AbstractCurrently, non-invasive methods for studying the human brain do not reliably measure signals that depend on the rate of action potentials (spikes) in a neural population, independent of other responses such as hemodynamic coupling (functional magnetic resonance imaging) and subthreshold neuronal synchrony (oscillations and event-related potentials). In contrast, invasive methods - animal microelectrode recordings and human intracortical recordings (electrocorticography, or ECoG) - have recently measured broadband power elevation spanning 50-200 Hz in electrical fields generated by neuronal activity as a proxy for the locally averaged spike rates. Here, we sought to detect and quantify stimulus-related broadband responses using a non-invasive method - magnetoencephalography (MEG) - in individual subjects. Because extracranial measurements like MEG have multiple global noise sources and a relatively low signal-to-noise ratio, we developed an automated denoising technique, adapted from Kay et al, 2013 (1), that helps reveal the broadband signal of interest. Subjects viewed 12-Hz contrast-reversing patterns in the left, right, or bilateral visual field. Sensor time series were separated into an evoked component (12-Hz amplitude) and a broadband component (60–150 Hz, excluding stimulus harmonics). In all subjects, denoised broadband responses were reliably measured in sensors over occipital cortex. The spatial pattern of the broadband measure depended on the stimulus, with greater broadband power in sensors contralateral to the stimulus. Because we obtain reliable broadband estimates with relatively short experiments (~20 minutes), with a sufficient signal-to-noise-ratio to distinguish responses to different stimuli, we conclude that MEG broadband signals, denoised with our method, offer a practical, non-invasive means for characterizing spike-rate-dependent neural activity for a wide range of scientific questions about human brain function.Author SummaryNeuronal activity causes perturbations in nearby electrical fields. These perturbations can be measured non-invasively in the living human brain using electro- and magneto-encephalography (EEG and MEG). These two techniques have generally emphasized two kinds of measurements: oscillations and event-related responses, both of which reflect synchronous activity from large populations of neurons. A third type of signal, a stimulus-related increase in power spanning a wide range of frequencies (‘broadband’), is routinely measured in invasive recordings in animals and pre-surgical patients with implanted electrodes, but not with MEG and EEG. This broadband response is of great interest because unlike oscillations and event-related responses, it is correlated with neuronal spike rates. Here we report quantitative, spatially specific measurements of broadband fields in individual human subjects using MEG. These results demonstrate that a spike- rate-dependent measure of brain activity can be obtained non-invasively from the living human brain, and is suitable for investigating a wide range of questions about spiking activity in the human brain.