An Improved Methodology for the Spectro-Temporal Analysis of the Frequency-Following Response

The variety of electrophysiological tests currently available allows objective audiograms to be reliably obtained in patients who cannot participate in behavioral (psycho-acoustical) measurements. However, many patients with thresholds within the normal range, report difficulties in understanding speech in noisy environment. One possible cause of such supra-threshold deficit is related to a faulty mode of neural coding, called temporal coding that is in part responsible to convey the full spectro-temporal characteristics of the sound pressure wave into the neural pathways. One electrophysiological measure that could prove itself to be more sensible to probing the neural temporal code is the Frequency-Following Response (FFR). The FFR is a steady-state auditory evoked potential that can be recorded with scalp electrodes following an auditory stimulation. The FFR is a short latency response ($<$10ms), that mimics the spectro-temporal profile of sustained stimuli. Depending on the recording parameters and subjects characteristics, FFR generators can be of pre-neural and neural origin, reflecting different stages of auditory stimuli processing operating from the cochlea to the cortex. In particular, the neural origin of the FFR, reflect the neural phase-locking process and thus offers a means to probe the quality of the neural temporal code representing one of the sensory versions of the stimulus in the auditory pathways.In addition to the sustained components, most stimuli also evoke the transient Auditory Brainstem Response (ABR) triggered by stimulus onset and offset. Complex stimuli evoke FFRs exhibiting phase-locking to both the stimulus Envelope (ENV) and its Temporal Fine Structure (TFS), i.e. to the instantaneous sound pressure variations. The former, also called the envelope-following response (EFR), mainly results from the half-wave rectification process at the inner hair cell synapse and therefore, is usually considered of neural origin. Specifically, for the purpose of this work, when evoked by a two-tone stimulus $f_1&f_2$, the EFR component is inherently embedded into multicomponent structure, containing higher harmonic distortions and the transient ABR.This thesis aims at developing a set of tools that could help to advance our knowledge about the neural mechanisms underlying the generation of the EFR. We first proceed by proposing a novel technique to record the two-tone evoked EFR component ($f_2-f_1$) and disentangle the multicomponent structure that is inherent to the signal. This method, termed the generalized primary tone phase variation (gPTPV), isolated the EFR component in the time domain without the need to deploy filtering techniques that might be deleterious for the subsequent phase analysis and that best suit the nature of the signal. We developed a new latency measurement technique, the phase-stationarity method (PSM), which in combination with the gPTPV opens up new possibilities to probe the dynamics of the EFR with unprecedented precision.When applying this methodology to the vertex-to-neck recorded EFR of N=12 awake adults and N=10 sleeping/sedated children, we were able to highlight the presence of two sequential generators in the adults group but only one in the children group. The explanation we favored to explain this systematic difference between the members of the two groups referred to their different sleep/wake state, although maturational effects could not be excluded. Furthermore we proceeded to study the EFR transfer function by recording responses phase-locked to different envelope frequencies in N=30 children along two acquisition channels; a vertical (V) vertex-to-neck and a horizontal (H) earlobe-to-earlobe. We measured the phase-locking-frequency function of both EFR-H and EFR-V and noted a lowpass profile where the second response had a lower cutoff frequency than the first. Moreover we constructed the latency-frequency relations of both responses to delineate their respective fixed transport time from the frequency dependent delay. On the basis of the phase-locking frequency profile and derive a neural transport time (1.2 ms) associated to the EFR-H, we hypothesized the cochlear nerve to be the generator of the response. This claim was additionally substantiated by the recording of an EFR-H component in a Leigh syndrome patient that presented a complete absence of central ABR waves with an isolated cochlear nerve compound action potential (ABR wave). We applied the same transport time derivation to the EFR interchannel delay and derived a fixed delay (2 ms) that is commensurate with a Wave I-III interpeak latency. Moreover, the EFR-V response exhibited an improved phase-locking value with an enhanced degree of harmonic distortion with respect to the cochlear nerve. This observation led us to believe that the cochlear nucleus was the generator of the EFR-V component.Doctorat en Sciences biomédicales et pharmaceutiques (Médecine)