit error compared to conventional 320 transient reconstructions. However, some DL models optimized linewidth and SNR without actually improving overall spectral quality, indicating a need for more robust metrics. DL-based reconstruction pipelines have the promise to reduce the number of transients required for GABA-edited MRS.

Continuous theta-burst stimulation to the sensorimotor cortex affects contralateral gamma-aminobutyric acid level and resting-state networks.

Continuous theta-burst stimulation (cTBS) is a noninvasive repetitive brain stimulation protocol that suppresses the excitability of the primary motor cortex. It induces cerebral cortical inhibition by increasing inhibitory interneuronal excitability that is associated with increases in gamma-aminobutyric acid (GABA) concentration in the stimulated cortices. cTBS has been applied in the rehabilitation of stroke patients to modulate interhemispheric imbalance. However, the precise mechanisms of cTBS in remote brain areas remain uncertain. We evaluated cTBS-induced GABA level changes in bilateral sensorimotor cortices using GABA-edited magnetic resonance spectroscopy, alternations of motor evoked potentials (MEPs), and resting-state networks (RSNs) using resting-state functional magnetic resonance imaging in 24 healthy right-handed adults (mean age: 34.4 ± 5.0 years). GABA levels in the stimulated left hemisphere significantly increased from baseline (p = 0.013), which was comparable with those of previous reports. GABA levels in the unstimulated right hemisphere showed a trend decrease. cTBS induced a significant decrease in right hand-MEP amplitudes (22.06% ± 43.50%) from baseline (p = 0.026) in accordance with GABA concentrations. However, multiple RSNs, including the default mode and primary motor networks, did not show any obvious differences between pre- and post-stimulus comparisons in the sensorimotor network using the dual regression approach. These results suggest that cTBS simultaneously increases ipsilateral GABA in the stimulated left hemisphere and decreases contralateral GABA in the unstimulated right hemisphere. Neuromodulation following cTBS may be associated with the interhemispheric inhibition because of alterations in GABA levels between the stimulated and unstimulated cortices.

Localizing the Seizure Onset Site Through Metabolic Imaging of GABA.

In Vivo Gamma-Aminobutyric Acid Increase as a Biomarker of the Epileptogenic Zone: An Unbiased Metabolomics Approach Hamelin S, Stupar V, Maziere L, et al. Epilepsia. 2021;62(1):163-175.Objective:Following surgery, focal seizures relapse in 20% to 50% of cases due to the difficulty of delimiting the epileptogenic zone (EZ) by current imaging or electrophysiological techniques. Here, we evaluate an unbiased metabolomics approach based on ex vivo and in vivo nuclear magnetic resonance spectroscopy (MRS) methods to discriminate the EZ in a mouse model of mesiotemporal lobe epilepsy (MTLE).Methods:Four weeks after unilateral injection of kainic acid (KA) into the dorsal hippocampus of mice (KA-MTLE model), we analyzed hippocampal and cortical samples with high-resolution magic angle spinning (HRMAS) MRS. Using advanced multivariate statistics, we identified the metabolites that best discriminate the injected dorsal hippocampus (EZ) and developed an in vivo MEGAPRESS MRS method to focus on the detection of these metabolites in the same mouse model.Results:Multivariate analysis of HRMAS data provided evidence that γ-aminobutyric acid (GABA) is largely increased in the EZ of KA-MTLE mice and is the metabolite that best discriminates the EZ when compared with sham and, more importantly, when compared with adjacent brain regions. These results were confirmed by capillary electrophoresis analysis and were not reversed by a chronic exposition to an antiepileptic drug (carbamazepine). Then, using in vivo noninvasive GABA-edited MRS, we confirmed that a high GABA increase is specific to the injected hippocampus of KA-MTLE mice.Significance:Our strategy using ex vivo MRS-based untargeted metabolomics to select the most discriminant metabolite(s), followed by in vivo MRS-based targeted metabolomics, is an unbiased approach to accurately define the EZ in a mouse model of focal epilepsy. Results suggest that GABA is a specific biomarker of the EZ in MTLE.

