scholarly journals O2.2. EVALUATION OF THE RELATIONSHIP BETWEEN GLUTAMATE AND BRAIN CONNECTIVITY IN ANTIPSYCHOTIC-NAïVE FIRST EPISODE PATIENTS – A COMBINED MAGNETIC RESONANCE SPECTROSCOPY AND RESTING STATE FUNCTIONAL CONNECTIVITY MRI STUDY

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S4-S4
Author(s):  
Jose Maximo ◽  
Frederic Briend ◽  
William Armstrong ◽  
Nina Kraguljac ◽  
Adrienne Lahti

Abstract Background Schizophrenia is thought to be a disorder of brain dysconnectivity. An imbalance between cortical excitation/inhibition is also implicated, but the link between these abnormalities remains unclear. The present study used resting state functional connectivity MRI (rs-fcMRI) and magnetic resonance spectroscopy (MRS) to investigate how measurements of glutamate + glutamine (Glx) in the anterior cingulate cortex (ACC) relate to rs-fcMRI in medication-naïve first episode psychosis (FEP) subjects compared to healthy controls (HC). Based on our previous findings, we hypothesized that in HC would show correlations between Glx and rs-fMRI in the salience and default mode network, but these relationships would be altered in FEP. Methods Data from 53 HC (age = 24.70 ±6.23, 34M/19F) and 60 FEP (age = 24.08 ±6.29, 38M/22F) were analyzed. To obtain MRS data, a voxel was placed in the ACC (PRESS, TR/TE = 2000/80ms). Metabolite concentrations were quantified with respect to internal water using the AMARES algorithm in jMRUI. rs-fMRI data were processed using a standard preprocessing pipeline in the CONN toolbox. BOLD signal from a priori brain regions of interest from posterior cingulate cortex (default mode network, DMN), anterior cingulate cortex (salience network, SN), and right posterior parietal cortex (central executive network, CEN) were extracted and correlated with the rest of the brain to measure functional connectivity (FC). Group analyses were performed on Glx, FC, and Glx-FC interactions while controlling for age, gender, and motion when applicable. FC and Glx-FC analyses were performed using small volume correction [(p < 0.01, threshold-free cluster enhancement corrected (TFCE)]. Results No significant between-group differences were found in Glx concentration in the ACC [F(1, 108) = 0.34, p = 0.56], but reduced FC was found on each network in FEP compared to HC (pTFCE corrected). Group Glx-FC interactions were found in the form of positive correlations between Glx and FC in DMN and SN in the HC group, but not in FEP; and negative correlations in CEN in HC, but not in FEP. Discussion While we did not find significant group differences in ACC Glx measurements, ACC Glx modulated FC differentially in FEP and HC. Positive correlations between Glx and FC were found in the SN and DMN, suggesting long range modulation of the two networks in HC, but not in FEP. Additionally, negative correlations between Glx and FC were found in CEN in HC, but not in FEP. Overall, these results suggest that even in the absence of group differences in Glx concentration, the long-range modulation of these 3 networks by ACC Glx is altered in FEP.

2019 ◽  
Vol 237 (2) ◽  
pp. 443-451 ◽  
Author(s):  
Grant McQueen ◽  
Aderlee Lay ◽  
John Lally ◽  
Anthony S. Gabay ◽  
Tracy Collier ◽  
...  

Abstract Rationale There is interest in employing N-acetylcysteine (NAC) in the treatment of schizophrenia, but investigations of the functional signatures of its pharmacological action are scarce. Objectives The aim of this study was to identify the changes in resting-state functional connectivity (rs-FC) that occur following administration of a single dose of NAC in patients with schizophrenia. A secondary aim was to examine whether differences in rs-FC between conditions were mediated by glutamate metabolites in the anterior cingulate cortex (ACC). Methods In a double-blind, placebo-controlled crossover design, 20 patients with schizophrenia had two MRI scans administered 7 days apart, following oral administration of either 2400 mg NAC or placebo. Resting state functional fMRI (rsfMRI) assessed the effect of NAC on rs-FC within the default mode network (DMN) and the salience network (SN). Proton magnetic resonance spectroscopy was used to measure Glx/Cr (glutamate plus glutamine, in ratio to creatine) levels in the ACC during the same scanning sessions. Results Compared to the placebo condition, the NAC condition was associated with reduced within the DMN and SN, specifically between the medial pre-frontal cortex to mid frontal gyrus, and ACC to frontal pole (all p < 0.04). There were no significant correlations between ACC Glx/Cr and rs-FC in either condition (p > 0.6). Conclusions These findings provide preliminary evidence that NAC can reduce medial frontal rs-FC in schizophrenia. Future studies assessing the effects of NAC on rs-FC in early psychosis and on repeated administration in relation to efficacy would be of 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 ◽  
Vol 33 (12) ◽  
pp. 1600-1609 ◽  
Author(s):  
Robin N Perry ◽  
Hera E Schlagintweit ◽  
Christine Darredeau ◽  
Carl Helmick ◽  
Aaron J Newman ◽  
...  

