Publications by authors named "Richard A E Edden"

156 Publications

Hippocampal and striatal responses during motor learning are modulated by prefrontal cortex stimulation.

Neuroimage 2021 May 12;237:118158. Epub 2021 May 12.

Department of Movement Sciences, Movement Control and Neuroplasticity Research Group, KU Leuven, 3001 Leuven, Belgium; LBI - KU Leuven Brain Institute, KU Leuven, 3001 Leuven, Belgium. Electronic address:

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.
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http://dx.doi.org/10.1016/j.neuroimage.2021.118158DOI Listing
May 2021

Relationship between GABA levels and task-dependent cortical excitability in children with attention-deficit/hyperactivity disorder.

Clin Neurophysiol 2021 May 10;132(5):1163-1172. Epub 2021 Mar 10.

Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, MD, United States; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States; Department of Forensic and Neurodevelopmental Sciences, Sackler Institute for Translational Neurodevelopment, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.

Objective: Compared to typically developing (TD) peers, children with attention deficit hyperactivity disorder (ADHD) manifest reduced short interval cortical inhibition (SICI) in the dominant motor cortex measured with transcranial magnetic stimulation (TMS). This multimodal study investigates the inhibitory neurophysiology and neurochemistry by evaluating the relationship between SICI and γ-amino butyric acid (GABA+) levels, measured with magnetic resonance spectroscopy (MRS).

Methods: Across two sites, 37 children with ADHD and 45 TD children, ages 8-12 years, participated. Single and paired pulse TMS to left motor cortex quantified SICI during REST and at times of action selection (GO) and inhibition (STOP) during a modified Slater-Hammel stop signal reaction task. MRS quantified GABA+ levels in the left sensorimotor cortex. Relationships between SICI and GABA+, as well as stopping efficiency and clinical symptoms, were analyzed with correlations and repeated-measure, mixed-models.

Results: In both groups, higher GABA+ levels correlated with less SICI. In TD children only, higher GABA+ levels correlated with larger TMS motor evoked potentials (MEPs) at REST. In GO and STOP trials, higher GABA+ was associated with smaller MEP amplitudes, for both groups. Overall, GABA+ levels did not differ between groups or correlate with ADHD clinical symptoms.

Conclusions: In children with higher motor cortex GABA+, motor cortex is less responsive to inhibitory TMS (SICI). Comparing the relationships between MRS-GABA+ levels and responses to TMS at REST vs. GO/STOP trials suggests differences in inhibitory neurophysiology and neurotransmitters in children with ADHD. These differences are more prominent at rest than during response inhibition task engagement.

Significance: Evaluating relationships between GABA+ and SICI may provide a biomarker useful for understanding behavioral diagnoses.
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http://dx.doi.org/10.1016/j.clinph.2021.01.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106665PMC
May 2021

Upper brainstem GABA levels in Parkinson's disease.

MAGMA 2021 Mar 20. Epub 2021 Mar 20.

Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Objective: The dopaminergic pathology of Parkinson's disease (PD) impacts circuits involving GABAergic neurons, especially in the brainstem, where the disease manifests early. The aim of this study is to test the hypothesis that levels of gamma-aminobutyric acid (GABA) in the upper brainstem are reduced in patients with PD compared to healthy controls, using edited magnetic resonance spectroscopy (MRS of GABA +).

Materials And Methods: GABA + levels were examined in 18 PD patients and 18 age- and sex-matched healthy controls (HCs). GABA + -edited MRS was performed in 7.5-ml voxels in the upper brainstem, and the spectra were processed using the Gannet software. Differences in GABA + levels between the two groups were analyzed using independent t test analysis.

Results: GABA + levels were significantly lower (p < 0.05) in the upper brainstem of the patients with PD (4.57 ± 0.94 mM) than the HCs (5.89 ± 1.16 mM).

Conclusion: The lower GABA + levels in the upper brainstem of the PD patients suggest that a GABAergic deficit in the brainstem may contribute to the pathology in PD.
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http://dx.doi.org/10.1007/s10334-021-00910-7DOI Listing
March 2021

Simultaneous quantification of GABA, Glx and GSH in the neonatal human brain using magnetic resonance spectroscopy.

Neuroimage 2021 06 9;233:117930. Epub 2021 Mar 9.

Centre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King's College London, London, United Kingdom; Biomedical Engineering Department, School of Biomedical Engineering and Imaging Sciences, St Thomas' Hospital, Westminster Bridge Road, Lambeth Wing, 3rd Floor, London SE1 7EH, United Kingdom. Electronic address:

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.
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http://dx.doi.org/10.1016/j.neuroimage.2021.117930DOI Listing
June 2021

Comparison of methods for spectral alignment and signal modelling of GABA-edited MR spectroscopy data.

Neuroimage 2021 05 27;232:117900. Epub 2021 Feb 27.

Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States.