Macromolecule suppressed GABA levels show no relationship with age in a pediatric sample

The inhibitory neurotransmitter γ-Aminobutyric acid (GABA) plays a crucial role in cortical development. Therefore, characterizing changes in GABA levels during development has important implications for the study of healthy development and developmental disorders. Brain GABA levels can be measured non-invasively using GABA-edited magnetic resonance spectroscopy (MRS). However, the most commonly used editing technique to measure GABA results in contamination of the GABA signal with macromolecules (MM). Therefore, GABA measured using this technique is often referred to as GABA+ . While few in number, previous studies have shown GABA+ levels increase with age during development. However, these studies are unable to specify whether it is specifically GABA that is increasing or, instead, if levels of MM increase. In this study, we use a GABA-editing technique specifically designed to suppress the MM signal (MM-supp GABA). We find no relationship between MM-supp GABA and age in healthy children aged 7–14 years. These findings suggest that the relationship between GABA+ and age is driven by changes in MM levels, not by changes in GABA levels. Moreover, these findings highlight the importance of accounting for MM levels in MRS quantification.

In vivo γ-aminobutyric acid increase as a biomarker of the epileptogenic zone: An unbiased metabolomics approach.

Following surgery, focal seizures relapse in 20% to 50% of cases due to the difficulty of delimiting the epileptogenic zone (EZ) by current imaging or electrophysiological techniques. Here, we evaluate an unbiased metabolomics approach based on ex vivo and in vivo nuclear magnetic resonance spectroscopy (MRS) methods to discriminate the EZ in a mouse model of mesiotemporal lobe epilepsy (MTLE). Four weeks after unilateral injection of kainic acid (KA) into the dorsal hippocampus of mice (KA-MTLE model), we analyzed hippocampal and cortical samples with high-resolution magic angle spinning (HRMAS) magnetic resonance spectroscopy (MRS). Using advanced multivariate statistics, we identified the metabolites that best discriminate the injected dorsal hippocampus (EZ) and developed an in vivo MEGAPRESS MRS method to focus on the detection of these metabolites in the same mouse model. Multivariate analysis of HRMAS data provided evidence that γ-aminobutyric acid (GABA) is largely increased in the EZ of KA-MTLE mice and is the metabolite that best discriminates the EZ when compared to sham and, more importantly, when compared to adjacent brain regions. These results were confirmed by capillary electrophoresis analysis and were not reversed by a chronic exposition to an antiepileptic drug (carbamazepine). Then, using in vivo noninvasive GABA-edited MRS, we confirmed that a high GABA increase is specific to the injected hippocampus of KA-MTLE mice. Our strategy using ex vivo MRS-based untargeted metabolomics to select the most discriminant metabolite(s), followed by in vivo MRS-based targeted metabolomics, is an unbiased approach to accurately define the EZ in a mouse model of focal epilepsy. Results suggest that GABA is a specific biomarker of the EZ in MTLE.

GABA and glutamate in pediatric migraine.

Migraine is one of the top 5 most prevalent childhood diseases; however, effective treatment strategies for pediatric migraine are limited. For example, standard adult pharmaceutical therapies are less effective in children and can carry undesirable side effects. To develop more effective treatments, improved knowledge of the biology underlying pediatric migraine is necessary. One theory is that migraine results from an imbalance in cortical excitability. Magnetic resonance spectroscopy (MRS) studies show changes in GABA and glutamate levels (the primary inhibitory and excitatory neurotransmitters in the brain, respectively) in multiple brain regions in adults with migraine; however, they have yet to be assessed in children with migraine. Using MRS and GABA-edited MRS, we show that children (7-13 years) with migraine and aura had significantly lower glutamate levels in the visual cortex compared to controls, the opposite to results seen in adults. In addition, we found significant correlations between metabolite levels and migraine characteristics; higher GABA levels were associated with higher migraine burden. We also found that higher glutamate in the thalamus and higher GABA/Glx ratios in the sensorimotor cortex were associated with duration since diagnosis, i.e., having migraines longer. Lower GABA levels in the sensorimotor cortex were associated with being closer to their next migraine attack. Together, this indicates that GABA and glutamate disturbances occur early in migraine pathophysiology and emphasizes that evidence from adults with migraine cannot be immediately translated to pediatric sufferers. This highlights the need for further mechanistic studies of migraine in children, to aid in development of more effective treatments.

Baseline sensorimotor GABA levels shape neuroplastic processes induced by motor learning in older adults.