Background: Changes in resting state functional connectivity between the insula and dorsal anterior cingulate cortex as well as between the insula and nucleus accumbens have been linked to nicotine withdrawal and/or administration. However, because many of nicotine’s effects in humans appear to depend, at least in part, on the belief that nicotine has been administered, the relative contribution of nicotine’s pharmacological actions to such effects requires clarification. Aims: The purpose of this study was to examine the impacts of perceived and actual nicotine administration on neural responses. Methods: Twenty-six smokers were randomly assigned to receive either a nicotine inhaler (4 mg deliverable) or a nicotine-free inhaler across two sessions. Inhaler content instructions (told nicotine vs told nicotine-free) differed across sessions. Resting state functional connectivity between sub-regions of the insula and the dorsal anterior cingulate cortex and nucleus accumbens was measured using magnetic resonance imaging before and after inhaler administration. Results: Both actual and perceived nicotine administration independently altered resting state functional connectivity between the anterior insula and the dorsal anterior cingulate cortex, with actual administration being associated with decreased resting state functional connectivity, and perceived administration with increased resting state functional connectivity. Actual nicotine administration also contralaterally reduced resting state functional connectivity between the anterior insula and nucleus accumbens, while reductions in resting state functional connectivity between the mid-insula and right nucleus accumbens were observed when nicotine was administered unexpectedly. Changes in resting state functional connectivity associated with actual or perceived nicotine administration were unrelated to changes in subjective withdrawal and craving. Changes in withdrawal and craving were however independently associated with resting state functional connectivity between the nucleus accumbens and insula. Conclusions: Our findings highlight the importance of considering non-pharmacological factors when examining drug mechanisms of action.


2021 ◽  
Vol 11 (11) ◽  
pp. 1539
Author(s):  
Gianluca Cruciani ◽  
Maddalena Boccia ◽  
Vittorio Lingiardi ◽  
Guido Giovanardi ◽  
Pietro Zingaretti ◽  
...  

Studies comparing organized (O) and unresolved/disorganized (UD) attachment have consistently shown structural and functional brain abnormalities, although whether and how attachment patterns may affect resting state functional connectivity (RSFC) is still little characterized. Here, we investigated RSFC of temporal and limbic regions of interest for UD attachment. Participants’ attachment was classified via the Adult Attachment Interview, and all participants underwent clinical assessment. Functional magnetic resonance imaging data were collected from 11 UD individuals and seven matched O participants during rest. A seed-to-voxel analysis was performed, including the anterior and the posterior cingulate cortex, the bilateral insula, amygdala and hippocampus as seed regions. No group differences in the clinical scales emerged. Compared to O, the UD group showed lower RSFC between the left amygdala and the left cerebellum (lobules VIII), and lower functional coupling between the right hippocampus and the posterior portion of the right middle temporal gyrus. Moreover, UD participants showed higher RSFC between the right amygdala and the anterior cingulate cortex. Our findings suggest RSFC alterations in regions associated with encoding of salient events, emotion processing, memories retrieval and self-referential processing in UD participants, highlighting the potential role of attachment experiences in shaping brain abnormalities also in non-clinical UD individuals.


2020 ◽  
Author(s):  
Isabel M. Berwian ◽  
Julia G. Wenzel ◽  
Leonie Kuehn ◽  
Inga Schnuerer ◽  
Lars Kasper ◽  
...  

AbstractThe risk of relapsing into depression after stopping antidepressants is high, but no established predictors exist. Resting-state functional magnetic resonance imaging (rsfMRI) measures may help predict relapse and identify the mechanisms by which relapses occur. rsfMRI data were acquired from healthy controls and from patients with remitted major depressive disorder on antidepressants. Patients were assessed a second time either before or after discontinuation of the antidepressant, and followed up for six months to assess relapse. A seed-based functional connectivity analysis was conducted focusing on the left subgenual anterior cingulate cortex and left posterior cingulate cortex. Seeds in the amygdala and dorsolateral prefrontal cortex were explored. 44 healthy controls (age: 33.8 (10.5), 73% female) and 84 patients (age: 34.23 (10.8), 80% female) were included in the analysis. 29 patients went on to relapse and 38 remained well. The seed-based analysis showed that discontinuation resulted in an increased functional connectivity between the right dorsolateral prefrontal cortex and the parietal cortex in non-relapsers. In an exploratory analysis, this functional connectivity predicted relapse risk with a balanced accuracy of 0.86. Further seed-based analyses, however, failed to reveal differences in functional connectivity between patients and controls, between relapsers and non-relapsers before discontinuation and changes due to discontinuation independent of relapse. In conclusion, changes in the connectivity between the dorsolateral prefrontal cortex and the posterior default mode network were associated with and predictive of relapse after open-label antidepressant discontinuation. This finding requires replication in a larger dataset.


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