scholarly journals Glutamate connectivity associations converge upon the salience network in schizophrenia and healthy controls

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Robert A. McCutcheon ◽  
Toby Pillinger ◽  
Maria Rogdaki ◽  
Juan Bustillo ◽  
Oliver D. Howes

AbstractAlterations in cortical inter-areal functional connectivity, and aberrant glutamatergic signalling are implicated in the pathophysiology of schizophrenia but the relationship between the two is unclear. We used multimodal imaging to identify areas of convergence between the two systems. Two separate cohorts were examined, comprising 195 participants in total. All participants received resting state functional MRI to characterise functional brain networks and proton magnetic resonance spectroscopy (1H-MRS) to measure glutamate concentrations in the frontal cortex. Study A investigated the relationship between frontal cortex glutamate concentrations and network connectivity in individuals with schizophrenia and healthy controls. Study B also used 1H-MRS, and scanned individuals with schizophrenia and healthy controls before and after a challenge with the glutamatergic modulator riluzole, to investigate the relationship between changes in glutamate concentrations and changes in network connectivity. In both studies the network based statistic was used to probe associations between glutamate and connectivity, and glutamate associated networks were then characterised in terms of their overlap with canonical functional networks. Study A involved 76 individuals with schizophrenia and 82 controls, and identified a functional network negatively associated with glutamate concentrations that was concentrated within the salience network (p < 0.05) and did not differ significantly between patients and controls (p > 0.85). Study B involved 19 individuals with schizophrenia and 17 controls and found that increases in glutamate concentrations induced by riluzole were linked to increases in connectivity localised to the salience network (p < 0.05), and the relationship did not differ between patients and controls (p > 0.4). Frontal cortex glutamate concentrations are associated with inter-areal functional connectivity of a network that localises to the salience network. Changes in network connectivity in response to glutamate modulation show an opposite effect compared to the relationship observed at baseline, which may complicate pharmacological attempts to simultaneously correct glutamatergic and connectivity aberrations.

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S102-S103
Author(s):  
Rob McCutcheon ◽  
Toby Pillinger ◽  
Sameer Jauhar ◽  
Fiona Pepper ◽  
Maria Rogdaki ◽  
...  

Abstract Background Cortical dysconnectivity and dysfunctional glutamatergic signalling are both implicated in the pathophysiology of psychotic illness. The relationship between these two systems, and the relevance to psychotic disorders remains unknown. Methods 50 individuals with a psychotic disorder and 54 healthy controls received baseline imaging using 1H-MRS to measure anterior cingulate glutamate concentrations, and resting state MRI to characterise functional brain networks. These measures were subsequently repeated following 3 days treatment with either the glutamatergic regulator riluzole (N=36), or a dopamine antagonist (N=14). The network-based statistic was used to examine relationships between glutamate concentrations and connectivity of the salience and default mode networks in patients and controls, and to investigate how this changed following pharmacological manipulation. Results In healthy controls higher baseline anterior cingulate glutamate concentrations were associated with reduced salience network connectivity, particularly for interhemispheric connections. This pattern was not seen in patients, and the greater the divergence from the relationship observed in controls, the greater the severity of negative symptoms. Default mode-salience internetwork connectivity was greater in patients compared to controls, and inversely correlated with baseline glutamate concentrations. Furthermore, riluzole associated changes in glutamate concentrations were associated with an inverse change in internetwork connectivity suggesting a causal relationship. Discussion Individuals with a psychotic disorder showed marked alterations in the relationship between anterior cingulate cortex glutamate concentration and connectivity of the salience and default mode networks. A pharmacological challenge with a glutamate regulating agent modulated this association, highlighting that the relationship is potentially malleable.


Author(s):  
Lisa Bartha-Doering ◽  
Ernst Schwartz ◽  
Kathrin Kollndorfer ◽  
Florian Ph. S. Fischmeister ◽  
Astrid Novak ◽  
...  

AbstractThe present study is interested in the role of the corpus callosum in the development of the language network. We, therefore, investigated language abilities and the language network using task-based fMRI in three cases of complete agenesis of the corpus callosum (ACC), three cases of partial ACC and six controls. Although the children with complete ACC revealed impaired functions in specific language domains, no child with partial ACC showed a test score below average. As a group, ACC children performed significantly worse than healthy controls in verbal fluency and naming. Furthermore, whole-brain ROI-to-ROI connectivity analyses revealed reduced intrahemispheric and right intrahemispheric functional connectivity in ACC patients as compared to controls. In addition, stronger functional connectivity between left and right temporal areas was associated with better language abilities in the ACC group. In healthy controls, no association between language abilities and connectivity was found. Our results show that ACC is associated not only with less interhemispheric, but also with less right intrahemispheric language network connectivity in line with reduced verbal abilities. The present study, thus, supports the excitatory role of the corpus callosum in functional language network connectivity and language abilities.


eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Charlotte J Stagg ◽  
Velicia Bachtiar ◽  
Ugwechi Amadi ◽  
Christel A Gudberg ◽  
Andrei S Ilie ◽  
...  

