TRD1: Multimodal Imaging for Spanning Multiple Spatial Scales in the Brain; Expansion to New Technologies and Species

Abstract/Summary All current techniques for the study of brain functions have limitations. Human brain activity and functional connectivity for example, can be studied with non-invasive functional whole brain MR methods. However, the spatiotemporal resolution and neuronal specificity of the MR technique is limited. This limitation is imposed at two levels irrespective of the functional MR approach employed: First, the inherent sensitivity of the MR approach limits the achievable spatial resolution. Although the development of UHF fMRI has enabled human studies with nominal voxel volumes of ~0.5 to1 µL to permit the detection of activity in cortical layers, columns, and other fine scale organizations such voxels still contain more than forty to eighty thousand neurons, capable of performing a multitude of different computations. The second limitation is the indirect nature of the MR based functional mapping signals. Irrespective of the functional contrast mechanism employed, they reflect physiological changes mediated by neurovascular coupling and subsequent coupling to and perturbations of MR parameters and these intermediary steps lead to ambiguities in spatiotemporal fidelity to neuronal activity especially at the mesoscopic scale or cortical column and layers. More importantly, the relationship between the MR based functional mapping signals and the underlying neuronal computations generated by a plethora of neuronal processes and cell types organized in complex local circuits remains largely unknown. This TRD seeks to overcome these limitations by improving the MR measurements by exploiting advantages of uniquely high magnetic fields (10.5T and 16.4T) and developing rigorous multi-modal (MRI-Electrophysiology and MRI-Multi Photon Imaging) data acquisition approaches these ultrahigh magnetic fields to build sharable technologies as well as to understand the nature of the functional MR signals.