Impact of glutamate levels on neuronal response and cognitive abilities in schizophrenia

Falkenberg, Liv E.; Westerhausen, René; Craven, Alexander R.; Johnsen, Erik; Kroken, Rune A.; L⊘berg, Else-Marie; Specht, Karsten; Hugdahl, Kenneth

doi:10.1016/j.nicl.2014.03.014

Cited by 51 publications

(40 citation statements)

References 77 publications

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“…We plan to pursue this approach. In addition, the assumption here is that the correlation trends between the imaging maps and MCCB scores would be similar in both groups, in consistent with (81, 82), whereas our method also allows patients and controls to exhibit opposite correlations between imaging signatures and cognition by separately calculating correlations within each group, as shown in (83). In future studies with more subjects and greater statistical power or with task-related fMRI, we may expect to find such relationships.…”

Section: Discussionmentioning

confidence: 95%

In Search of Multimodal Neuroimaging Biomarkers of Cognitive Deficits in Schizophrenia

Sui

Pearlson

et al. 2015

Biological Psychiatry

167

122

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BACKGROUND The cognitive deficits of schizophrenia are largely resistant to current treatments, thus are a life-long illness burden. The MATRICS Consensus Cognitive Battery (MCCB) provides a reliable and valid assessment of cognition across major cognitive domains; however, the multimodal brain alterations specifically associated with MCCB in schizophrenia have not been examined. METHODS The interrelationships between MCCB and the abnormalities seen in three types of neuroimaging-derived maps—fractional amplitude of low frequency fluctuations (fALFF) from resting-state functional magnetic resonance imaging (MRI), grey matter density (GM) from structural MRI and fractional anisotropy (FA) from diffusion MRI, were investigated by using multi-set canonical correlation analysis in data from 47 schizophrenia patients treated with antipsychotic medications and 50 age-matched healthy controls. RESULTS One multimodal component (CV8) was identified as both group-differentiating and significantly correlated with the MCCB composite. It demonstrated: 1) Increased cognitive performance associated with higher fALFF (intensity of regional spontaneous brain activity) and higher GM volumes in thalamus, striatum, hippocampus, and the mid-occipital region, with co-occurring FA changes in superior longitudinal fascicules, anterior thalamic radiation and forceps major. 2) Higher fALFF but lower GM volume in dorsolateral prefrontal cortex related to worse cognition in schizophrenia. 3) Distinct domains of MCCB might exhibit dissociable multimodal signatures, e.g., increased fALFF in inferior parietal lobule particularly correlated with decreased social cognition. Medication dose did not relate to these findings in schizophrenia. CONCLUSIONS Our results suggest linked functional and structural deficits in distributed cortico-striato-thalamic circuits may be closely related to MCCB-measured cognitive impairments in schizophrenia.

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Section: Discussionmentioning

confidence: 95%

In Search of Multimodal Neuroimaging Biomarkers of Cognitive Deficits in Schizophrenia

Sui

Pearlson

et al. 2015

Biological Psychiatry

167

122

View full text Add to dashboard Cite

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“…For example, the anterior and posterior insula [Shepherd et al, ] and STG [Vita et al, ] exhibit volume loss in SP, and abnormal levels of glutamate/glutamine/GABA have been reported in SP [Poels et al, ; Taylor and Tso, ]. The former affects perfusion whereas glutamate and GABA directly affect the shape of the HRF, potentially differentially in HC and SP [Falkenberg et al, ; Muthukumaraswamy et al, ].…”

Section: Discussionmentioning

confidence: 99%

Hemodynamic response function abnormalities in schizophrenia during a multisensory detection task

