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• DLPFC stimulation prior to motor learning did not affect motor performance. • DLPFC stimulation modulated task-related hippocampo-frontal/striatal connectivity. • DLPFC stimulation altered GABA/BOLD relationships in these networks. While it is widely accepted that motor sequence learning (MSL) is supported by a prefrontal-mediated interaction between hippocampal and striatal networks, it remains unknown whether the functional responses of these networks can be modulated in humans with targeted experimental interventions. The present proof-of-concept study employed a multimodal neuroimaging approach, including functional magnetic resonance (MR) imaging and MR spectroscopy, to investigate whether individually-tailored theta-burst stimulation of the dorsolateral prefrontal cortex can modulate responses in the hippocampus and the basal ganglia during motor learning. Our results indicate that while stimulation did not modulate motor performance nor task-related brain activity, it influenced connectivity patterns within hippocampo-frontal and striatal networks. Stimulation also altered the relationship between the levels of gamma-aminobutyric acid (GABA) in the stimulated prefrontal cortex and learning-related changes in both activity and connectivity in fronto-striato-hippocampal networks. This study provides the first experimental evidence, to the best of our knowledge, that brain stimulation can alter motor learning-related functional responses in the striatum and hippocampus. [ABSTRACT FROM AUTHOR]

• First simultaneous measurement of GABA+, Glx and GSH in the neonatal human brain. • Robust metabolic estimation in neonates requires a specific quantification strategy. • GABA+ has a doublet peak in neonates indicating lower macromolecular contributions. • Future application can inform about pathophysiology in neurodevelopment. Balance between inhibitory and excitatory neurotransmitter systems and the protective role of the major antioxidant glutathione (GSH) are central to early healthy brain development. Disruption has been implicated in the early life pathophysiology of psychiatric disorders and neurodevelopmental conditions including Autism Spectrum Disorder. Edited magnetic resonance spectroscopy (MRS) methods such as HERMES have great potential for providing important new non-invasive insights into these crucial processes in human infancy. In this work, we describe a systematic approach to minimise the impact of specific technical challenges inherent to acquiring MRS data in a neonatal population, including automatic segmentation, full tissue-correction and optimised GABA+ fitting and consider the minimum requirements for a robust edited-MRS acquisition. With this approach we report for the first time simultaneous GABA+, Glx (glutamate + glutamine) and GSH concentrations in the neonatal brain (n = 18) in two distinct regions (thalamus and anterior cingulate cortex (ACC)) using edited MRS at 3T. The improved sensitivity provided by our method allows specific regional neurochemical differences to be identified including: significantly lower Glx and GSH ratios to total creatine in the thalamus compared to the ACC (p < 0.001 for both), and significantly higher GSH levels in the ACC following tissue-correction (p < 0.01). Furthermore, in contrast to adult GABA+ which can typically be accurately fitted with a single peak, all neonate spectra displayed a characteristic doublet GABA+ peak at 3 ppm, indicating a lower macromolecule (MM) contribution to the 3 ppm signal in neonates. Relatively high group-level variance shows the need to maximise voxel size/acquisition time in edited neonatal MRS acquisitions for robust estimation of metabolites. Application of this method to study how these levels and balance are altered by early-life brain injury or genetic risk can provide important new knowledge about the pathophysiology underlying neurodevelopmental disorders. [ABSTRACT FROM AUTHOR]

