Temporal predictability modulates putative midbrain activity: evidence from human EEG

Predictable timing has been shown to modulate the neural processing of auditory stimuli at multiple stages and time scales, e.g. reducing the amplitude of the P50 and N1 potentials in the EEG. The modulatory effects of predictable timing include an enhancement of repetition suppression (see these examples) and omission responses to tones whose identity can also be predicted. However, most of the previously reported modulations of evoked responses occur relatively late, and have primarily been attributed to cortical processing. Can similar modulatory effects of predictable timing be observed at earlier, putatively subcortical stages?

A recent paper by Gorina-Careta et al. addresses this question by focusing on the human auditory frequency-following response (FFR) – a sustained EEG component serving as a proxy for the auditory brainstem response. The FFR signal is phase-locked to the periodic characteristics of the eliciting stimulus with a short delay (~15 ms), and has previously been shown to be sensitive to contextual factors. The authors recorded the FFR at the central electrode (Cz) in response to an auditory sequence consisting of a rapidly repeated syllable /wa/. The F0 formant of the /wa/ syllable – describing the most prominent frequency component of the auditory stimulus – was set to 100 Hz.

Accordingly, the 100 Hz component of the FFR signal was significantly reduced by temporal predictability (although the reported effect sizes were rather modest), suggesting that even very early auditory processing stages can be modulated by predictable timing. However, the modulatory effect of predictability appeared only after several hundred repetitions, indicating that the putative subcortical responses are shaped over the course of learning. While a closer inspection of Figure 1B might suggest that perhaps the most prominent modulation of the 100 Hz FFR component occurs not in the analysed time window (65-180 ms, corresponding to the steady-state part of the FFR) but in a pre-stimulus time window (shown from -40 ms), this is likely due to a contamination of the baseline in the unpredictable condition by stimulus presentation.

The authors also analysed the extent to which timing predictability influences the neural pitch strength, using a metric that quantified the magnitude of EEG phase-locking to the syllable pitch. While this metric also showed a modulation by timing predictability and its sensitivity to stimulus repetition, the pattern of results was opposite to the FFR. Thus, neural pitch strength was stronger under predictable timing, an effect which was especially prominent during the first 200 repetitions and disappeared after 500 repetitions. This interaction was due to a gradual reduction of the neural phase-locking to the stimulus pitch over the course of learning in the predictable condition, and no learning-related differences in pitch strength in the unpredictable condition.

On a methodological note, it would be interesting to see if the effects would be similar – or perhaps more robust and/or consistent over time – had the authors chosen a different F0 of the acoustic stimuli. In this paper, the F0 at 100 Hz falls exactly at the first harmonic of line noise (50 Hz), one of the most prominent artefacts in EEG signals. Thus, especially in the predictable condition (in which the stimulus onset asynchrony was fixed at 366 ms), approximately every third stimulus might be presented at a phase interfering with line noise.

Nevertheless, these results suggest two complementary mechanisms of temporal predictability: an initially increased neural phase-locking to the physical stimulus which disappears over the course of learning, and a gradual suppression of the neural response to the primary stimulus frequency (F0) occurring at later stages of learning. The authors interpret the first result as a reflection of more reliable processing of complex acoustic inputs. Thus, by increasing the signal-to-noise ratio, temporal predictability might facilitate the extraction of characteristic input features and the forming of neural predictions, which in turn suppress the responses to the most predictable (i.e. highly repetitive) aspects of the stimuli. The latter finding might therefore reflect a gradual deployment of neural predictions formed under temporal predictability to lower (subcortical) stages of auditory processing.

Invasive work in the rodent auditory system shows that the modulation of neural responses to predictable (e.g. repetitive) stimuli occurs already at subcortical stages, including the midbrain. This paper suggests that also the temporal predictability of stimuli might influence the short-latency neural responses associated with activity in the auditory brainstem. While invasive recordings might be necessary to establish an unequivocal link between the modulation of neural activity by temporal predictability and specific subcortical structures, these results offer further support for proposals that even the very early stages of sensory processing might be shaped by statistical regularities in the environment.

Ryszard Auksztulewicz, Oxford Centre for Human Brain Activity

Source article: Gorina-Careta N, Zarnowiec K, Costa-Faidella J, Escera C (2016) Timing predictability enhances regularity encoding in the human subcortical auditory pathway. Scientific Reports 6:37405. doi: 10.1038/srep37405.