Many methods exist for aligning and quantifying magnetic resonance spectroscopy (MRS) data to measure in vivo γ-aminobutyric acid (GABA). Research comparing the performance of these methods is scarce partly due to the lack of ground-truth measurements. The concentration of GABA is approximately two times higher in grey matter than in white matter. Here we use the proportion of grey matter within the MRS voxel as a proxy for ground-truth GABA concentration to compare the performance of four spectral alignment methods (i.e., retrospective frequency and phase drift correction) and six GABA signal modelling methods. We analyse a diverse dataset of 432 MEGA-PRESS scans targeting multiple brain regions and find that alignment to the creatine (Cr) signal produces GABA+ estimates that account for approximately twice as much of the variance in grey matter as the next best performing alignment method. Further, Cr alignment was the most robust, producing the fewest outliers. By contrast, all signal modelling methods, except for the single-Lorentzian model, performed similarly well. Our results suggest that variability in performance is primarily caused by differences in the zero-order phase estimated by each alignment method, rather than frequency, resulting from first-order phase offsets within subspectra. These results provide support for Cr alignment as the optimal method of processing MEGA-PRESS to quantify GABA. However, more broadly, they demonstrate a method of benchmarking quantification of in vivo metabolite concentration from other MRS sequences.
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http://dx.doi.org/10.1016/j.neuroimage.2021.117900DOI Listing
May 2021

GABA levels are differentially associated with bimanual motor performance in older as compared to young adults.

Neuroimage 2021 05 16;231:117871. Epub 2021 Feb 16.

Movement Control & Neuroplasticity Research Group, Department of Movement Sciences, Group Biomedical Sciences, KU Leuven, Leuven, Belgium; KU Leuven Brain Institute (LBI), Tervuursevest 101 box, Leuven 1501 3001, Belgium. Electronic address:

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.
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http://dx.doi.org/10.1016/j.neuroimage.2021.117871DOI Listing
May 2021

Single-dose L-dopa increases upper brainstem GABA in Parkinson's disease: A preliminary study.

J Neurol Sci 2021 Mar 17;422:117309. Epub 2021 Jan 17.

Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; FM Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA. Electronic address:

Purpose: 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.

Methods: Eleven PD patients and eleven age-and gender-matched healthy controls underwent a H-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.

Results: 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).

Conclusion: 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.
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http://dx.doi.org/10.1016/j.jns.2021.117309DOI Listing
March 2021

Comparison of different linear-combination modeling algorithms for short-TE proton spectra.

NMR Biomed 2021 Apr 2;34(4):e4482. Epub 2021 Feb 2.

Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Short-TE proton MRS is used to study metabolism in the human brain. Common analysis methods model the data as a linear combination of metabolite basis spectra. This large-scale multi-site study compares the levels of the four major metabolite complexes in short-TE spectra estimated by three linear-combination modeling (LCM) algorithms. 277 medial parietal lobe short-TE PRESS spectra (TE = 35 ms) from a recent 3 T multi-site study were preprocessed with the Osprey software. The resulting spectra were modeled with Osprey, Tarquin and LCModel, using the same three vendor-specific basis sets (GE, Philips and Siemens) for each algorithm. Levels of total N-acetylaspartate (tNAA), total choline (tCho), myo-inositol (mI) and glutamate + glutamine (Glx) were quantified with respect to total creatine (tCr). Group means and coefficient of variations of metabolite estimates agreed well for tNAA and tCho across vendors and algorithms, but substantially less so for Glx and mI, with mI systematically estimated as lower by Tarquin. The cohort mean coefficient of determination for all pairs of LCM algorithms across all datasets and metabolites was = 0.39, indicating generally only moderate agreement of individual metabolite estimates between algorithms. There was a significant correlation between local baseline amplitude and metabolite estimates (cohort mean = 0.10). While mean estimates of major metabolite complexes broadly agree between linear-combination modeling algorithms at group level, correlations between algorithms are only weak-to-moderate, despite standardized preprocessing, a large sample of young, healthy and cooperative subjects, and high spectral quality. These findings raise concerns about the comparability of MRS studies, which typically use one LCM software and much smaller sample sizes.
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http://dx.doi.org/10.1002/nbm.4482DOI Listing
April 2021

Disorder-specific alterations of tactile sensitivity in neurodevelopmental disorders.

Commun Biol 2021 01 22;4(1):97. Epub 2021 Jan 22.

Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.

Alterations of tactile processing have long been identified in autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). However, the extent to which these alterations are disorder-specific, rather than disorder-general, and how they relate to the core symptoms of each disorder, remains unclear. We measured and compared tactile detection, discrimination, and order judgment thresholds between a large sample of children with ASD, ADHD, ASD + ADHD combined and typically developing controls. The pattern of results suggested that while difficulties with tactile detection and order judgement were more common in children with ADHD, difficulties with tactile discrimination were more common in children with ASD. Interestingly, in our subsequent correlation analyses between tactile perception and disorder-specific clinical symptoms, tactile detection and order judgment correlated exclusively with the core symptoms of ADHD, while tactile discrimination correlated exclusively with the symptoms of ASD. When taken together, these results suggest that disorder-specific alterations of lower-level sensory processes exist and are specifically related to higher-level clinical symptoms of each disorder.
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http://dx.doi.org/10.1038/s42003-020-01592-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822903PMC
January 2021

Brain GABA+ changes in primary hypothyroidism patients before and after levothyroxine treatment: A longitudinal magnetic resonance spectroscopy study.

Neuroimage Clin 2020 31;28:102473. Epub 2020 Oct 31.

Shandong Medical Imaging Research Institute, Shandong University, Jinan, China. Electronic address:

Objective: Increasing evidence indicates the involvement of the GABAergic system in the pathophysiology of hypothyroidism. We aimed to investigate longitudinal changes of brain GABA in primary hypothyroidism before and after levothyroxine (L-T4) treatment.

