Understanding the electrophysiology of neural circuits in the human brain is critical for advancing our knowledge of human nature since fast neural communication underlies our remarkable perceptual, motor, and cognitive abilities. Studying such networks requires a method to stimulate one or more nodes of any network with precise timing and a method to accurately measure electrophysiological activity with millisecond time resolution. At present, single-channel transcranial magnetic stimulation (TMS) devices are used to stimulate one focal region of the cortex and an array of EEG electrodes to measure the consequences of such stimulations on network functions. This type of device can stimulate only one region at a time with a rather diffuse area of stimulation and record brain activity smeared by the intervening scalp, skull and cerebral spinal fluid (CSF). We propose to develop and test a novel noninvasive system with the stimulation and recording capabilities required for understanding functional roles of neural circuits in the human brain with high time resolution. In this SBIR Fast-Track project, we will first test the basic 1-channel unit during Phase I. In Phase II, we will construct a 16-channel cryogenically cooled high-density TMS coil array integrated with a 25-channel TMS-compatible atomic gradiometer (AG) array. Phase I - Aim 1A: Construct a 1-channel cryoTMS system with a 30-mm OD coil encased in a tubular miniature cryostat with a 1-cm diameter hole in the middle and an OD of 38 mm and a remote-control positioning mechanism for radially moving the probe to touch the scalp. It will be connected to a liquid nitrogen (LN2) reservoir via a flexible transfer tube for cooling the TMS coil.
Aim 1 B: Construct an axial miniature AG encased in a rod-like 10 mm2 probe. Phase II - Aim 2A: Construct a 16- channel TMS coil array based on the 1-channel system with an automated positioning system, cooled by a closed-loop 100% LN2 recycler.
Aim 2 B: MagVenture will construct a 16-channel TMS stimulator specifically for this project and deliver it to Tristan for integration with the TMS system.
Aim 2 C: Construct a 25-channel AG array based on the 1-channel AG and a controller with a high laser pump power for shortening the recovery time after each TMS pulse to <2 ms We will develop techniques for mass production of these AGs using the MEMS technology.
Aim 2 D: Develop the software for controlling the TMS stimulator for targeting the E field to desired locations with optimal orientations.
Aim 2 E: Integrate the 16 TMS coils and 25 AG probes into a single system, inserting an AG probe into the middle hole of each cryostat and between the cryostats for high spatial resolution and test the functionality of the system. Phase II - Aim 3: Evaluate its capabilities on 20 healthy adult volunteers in a magnetic shielding enclosure, using the software capable of controlling the TMS system and measuring MEG signals in real time. We will test if the TMS-MEG system can be used to stimulate one or more nodes of a sensorimotor network and to study functional roles of each node of the network.
We propose to develop and evaluate a novel integrated multichannel system for human functional brain mapping. This system will consist of: (1) a novel transcranial magnetic stimulation (TMS) system based on a dense array of cryogenically cooled TMS coils and (2) magnetoencephalography based on a dense array of room-temperature miniature atomic magnetometer probes. We will evaluate the capabilities of the multichannel TMS system in stimulating one or more nodes of any cortical neural network and the capabilities of the novel MEG system for identifying the cortical activity produced by the TMS stimulation on cortical networks with sensitivies that are 5-10 higher than existing MEG and EEG systems. This new system will provide a novel approach for determining functional connectivity and functional roles of cortical networks in human brain in health and disease.
| Sheng, D; Perry, A R; Krzyzewski, S P et al. (2017) A microfabricated optically-pumped magnetic gradiometer. Appl Phys Lett 110:031106 |
