Mismatch negativity as EEG biomarker supporting CNS drug development: a transnosographic and translational study.

The lack of translation from basic research into new medicines is a major challenge in CNS drug development. The need to use novel approaches relying on (i) patient clustering based on neurobiology irrespective to symptomatology and (ii) quantitative biomarkers focusing on evolutionarily preserved neurobiological systems allowing back-translation from clinical to nonclinical research has been highlighted. Here we sought to evaluate the mismatch negativity (MMN) response in schizophrenic (SZ) patients, Alzheimer's disease (AD) patients, and age-matched healthy controls. To evaluate back-translation of the MMN response, we developed EEG-based procedures allowing the measurement of MMN-like responses in a rat model of schizophrenia and a mouse model of AD. Our results indicate a significant MMN attenuation in SZ but not in AD patients. Consistently with the clinical findings, we observed a significant attenuation of deviance detection (~104.7%) in rats subchronically exposed to phencyclidine, while no change was observed in APP/PS1 transgenic mice when compared to wild type. This study provides new insight into the cross-disease evaluation of the MMN response. Our findings suggest further investigations to support the identification of neurobehavioral subtypes that may help patients clustering for precision medicine intervention. Furthermore, we provide evidence that MMN could be used as a quantitative/objective efficacy biomarker during both preclinical and clinical stages of SZ drug development.

Simultaneous EEG-fMRI during a neurofeedback task, a brain imaging dataset for multimodal data integration.

Combining EEG and fMRI allows for integration of fine spatial and accurate temporal resolution yet presents numerous challenges, noticeably if performed in real-time to implement a Neurofeedback (NF) loop. Here we describe a multimodal dataset of EEG and fMRI acquired simultaneously during a motor imagery NF task, supplemented with MRI structural data. The study involved 30 healthy volunteers undergoing five training sessions. We showed the potential and merit of simultaneous EEG-fMRI NF in previous work. Here we illustrate the type of information that can be extracted from this dataset and show its potential use. This represents one of the first simultaneous recording of EEG and fMRI for NF and here we present the first open access bi-modal NF dataset integrating EEG and fMRI. We believe that it will be a valuable tool to (1) advance and test methodologies for multi-modal data integration, (2) improve the quality of NF provided, (3) improve methodologies for de-noising EEG acquired under MRI and (4) investigate the neuromarkers of motor-imagery using multi-modal information.

Unimodal Versus Bimodal EEG-fMRI Neurofeedback of a Motor Imagery Task.

Neurofeedback is a promising tool for brain rehabilitation and peak performance training. Neurofeedback approaches usually rely on a single brain imaging modality such as EEG or fMRI. Combining these modalities for neurofeedback training could allow to provide richer information to the subject and could thus enable him/her to achieve faster and more specific self-regulation. Yet unimodal and multimodal neurofeedback have never been compared before. In the present work, we introduce a simultaneous EEG-fMRI experimental protocol in which participants performed a motor-imagery task in unimodal and bimodal NF conditions. With this protocol we were able to compare for the first time the effects of unimodal EEG-neurofeedback and fMRI-neurofeedback versus bimodal EEG-fMRI-neurofeedback by looking both at EEG and fMRI activations. We also propose a new feedback metaphor for bimodal EEG-fMRI-neurofeedback that integrates both EEG and fMRI signal in a single bi-dimensional feedback (a ball moving in 2D). Such a feedback is intended to relieve the cognitive load of the subject by presenting the bimodal neurofeedback task as a single regulation task instead of two. Additionally, this integrated feedback metaphor gives flexibility on defining a bimodal neurofeedback target. Participants were able to regulate activity in their motor regions in all NF conditions. Moreover, motor activations as revealed by offline fMRI analysis were stronger during EEG-fMRI-neurofeedback than during EEG-neurofeedback. This result suggests that EEG-fMRI-neurofeedback could be more specific or more engaging than EEG-neurofeedback. Our results also suggest that during EEG-fMRI-neurofeedback, participants tended to regulate more the modality that was harder to control. Taken together our results shed first light on the specific mechanisms of bimodal EEG-fMRI-neurofeedback and on its added-value as compared to unimodal EEG-neurofeedback and fMRI-neurofeedback.

How to Build a Hybrid Neurofeedback Platform Combining EEG and fMRI.

Multimodal neurofeedback estimates brain activity using information acquired with more than one neurosignal measurement technology. In this paper we describe how to set up and use a hybrid platform based on simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), then we illustrate how to use it for conducting bimodal neurofeedback experiments. The paper is intended for those willing to build a multimodal neurofeedback system, to guide them through the different steps of the design, setup, and experimental applications, and help them choose a suitable hardware and software configuration. Furthermore, it reports practical information from bimodal neurofeedback experiments conducted in our lab. The platform presented here has a modular parallel processing architecture that promotes real-time signal processing performance and simple future addition and/or replacement of processing modules. Various unimodal and bimodal neurofeedback experiments conducted in our lab showed high performance and accuracy. Currently, the platform is able to provide neurofeedback based on electroencephalography and functional magnetic resonance imaging, but the architecture and the working principles described here are valid for any other combination of two or more real-time brain activity measurement technologies.