Material And Methods: In 18 patients with hypothyroidism, we used the MEGA-PRESS (Mescher-Garwood point-resolved spectroscopy) editing sequence to measure brain GABA levels from medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC) at baseline and after 6-months of L-T4 treatment. Sex- and age-matched healthy controls (n = 18) were scanned at baseline. Thyroid function and neuropsychological tests were also performed.

Results: GABA signals were successfully quantified from all participants with fitting errors lower than 15%. GABA signal was labeled as GABA+ due to contamination from co-edited macromoleculars and homocarnosine. In hypothyroid patients, mean GABA+ was significantly lower in the mPFC region compared with controls (p = 0.031), and the mPFC GABA+ measurements were significantly correlated with depressive symptoms and memory function (r = -0.558, p = 0.016; r = 0.522, p = 0.026, respectively). After adequate L-T4 treatment, the mPFC GABA+ in hypothyroid patients increased to normal level, along with relieved neuropsychological impairments.

Conclusion: The study suggested the decrease of GABA+ may be an important neurobiological factor in the pathophysiology of hypothyroidism. Treatment of L-T4 may reverse the abnormal GABA+ and hypothyroidism-induced neuropsychiatric impairments, indicating the action mode of L-T4 in adjunctive treatment of affective disorders.
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http://dx.doi.org/10.1016/j.nicl.2020.102473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663215PMC
October 2020

Cerebellar GABA Levels and Cognitive Interference in Parkinson's disease and Healthy Comparators.

J Pers Med 2020 Dec 28;11(1). Epub 2020 Dec 28.

Neuropsychiatry Laboratory, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Via Ardeatina 306/354, 00179 Rome, Italy.

The neuroanatomical and molecular substrates for cognitive impairment in Parkinson Disease (PD) are far from clear. Evidence suggests a non-dopaminergic basis, and a crucial role for cerebellum in cognitive control in PD. We investigated whether a PD cognitive marker (response inhibition) was differently controlled by g-amino butyric acid (GABA) and/or by glutamate-glutamine (Glx) levels in the cerebellum of idiopathic PD patients, and healthy comparators (HC). Magnetic resonance spectroscopy of GABA/Glx (MEGA-PRESS acquisition sequence) was performed at 3 Tesla, and response inhibition assessed by the Stroop Word-Color Test (SWCT) and the Wisconsin Card Sorting Test (WCST). Linear correlations between cerebellar GABA/Glx levels, SWCT time/error interference effects and WCST perseverative errors were performed to test differences between correlation coefficients in PD and HC. Results showed that higher levels of mean cerebellar GABA were associated to SWCT increased time and error interference effects in PD, and the contrary in HC. Such effect dissociated by hemisphere, while correlation coefficients differences were significant in both right and left cerebellum. We conclude that MRS measured levels of cerebellar GABA are related in PD patients with decreased efficiency in filtering task-irrelevant information. This is crucial for developing pharmacological treatments for PD to potentially preserve cognitive functioning.
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http://dx.doi.org/10.3390/jpm11010016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823866PMC
December 2020

Greater Somatosensory Afference With Acupuncture Increases Primary Somatosensory Connectivity and Alleviates Fibromyalgia Pain via Insular γ-Aminobutyric Acid: A Randomized Neuroimaging Trial.

Arthritis Rheumatol 2020 Dec 13. Epub 2020 Dec 13.

University of Michigan, Ann Arbor.

Objective: Acupuncture is a complex multicomponent treatment that has shown promise in the treatment of fibromyalgia (FM). However, clinical trials have shown mixed results, possibly due to heterogeneous methodology and lack of understanding of the underlying mechanism of action. The present study was undertaken to understand the specific contribution of somatosensory afference to improvements in clinical pain, and the specific brain circuits involved.

Methods: Seventy-six patients with FM were randomized to receive either electroacupuncture (EA), with somatosensory afference, or mock laser acupuncture (ML), with no somatosensory afference, twice a week over 8 treatments. Patients with FM in each treatment group were assessed for pain severity levels, measured using Brief Pain Inventory (BPI) scores, and for levels of functional brain network connectivity, assessed using resting state functional magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy in the right anterior insula, before and after treatment.

Results: Fibromyalgia patients who received EA therapy experienced a greater reduction in pain severity, as measured by the BPI, compared to patients who received ML therapy (mean difference in BPI from pre- to posttreatment was -1.14 in the EA group versus -0.46 in the ML group; P for group × time interaction = 0.036). Participants receiving EA treatment, as compared to ML treatment, also exhibited resting functional connectivity between the primary somatosensory cortical representation of the leg (S1 ; i.e. primary somatosensory subregion activated by EA) and the anterior insula. Increased S1 -anterior insula connectivity was associated with both reduced levels of pain severity as measured by the BPI (r = -0.44, P = 0.01) and increased levels of γ-aminobutyric acid (GABA+) in the anterior insula (r = 0.48, P = 0.046) following EA therapy. Moreover, increased levels of GABA+ in the anterior insula were associated with reduced levels of pain severity as measured by the BPI (r = -0.59, P = 0.01). Finally, post-EA treatment changes in levels of GABA+ in the anterior insula mediated the relationship between changes in S1 -anterior insula connectivity and pain severity on the BPI (bootstrap confidence interval -0.533, -0.037).