Hanlon

Shaff

Dodd

et al. 2015

Human Brain Mapping

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Functional magnetic resonance imaging (fMRI) of the blood oxygen level dependent (BOLD) response has commonly been used to investigate the neuropathology underlying cognitive and sensory deficits in patients with schizophrenia (SP) by examining the positive phase of the BOLD response, assuming a fixed shape for the hemodynamic response function (HRF). However, the individual phases (positive and post-stimulus undershoot (PSU)) of the HRF may be differentially affected by a variety of underlying pathologies. The current experiment used a multisensory detection task with a rapid event-related fMRI paradigm to investigate both the positive and PSU phases of the HRF in SP and healthy controls (HC). Behavioral results indicated no significant group differences during task performance. Analyses that examined the shape of the HRF indicated two distinct group differences. First, SP exhibited a reduced and/or prolonged PSU following normal task-related positive BOLD activation in secondary auditory and visual sensory areas relative to HC. Second, SP did not show task-induced deactivation in the anterior node of the default-mode network (aDMN) relative to HC. In contrast, when performing traditional analyses that focus on the positive phase, there were no group differences. Interestingly, the magnitude of the PSU in secondary auditory and visual areas was positively associated with the magnitude of task-induced deactivation within the aDMN, suggesting a possible common neural mechanism underlying both of these abnormalities (failure in neural inhibition). Results are consistent with recent views that separate neural processes underlie the two phases of the HRF and that they are differentially affected in SP.

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“…Hyper-activation, consistent with disinhibition, was observed in auditory cortex following presentation of single-tone stimuli(124). Higher glutamate levels (measured at rest by 1 H-MRS) associated with greater inferior parietal BOLD signal during auditory cognitive control in SCZ, whereas this correlation was negative in controls(125). These task-based findings converge with the E/I imbalance hypothesis in SCZ, with the third study suggesting a functional link between task-related hyper-excitability and altered glutamate neurotransmission.…”

Section: Functional Neuroimagingmentioning

confidence: 90%

Searching for Cross-Diagnostic Convergence: Neural Mechanisms Governing Excitation and Inhibition Balance in Schizophrenia and Autism Spectrum Disorders

Foss‐Feig

Adkinson

et al. 2017

Biological Psychiatry

233

183

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Recent theoretical accounts have proposed excitation (E) and inhibition (I) imbalance as a possible mechanistic, network-level hypothesis underlying neural and behavioral dysfunction across neurodevelopmental disorders, particularly autism spectrum disorder (ASD) and schizophrenia (SCZ). These two disorders share some overlap in their clinical presentation as well as convergence in their underlying genes and neurobiology. However, there are also clear points of dissociation in terms of phenotypes and putatively affected neural circuitry. Here we highlight emerging work from the clinical neuroscience literature examining neural correlates of E/I imbalance across children and adults with ASD and adults with both chronic and early-course SCZ. We discuss findings from diverse neuroimaging studies across distinct modalities, conducted with EEG, MEG, 1H-MRS, and fMRI, including effects observed both during task and at rest. Throughout this review we discuss points of convergence and divergence in the ASD and SCZ literature, with a focus on disruptions in neural E/I balance. We also consider these findings in relation to predictions generated by theoretical neuroscience, particularly computational models predicting E/I imbalance across disorders. Finally, we discuss how human non-invasive neuroimaging can benefit from pharmacological challenge studies to reveal mechanisms in ASD and SCZ. Collectively, we attempt to shed light on shared and divergent neuroimaging effects across disorders with the goal of informing future research examining the mechanisms underlying the E/I imbalance hypothesis across neurodevelopmental disorders. We posit that such translational efforts are vital to facilitate development of neurobiologically informed treatment strategies across neuropsychiatric conditions.

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Impact of glutamate levels on neuronal response and cognitive abilities in schizophrenia

Cited by 51 publications

References 77 publications

In Search of Multimodal Neuroimaging Biomarkers of Cognitive Deficits in Schizophrenia

In Search of Multimodal Neuroimaging Biomarkers of Cognitive Deficits in Schizophrenia

Hemodynamic response function abnormalities in schizophrenia during a multisensory detection task

Searching for Cross-Diagnostic Convergence: Neural Mechanisms Governing Excitation and Inhibition Balance in Schizophrenia and Autism Spectrum Disorders

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