Human thalamus regulates cortical activity via spatially specific and structurally constrained phase-amplitude coupling.

Although the thalamus is believed to regulate and coordinate cortical activity both within and across functional regions, such as motor and visual cortices, direct evidence for such regulation and the mechanism of regulation remains poorly described. Using simultaneous invasive recordings of cortical and thalamic electrophysiological activity in 2 awake and spontaneously behaving human subjects, we provide direct evidence of thalamic regulation of cortical activity through a mechanism of phase-amplitude coupling (PAC), in which the phase of low frequency oscillations regulates the amplitude of higher frequency oscillations. Specifically, we show that cortical PAC between the theta phase and beta amplitude is spatially dependent on and time variant with the magnitude of thalamocortical theta coherence. Moreover, using causality analysis and MR diffusion tractography, we provide evidence that thalamic theta activity drives cortical theta oscillations and PAC across structures and that these thalamocortical relationships are structurally constrained by anatomic pathways. This relationship allows for new evidence of thalamocortical PAC. Given the diffuse connectivity of the thalamus with the cerebral cortex, thalamocortical PAC may play an important role in addressing the binding problem, including both integration and segregation of information within and across cortical areas.