Conclusion: The somatosensory component of acupuncture modulates primary somatosensory functional connectivity associated with insular neurochemistry to reduce pain severity in FM.
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http://dx.doi.org/10.1002/art.41620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197768PMC
December 2020

Frequency and phase correction of J-difference edited MR spectra using deep learning.

Magn Reson Med 2021 04 18;85(4):1755-1765. Epub 2020 Nov 18.

Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Purpose: To investigate whether a deep learning-based (DL) approach can be used for frequency-and-phase correction (FPC) of MEGA-edited MRS data.

Methods: Two neural networks (1 for frequency, 1 for phase) consisting of fully connected layers were trained and validated using simulated MEGA-edited MRS data. This DL-FPC was subsequently tested and compared to a conventional approach (spectral registration [SR]) and to a model-based SR implementation (mSR) using in vivo MEGA-edited MRS datasets. Additional artificial offsets were added to these datasets to further investigate performance.

Results: The validation showed that DL-based FPC was capable of correcting within 0.03 Hz of frequency and 0.4°of phase offset for unseen simulated data. DL-based FPC performed similarly to SR for the unmanipulated in vivo test datasets. When additional offsets were added to these datasets, the networks still performed well. However, although SR accurately corrected for smaller offsets, it often failed for larger offsets. The mSR algorithm performed well for larger offsets, which was because the model was generated from the in vivo datasets. In addition, the computation times were much shorter using DL-based FPC or mSR compared to SR for heavily distorted spectra.

Conclusion: These results represent a proof of principle for the use of DL for preprocessing MRS data.
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http://dx.doi.org/10.1002/mrm.28525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063593PMC
April 2021

Neurotransmitters and Neurometabolites in Late-Life Depression: A Preliminary Magnetic Resonance Spectroscopy Study at 7T.

J Affect Disord 2021 01 7;279:417-425. Epub 2020 Oct 7.

Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, United States.

Background: Magnetic resonance spectroscopy (MRS) methods have quantified changes in levels of neurotransmitters and neurometabolites in patients with major depression across the lifespan. The application of 7T field strengths and greater have not been a major focus of study in patients with late-life depression (LLD).

Methods: Nine LLD patients who met DSM-IV criteria for a current major depressive episode and nine non-depressed, healthy, age-matched controls underwent clinical and neuropsychological assessment and single-voxel 7T H-MRS at baseline and after 10-12 weeks of antidepressant treatment (Citalopram; patients only). Spectra were acquired from two brain regions implicated in both depressive symptoms and neuropsychological deficits in LLD, the anterior (ACC) and posterior cingulate (PCC). Levels of γ-aminobutyric acid (GABA), glutamate (Glu), glutathione (GSH), N-acetylaspartylglutamate (NAAG), N-acetylaspartate (NAA), and myo-inositol (mI) were quantified relative to total creatine (tCr) using linear-combination modeling.

Results: Baseline Glu/tCr levels were not significantly different between groups. Decreased Glu/tCr levels after Citalopram treatment were observed in a subset of LLD patients. Exploratory analyses showed that LLD patients had lower NAA levels in the PCC relative to controls. Higher levels of ml in the LLD patients relative to the controls and decreases after Citalopram treatment had large effect sizes but were not statistically significant. Further, decreases in PCC Glu/tCr and increases in ACC GSH/tCr were associated with improvement in depressive symptoms.

Limitations: Sample size.

Conclusions: These preliminary results suggest a role of neurochemicals and neurometabolites in the neurobiology of LLD and antidepressant treatment response.
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http://dx.doi.org/10.1016/j.jad.2020.10.011DOI Listing
January 2021

A multimodal approach to studying the relationship between peripheral glutathione, brain glutamate, and cognition in health and in schizophrenia.

Mol Psychiatry 2020 Oct 19. Epub 2020 Oct 19.

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Involvement of oxidative stress in the pathophysiology of schizophrenia (SZ) is suggested by studies of peripheral tissue. Nonetheless, it is unclear how such biological changes are linked to relevant, pathological neurochemistry, and brain function. We designed a multi-faceted study by combining biochemistry, neuroimaging, and neuropsychology to test how peripheral changes in a key marker for oxidative stress, glutathione (GSH), may associate with central neurochemicals or neuropsychological performance in health and in SZ. GSH in dorsal anterior cingulate cortex (dACC) was acquired as a secondary 3T H-MRS outcome using a MEGA-PRESS sequence. Fifty healthy controls and 46 patients with SZ were studied cross-sectionally, and analyses were adjusted for effects of confounding variables. We observed lower peripheral total GSH in SZ compared to controls in extracellular (plasma) and intracellular (lymphoblast) pools. Total GSH levels in plasma positively correlated with composite neuropsychological performance across the total population and within patients. Total plasma GSH levels were also positively correlated with the levels of Glx in the dACC across the total population, as well as within each individual group (controls, patients). Furthermore, the levels of dACC Glx and dACC GSH positively correlated with composite neuropsychological performance in the patient group. Exploring the relationship between systemic oxidative stress (in particular GSH), central glutamate, and cognition in SZ will benefit further from assessment of patients with more varied neuropsychological performance.
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http://dx.doi.org/10.1038/s41380-020-00901-5DOI Listing
October 2020

Spectral editing in H magnetic resonance spectroscopy: Experts' consensus recommendations.

