Reference number : GC-2017-Q1-03260, amendment number : , agreement type : G, recipient legal name : Bardakjian, Berj (University of Toronto), recipient country : CA, recipient province : nan, recipient city : Ontario, recipient postal code : nan, program name english : Discovery Grants Program - Individual, program name french : Programme de subventions à la découverte - individuelles, program purpose english : O bjectives: (a) Develop macro and micro level computer models of the electrical rhythmic activity in hippocampal neuro-glial networks under normal and pathological states exhibiting seizure-like events (SLEs). (i) Macro level models characterize system behaviour by populations of coupled cognitive rhythm generator (CRG) models (previously reported by our lab team). Each CRG consists of an input layer of neuronal modes (whose transfer functions are measured from Volterra series or alternately chosen from predetermined design functions) for sensing the input environment. The outputs of the neuronal modes layer are feed-forward to a Winfree type ring device whose variables are mapped by a static nonlinearity (representing the wave shape) into an observable output variable. The frequencies of the ring device are modulated by the outputs of the neuronal modes to provide &ldquo;responsive adaptation&rdquo; to changes in the input environment. Coupled CRGs are utilized to model pathological states and are used as testing platforms of neuromodulation strategies for abolishment of SLEs. (ii) Micro level models of traditional and "stochastic" Hodgkin-Huxley type models to characterize ionic transport mechanisms in "cellular" models of pyramidal, interneuron and glial cells. These models are used to investigate (1) the effects of astrocytes on hyper-excitability, and (2) the mechanisms of cross frequency coupling in the electrical rhythms of the neuro-glial networks characterizing their states. 
(b) Develop neuromodulators using coupled CRGs as therapeutic network to abolish onset of spontaneous SLEs in computer models. With the long term objective of miniaturization as electronic hardware implementation to be used as brain implants and substitutes for damaged neurons in the hippocampus. Our preliminary results on computer models demonstrated the &ldquo;proof of principle&rdquo; (previously reported by our lab team). 
 
Scientific Approach: The main hypothesis is that pathological brain states can be anticipated, detected and abolished by "cognitive devices" in feedback loop with the biological system. The main approach is to develop computer models of hippocampal neuro-glial networks, validated using reported biological data, which elucidate the physical basis for the phenomena of cross frequency coupling in their electrical rhythms. 
 
 Significance: (a) Develop novel cognitive devices as tools for (1) neurogenic disorder therapies, and (2) in information and communication technology. 
(b) Provide insights into the (1) mechanisms of cross frequency coupling between low and high frequency rhythms of neuro-glial networks, (2) classification of brain states, (3) role of astrocytes in moderating neuronal firing in hyper-excitable networks underlying many neurogenic brain disorders. 
(c) Provide computer model platform for &ldquo;proof of principle&rdquo; testing and comparison of various neuromodulation strategies., program purpose french : O bjectives: (a) Develop macro and micro level computer models of the electrical rhythmic activity in hippocampal neuro-glial networks under normal and pathological states exhibiting seizure-like events (SLEs). (i) Macro level models characterize system behaviour by populations of coupled cognitive rhythm generator (CRG) models (previously reported by our lab team). Each CRG consists of an input layer of neuronal modes (whose transfer functions are measured from Volterra series or alternately chosen from predetermined design functions) for sensing the input environment. The outputs of the neuronal modes layer are feed-forward to a Winfree type ring device whose variables are mapped by a static nonlinearity (representing the wave shape) into an observable output variable. The frequencies of the ring device are modulated by the outputs of the neuronal modes to provide &ldquo;responsive adaptation&rdquo; to changes in the input environment. Coupled CRGs are utilized to model pathological states and are used as testing platforms of neuromodulation strategies for abolishment of SLEs. (ii) Micro level models of traditional and "stochastic" Hodgkin-Huxley type models to characterize ionic transport mechanisms in "cellular" models of pyramidal, interneuron and glial cells. These models are used to investigate (1) the effects of astrocytes on hyper-excitability, and (2) the mechanisms of cross frequency coupling in the electrical rhythms of the neuro-glial networks characterizing their states. 
(b) Develop neuromodulators using coupled CRGs as therapeutic network to abolish onset of spontaneous SLEs in computer models. With the long term objective of miniaturization as electronic hardware implementation to be used as brain implants and substitutes for damaged neurons in the hippocampus. Our preliminary results on computer models demonstrated the &ldquo;proof of principle&rdquo; (previously reported by our lab team). 
 
Scientific Approach: The main hypothesis is that pathological brain states can be anticipated, detected and abolished by "cognitive devices" in feedback loop with the biological system. The main approach is to develop computer models of hippocampal neuro-glial networks, validated using reported biological data, which elucidate the physical basis for the phenomena of cross frequency coupling in their electrical rhythms. 
 
 Significance: (a) Develop novel cognitive devices as tools for (1) neurogenic disorder therapies, and (2) in information and communication technology. 
(b) Provide insights into the (1) mechanisms of cross frequency coupling between low and high frequency rhythms of neuro-glial networks, (2) classification of brain states, (3) role of astrocytes in moderating neuronal firing in hyper-excitable networks underlying many neurogenic brain disorders. 
(c) Provide computer model platform for &ldquo;proof of principle&rdquo; testing and comparison of various neuromodulation strategies., agreement title english : Computer models of the electrical rhythmic activities in hippocampal neurons, agreement title french : Computer models of the electrical rhythmic activities in hippocampal neurons, agreement number : RGPIN, agreement value : 140000.0, agreement start date : 2017-05-10, agreement end date : nan, description english : nan, description french : nan, expected results english : nan, expected results french : nan, additional information english : Grant or Award spanning more than one fiscal year. (2017-2018 to 2022-2023), additional information french : Subvention ou bourse octroyée s'appliquant à plus d'un exercice financier. (2017-2018 à 2022-2023), owner organization : nserc-crsng, owner organization title : Natural Sciences and Engineering Research Council of Canada | Conseil de recherches en sciences naturelles et en génie du Canada