Do NMDA-R antagonists re-create patterns of spontaneous gamma-band activity in schizophrenia? A systematic review and perspective

Bianciardi, Bianca; Uhlhaas, Peter J.

doi:10.1016/j.neubiorev.2021.02.005

Cited by 35 publications

(39 citation statements)

References 111 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Di Lorenzo et al ( 64 ) observed significantly higher connectivity between right occipital-prefrontal, occipital-parieto-temporal, and occipital-cingulate ROI-pairs, while Andreou et al found increased connectivity in bilateral frontal and insula regions and left temporal-midline regions. This study's connectivity patterns with an involvement of the right occipital and cingulate area parallel the findings from schizophrenia patients and are consistent with other RS-ketamine-studies, which found increased RS-GBO ( 42 – 44 , 65 ). The gamma network involved areas relevant for auditory–spatial processing, working memory, attention and regions of the default mode network, which have been described to be affected in schizophrenia ( 66 – 69 ).…”

Section: Discussionsupporting

confidence: 90%

“…While animal studies influencing the NMDA-R are consistent with NMDA-R-modulation in humans with respect to GBO, paralleling these findings with schizophrenia patients remains challenging, as both increased and decreased RS-GBOs have been observed in patients [reviewed by Bianciardi and Uhlhaas ( 44 )]. This emphasizes the need for further studies characterizing the spectral characteristics in both the ketamine-model of schizophrenia and patient populations.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Ketamine Alters Functional Gamma and Theta Resting-State Connectivity in Healthy Humans: Implications for Schizophrenia Treatment Targeting the Glutamate System

et al. 2021

View full text Add to dashboard Cite

Disturbed functional connectivity is assumed to cause neurocognitive deficits in patients suffering from schizophrenia. A Glutamate N-methyl-D-aspartate receptor (NMDAR) dysfunction has been suggested as a possible mechanism underlying altered connectivity in schizophrenia, especially in the gamma- and theta-frequency range. The present study aimed to investigate the effects of the NMDAR-antagonist ketamine on resting-state power, functional connectivity, and schizophrenia-like psychopathological changes in healthy volunteers. In a placebo-controlled crossover design, 25 healthy subjects were recorded using resting-state 64-channel-electroencephalography (EEG) (eyes closed). The imaginary coherence-based Multivariate Interaction Measure (MIM) was used to measure gamma and theta connectivity across 80 cortical regions. The network-based statistic was applied to identify involved networks under ketamine. Psychopathology was assessed with the Positive and Negative Syndrome Scale (PANSS) and the 5-Dimensional Altered States of Consciousness Rating Scale (5D-ASC). Ketamine caused an increase in all PANSS (p < 0.001) as well as 5D-ASC scores (p < 0.01). Significant increases in resting-state gamma and theta power were observed under ketamine compared to placebo (p < 0.05). The source-space analysis revealed two distinct networks with an increased mean functional gamma- or theta-band connectivity during the ketamine session. The gamma-network consisted of midline regions, the cuneus, the precuneus, and the bilateral posterior cingulate cortices, while the theta-band network involved the Heschl gyrus, midline regions, the insula, and the middle cingulate cortex. The current source density (CSD) within the gamma-band correlated negatively with the PANSS negative symptom score, and the activity within the gamma-band network correlated negatively with the subjective changed meaning of percepts subscale of the 5D-ASC. These results are in line with resting-state patterns seen in people who have schizophrenia and argue for a crucial role of the glutamate system in mediating dysfunctional gamma- and theta-band-connectivity in schizophrenia. Resting-state networks could serve as biomarkers for the response to glutamatergic drugs or drug development efforts within the glutamate system.

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Ketamine Alters Functional Gamma and Theta Resting-State Connectivity in Healthy Humans: Implications for Schizophrenia Treatment Targeting the Glutamate System

et al. 2021

View full text Add to dashboard Cite

show abstract

“…However, social task-elicited gamma power was normalized to background gamma which minimizes inter-mouse variability, and our discovery of lower elicited gamma in SRKO mice during novel mouse investigations was replicated across two trials (sociability and social novelty) suggesting a large effect size. This is supported by clinical and preclinical literature that finds schizophrenia-associated changes in stimulus-evoked gamma are larger and more consistent than changes in resting state gamma 26,70 .…”

Section: Deficient Task-associated Gamma In Srko Mice Is Associated With Behavioral Impairmentssupporting

confidence: 66%

“…These include the auditory steady-state response, sleep spindles, and state-specific power spectral density. Although they do not fully recapitulate symptoms of schizophrenia, these mice may be useful for modeling patients with chronic schizophrenia more accurately than pharmacologic models in specific domains 71 including sensory gating and resting state gamma 70 . Future studies of SRKO mice can confirm whether (1) the abnormal biomarker phenotypes persist among antipsychotic or D-serine treatment, (2) glycine-related compensatory responses are occurring, (3) thalamocortical circuitry is intact, or (4) abnormalities in dopamine levels, cholinergic signaling, or parvalbumin-containing neurons exist in the neocortex.…”