NMR Biomed 2021 May 18;34(5):e4411. Epub 2020 Sep 18.

Department of Radiology and Biomedical Imaging, Yale University, New Haven, Connecticut.

Spectral editing in in vivo H-MRS provides an effective means to measure low-concentration metabolite signals that cannot be reliably measured by conventional MRS techniques due to signal overlap, for example, γ-aminobutyric acid, glutathione and D-2-hydroxyglutarate. Spectral editing strategies utilize known J-coupling relationships within the metabolite of interest to discriminate their resonances from overlying signals. This consensus recommendation paper provides a brief overview of commonly used homonuclear editing techniques and considerations for data acquisition, processing and quantification. Also, we have listed the experts' recommendations for minimum requirements to achieve adequate spectral editing and reliable quantification. These include selecting the right editing sequence, dealing with frequency drift, handling unwanted coedited resonances, spectral fitting of edited spectra, setting up multicenter clinical trials and recommending sequence parameters to be reported in publications.
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http://dx.doi.org/10.1002/nbm.4411DOI Listing
May 2021

Associations Between Cognitive Function and Levels of Glutamatergic Metabolites and Gamma-Aminobutyric Acid in Antipsychotic-Naïve Patients With Schizophrenia or Psychosis.

Biol Psychiatry 2021 02 10;89(3):278-287. Epub 2020 Jul 10.

Center for Neuropsychiatric Schizophrenia Research and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Mental Health Center Glostrup, University of Copenhagen, Glostrup, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Glostrup, Denmark.

Background: Abnormal glutamate and GABA (gamma-aminobutyric acid) levels have been found in the early phase of schizophrenia and may underlie cognitive deficits. However, the association between cognitive function and levels of glutamatergic metabolites and GABA has not been investigated in a large group of antipsychotic-naïve patients.

Methods: In total, 56 antipsychotic-naïve patients with schizophrenia or psychotic disorder and 51 healthy control subjects underwent magnetic resonance spectroscopy to measure glutamate, glutamate+glutamine (Glx), and GABA levels in dorsal anterior cingulate cortex (ACC) and glutamate and Glx levels in left thalamus. The cognitive domains of attention, working memory, and IQ were assessed.

Results: The whole group of antipsychotic-naïve patients had lower levels of GABA in dorsal ACC (p = .03), and the subgroup of patients with a schizophrenia diagnosis had higher glutamate levels in thalamus (p = .01), but Glx levels in dorsal ACC and thalamus did not differ between groups. Glx levels in dorsal ACC were positively associated with working memory (logarithmically transformed: b = -.016 [higher score indicates worse performance], p = .005) and attention (b = .056, p = .035) in both patients and healthy control subjects, although the association with attention did not survive adjustment for multiple comparisons.

Conclusions: The findings suggest a positive association between glutamatergic metabolites and cognitive function that do not differ between patients and healthy control subjects. Moreover, our data indicate that decreased GABAergic levels in dorsal ACC are involved in schizophrenia and psychotic disorder, whereas increased glutamate levels in thalamus seem to be implicated in schizophrenia pathophysiology. The findings imply that first-episode patients with cognitive deficits may gain from glutamate-modulating compounds.
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http://dx.doi.org/10.1016/j.biopsych.2020.06.027DOI Listing
February 2021

Feasibility of Measuring GABA Levels in the Upper Brainstem in Healthy Volunteers Using Edited MRS.

Front Psychiatry 2020 14;11:813. Epub 2020 Aug 14.

Department of Imaging and Nuclear Medicine, Shandong Medical Imaging Research Institute, Cheeloo College of Medicine, Shandong University, Jinn, China.

Purpose: To assess the feasibility of small-voxel MEGA-PRESS in detecting gamma-aminobutyric acid (GABA) levels of the upper brainstem in healthy volunteers.

Materials And Methods: Forty-two healthy volunteers, aged between 20 and 76 years were enrolled in this study, and underwent a 3.0T MRI scan using an eight-channel phased-array head coil. The MEGA-PRESS sequence was used to edit GABA signal from a 10x25x30 mm voxel in the upper brain stem. The detected signal includes contributions from macromolecules (MM) and homocarnosine and is therefore referred to as GABA+. All the data were processed using Gannet.

Results: Thirty-four cases were successful in measuring GABA in the upper brainstem and 8 cases failed (based on poor modeling of spectra). The GABA+ levels were 2.66 ± 0.75 i.u. in the upper brainstem of healthy volunteers, ranging from 1.50 to 4.40 i.u. The normalized fitting residual (FitErr in Gannet) was 12.1 ± 2.8%, ranging from 7.4% to 19.1%; it was below 15.5% in 30 cases (71%).

Conclusions: It is possible to measure GABA levels in the upper brainstem using MEGA-PRESS with a relatively small ROI, with a moderate between-subject variance of under 30%.
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http://dx.doi.org/10.3389/fpsyt.2020.00813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456914PMC
August 2020

High γ-Aminobutyric Acid Content Within the Medial Prefrontal Cortex Is a Functional Signature of Somatic Symptoms Disorder in Patients With Parkinson's Disease.