Previous research in young adults has demonstrated that both motor learning and transcranial direct current stimulation (tDCS) trigger decreases in the levels of gamma‐aminobutyric acid (GABA) in the sensorimotor cortex, and these decreases are linked to greater learning. Less is known about the role of GABA in motor learning in healthy older adults, a knowledge gap that is surprising given the established aging‐related reductions in sensorimotor GABA. Here, we examined the effects of motor learning and subsequent tDCS on sensorimotor GABA levels and resting‐state functional connectivity in the brains of healthy older participants. Thirty‐six older men and women completed a motor sequence learning task before receiving anodal or sham tDCS to the sensorimotor cortex. GABA‐edited magnetic resonance spectroscopy of the sensorimotor cortex and resting‐state (RS) functional magnetic resonance imaging data were acquired before and after learning/stimulation. At the group level, neither learning nor anodal tDCS significantly modulated GABA levels or RS connectivity among task‐relevant regions. However, changes in GABA levels from the baseline to post‐learning session were significantly related to motor learning magnitude, age, and baseline GABA. Moreover, the change in functional connectivity between task‐relevant regions, including bilateral motor cortices, was correlated with baseline GABA levels. These data collectively indicate that motor learning‐related decreases in sensorimotor GABA levels and increases in functional connectivity are limited to those older adults with higher baseline GABA levels and who learn the most. Post‐learning tDCS exerted no influence on GABA levels, functional connectivity or the relationships among these variables in older adults.

Effects of Transcranial Direct Current Stimulation on GABA and Glx in Children: A pilot study.

Transcranial direct current stimulation (tDCS) is a form of non-invasive brain stimulation that safely modulates brain excitability and has therapeutic potential for many conditions. Several studies have shown that anodal tDCS of the primary motor cortex (M1) facilitates motor learning and plasticity, but there is little information about the underlying mechanisms. Using magnetic resonance spectroscopy (MRS), it has been shown that tDCS can affect local levels of γ-aminobutyric acid (GABA) and Glx (a measure of glutamate and glutamine combined) in adults, both of which are known to be associated with skill acquisition and plasticity; however this has yet to be studied in children and adolescents. This study examined GABA and Glx in response to conventional anodal tDCS (a-tDCS) and high definition tDCS (HD-tDCS) targeting the M1 in a pediatric population. Twenty-four typically developing, right-handed children ages 12–18 years participated in five consecutive days of tDCS intervention (sham, a-tDCS or HD-tDCS) targeting the right M1 while training in a fine motor task (Purdue Pegboard Task) with their left hand. Glx and GABA were measured before and after the protocol (at day 5 and 6 weeks) using a PRESS and GABA-edited MEGA-PRESS MRS sequence in the sensorimotor cortices. Glx measured in the left sensorimotor cortex was higher in the HD-tDCS group compared to a-tDCS and sham at 6 weeks (p = 0.001). No changes in GABA were observed in either sensorimotor cortex at any time. These results suggest that neither a-tDCS or HD-tDCS locally affect GABA and Glx in the developing brain and therefore it may demonstrate different responses in adults.

Reductions in GABA following a tDCS-language intervention for primary progressive aphasia

Transcranial direct current stimulation (tDCS) has shown efficacy in augmenting the effects of language therapy in primary progressive aphasia (PPA). The mechanism of action of tDCS is not understood, but preliminary work in healthy adults suggests it modulates γ-aminobutyric acid (GABA) levels to create an environment optimal for learning. It is unknown if this proposed mechanism translates to aging or neurodegenerative conditions. This study tested the hypothesis that tDCS reduces GABA at the stimulated tissue in PPA. We applied GABA-edited magnetic resonance spectroscopy to quantify GABA levels before and after a sham-controlled tDCS intervention with language therapy in PPA. All participants showed improvements but those receiving active tDCS showed significantly greater language improvements compared to sham both immediately after the intervention and at 2-month follow-up. GABA levels in the targeted tissue decreased from baseline after the intervention and remained decreased 2 months after the intervention. This work supports the hypothesis that tDCS modulates GABAergic inhibition to augment learning and is clinically useful for PPA combined with language therapy.

