Using EEG-Guided Basket and Umbrella Trials in Psychiatry: A Precision Medicine Approach for Cognitive Impairment in Schizophrenia

Joshi, Yash B.; Light, Gregory A.

doi:10.3389/fpsyt.2018.00554

Cited by 15 publications

(9 citation statements)

References 118 publications

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“…The paucity of reliable translational biomarkers that capture functional modulation of brain circuitry is a key challenge in the field of neuropsychiatric drug development 12 . With the exception of evoked potentials sensitive to Nmethyl-D-aspartate (NMDA) receptor function, such as mismatch negativity and auditory steady-state responses [13][14][15] , there has been little progress toward translatable glutamatesensitive circuitry function biomarkers. Reliable PD biomarkers are needed to evaluate the functional impact of novel glutamatergic drugs on defined neurocircuits in order to guide dose selection in clinical studies and to support go/ no-go decisions during drug development 12,16 .…”

Section: Introductionmentioning

confidence: 99%

Transcranial magnetic stimulation as a translational biomarker for AMPA receptor modulation

et al. 2021

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TAK-653 is a novel α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-positive allosteric modulator being developed as a potential therapeutic for major depressive disorder (MDD). Currently, there are no translational biomarkers that evaluate physiological responses to the activation of glutamatergic brain circuits available. Here, we tested whether noninvasive neurostimulation, specifically single-pulse or paired-pulse motor cortex transcranial magnetic stimulation (spTMS and ppTMS, respectively), coupled with measures of evoked motor response captures the pharmacodynamic effects of TAK-653 in rats and healthy humans. In the rat study, five escalating TAK-653 doses (0.1–50 mg/kg) or vehicle were administered to 31 adult male rats, while measures of cortical excitability were obtained by spTMS coupled with mechanomyography. Twenty additional rats were used to measure brain and plasma TAK-653 concentrations. The human study was conducted in 24 healthy volunteers (23 males, 1 female) to assess the impact on cortical excitability of 0.5 and 6 mg TAK-653 compared with placebo, measured by spTMS and ppTMS coupled with electromyography in a double-blind crossover design. Plasma TAK-653 levels were also measured. TAK-653 increased both the mechanomyographic response to spTMS in rats and the amplitude of motor-evoked potentials in humans at doses yielding similar plasma concentrations. TAK-653 did not affect resting motor threshold or paired-pulse responses in humans. This is the first report of a translational functional biomarker for AMPA receptor potentiation and indicates that TMS may be a useful translational platform to assess the pharmacodynamic profile of glutamate receptor modulators.

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Section: Introductionmentioning

confidence: 99%

Transcranial magnetic stimulation as a translational biomarker for AMPA receptor modulation

et al. 2021

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“…EAIP is commonly measured via mismatch negativity (MMN) and P3a, event-related potentials (ERP) that are translatable across model systems (Avissar et al, 2017;Näätänen et al, 2007;Thomas et al, 2017). Deficits in MMN and P3a are well-documented in schizophrenia, and since they strongly index the functioning of cognitively and functionally relevant networks, they increasingly used as biomarkers in trials of procognitive treatment strategies (Hochberger et al, 2018;Joshi and Light, 2018;Light and Näätänen, 2013;Light and Braff, 2005a;Perez et al, 2017;Swerdlow et al, 2018;Joshi and Light, 2018). Indeed, MMN and P3a are sensitive to both pharmacologic and nonpharmacologic interventions (Dulude et al, 2010;Hochberger et al, 2018;Kantrowitz et al, 2010;Kawakubo et al, 2007;Lavoie et al, 2017;Perez et al, 2017;Swerdlow et al, 2016), and have been extensively used in animal models of schizophrenia with high translational homology (Amann et al, 2010;Featherstone et al, 2015;Todd et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Decomposing the constituent oscillatory dynamics underlying mismatch negativity generation in schizophrenia: Distinct relationships to clinical and cognitive functioning