Mov Disord 2020 12 3;35(12):2184-2192. Epub 2020 Aug 3.

Department of Neuroscience, Imaging and Clinical Sciences, University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy.

Background: The dysfunctional activity of the medial prefrontal cortex has been associated with the appearance of the somatic symptom disorder, a key feature of the Parkinson's disease (PD) psychosis complex.

Objectives: The objectives of this study were to investigate whether the basal contents of inhibitory γ-aminobutyric acid and excitatory glutamate plus glutamine neurotransmitter levels are changed in the medial prefrontal cortex of patients with PD with somatic symptom disorder and whether this alteration represents a marker of susceptibility of PD to somatic symptom disorder, thus representing a signature of psychosis complex of PD.

Methods: Levels of the γ-aminobutyric acid and glutamate plus glutamine were investigated, at rest, with proton magnetic resonance spectroscopy. Total creatine was used as an internal reference. The study cohort included 23 patients with somatic symptom disorder plus PD, 19 patients with PD without somatic symptom disorder, 19 healthy control subjects, and 14 individuals with somatic symptom disorder who did not show other psychiatric or neurological disorders.

Results: We found that, compared with patients with PD without somatic symptom disorder or healthy control individuals, patients with somatic symptom disorder, with or without PD, show increased γ-aminobutyric acid/total creatine levels in the medial prefrontal cortex. The medial prefrontal cortex contents of glutamate plus glutamine/total creatine levels or γ-aminobutyric acid/glutamate plus glutamine were not different among groups.

Conclusions: Our findings highlight a crucial pathophysiologic role played by high γ-aminobutyric acid within the medial prefrontal cortex in the production of somatic symptom disorder. This phenomenon represents a signature of psychosis complex in patients with PD. © 2020 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28221DOI Listing
December 2020

Correcting frequency and phase offsets in MRS data using robust spectral registration.

NMR Biomed 2020 10 12;33(10):e4368. Epub 2020 Jul 12.

Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland.

An algorithm for retrospective correction of frequency and phase offsets in MRS data is presented. The algorithm, termed robust spectral registration (rSR), contains a set of subroutines designed to robustly align individual transients in a given dataset even in cases of significant frequency and phase offsets or unstable lipid contamination and residual water signals. Data acquired by complex multiplexed editing approaches with distinct subspectral profiles are also accurately aligned. Automated removal of unstable lipid contamination and residual water signals is applied first, when needed. Frequency and phase offsets are corrected in the time domain by aligning each transient to a weighted average reference in a statistically optimal order using nonlinear least-squares optimization. The alignment of subspectra in edited datasets is performed using an approach that specifically targets subtraction artifacts in the frequency domain. Weighted averaging is then used for signal averaging to down-weight poorer-quality transients. Algorithm performance was assessed on one simulated and 67 in vivo pediatric GABA-/GSH-edited HERMES datasets and compared with the performance of a multistep correction method previously developed for aligning HERMES data. The performance of the novel approach was quantitatively assessed by comparing the estimated frequency/phase offsets against the known values for the simulated dataset or by examining the presence of subtraction artifacts in the in vivo data. Spectral quality was improved following robust alignment, especially in cases of significant spectral distortion. rSR reduced more subtraction artifacts than the multistep method in 64% of the GABA difference spectra and 75% of the GSH difference spectra. rSR overcomes the major challenges of frequency and phase correction.
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http://dx.doi.org/10.1002/nbm.4368DOI Listing
October 2020

Regional balance between glutamate+glutamine and GABA+ in the resting human brain.

Neuroimage 2020 10 30;220:117112. Epub 2020 Jun 30.

Department of Psychology and Brain Sciences, Dartmouth College, Hanover, NH, USA.

Models of healthy brain function and psychiatric conditions assume that excitatory and inhibitory activity are balanced in the human brain at multiple spatial and temporal scales. In human neuroimaging, concentrations of the major excitatory (glutamate) and inhibitory (γ-aminobutyric acid, GABA) neurotransmitters are measured in vivo using magnetic resonance spectroscopy (MRS). However, despite the central importance of E/I balance to theories of brain function, a relationship between regional glutamate and GABA levels in the human brain has not been shown. We addressed this question in a large corpus of edited MRS data collected at 19 different sites (n ​= ​220). Consistent with the notion of E/I balance, we found that levels of glutamate+glutamine (Glx) and GABA+ were highly correlated (R ​= ​0.52, p ​= ​2.86 x 10). This relationship held when controlling for site, scanner vendor, and demographics. Controlling for neurochemicals associated with neuronal density and metabolism (i.e. N-acetylaspartate and creatine) significantly reduced the correlation between GABA+ and Glx, suggesting that the levels of GABA+ and Glx may be critically linked to regional metabolism. These results are consistent with the notion that excitation and inhibition are balanced in the human brain.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117112DOI Listing
October 2020

Osprey: Open-source processing, reconstruction & estimation of magnetic resonance spectroscopy data.

J Neurosci Methods 2020 09 27;343:108827. Epub 2020 Jun 27.

Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States.

Background: 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.

New Method: 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.

Results: Osprey successfully loads, processes, models, and quantifies MRS data acquired with a variety of conventional and spectral editing techniques.

Comparison With Existing Method(s): 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.