Designing GABA-edited magnetic resonance spectroscopy studies: Considerations of scan duration, signal-to-noise ratio and sample size

BackgroundThe relationships between scan duration, signal-to-noise ratio (SNR) and sample size must be considered and understood to design optimal GABA-edited magnetic resonance spectroscopy (MRS) studies. New methodSimulations investigated the effects of signal averaging on SNR, measurement error and group-level variance against a known ground truth. Relative root mean square errors (measurement error) and coefficients of variation (group-level variance) were calculated. GABA-edited data from 18 participants acquired from five voxels were used to examine the relationships between scan duration, SNR and quantitative outcomes in vivo. These relationships were then used to determine the sample sizes required to observe different effect sizes. ResultsIn both simulated and in vivo data, SNR increased with the square root of the number of averages. Both measurement error and group-level variance were shown to follow an inverse-square-root function, indicating no significant impact of cumulative artifacts. Comparisons between the first two-thirds of the data and the full dataset showed no statistical difference in group-level variance. There was, however, some variability across the five voxels depending on SNR, which impacted the sample sizes needed to detect group differences in specific brain regions. Comparison with existing methodsTypical scan durations can be reduced if taking into account a statistically acceptable amount of variance and the magnitudes of predicted effects. ConclusionsWhile scan duration in GABA-edited MRS has typically been considered in terms of SNR, it is more appropriate to think in terms of the amount of measurement error and group-level variance that provides sufficient statistical power.

Big GABA: Edited MR spectroscopy at 24 research sites

Magnetic resonance spectroscopy (MRS) is the only biomedical imaging method that can noninvasively detect endogenous signals from the neurotransmitter γ-aminobutyric acid (GABA) in the human brain. Its increasing popularity has been aided by improvements in scanner hardware and acquisition methodology, as well as by broader access to pulse sequences that can selectively detect GABA, in particular J-difference spectral editing sequences. Nevertheless, implementations of GABA-edited MRS remain diverse across research sites, making comparisons between studies challenging. This large-scale multi-vendor, multi-site study seeks to better understand the factors that impact measurement outcomes of GABA-edited MRS. An international consortium of 24 research sites was formed. Data from 272 healthy adults were acquired on scanners from the three major MRI vendors and analyzed using the Gannet processing pipeline. MRS data were acquired in the medial parietal lobe with standard GABA+ and macromolecule- (MM-) suppressed GABA editing. The coefficient of variation across the entire cohort was 12% for GABA+ measurements and 28% for MM-suppressed GABA measurements. A multilevel analysis revealed that most of the variance (72%) in the GABA+ data was accounted for by differences between participants within-site, while site-level differences accounted for comparatively more variance (20%) than vendor-level differences (8%). For MM-suppressed GABA data, the variance was distributed equally between site- (50%) and participant-level (50%) differences. The findings show that GABA+ measurements exhibit strong agreement when implemented with a standard protocol. There is, however, increased variability for MM-suppressed GABA measurements that is attributed in part to differences in site-to-site data acquisition. This study's protocol establishes a framework for future methodological standardization of GABA-edited MRS, while the results provide valuable benchmarks for the MRS community.

Voxel Placement Precision for GABA-Edited Magnetic Resonance Spectroscopy.

The purpose of the present study was to assess the reproducibility of voxel placement for GABA-edited MRS. GABA-edited MRS data were acquired in 13 healthy volunteers from (3 cm)3 voxel; and within the same session a second acquisition was independently prescribed. A three-dimensional voxel mask image was reconstructed in T1-image-space using the SVMask tool (in house software). Reproducibility of voxel placement was assessed using the Dice overlap coefficient, both within-subject and between-subject following co-registration of T1 images and transformation of voxel mask images to standard space. Within-subject overlap coefficients were 86% ± 5%. Between-subject overlap coefficients were 75% ± 10%. For the two voxel locations considered (occipital and sensorimotor), voxel overlap was very similar. Between-subject values are higher due to between-session effects, anatomical variability and volume mismatch in standard space. While surprisingly low in terms of volume overlap, the overlap coefficients correspond to acceptable linear displacements.

Reduced GABA and altered somatosensory function in children with autism spectrum disorder.

