Noninvasive neuromagnetic single-trial analysis of human neocortical population spikes

Neuronal spiking is commonly recorded by invasive sharp microelectrodes, whereas standard noninvasive macroapproaches (e.g., electroencephalography [EEG] and magnetoencephalography [MEG]) predominantly represent mass postsynaptic potentials. A notable exception are low-amplitude high-frequency (∼600 Hz) somatosensory EEG/MEG responses that can represent population spikes when averaged over hundreds of trials to raise the signal-to-noise ratio. Here, a recent leap in MEG technology-featuring a factor 10 reduction in white noise level compared with standard systems-is leveraged to establish an effective single-trial portrayal of evoked cortical population spike bursts in healthy human subjects. This time-resolved approach proved instrumental in revealing a significant trial-to-trial variability of burst amplitudes as well as time-correlated (∼10 s) fluctuations of burst response latencies. Thus, ultralow-noise MEG enables noninvasive single-trial analyses of human cortical population spikes concurrent with low-frequency mass postsynaptic activity and thereby could comprehensively characterize cortical processing, potentially also in diseases not amenable to invasive microelectrode recordings.