Conclusions: 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.
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http://dx.doi.org/10.1016/j.jneumeth.2020.108827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477913PMC
September 2020

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

Hum Brain Mapp 2020 09 25;41(13):3680-3695. Epub 2020 Jun 25.

Department of Movement Sciences, Movement Control and Neuroplasticity Research Group, KU Leuven, Leuven, Belgium.

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.
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http://dx.doi.org/10.1002/hbm.25041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416055PMC
September 2020

Weaker neural suppression in autism.

Nat Commun 2020 05 29;11(1):2675. Epub 2020 May 29.

Department of Psychology, University of Washington, UW Box 351525, Seattle, WA, 98195, USA.

Abnormal sensory processing has been observed in autism, including superior visual motion discrimination, but the neural basis for these sensory changes remains unknown. Leveraging well-characterized suppressive neural circuits in the visual system, we used behavioral and fMRI tasks to demonstrate a significant reduction in neural suppression in young adults with autism spectrum disorder (ASD) compared to neurotypical controls. MR spectroscopy measurements revealed no group differences in neurotransmitter signals. We show how a computational model that incorporates divisive normalization, as well as narrower top-down gain (that could result, for example, from a narrower window of attention), can explain our observations and divergent previous findings. Thus, weaker neural suppression is reflected in visual task performance and fMRI measures in ASD, and may be attributable to differences in top-down processing.
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http://dx.doi.org/10.1038/s41467-020-16495-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260360PMC
May 2020

Neurometabolic underpinning of the intergenerational transmission of prosociality.

Neuroimage 2020 09 24;218:116965. Epub 2020 May 24.

Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; International Research Center for Neurointelligence (WPI-IRCN), The University of Tokyo Institutes for Advanced Study (UTIAS), The University of Tokyo, Tokyo, Japan.

Parent-child personality transmission can occur via biological gene-driven processes as well as through environmental factors such as shared environment and parenting style. We recently revealed a negative association between prosociality, a highly valued personality attribute in human society, and anterior cingulate cortex (ACC) γ-aminobutyric acid (GABA) levels in children at the age of 10 years. We thus hypothesized that prosociality would be intergenerationally transmitted, and that transmission would be underwritten by neurometabolic heritability. Here, we collected prosociality data from children aged 10 years and their parents in a large-scale population-based birth cohort study. We also measured ACC GABA+ and glutamate plus glutamine (Glx) levels in a follow-up assessment with a subsample of the participants (aged 11 years) using magnetic resonance spectroscopy. We analyzed the associations among children's and parents' prosociality and GABA+/Glx ratios. We also examined the effect of socioeconomic status (SES) and verbalized parental affection (VPA) on these associations. We found a significant positive parent-child association for prosociality (N ​= ​3026; children's mean age 10.2 years) and GABA+/Glx ratio (N ​= ​99; children's mean age 11.4 years). There was a significant negative association between GABA+/Glx ratio and prosociality in both children (N ​= ​208) and parents (N ​= ​128). Our model accounting for the effects of neurometabolic heritability on prosociality transmission fitted well. Moreover, in this model, a significant positive effect of VPA but not SES on children's prosociality was observed independently of the effect of neurometabolic transmission, while SES but not VPA was significantly associated with parental prosociality. Our results provide novel insights into the neurometabolic substrates of parent-child transmission of social behavior.
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http://dx.doi.org/10.1016/j.neuroimage.2020.116965DOI Listing
September 2020

Shorter sleep duration is associated with lower GABA levels in the anterior cingulate cortex.

Sleep Med 2020 07 28;71:1-7. Epub 2020 Feb 28.

Ewha Brain Institute, Ewha W. University, Seoul, South Korea; Department of Brain and Cognitive Sciences, Ewha W. University, Seoul, South Korea. Electronic address:

Background: Alterations in the levels of gamma-aminobutyric acid (GABA) and glutamate + glutamine (Glx), which are major inhibitory and excitatory neurotransmitters, respectively, are frequently associated with insomnia. Previous reports also suggested the involvement of the anterior cingulate cortex (ACC) and medial prefrontal cortex (mPFC) in insomnia and shorter sleep duration. In the current study, we investigated whether the GABA and Glx levels were altered in the ACC/mPFC in subclinical insomnia while focusing on the sleep duration.

Methods: We examined levels of GABA and Glx in the ACC/mPFC of the brain with magnetic resonance spectroscopy in 166 individuals with subjective sleep complaints but without a diagnosis of insomnia. Participants were divided into two groups according to sleep duration (≥6 h/night: n = 79 vs. < 6 h/night: n = 74), which was measured using a wrist-worn actigraphy. Working memory function and overall subjective sleep quality were assessed with a computerized neuropsychological test and self-report questionnaire, respectively.

Results: GABA levels in the ACC/mPFC were lower in the shorter sleep duration group relative to the longer sleep duration group (t = -2.21, p = 0.03). Glx levels did not differ between the two groups (t = -0.20, p = 0.84). Lower GABA levels were associated with lower spatial working memory performance in the shorter sleep duration group (β = -0.21, p = 0.03), but not the longer sleep duration group (β = 0.04, p = 0.72).