Abnormal responses to tactile stimuli are a common feature of autism spectrum disorder (ASD). Several lines of evidence suggest that GABAergic function, which has a crucial role in tactile processing, is altered in ASD. In this study, we determine whether in vivo GABA levels are altered in children with ASD, and whether alterations in GABA levels are associated with abnormal tactile function in these children. GABA-edited magnetic resonance spectroscopy was acquired in 37 children with Autism and 35 typically developing children (TDC) from voxels over primary sensorimotor and occipital cortices. Children performed tactile tasks previously shown to be altered in ASD, linked to inhibitory mechanisms. Detection threshold was measured with- and without the presence of a slowly increasing sub-threshold stimulus. Amplitude discrimination was measured with- and without the presence of an adapting stimulus, and frequency discrimination was measured. Sensorimotor GABA levels were significantly reduced in children with autism compared to healthy controls. Occipital GABA levels were normal. Sensorimotor GABA levels correlated with dynamic detection threshold as well as with the effect of sub-threshold stimulation. Sensorimotor GABA levels also correlated with amplitude discrimination after adaptation (an effect absent in autism) and frequency discrimination in controls, but not in children with autism. GABA levels correlate with behavioral measures of inhibition. Children with autism have reduced GABA, associated with abnormalities in tactile performance. We show here that altered in vivo GABA levels might predict abnormal tactile information processing in ASD and that the GABA system may be a future target for therapies. Autism Res 2016. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Advanced processing and simulation of MRS data using the FID appliance (FID‐A)—An open source, MATLAB‐based toolkit

To introduce a new toolkit for simulation and processing of magnetic resonance spectroscopy (MRS) data, and to demonstrate some of its novel features. The FID appliance (FID-A) is an open-source, MATLAB-based software toolkit for simulation and processing of MRS data. The software is designed specifically for processing data with multiple dimensions (eg, multiple radiofrequency channels, averages, spectral editing dimensions). It is equipped with functions for importing data in the formats of most major MRI vendors (eg, Siemens, Philips, GE, Agilent) and for exporting data into the formats of several common processing software packages (eg, LCModel, jMRUI, Tarquin). This paper introduces the FID-A software toolkit and uses examples to demonstrate its novel features, namely 1) the use of a spectral registration algorithm to carry out useful processing routines automatically, 2) automatic detection and removal of motion-corrupted scans, and 3) the ability to perform several major aspects of the MRS computational workflow from a single piece of software. This latter feature is illustrated through both high-level processing of in vivo GABA-edited MEGA-PRESS MRS data, as well as detailed quantum mechanical simulations to generate an accurate LCModel basis set for analysis of the same data. All of the described processing steps resulted in a marked improvement in spectral quality compared with unprocessed data. Fitting of MEGA-PRESS data using a customized basis set resulted in improved fitting accuracy compared with a generic MEGA-PRESS basis set. The FID-A software toolkit enables high-level processing of MRS data and accurate simulation of in vivo MRS experiments. Magn Reson Med 77:23-33, 2017. © 2015 Wiley Periodicals, Inc.

Tissue correction for GABA-edited MRS: Considerations of voxel composition, tissue segmentation, and tissue relaxations.

To develop a tissue correction for GABA-edited magnetic resonance spectroscopy (MRS) that appropriately addresses differences in voxel gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) fractions. Simulations compared the performance of tissue correction approaches. Corrections were then applied to in vivo data from 16 healthy volunteers, acquired at 3T. GM, WM, and CSF fractions were determined from T1 -weighted images. Corrections for CSF content, GM/WM GABA content, and water relaxation of the three compartments are combined into a single, fully corrected measurement. Simulations show that CSF correction increases the dependence of GABA measurements on GM/WM fraction, by an amount equal to the fraction of CSF. Furthermore, GM correction substantially (and nonlinearly) increases the dependence of GABA measurements on GM/WM fraction, for example, by a factor of over four when the voxel GM tissue fraction is 50%. At this tissue fraction, GABA is overestimated by a factor of 1.5. For the in vivo data, correcting for voxel composition increased measured GABA values (P < 0.001 for all regions), but did not reduce intersubject variance (P > 0.5 for all regions). Corrected GABA values differ significantly based on the segmentation procedure used (P < 0.0001) and tissue parameter assumptions made (P < 0.0001). We introduce a comprehensive tissue correction factor that adjusts GABA measurements to correct for different voxel compositions of GM, WM, and CSF.