Section: Discussionmentioning

confidence: 99%

Altered neural oscillations and behavior in a genetic mouse model of NMDA receptor hypofunction

Aguilar

Radzik

Schiffino

et al. 2021

Sci Rep

View full text Add to dashboard Cite

Abnormalities in electroencephalographic (EEG) biomarkers occur in patients with schizophrenia and those clinically at high risk for transition to psychosis and are associated with cognitive impairment. Converging evidence suggests N-methyl-D-aspartate receptor (NMDAR) hypofunction plays a central role in the pathophysiology of schizophrenia and likely contributes to biomarker impairments. Thus, characterizing these biomarkers is of significant interest for early diagnosis of schizophrenia and development of novel treatments. We utilized in vivo EEG recordings and behavioral analyses to perform a battery of electrophysiological biomarkers in an established model of chronic NMDAR hypofunction, serine racemase knockout (SRKO) mice, and their wild-type littermates. SRKO mice displayed impairments in investigation-elicited gamma power that corresponded with reduced short-term social recognition and enhanced background (pre-investigation) gamma activity. Additionally, SRKO mice exhibited sensory gating impairments in both evoked-gamma power and event-related potential amplitude. However, other biomarkers including the auditory steady-state response, sleep spindles, and state-specific power spectral density were generally neurotypical. In conclusion, SRKO mice demonstrate how chronic NMDAR hypofunction contributes to deficits in certain translationally-relevant EEG biomarkers altered in schizophrenia. Importantly, our gamma band findings suggest an aberrant signal-to-noise ratio impairing cognition that occurs with NMDAR hypofunction, potentially tied to impaired task-dependent alteration in functional connectivity.

show abstract

“…Like behavior-to-cognitive variables, functional oscillations would be appropriate as both cognitive processes and brain oscillations are altered in ARMS individuals [ 8 , 80 , 81 ]. However, the oscillopathies recorded in ARMS patients are subtler than those recorded during a ketamine-induced psychosis-relevant brain state in both humans and rodents [ 82 ]. The behavior-to-cognitive variables should therefore probably also be followed.…”

Section: Discussionmentioning

confidence: 99%

Frontoparietal anodal tDCS reduces ketamine-induced oscillopathies

Lahogue

Pinault

2021

Translational Neuroscience

View full text Add to dashboard Cite

During the prodromal phase of schizophrenia with its complex and insidious clinical picture, electroencephalographic recordings detect widespread oscillation disturbances (or oscillopathies) during the wake–sleep cycle. Neural oscillations are electrobiomarkers of the connectivity state within systems. A single-systemic administration of ketamine, a non-competitive NMDA glutamate receptor antagonist, transiently reproduces the oscillopathies with a clinical picture reminiscent of the psychosis prodrome. This acute pharmacological model may help the research and development of innovative treatments against psychotic transition. Transcranial electrical stimulation is recognized as an appropriate non-invasive therapeutic modality since it can increase cognitive performance and modulate neural oscillations with little or no side effects. Therefore, our objective was to set up, in the sedated adult rat, a stimulation method that is able to normalize ketamine-induced increase in gamma-frequency (30–80 Hz) oscillations and decrease in sigma-frequency (10–17 Hz) oscillations. Unilateral and bipolar frontoparietal (FP), transcranial anodal stimulation by direct current (<+1 mA) was applied in ketamine-treated rats. A concomitant bilateral electroencephalographic recording of the parietal cortex measured the stimulation effects on its spontaneously occurring oscillations. A 5 min FP anodal tDCS immediately and quickly reduced, significantly with an intensity-effect relationship, the ketamine-induced gamma hyperactivity, and sigma hypoactivity at least in the bilateral parietal cortex. A duration effect was also recorded. The tDCS also tended to diminish the ketamine-induced delta hypoactivity. These preliminary neurophysiological findings are promising for developing a therapeutic proof-of-concept against neuropsychiatric disorders.

show abstract

Do NMDA-R antagonists re-create patterns of spontaneous gamma-band activity in schizophrenia? A systematic review and perspective

Cited by 35 publications

References 111 publications

Ketamine Alters Functional Gamma and Theta Resting-State Connectivity in Healthy Humans: Implications for Schizophrenia Treatment Targeting the Glutamate System

Ketamine Alters Functional Gamma and Theta Resting-State Connectivity in Healthy Humans: Implications for Schizophrenia Treatment Targeting the Glutamate System

Altered neural oscillations and behavior in a genetic mouse model of NMDA receptor hypofunction

Frontoparietal anodal tDCS reduces ketamine-induced oscillopathies

Contact Info

Product

Resources

About