Conclusion: Shorter sleep duration was associated with lower GABA levels in the ACC/mPFC. These findings may provide insight into the underlying mechanisms of impaired working memory function related to insomnia and sleep loss.
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http://dx.doi.org/10.1016/j.sleep.2020.02.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7302996PMC
July 2020

Reduced striatal GABA in unmedicated children with ADHD at 7T.

Psychiatry Res Neuroimaging 2020 07 18;301:111082. Epub 2020 May 18.

Department of Neuropsychology, Kennedy Krieger Institute, 1750 E. Fairmount Ave., Baltimore, MD 21231 United States; Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, 600 N Wolfe St., Baltimore, MD 21287, United States.

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.
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http://dx.doi.org/10.1016/j.pscychresns.2020.111082DOI Listing
July 2020

Motion correction in magnetic resonance spectroscopy.

Magn Reson Med 2020 11 17;84(5):2312-2326. Epub 2020 Apr 17.

Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland, Baltimore, Maryland, USA.

In vivo proton magnetic resonance spectroscopy and spectroscopic imaging (MRS/MRSI) are valuable tools to study normal and abnormal human brain physiology. However, they are sensitive to motion, due to strong crusher gradients, long acquisition times, reliance on high magnetic field homogeneity, and particular acquisition methods such as spectral editing. The effects of motion include incorrect spatial localization, phase fluctuations, incoherent averaging, line broadening, and ultimately quantitation errors. Several retrospective methods have been proposed to correct motion-related artifacts. Recent advances in hardware also allow prospective (real-time) correction of the effects of motion, including adjusting voxel location, center frequency, and magnetic field homogeneity. This article reviews prospective and retrospective methods available in the literature and their implications for clinical MRS/MRSI. In combination, these methods can attenuate or eliminate most motion-related artifacts and facilitate the acquisition of high-quality data in the clinical research setting.
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http://dx.doi.org/10.1002/mrm.28287DOI Listing
November 2020

Reproducibility of flutter-range vibrotactile detection and discrimination thresholds.

Sci Rep 2020 04 16;10(1):6528. Epub 2020 Apr 16.

Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Somatosensory processing can be probed empirically through vibrotactile psychophysical experiments. Psychophysical approaches are valuable for investigating both normal and abnormal tactile function in healthy and clinical populations. To date, the test-retest reliability of vibrotactile detection and discrimination thresholds has yet to be established. This study sought to assess the reproducibility of vibrotactile detection and discrimination thresholds in human adults using an established vibrotactile psychophysical battery. Fifteen healthy adults underwent three repeat sessions of an eleven-task battery that measured a range of vibrotactile measures, including reaction time, detection threshold, amplitude and frequency discrimination, and temporal order judgement. Coefficients of variation and intraclass correlation coefficients (ICCs) were calculated for the measures in each task. Linear mixed-effects models were used to test for length and training effects and differences between tasks within the same domain. Reaction times were shown to be the most reproducible (ICC: ~0.9) followed by detection thresholds (ICC: ~0.7). Frequency discrimination thresholds were the least reproducible (ICC: ~0.3). As reported in prior studies, significant differences in measures between related tasks were also found, demonstrating the reproducibility of task-related effects. These findings show that vibrotactile detection and discrimination thresholds are reliable, further supporting the use of psychophysical experiments to probe tactile function.
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http://dx.doi.org/10.1038/s41598-020-63208-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7162987PMC
April 2020

Concentrations of Cortical GABA and Glutamate in Young Adults With Autism Spectrum Disorder.

Autism Res 2020 07 16;13(7):1111-1129. Epub 2020 Apr 16.

Department of Psychology, University of Washington, Seattle, Washington, USA.

The balance of excitation and inhibition in neural circuits is hypothesized to be increased in autism spectrum disorder, possibly mediated by altered signaling of the inhibitory neurotransmitter γ-aminobutyric acid (GABA), yet empirical evidence in humans is inconsistent. We used edited magnetic resonance spectroscopy (MRS) to quantify signals associated with both GABA and the excitatory neurotransmitter glutamate in multiple regions of the sensory and sensorimotor cortex, including primary visual, auditory, and motor areas in adult individuals with autism and in neurotypical controls. Despite the strong a priori hypothesis of reduced GABA in autism spectrum disorder, we found no group differences in neurometabolite concentrations in any of the examined regions and no correlations of MRS measure with psychophysical visual sensitivity or autism symptomatology. We demonstrate high data quality that is comparable across groups, with a relatively large sample of well-characterized participants, and use Bayesian statistics to corroborate the lack of any group differences. We conclude that levels of GABA and Glx (glutamate, glutamine, and glutathione) in the sensory and sensorimotor cortex, as measured with MRS at 3T, are comparable in adults with autism and neurotypical individuals. Autism Res 2020, 13: 1111-1129. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: γ-Aminobutyric acid (GABA) and glutamate are the main inhibitory and excitatory neurotransmitters in the human brain, respectively, and their balanced interaction is necessary for neural function. Previous research suggests that the GABA and glutamate systems might be altered in autism. In this study, we used magnetic resonance spectroscopy to measure concentrations of these neurotransmitters in the sensory areas in the brains of young adults with autism. In contradiction to the common hypothesis of reduced GABA in autism, we demonstrate that concentrations of both GABA and glutamate, in all the brain regions examined, are comparable in individuals with autism and in neurotypical adults. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/aur.2300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387217PMC
July 2020