The core aim of this proposal is to implement a novel technique to assess the connectivity in the human brain by developing optically pumped magnetometers (OPMs) that can be combined with transcranial magnetic stimulation (TMS). This allows us to assess brain connectivity by stimulating one region and measuring the response in another region. The approach holds the promise of providing capabilities needed for understanding the brain as a network and to investigate brain connectivity in cognition and disorders. Currently there is strong enthusiasm for OPMs. This new type of sensor has the potential of revolutionizing human electrophysiology. In particular OPMs allow us to measure small magnetic fields from neuronal currents in the brain, which so far is usually done using conventional SQUID-based magnetoencephalography (MEG). The disadvantages of conventional MEG are that 1) the sensors rely on cooling by liquid Helium which is highly expensive and 2) the sensors cannot work with brain stimulation. OPMs solve both concerns but need to be further developed to be integrated with brain stimulation. Brain stimulation using TMS is used to activate a given brain region by delivering a brief but strong magnetic pulse. The technique can also be used to stimulate one brain region and measure the response in connected regions. This has recently been attempted by combining TMS with electroencephalography (EEG); however, the resulting signals are spatially blurred and therefore difficult to interpret. Combining TMS with OPMs holds the promise of better identifying the regions responding to a specific perturbation. As such it will allow us to measure connectivity in the brain and quantify how this connectivity is modulated in a task specific manner. Furthermore, the technique can be used to assess connectivity changes associated with brain injuries and neurological disorders. Specifically, we will develop a new type of OPMs that can be used together with TMS. These new sensors will be benchmarked against conventional MEG sensors. Subsequently we will test the OPMs together with TMS. This will first be done using phantom recordings and subsequently tested in humans performing various tasks hypothesized to modulate brain connectivity. Within this proposal we are aiming at using up to 5 sensors. Therefore, B-conn will provide the stepping-stone for developing a whole-head OPM-MEG system with ~100 sensors in collaboration with commercial and academic partners. The longer-term goal is to develop an integrated stimulus-response system that can be used in clinical settings for diagnostic purposes by quantifying alterations in brain connectivity associated with communication delays and strengths. Examples are traumatic brain injury and neurodegenerative diseases.