Hochberger

Joshi

Zhang

et al. 2019

International Journal of Psychophysiology

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Abnormalities in early auditory information processing (EAIP) contribute to higher-order deficits in cognition and psychosocial functioning in schizophrenia. A passive auditory oddball paradigm is commonly used to evoke event-related potential (ERP) measures of EAIP reflecting auditory sensory registration and deviance detection, including mismatch negativity (MMN) and P3a responses. MMN and P3a have been extensively studied in healthy subjects and neuropsychiatric patient populations and are increasingly used as translational biomarkers in the development of novel therapeutics. Despite widespread use, relatively few studies have examined the constituent oscillatory elements and the extent to which sensory registration and deviance detection represent distinct or intercorrelated processes. This study aimed to determine the factor structure and clinical correlates of these oscillatory measures in schizophrenia patients (n=706) and healthy comparison subjects (n=615) who underwent clinical, cognitive, and functional characterization and EEG testing via their participation in the Consortium of Genomics in Schizophrenia (COGS-2) study. Results revealed significant deficits in theta-band (4-7 Hz) evoked power and phase locking in patients. Exploratory factor analyses of both ERP and oscillatory measures revealed two dissociable factors reflecting sensory registration and deviance detection. While each factor shared a significant correlation with social cognition, the deviance detection factor had a unique relationship to multiple cognitive and clinical domains. Results support the continued advancement of functionally relevant oscillatory measures underlying EAIP in the development of precognitive therapeutics.

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“…A reduction in auditory MMN amplitude was reported over two decades ago in patients with schizophrenia [16]. It has been replicated numerous times as a mature neurophysiological biomarker based on criteria such as scalability, low cost, and suitability for use in multicenter studies [3].…”

Section: Introductionmentioning

confidence: 93%

“…Individualized prediction models have been shown in psychiatry, and a new department of precision psychiatry has come out [2]. Despite the growing interest and clinicians' efforts to find alternatives, diagnosis and treatment have relied heavily on clinical interviews rather than direct, reliable assessments of brain function, and we could not have improved clinically reasonable points for various psychiatric disorders over the past years [3]. Recent advances in biomarker development hold promise for guiding a new era of precision medicine style trials for psychiatric disorders [3].…”

Section: Introductionmentioning

confidence: 99%

Implication of Electrophysiological Biomarkers in Psychosis: Focusing on Diagnosis and Treatment Response

Lee

Kim

2022

JPM

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Precision medicine has been considered a promising approach to diagnosis, treatment, and various interventions, considering the individual clinical and biological characteristics. Recent advances in biomarker development hold promise for guiding a new era of precision medicine style trials for psychiatric illnesses, including psychosis. Electroencephalography (EEG) can directly measure the full spatiotemporal dynamics of neural activation associated with a wide variety of cognitive processes. This manuscript reviews three aspects: prediction of diagnosis, prognostic aspects of disease progression and outcome, and prediction of treatment response that might be helpful in understanding the current status of electrophysiological biomarkers in precision medicine for patients with psychosis. Although previous EEG analysis could not be a powerful method for the diagnosis of psychiatric illness, recent methodological advances have shown the possibility of classifying and detecting mental illness. Some event-related potentials, such as mismatch negativity, have been associated with neurocognition, functioning, and illness progression in schizophrenia. Resting state studies, sophisticated ERP measures, and machine-learning approaches could make technical progress and provide important knowledge regarding neurophysiology, disease progression, and treatment response in patients with schizophrenia. Identifying potential biomarkers for the diagnosis and treatment response in schizophrenia is the first step towards precision medicine.

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Using EEG-Guided Basket and Umbrella Trials in Psychiatry: A Precision Medicine Approach for Cognitive Impairment in Schizophrenia

Cited by 15 publications

References 118 publications

Transcranial magnetic stimulation as a translational biomarker for AMPA receptor modulation

Transcranial magnetic stimulation as a translational biomarker for AMPA receptor modulation

Decomposing the constituent oscillatory dynamics underlying mismatch negativity generation in schizophrenia: Distinct relationships to clinical and cognitive functioning

Implication of Electrophysiological Biomarkers in Psychosis: Focusing on Diagnosis and Treatment Response

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