• GABA levels were lower in older as compared to young adults for the SM1 voxel only. • The association between GABA levels and motor performance was task-dependent. • Age affected the association between GABA levels and motor performance. Although gamma aminobutyric acid (GABA) is of particular importance for efficient motor functioning, very little is known about the relationship between regional GABA levels and motor performance. Some studies suggest this relation to be subject to age-related differences even though literature is scarce. To clarify this matter, we employed a comprehensive approach and investigated GABA levels within young and older adults across multiple motor tasks as well as multiple brain regions. Specifically, 30 young and 30 older adults completed a task battery of three different bimanual tasks. Furthermore, GABA levels were obtained within bilateral primary sensorimotor cortex (SM1), bilateral dorsal premotor cortex, the supplementary motor area and bilateral dorsolateral prefrontal cortex (DLPFC) using magnetic resonance spectroscopy. Results indicated that older adults, as compared to their younger counterparts, performed worse on all bimanual tasks and exhibited lower GABA levels in bilateral SM1 only. Moreover, GABA levels across the motor network and DLPFC were differentially associated with performance in young as opposed to older adults on a manual dexterity and bimanual coordination task but not a finger tapping task. Specifically, whereas higher GABA levels related to better manual dexterity within older adults, higher GABA levels predicted poorer bimanual coordination performance in young adults. By determining a task-specific and age-dependent association between GABA levels across the cortical motor network and performance on distinct bimanual tasks, the current study advances insights in the role of GABA for motor performance in the context of aging. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a heterogeneous neurodegenerative disorder, characterized by the dysfunction between dopaminergic and GABAergic neuronal activities. Dopamine (DA) replacement by its precursor L-dopa remains the primary treatment for PD. In this preliminary study, we test the hypotheses that GABA+ levels would be lower in PD patients than controls, and normalized by L-dopa. Eleven PD patients and eleven age-and gender-matched healthy controls underwent a 1H-MRS scan of the upper brainstem using a J-difference-edited sequence to resolve signals of GABA. PD patients did not take all dopaminergic medicines for at least twelve hours prior to the first scan, and were scanned again after resuming L -dopa (pre- and post-L-dopa). MRS data were processed using the Gannet. Differences of GABA+ (GABA, macromolecules, and homocarnosine) levels within-subject (PD: pre- and post-L-dopa) and between-subjects (HC vs. PD-pre or PD-post) were tested using linear mixed-effects models with Holm-Bonferroni correction applied to pairwise comparisons. Significant increased GABA+ levels were observed in the upper brainstem of PD patients post-L-dopa compared with pre-L-dopa (p < 0.001). Patients' GABA+ levels before administration of L-dopa were significantly lower than HCs (p = 0.001). Increased GABA+ level by administration of L-dopa in PD patients (post-L-dopa) was lower compared with HCs, but not significantly (p = 0.52). Increased GABA+ levels were present in the upper brainstem with PD patients post-L-dopa, suggesting dopaminergic therapy capable of improving dopamine may improve the GABA+ levels in the upper brainstem, thereby achieving the effect of modulating the GABAergic system in the treatment of PD. • Patients with Parkinson's disease show decreased GABA+ levels in the upper brainstem, measured with edited MRS. • Edited MRS reveals increased GABA+ levels in the upper brainstem in patients with PD by single-dose of L-dopa. • GABAergic neurotransmission may play a role in the therapeutic mechanism of L-dopa. [ABSTRACT FROM AUTHOR]

• Osprey is an open-source analysis toolbox for magnetic resonance spectroscopy data. • Includes pre-processing, linear-combination modelling, and quantification. • Includes a graphical user interface for visualization of each analysis step. Processing and quantitative analysis of magnetic resonance spectroscopy (MRS) data are far from standardized and require interfacing with third-party software. Here, we present Osprey, a fully integrated open-source data analysis pipeline for MRS data, with seamless integration of pre-processing, linear-combination modelling, quantification, and data visualization. Osprey loads multiple common MRS data formats, performs phased-array coil combination, frequency-and phase-correction of individual transients, signal averaging and Fourier transformation. Linear combination modelling of the processed spectrum is carried out using simulated basis sets and a spline baseline. The MRS voxel is coregistered to an anatomical image, which is segmented for tissue correction and quantification is performed based upon modelling parameters and tissue segmentation. The results of each analysis step are visualized in the Osprey GUI. The analysis pipeline is demonstrated in 12 PRESS, 11 MEGA-PRESS, and 8 HERMES datasets acquired in healthy subjects. Osprey successfully loads, processes, models, and quantifies MRS data acquired with a variety of conventional and spectral editing techniques. Osprey is the first MRS software to combine uniform pre-processing, linear-combination modelling, tissue correction and quantification into a coherent ecosystem. Compared to existing compiled, often closed-source modelling software, Osprey's open-source code philosophy allows researchers to integrate state-of-the-art data processing and modelling routines, and potentially converge towards standardization of analysis. Osprey combines robust, peer-reviewed data processing methods into a modular workflow that is easily augmented by community developers, allowing the rapid implementation of new methods. [ABSTRACT FROM AUTHOR]

Attention-deficit hyperactive disorder (ADHD) is characterized by inattention and increased impulsive and hypermotoric behaviors.Despite the high prevalence and impact of ADHD, little is known about the underlying neurophysiology of ADHD. The main inhibitory and excitatory neurotransmitters γ-aminobutyric acid (GABA) and glutamate are receiving increased attention in ADHD and can be measured using Magnetic Resonance Spectroscopy (MRS). However, MRS studies in ADHD are limited. We measured GABA and glutamate in young unmedicated participants, utilizing high magnetic field strength. Fifty unmedicated children (26 with ADHD, 24 controls) aged 5–9 years completed MRS at 7T and behavioral testing. GABA and glutamate were measured in dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), premotor cortex (PMC), and striatum, and estimated using LCModel. Children with ADHD showed poorer inhibitory control and significantly reduced GABA/Cr in the striatum, but not in ACC, DLPFC, or PMC regions. There were no significant group differences for Glu/Cr levels, or correlations with behavioral manifestations of ADHD. The primary finding of this study is a reduction of striatal GABA levels in unmedicated children with ADHD at 7T. These findings provide guidance for future studies or interventions. Reduced striatal GABA may be a marker for specific GABA-related treatment for ADHD. [ABSTRACT FROM AUTHOR]