Anatomically plausible networks of functionally inter-connected regions have been reliably demonstrated at rest, although the neurochemical basis of these ‘resting state networks’ is not well understood. In this study, we combined magnetic resonance spectroscopy (MRS) and resting state fMRI and demonstrated an inverse relationship between levels of the inhibitory neurotransmitter GABA within the primary motor cortex (M1) and the strength of functional connectivity across the resting motor network. This relationship was both neurochemically and anatomically specific. We then went on to show that anodal transcranial direct current stimulation (tDCS), an intervention previously shown to decrease GABA levels within M1, increased resting motor network connectivity. We therefore suggest that network-level functional connectivity within the motor system is related to the degree of inhibition in M1, a major node within the motor network, a finding in line with converging evidence from both simulation and empirical studies.


2020 ◽  
Vol 9 (12) ◽  
pp. 3909
Author(s):  
Wojciech Guenter ◽  
Maciej Bieliński ◽  
Robert Bonek ◽  
Alina Borkowska

To assess cognitive impairment and affective symptoms and their association with damage to normal-appearing white matter (NAWM) in patients with clinically isolated syndrome (CIS), we compared neuropsychological test scores between patients with CIS and healthy controls and examined correlations between these and proton magnetic resonance spectroscopy (1H-MRS) outcomes in patients with CIS. Forty patients with CIS and 40 healthy participants were tested with a set of neuropsychological tests, which included the Beck Depression Inventory (BDI) and the Hospital Anxiety and Depression Scale (HADS). Single-voxel 1H-MRS was performed on frontal and parietal NAWM of patients with CIS to assess ratios of N-acetyl-aspartate (NAA) to creatine (Cr), myo-inositol (mI), and choline (Cho), as well as mI/Cr and Cho/Cr ratios. Patients with CIS had lower cognitive performance and higher scores for the BDI and anxiety subscale of HADS than healthy controls. There were significant correlations between the following neuropsychological tests and metabolic ratios in the frontal NAWM: Stroop Color-Word Test and Cho/Cr, Symbol Digit Modalities Test and mI/Cr, as well as NAA/mI, Go/no-go reaction time, and NAA/Cho, as well as NAA/mI, Californian Verbal Learning Test, and NAA/Cr. BDI scores were related to frontal NAA/mI and parietal NAA/Cr and Cho/Cr ratios, whereas HADS-depression scores were associated with frontal NAA/Cr and NAA/mI and parietal NAA/Cr and Cho/Cr ratios. HADS-anxiety correlated with parietal NAA/Cr ratio. This study suggests that neurochemical changes in the NAWM assessed with single-voxel 1H-MRS are associated with cognitive performance and affective symptoms in patients with CIS.


2006 ◽  
Vol 291 (2) ◽  
pp. R277-R284 ◽  
Author(s):  
Lin Chang ◽  
Emeran A. Mayer ◽  
Jennifer S. Labus ◽  
Max Schmulson ◽  
Oh Young Lee ◽  
...  

In irritable bowel syndrome (IBS) patients, the relationship between sex and sensitivity to visceral stimuli is incompletely understood. Our aim was to evaluate the effect of sex on perceptual responses to visceral stimulation in IBS. Fifty-eight IBS patients (mean age 42 ± 1 yr; 34 men, 24 women) and 26 healthy controls (mean age 38 ± 3 yr; 9 men, 17 women) underwent barostat-assisted distensions of the rectum and sigmoid colon. Rectal discomfort thresholds were measured using a randomized, phasic distension paradigm before and after repeated noxious sigmoid stimulation (SIG, 60-mmHg pulses). Sex had a significant effect on rectal discomfort thresholds. Women with IBS were the most sensitive (lower thresholds [27 ± 2.7 mmHg] and higher ratings), with significantly lower rectal discomfort thresholds compared with men with IBS (38 ± 2.3 mmHg) and healthy women who were the least sensitive (41.9 ± 3.2 mmHg; both P < 0.01). There were no significant differences in rectal discomfort thresholds between healthy men (34 ± 4.3 mmHg) and men with IBS. Across both IBS and control groups, women demonstrated a significant lowering of discomfort thresholds after noxious sigmoid stimulation ( P < 0.01), while men did not. Sex significantly influences perceptual sensitivity to rectosigmoid distension. Women show greater perceptual responses to this paradigm.


2017 ◽  
Vol 41 (S1) ◽  
pp. S351-S351
Author(s):  
A.S. Urrila ◽  
A. Hakkarainen ◽  
A. Castaneda ◽  
T. Paunio ◽  
M. Marttunen ◽  
...  

