Hybrid TMS/MRI system for regionally tailored causal mapping of human cortical circuits and connectivity - Project Summary. We propose a new coil array that will enable next-generation causal brain mapping with unprecedented flexibility, resolution and precision. The proposed ARES2 hybrid array generates E-fields in the cortex for transcranial mag- netic stimulation (TMS) as well as B-fields for spatial and diffusion encoding applications including high-resolu- tion, high b-value diffusion MRI and fMRI. Multi-channel TMS allows different cortical targets to be probed either sequentially or simultaneously, providing a flexible tool for modulating brain activity that is imaged concurrently with MRI. By virtue of their close proximity to the head, the coil elements will provide a large boost in diffusion MRI encoding in the cortex beyond what is possible with current MRI gradient technology, enabling improved sensitivity to mapping neuronal and dendritic sizes and their distribution following targeted neuromodulation and providing sub-millimeter spatial resolution for BOLD-fMRI in the cortex following stimulation. In Aim1, we will test a 3-channel prototype of the proposed head array, ARES2 (Array for Reception, Encoding, Shimming, and Stimulation) by leveraging our recent developments in MR-compatible transcranial magnetic stimulation (TMS) coils. The coils will be driven by large currents to yield 1000 mT/m max. gradients and high slew rates. The parallel design comprising 48 encoding coils permit B0-shimming capability, while 28 radiofre- quency coils interlaced with the encoding coils provide parallel imaging. Custom drive amplifiers and switching electronics will allow alternation between “stimulation” and “imaging” modes. A comprehensive electronic control system will allow arbitrary waveforms to be played out on all channels in sync with the scanner’s pulse sequence. In Aim2, we will scale the system up to the full 48-ch array. We build a new TMS-compatible 28-ch RF receive array that is mechanically integrated with a TMS probe holder device. The TMS probe holder will allow radial adjustment of the TMS probe to allow it to be placed against the head surface. In Aim3, we will apply the system in vivo to perform next-generation causal brain mapping at submillimeter resolution. We will demonstrate ARES2’s ability to provide regionally specific measures of cell body (soma) and neurite size and density in the motor (M1) and somatosensory cortex (S1). These diffusion MRI experiments will make use of gSlider volumetric diffusion encoding to boost SNR and reach submillimeter resolution. For TMS- fMRI, we will use the 9ch TMS and 48ch MRI gradient system in an interleaved manner for successive stimulation and fMRI recording in M1 and S1.
