A high-density EEG and structural MRI source analysis of the frequency following response to missing fundamental stimuli reveals subcortical and cortical activation to low and high frequency stimuli

Pitch is a perceptual rather than physical phenomenon, important for spoken language use, musical communication, and other aspects of everyday life. Auditory stimuli can be designed to probe the relationship between perception and physiological responses to pitch-evoking stimuli. One technique for measuring physiological responses to pitch-evoking stimuli is the frequency following response (FFR). The FFR is an electroencephalographic (EEG) response to periodic auditory stimuli. The FFR contains nonlinearities not present in the stimuli, including correlates of the amplitude envelope of the stimulus; however, these nonlinearities remain undercharacterized. The FFR is a composite response reflecting multiple neural and peripheral generators, and their contributions to the scalp-recorded FFR vary in ill-understood ways depending on the electrode montage, stimulus, and imaging technique. The FFR is typically assumed to be generated in the auditory brainstem; there is also evidence both for and against a cortical contribution to the FFR. Here a methodology is used to examine the FFR correlates of pitch and the generators of the FFR to stimuli with different pitches. Stimuli were designed to tease apart biological correlates of pitch and amplitude envelope. FFRs were recorded with 256-electrode EEG nets, in contrast to a typical FFR setup which only contains a single active electrode. Structural MRI scans were obtained for each participant to co-register with the electrode locations and constrain a source localization algorithm. The results of this localization shed light on the generating mechanisms of the FFR, including providing evidence for both cortical and subcortical auditory sources.