Striatal and thalamic GABA level concentrations play differential roles for the modulation of response selection processes by proprioceptive information

The selection of appropriate responses is a complex endeavor requiring the integration of many different sources of information in fronto-striatal-thalamic circuits. An often neglected but relevant piece of information is provided by proprioceptive inputs about the current position of our limbs. This study examines the importance of striatal and thalamic GABA levels in these processes using GABA-edited magnetic resonance spectroscopy (GABA-MRS) and a Simon task featuring proprioception-induced interference in healthy subjects. As a possible model of deficits in the processing of proprioceptive information, we also included Parkinson's disease (PD) patients in this study.The results show that proprioceptive information about unusual postures complicates response selection processes in controls, but not in PD patients. The well-known deficits of PD patients in processing proprioceptive information can turn into a benefit when altered proprioceptive information would normally complicate response selection processes. Striatal and thalamic GABA levels play dissociable roles in the modulation of response selection processes by proprioceptive information: Striatal GABA levels seem to be important for the general speed of responding, most likely because striatal GABA promotes response selection. In contrast, the modulation of response conflict by proprioceptive information is closely related to thalamic GABA concentrations with higher concentration being related to a smaller response conflict effect. The most likely explanation for this finding is that the thalamus is involved in the integration of sensorimotor, attentional, and cognitive information for the purpose of response formation. Yet, this effect in the thalamus vanishes when controls and PD patients were analyzed separately.

Reduced GABAergic inhibition and abnormal sensory symptoms in children with Tourette syndrome.

Tourette Syndrome (TS) is characterized by the presence of chronic tics. Individuals with TS often report difficulty with ignoring (habituating to) tactile sensations, and some patients perceive that this contributes to a "premonitory urge" to tic. While common, the physiological basis of impaired tactile processing in TS, and indeed tics themselves, remain poorly understood. It has been well established that GABAergic processing plays an important role in shaping the neurophysiological response to tactile stimulation. Furthermore, there are multiple lines of evidence suggesting that a deficit in GABAergic transmission may contribute to symptoms found in TS. In this study, GABA-edited magnetic resonance spectroscopy (MRS) was combined with a battery of vibrotactile tasks to investigate the role of GABA and atypical sensory processing in children with TS. Our results show reduced primary sensorimotor cortex (SM1) GABA concentration in children with TS compared with healthy control subjects (HC), as well as patterns of impaired performance on tactile detection and adaptation tasks, consistent with altered GABAergic function. Moreover, in children with TS SM1 GABA concentration correlated with motor tic severity, linking the core feature of TS directly to in vivo brain neurochemistry. There was an absence of the typical correlation between GABA and frequency discrimination performance in TS as was seen in HC. These data show that reduced GABA concentration in TS may contribute to both motor tics and sensory impairments in children with TS. Understanding the mechanisms of altered sensory processing in TS may provide a foundation for novel interventions to alleviate these symptoms.

Comparison of the repeatability of GABA-edited magnetic resonance spectroscopy with and without macromolecule suppression.

The inhibitory neurotransmitter γ-aminobutyric acid (GABA) can be measured in vivo using edited magnetic resonance spectroscopy (MRS), but quantification suffers from contamination by macromolecules (MM). It is possible to suppress this contamination using symmetric editing, but this procedure potentially compromises reliability of the GABA measurement. The aim of this study was to compare the repeatability of GABA-edited MRS with and without MM suppression. GABA' (non-MM contaminated) and GABA'+MM (MM-contaminated) concentration was measured in the occipital lobe (OCC) and anterior cingulate (AC) using symmetric and standard editing (n = 15). Each method was performed twice in each region. Within-participant coefficients of variation for each technique were 4.0% (GABA'+MM) and 8.6% (GABA') in the OCC and 14.8% (GABA'+MM) and 12.6% (GABA') in the AC. Intraclass correlation coefficients were better for the suppression method than standard editing in both the OCC (0.72 versus 0.67) and AC (0.41 versus 0.16). These findings were replicated in the OCC of a second cohort (n = 15). Symmetric suppression is shown to be comparable in repeatability to standard GABA-editing. Measuring a purer quantification of GABA becomes increasingly important as more research is conducted on links between GABA concentration, pathology and healthy behavior.