Although non-invasive brain imaging has developed immensely in terms of measurement technologies, analysis methods and innovative paradigms, magnetoencephalography (MEG) and electroencephalography (EEG) remain the only non-invasive techniques capable of measuring electrophysiological activity with millisecond resolution and thus can be readily related to invasive measurements, such as electrocorticography (ECoG). Thanks to advances in low-noise room-temperature magnetic field sensors, notably optically pumped magnetometers (OPMs), and novel EEG leads, it is now possible to optimize sensor arrays to each individual’s unique brain anatomy, offering the potential for unprecedented improvements in the sensitivity and spatial resolution of MEG. These new sensor technologies offer a further important advance in that they can be directly coupled with non-invasive electromagnetic stimulation (not possible with traditional SQUID MEG detectors), allowing researchers to explore issues of functional causality and therapeutic effect. Further, since traditional transcranial magnetic stimulation (TMS) techniques employ one or two coils targeting specific regions of the brain, changing the focus of stimulation requires moving the coil(s) to new targets and is thus not possible in a dynamic setting. We therefore propose to introduce multichannel TMS array stimulation, designed to be fully compatible with OPM-MEG or fMRI, and EEG.
To maximize the benefits of integrating the emerging recording and stimulation technologies for a broad group of collaborators and service users, new auxiliary hardware and real-time capable software are needed. Our proposed real-time software will be designed to allow precise cortical targeting of the stimulation using a multichannel TMS device and data derived from models built with data acquired from TRDs 1-3, applying stimulation using a prescribed pulse-sequence, and recording MEG/EEG continuously before, during, and after stimulation. Using MEG/EEG source estimation techniques adapted for real-time use our proposed tools will be capable of displaying the brain activity modified by targeted stimulation in real time, allowing direct interrogation of the activated neural circuits with high spatial accuracy during the experiments. Although we will optimize our tools for multichannel TMS and MEG/EEG recording, they will be equally applicable in other brain stimulation settings, including conventional single-channel TMS/EEG, or focused ultrasound with concurrent acquisition of fMRI with EEG data.