AimThis study used proton magnetic resonance spectroscopy (1H MRS) to evaluate neurochemistry of the frontal cortex in adolescents with symptoms of sleep and depression.Methods19 non-medicated adolescent boys (mean age 16.0 y; n = 9 clinical cases with depression/sleep symptoms and n = 10 healthy controls) underwent 1H MRS at 3 T. MR spectra were acquired from the anterior cingulate cortex (ACC), the dorsolateral prefrontal cortex, and frontal white matter. Concentrations of N-acetyl aspartate, total creatine, choline-containing compounds, total glutamine plus glutamate, and myo-inositol (mI) were compared between the two subgroups and correlated with sleep and clinical measures in the total sample. Sleep was assessed with self-report questionnaires and ambulatory polysomnography recordings.ResultsConcentrations of mI were lower in both frontal cortical regions among the depressed adolescents as compared to healthy controls. No statistically significant differences in other metabolite concentrations were observed between the subgroups. Frontal cortex mI concentrations correlated negatively with depression severity, subjective daytime sleepiness, insomnia symptoms, and the level of anxiety, and positively with total sleep time and overall psychosocial functioning. The correlations between mI in the ACC and total sleep time as well as daytime sleepiness remained statistically significant when depression severity was controlled in the analyses.ConclusionLower frontal cortex mI may indicate a disturbed second messenger system. Frontal cortical mI may thus be linked to the pathophysiology of depression and concomitant sleep symptoms among maturing adolescents. Short sleep and daytime sleepiness may be associated with frontal cortex mI independently from depression.Disclosure of interestThe authors have not supplied their declaration of competing interest.


2018 ◽  
Author(s):  
Kristina M. Deligiannidis ◽  
Christina L. Fales ◽  
Aimee R. Kroll-Desrosiers ◽  
Scott A. Shaffer ◽  
Vanessa Villamarin ◽  
...  

ABSTRACTPostpartum depression (PPD) is associated with abnormalities in resting-state functional connectivity (RSFC) but the underlying neurochemistry is unclear. We hypothesized that peripartum GABAergic neuroactive steroids (NAS) are related to cortical GABA concentrations and RSFC in PPD as compared to healthy comparison women (HCW). To test this, we measured RSFC with fMRI and GABA+/Creatine (Cr) concentrations with proton magnetic resonance spectroscopy (1H MRS) in the pregenual anterior cingulate (pgACC) and occipital cortices (OCC) and quantified peripartum plasma NAS. We examined between-group differences in RSFC and the relationship between cortical GABA+/Cr concentrations with RSFC. We investigated the relationship between NAS, RSFC and cortical GABA+/Cr concentrations. Within the default mode network (DMN) an area of the dorsomedial prefrontal cortex (DMPFC) had greater connectivity with the rest of the DMN in PPD (peak voxel: MNI coordinates (2, 58, 32), p=0.002) and was correlated to depression scores (peak HAM-D17 voxel: MNI coordinates (0, 60, 34), p=0.008). pgACC GABA+/Cr correlated positively with DMPFC RSFC in a region spanning the right anterior/posterior insula and right temporal pole (r=+0.661, p=0.000). OCC GABA+/Cr correlated positively with regions spanning both amygdalae (right amygdala: r=+0.522, p=0.000; left amygdala: r=+0.651, p=0.000) as well as superior parietal areas. Plasma allopregnanolone was higher in PPD (p=0.03) and positively correlated with intra DMPFC connectivity (r=+0.548, p=0.000) but not GABA+/Cr. These results provide initial evidence that PPD is associated with altered DMN connectivity; cortical GABA+/Cr concentrations are associated with postpartum RSFC and allopregnanolone is associated with postpartum intra-DMPFC connectivity.


2019 ◽  
Author(s):  
Alexander Belden ◽  
Tima Zeng ◽  
Emily Przysinda ◽  
Sheeba Arnold Anteraper ◽  
Susan Whitfield-Gabrieli ◽  
...  

AbstractJazz improvisation offers a model for creative cognition, as it involves the real-time creation of a novel, information-rich product. Previous research has shown that when musicians improvise, they recruit regions in the Default Mode Network (DMN) and Executive Control Network (ECN). Here, we ask whether these findings from task-fMRI studies might extend to intrinsic differences in resting state functional connectivity. We compared Improvising musicians, Classical musicians, and Minimally Musically Trained (MMT) controls in seed-based functional connectivity and network analyses in resting state functional MRI. We also examined the functional correlates of behavioral performance in musical improvisation and divergent thinking. Seed-based analysis consistently showed higher connectivity in ventral DMN (vDMN) and bilateral ECN in both groups of musically trained individuals as compared to MMT controls, with additional group differences in primary visual network, precuneus network, and posterior salience network. In particular, primary visual network connectivity to DMN and ECN was highest in Improvisational musicians, whereas within-network connectivity of vDMN and precuneus network was higher in both Improvisational and Classical musicians than in MMT controls; in contrast, connectivity between posterior salience network and superior parietal lobule was highest in Classical musicians. Furthermore, graph-theoretical analysis indicated heightened betweenness centrality, clustering, and local efficiency in Classical musicians. Taken together, results suggest that heightened functional connectivity among musicians can be explained by higher within-network connectivity (more tight-knit cortical networks) in Classical musicians, as opposed to more disperse, globally-connected cortical networks in Improvisational musicians.HighlightsMusic training is associated with higher resting state connectivityHigher connectivity in Improvisational musicians from visual network to ECN and DMNClassical musicians show higher vDMN and Precuneus within-network connectivityImprovisation and divergent thinking performance correlate with similar connectivity patterns


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