Mapping brain activity with flexible graphene micro-transistors

Establishing a reliable communication interface between the brain and electronic devices is of paramount importance for exploiting the full potential of neural prostheses. Current microelectrode technologies for recording electrical activity, however, evidence important shortcomings, e.g. challenging high density integration. Solution-gated field-effect transistors (SGFETs), on the other hand, could overcome these shortcomings if a suitable transistor material were available. Graphene is particularly attractive due to its biocompatibility, chemical stability, flexibility, low intrinsic electronic noise and high charge carrier mobilities. Here, we report on the use of an array of flexible graphene SGFETs for recording spontaneous slow waves, as well as visually evoked and also pre-epileptic activity in vivo in rats. The flexible array of graphene SGFETs allows mapping brain electrical activity with excellent signal-to-noise ratio (SNR), suggesting that this technology could lay the foundation for a future generation of in vivo recording implants

Mapping brain activity with flexible graphene micro-transistors

Establishing a reliable communication interface between the brain and electronic devices is of paramount importance for exploiting the full potential of neural prostheses. Current microelectrode technologies for recording electrical activity, however, evidence important shortcomings, e.g. challenging high density integration. Solution-gated field-effect transistors (SGFETs), on the other hand, could overcome these shortcomings if a suitable transistor material were available. Graphene is particularly attractive due to its biocompatibility, chemical stability, flexibility, low intrinsic electronic noise and high charge carrier mobilities. Here, we report on the use of an array of flexible graphene SGFETs for recording spontaneous slow waves, as well as visually evoked and also pre-epileptic activity in vivo in rats. The flexible array of graphene SGFETs allows mapping brain electrical activity with excellent signal-to-noise ratio (SNR), suggesting that this technology could lay the foundation for a future generation of in vivo recording implants

Transfer entropy, symbolic transfer entropy and transcript mutual information indicators reveal a leading role of infragranular layers during slow oscillations

The recurrent circuitry of the cerebral cortex generates an emergent pattern of activity that is organized into rhythmic periods of firing and silence referred to as slow oscillations (ca 1 Hz). Slow oscillations not only are dominant during slow wave sleep and deep anaesthesia, but also can be generated by the isolated cortical network in vitro, being a sort of default activity of the cortical network. The cortex is densely and reciprocally connected with subcortical structures and, as a result, the slow oscillations in situ are the result of an interplay between cortex and thalamus. Due to this reciprocal connectivity and interplay, the mechanism responsible for the initiation of waves in the corticothalamocortical loop during slow oscillations is still a matter of debate. The prevalent view is that infragranular layers of the cortex, where the highest firing rates are found, are leading the periods of activity or Up states, from where activity rapidly spreads to all cortical layers and subcortical structures such as the thalamus. However, other authors support that the slow wave activity is an emergent property of corticothalamocortical networks defining the origin of this activity as a balance between cortical and thalamic contributions. To determine the directionality of the information flow between different layers of the cortex and the connected thalamus during spontaneous activity we obtained multilayer local field potentials from the rat visual cortex and from its connected thalamus, the lateral geniculate nucleus, during deep anaesthesia. We analyzed directionality of information flow between thalamus, cortical infragranular layers (5 and 6) and supragranular layers (2/3) by means of three information theoretical indicators: transfer entropy, symbolic transfer entropy and transcript mutual information. These three indicators coincided in finding that infragranular layers lead the information flow during slow oscillations both towards supragranular layers and towards the thalamus

Gradual emergence of spontaneous correlated brain activity during fading of general anesthesia in rats: Evidences from fMRI and local field potentials

