Resting state quantitative electroencephalogram gamma power spectra in patients with first episode psychosis: An observational study

Yadav, Shailly; Nizamie, S. Haque; Das, Basudeb; Das, Jnanamay; Tikka, Sai Krishna

doi:10.1016/j.ajp.2021.102550

Cited by 13 publications

(11 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The observation of increased resting-state gamma-band oscillations (RS-GBO) under the influence of ketamine parallels observations made in patients with schizophrenia (11)(12)(13)61). As elaborated in the introduction, the generation of GBO involves a neural microcircuit consisting of pyramidal cells, fast-spiking inhibitory GABA-releasing PV + -interneurons (23), and SST + -interneurons (28).…”

Section: Discussionmentioning

confidence: 58%

“…While task-specific oscillation patterns both in the theta- (6) and gamma-band (7) have been shown to be pathological among patients with schizophrenia, there is a growing body of evidence highlighting the significance of spontaneous, "restingstate" oscillatory activity relevant for schizophrenia (8)(9)(10). EEG and MEG studies have observed deviations in resting-state (RS) -GBO and -TBO patterns across different stages of schizophrenia: increased RS-GBO among patients with schizophrenia (11,12); increased RS-GBO in the first episode of schizophrenia (13); increased RS-TBO in chronic schizophrenia and patients at high risk (14)(15)(16)(17). Even patients with schizophrenia-like epilepsy showed increased RS-TBO compared to nonpsychotic epilepsy patients (18).…”

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: Discussionmentioning

confidence: 58%

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

“…Relative implications for selective alterations in low versus high frequency gamma band ranges are not completely understood from a biochemical or circuit perspective. Both gamma band ranges are implicated in working memory performance and psychosis, but high frequency gamma has further been implicated in visual and auditory processing (for review see Uhlhaas et al, 2011;Yadav et al, 2021). This may be more relevant for predicting psychotomimetic-like effects as deficits in these domains are commonly reported in schizophrenia.…”

Section: Discussionmentioning

confidence: 99%

Partial mGlu5 Negative Allosteric Modulator M-5MPEP Demonstrates Antidepressant-Like Effects on Sleep Without Affecting Cognition or Quantitative EEG

et al. 2021

View full text Add to dashboard Cite

Selective negative allosteric modulators (NAMs) targeting the metabotropic glutamate receptor subtype 5 (mGlu5) demonstrate anxiolytic-like and antidepressant-like effects yet concern regarding adverse effect liability remains. Functional coupling of mGlu5 with ionotropic N-methyl-D-aspartate receptors (NMDARs) represents a potential mechanism through which full inhibition leads to adverse effects, as NMDAR inhibition can induce cognitive impairments and psychotomimetic-like effects. Recent development of “partial” mGlu5 NAMs, characterized by submaximal but saturable levels of blockade, may represent a novel development approach to broaden the therapeutic index of mGlu5 NAMs. This study compared the partial mGlu5 NAM, M-5MPEP, with the full mGlu5 NAM, VU0424238 on sleep, cognition, and brain function alone and in combination with a subthreshold dose of the NMDAR antagonist, MK-801, using a paired-associates learning (PAL) cognition task and electroencephalography (EEG) in rats. M-5MPEP and VU0424238 decreased rapid eye movement (REM) sleep and increased REM sleep latency, both putative biomarkers of antidepressant-like activity. Neither compound alone affected accuracy, but 30 mg/kg VU0424238 combined with MK-801 decreased accuracy on the PAL task. Using quantitative EEG, VU0424238, but not M-5MPEP, prolonged arousal-related elevations in high gamma power, and, in combination, VU0424238 potentiated effects of MK-801 on high gamma power. Together, these studies further support a functional interaction between mGlu5 and NMDARs that may correspond with cognitive impairments. Present data support further development of partial mGlu5 NAMs given their potentially broader therapeutic index than full mGlu5 NAMs and use of EEG as a translational biomarker to titrate doses aligning with therapeutic versus adverse effects.

show abstract

“…34,41,42 Excessive resting frontal gamma activity has been found in first-degree relatives of people with schizophrenia and has been proposed as a potential endophenotype and biomarker for cortical dysfunction in the disorder. 40,41,43,44 Increased frontal resting gamma power has also been found in high-risk for psychosis populations, 45 unmedicated first episode patients, 39,46,47 and patients with chronic schizophrenia who are taking antipsychotic treatment, [48][49][50][51] which suggests that resting state gamma abnormalities are present at illness onset 6,52,53 and are not reversed by antipsychotic treatment. This is supported by other studies which have found no association between gamma power levels in schizophrenia and antipsychotic treatment 54,55 or dose of treatment.…”

Section: Introductionmentioning

confidence: 99%

Gamma Oscillations and Potassium Channel Modulation in Schizophrenia: Targeting GABAergic Dysfunction

et al. 2023

View full text Add to dashboard Cite

Impairments in gamma-aminobutyric acid (GABAergic) interneuron function lead to gamma power abnormalities and are thought to underlie symptoms in people with schizophrenia. Voltage-gated potassium 3.1 (Kv3.1) and 3.2 (Kv3.2) channels on GABAergic interneurons are critical to the generation of gamma oscillations suggesting that targeting Kv3.1/3.2 could augment GABAergic function and modulate gamma oscillation generation. Here, we studied the effect of a novel potassium Kv3.1/3.2 channel modulator, AUT00206, on resting state frontal gamma power in people with schizophrenia. We found a significant positive correlation between frontal resting gamma (35–45 Hz) power ( n = 22, r = 0.613, P < .002) and positive and negative syndrome scale (PANSS) positive symptom severity. We also found a significant reduction in frontal gamma power ( t13 = 3.635, P = .003) from baseline in patients who received AUT00206. This provides initial evidence that the Kv3.1/3.2 potassium channel modulator, AUT00206, may address gamma oscillation abnormalities in schizophrenia.

show abstract

Resting state quantitative electroencephalogram gamma power spectra in patients with first episode psychosis: An observational study

Cited by 13 publications

References 44 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

Partial mGlu5 Negative Allosteric Modulator M-5MPEP Demonstrates Antidepressant-Like Effects on Sleep Without Affecting Cognition or Quantitative EEG

Gamma Oscillations and Potassium Channel Modulation in Schizophrenia: Targeting GABAergic Dysfunction

Contact Info

Product

Resources

About