Functional significance of genetic advantage in the Frequency-Following Response (FFR)

PI: Imma Clemente, Marc Via, Carles Escera

Neurons in the subcortical auditory system replicate the frequency spectrum contained in the sounds we perceive via their phase-locking activity (recorded from the scalp as the Frequency-Following Response or FFR). The FFR sounds as the eliciting stimuli, and it has been used extensively to demonstrate that efficient speech encoding at subcortical stations is linked to better reading abilities, literacy and an improved capacity to synchronize movement to a rhythmic auditory input.

We have recently shown that serotonin transporter-linked polymorphic region (5-HTTLPR), a common functional polymorphism located in the promoter region of the serotonin transporter gene (SLC6A4), is implicated in an efficient speech encoding in the human subcortical auditory pathway. Specifically, individuals with low serotonin transporter expression had higher signal-to-noise ratios and a higher pitch strength representation of speech compared to individuals with medium or high expression (Selinger et al., 2016; Figure 1). Our current challenge is to characterize the functional implications of this genetic advantage by investigating whether such a more efficient speech neuronal encoding is associated in human healthy adults and infants, with better reading abilities and educational achievements.

Figure 1. The Frequency-Following Response (FFR) in individuals according to their expression of the serotonin transporter gene (low and medium-high). A) The grand-average FFR. B) Signal-to-noise and pitch strength bar plots. C) The autocorrelegram function in the two groups. Notice that genetic differences can be seen by the naked eye in the recordings (A) and in the autocorrelogram functions (C), and were confirmed statistically. From Selinger et al. (2016).

 

This research on the neurogenetics of speech encoding has roots back to our former neurocognitive genetic studies, in which we demonstrated modulation of contextual updating of mental representations by COMT and ANKK1 gene-gene interactions (Garcia-Garcia et al., 2011; Figure 2), and this very same genetic epistatis accounted for resetting of gamma neural oscillations to auditory stimulus-driven attention (Garcia-Garcia et al., 2017; Figure 3).

Figure 2. A) Brain potentials elicited to repeat, cue-switch and task switch conditions in a ERP-adapted version of the Wisconsin Card Sorting Test. Notice that novelty-P3 potential showed larger amplitudes in cue-switch relative to repeat trials in ValA1−andMetA1+ groups but appeared with similar amplitude for cue-switch and task-switch trials. In contrast, ValA1+ and MetA1− displayed similar amplitudes for repeat and cue-switch trials, but larger amplitudes in task-switch compared to cue switch trials. B) Scalp distribution of the nP3 brain potential for cue-switch trials and task-switch trials for all four groups. ValA1−and MetA1+ display a parietally distributed increase of the brain response in task-switch relative to cue-switch trials. C) Notice that the amplitude pattern of novelty-P3 as a function of genetic epistatis followed that of behavioral switch costs. From Garcia-Garcia et al. (2011).

Figure 3. Top) Standardized PLF values for 40 Hz activity elicited to novel and standard trials presented in our well characterized auditory-visual distraction paradigm (see Escera et al., 1998). Plots of standardized PLF values for novel and standard trials are shown for all four groups at Cz for frequencies from 30 to 55 Hz. ValA1- and MetA1+ groups showed enhanced PLF in novel compared to standard trials around 100 ms post-sound onset, whereas ValA1+ and MetA1- groups had similar PLF values to both stimulus types. Bottom) The left panel shows the mean RT for novel compared to standard trials; notice that only the ValA1+ and MetA1- groups had larger RT for novel as compared to standard trials (e.g., experienced behavioral distraction). The right panel shows the increase of the PLF of neural oscillations at 40 Hz locked to novels sounds relative to that locked to standard sounds at Cz. Notice that PLF was larger after novel compared to standard trials in only the ValA1- and MetA1+ groups. (*, p<0.05; **, p<0.01; ***, p<0.001; n.s., p>0.05). From Garcia-Garcia et al. (2017). The pattern of results obtained in this study parallels that obtained in Garcia-Garcia et al. (2011) for task-novelty (see Figure 2 above) and validate at a genetic level the proposal of Barceló and colleagues (2006) about a common neural network for cognitive control involved both in task and stimulus novelty. From Garcia-Garcia et al. (2017).