scholarly journals Glutamate and Dysconnection in the Salience Network: Neurochemical, Effective-connectivity, and Computational Evidence in Schizophrenia

2019 ◽  
Author(s):  
Roberto Limongi ◽  
Peter Jeon ◽  
Michael Mackinley ◽  
Tushar Das ◽  
Kara Dempster ◽  
...  

AbstractIn the dysconnection hypothesis, psychosis is caused by NMDA hypofunction resulting in aberrant network connectivity. Combining a cognitive-control task, functional magnetic resonance spectroscopy, and functional magnetic resonance imaging, we tested this hypothesis in the salience network of 20 first-episode psychosis (FEP) and 20 healthy control (HC) subjects. Across groups, glutamate concentration in the dorsal anterior cingulate cortex (dACC) was associated with higher and lower inhibitory connectivity in the dACC and in the anterior insula (AI) respectively. Crucially, glutamate concentration correlated negatively with the inhibitory influence on the excitatory neuronal population in the dACC of FEP subjects. Furthermore, aberrant computational parameters of the cognitive-control task performance were associated with aberrant inhibitory connections. Finally, the strength of connections from the dACC to the AI correlated negatively with severity of social withdrawal. These findings support a link between glutamate-mediated cortical disinhibition, deficits in effective connectivity, and computational performance in psychosis.

2021 ◽  
Vol 18 ◽  
Author(s):  
Soo-Hyun Cho ◽  
Hak Young Rhee ◽  
Janghoon Oh ◽  
Jin San Lee ◽  
Soonchan Park ◽  
...  

Background: Longitudinal changes of brain metabolites during a functional stimulation are unknown in amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) subjects. Objective: This study was to evaluate the longitudinal changes of brain metabolites using proton magnetic resonance spectroscopy (1H MRS) in response to treatment during a memory task in the subjects of cognitive normal (CN), aMCI, and AD. Methods: We acquired functional magnetic resonance spectroscopy (fMRS) data from 28 CN elderly, 16 aMCI and 12 AD subjects during a face-name association task. We measured fMRS metabolite ratios over 24 months in the 8-month apart, determined the temporal changes of the metabolites, and evaluated the differences among the three groups under the three different conditions (base, novel, repeat). Results: The results of comparisons for the three subject groups and the three-time points showed that tNAA/tCho and tCr/tCho were statistically significant among the three subject groups in any of the three conditions. The dynamic temporal change measurements for the metabolites for each condition showed that Glx/tCho and Glu/tCho levels at the third visit increased significantly compared with in the first visit in the novel condition in the AD group. Conclusion: We found declines in tNAA/tCho and tCr/tCho in the aMCI and AD subjects with increasing disease severity, being highest in CN and lowest in AD. The Glx/tCho level increased temporally in the AD subjects after they took an acetylcholine esterase inhibitor. Therefore, Glx may be suitable to demonstrate functional recovery after treatment.


2018 ◽  
Vol 32 (5) ◽  
pp. 497-508 ◽  
Author(s):  
Luke A Jelen ◽  
Sinead King ◽  
Paul G Mullins ◽  
James M Stone

Abnormalities of the glutamate system are increasingly implicated in schizophrenia but their exact nature remains unknown. Proton magnetic resonance spectroscopy (1H-MRS), while fundamental in revealing glutamatergic alterations in schizophrenia, has, until recently, been significantly limited and thought to only provide static measures. Functional magnetic resonance spectroscopy (fMRS), which uses sequential scans for dynamic measurement of a range of brain metabolites in activated brain areas, has lately been applied to a variety of task or stimulus conditions, producing interesting insights into neurometabolite responses to neural activation. Here, we summarise the existing 1H-MRS studies of brain glutamate in schizophrenia. We then present a comprehensive review of research studies that have utilised fMRS, and lastly consider how fMRS methods might further the understanding of glutamatergic abnormalities in schizophrenia.


2017 ◽  
Vol 43 (suppl_1) ◽  
pp. S5-S5
Author(s):  
James Stone ◽  
Sinead King ◽  
Luke Jelen ◽  
Charlotte Horne ◽  
David Lythgoe

Sign in / Sign up

Export Citation Format

Share Document