PDP2020-02
Multimodal exploration of pre-epileptic structural and circuit-levels changes in brain malformations
Abstract
Brain malformations characterized by brain structure abnormalities and faulty circuit wiring are the most frequent causes of epilepsy in children. Epilepsy and seizures are known to result from abnormal circuit activity; however, circuit-level changes that progressively “render epileptic” a developing brain with malformations remain poorly understood. Several factors limit the longitudinal exploration of circuit changes occurring during the pre-epileptic period: the invasiveness and bulkiness of “gold standard” instrumentation (i.e. depth electrodes), and the continuous developmental growth of brain structures and skull. To overcome these limitations we propose to combine two minimally invasive, yet very sensitive brain imaging modalities: 1) intrinsic optical signal imaging for localizing circuit activity changes, and 2) photoacoustic imaging for localizing structural abnormalities. Our ambition is to identify and localize early signs of circuit dysfunction that may serve as biomarkers or predictors of epilepsy outcomes.
Keywords
Brain development, brain malformation, functional imaging, electrophysiology, photoacoustics, signal processing
Objectives
1) to localize brain malformations located below the brain surface using photoacoustic imaging (PAi). This method relies on the emission of ultrasounds upon light absorption deep inside tissues and provides images of good depth-to-resolution ratio; 2) to localize physiologically relevant cortical activity changes and identify the underlying neuronal networks using intrinsic optical signal imaging (IOSi) and electrophysiology; 3) to co-register PAi and IOSi modalities to delineate pre-epileptic circuit changes and their evolution with age.
Expected profile
We seek to recruit a highly motivated candidate holding a PhD in neuroscience, biophysics, or equivalent. The successful candidate will have a good track record in in vivo rodent electrophysiology and in vivo brain imaging techniques, as well as previous experiences in data analysis, signal processing and programming.
Articles related to the project
1: Ntziachristos V. Going deeper than microscopy: the optical imaging frontier in biology. Nat Methods. 2010 Aug;7(8):603-14. doi: 10.1038/nmeth.1483
2: Guerrini R, Barba C. Malformations of cortical development and aberrant cortical networks: epileptogenesis and functional organization. J Clin Neurophysiol. 2010 Dec;27(6):372-9. doi:10.1097/WNP.0b013e3181fe0585