Intrinsic brain activity is characterized by the presence of highly structured networks of correlated fluctuations between different regions of the brain. Such networks encompass different functions, whose properties are known to be modulated by the ongoing global brain state and are altered in several neurobiological disorders. In the present study, we induced a deep state of anesthesia in rats by means of a ketamine/medetomidine peritoneal injection, and analyzed the time course of the correlation between the brain activity in different areas while anesthesia spontaneously decreased over time. We compared results separately obtained from fMRI and local field potentials (LFPs) under the same anesthesia protocol, finding that while most profound phases of anesthesia can be described by overall sparse connectivity, stereotypical activity and poor functional integration, during lighter states different frequency-specific functional networks emerge, endowing the gradual restoration of structured large-scale activity seen during rest. Noteworthy, our in vivo results show that those areas belonging to the same functional network (the default-mode) exhibited sustained correlated oscillations around 10 Hz throughout the protocol, suggesting the presence of a specific functional backbone that is preserved even during deeper phases of anesthesia. Finally, the overall pattern of results obtained from both imaging and in vivo-recordings suggests that the progressive emergence from deep anesthesia is reflected by a corresponding gradual increase of organized correlated oscillations across the cortex.The research reported herein was supported by the ERC Advanced Grant DYSTRUCTURE (No. 295129), FET Flagship Human Brain Project, Brain Network Recovery Group through the James S. McDonnell Foundation (220020255), FP7-ICT BrainScales (No. 269921), CORONET (No. 269459), Ministerio de Economia y Competitividad (MINECO-PSI2013-42091-P), and Agència Gestió d'Ajuts Universitaris i de Recerca (2009SGR292) to G.D. M.V.S.V. was supported by the Ministerio de Economía y Competitividad (Spain)BFU2011-27094 and EU project CORTICONIC Contract number 600806

Cholinergic switch between two types of slow waves in cerebral cortex

31 pages, 5 main figures, 3 supplementary figuresInternational audienceSleep slow waves are known to participate in memory consolidation, yet slow waves occurring under anesthetized states present no positive effects on memory. Here, we shed light onto this paradox, based on a combination of extracellular recordings in vivo, in vitro and computational models. We find two types of slow waves, based on analyzing the temporal patterns of successive slow-wave events. The first type of slow waves is seen during sleep, while the second type prevails in anesthetized states. Network models of spiking neurons predict that the two slow wave types emerge due to a different gain on inhibitory vs excitatory cells and that different levels of spike-frequency adaptation in excitatory cells can account for dynamical distinctions between the two types. This prediction was tested in vitro by varying adaptation strength using an agonist of acetylcholine receptors, which demonstrated a neuromodulatory switch between the two types of slow waves. Finally, we show that the first type of slow-wave dynamics is more sensitive to external stimuli, which can explain how slow waves in sleep and anesthesia differentially affect memory consolidation, as well as provide a link between slow-wave dynamics and memory diseases

Gradual emergence of spontaneous correlated brain activity during fading of general anesthesia in rats: Evidences from fMRI and local field potentials

Intrinsic brain activity is characterized by the presence of highly structured networks of correlated fluctuations between different regions of the brain. Such networks encompass different functions, whose properties are known to be modulated by the ongoing global brain state and are altered in several neurobiological disorders. In the present study, we induced a deep state of anesthesia in rats by means of a ketamine/medetomidine peritoneal injection, and analyzed the time course of the correlation between the brain activity in different areas while anesthesia spontaneously decreased over time. We compared results separately obtained from fMRI and local field potentials (LFPs) under the same anesthesia protocol, finding that while most profound phases of anesthesia can be described by overall sparse connectivity, stereotypical activity and poor functional integration, during lighter states different frequency-specific functional networks emerge, endowing the gradual restoration of structured large-scale activity seen during rest. Noteworthy, our in vivo results show that those areas belonging to the same functional network (the default-mode) exhibited sustained correlated oscillations around 10 Hz throughout the protocol, suggesting the presence of a specific functional backbone that is preserved even during deeper phases of anesthesia. Finally, the overall pattern of results obtained from both imaging and in vivo-recordings suggests that the progressive emergence from deep anesthesia is reflected by a corresponding gradual increase of organized correlated oscillations across the cortex.The research reported herein was supported by the ERC Advanced Grant DYSTRUCTURE (No. 295129), FET Flagship Human Brain Project, Brain Network Recovery Group through the James S. McDonnell Foundation (220020255), FP7-ICT BrainScales (No. 269921), CORONET (No. 269459), Ministerio de Economia y Competitividad (MINECO-PSI2013-42091-P), and Agència Gestió d'Ajuts Universitaris i de Recerca (2009SGR292) to G.D. M.V.S.V. was supported by the Ministerio de Economía y Competitividad (Spain)BFU2011-27094 and EU project CORTICONIC Contract number 600806