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This review intends to provide an overview of the current knowledge on neurologic sequelae of COVID-19 and their possible etiology, and, based on available data, proposes possible improvements in current medical care procedures. We conducted a thorough review of the scientific literature on neurologic manifestations of COVID-19, the neuroinvasive propensity of known coronaviruses (CoV) and their possible effects on brain structural and functional integrity. It appears that around one third of COVID-19 patients admitted to intensive care units (ICU) for respiratory difficulties exhibit neurologic symptoms. This may be due to progressive brain damage and dysfunction triggered by severe hypoxia and hypoxemia, heightened inflammation and SARS-CoV-2 dissemination into brain parenchyma, as suggested by current reports and analyses of previous CoV outbreaks. Viral invasion of the brain may particularly target and alter brainstem and thalamic functions and, consequently, result in sensorimotor dysfunctions and psychiatric disorders. Moreover, data collected from other structurally homologous CoV suggest that SARS-CoV-2 infection may lead to brain cell degeneration and demyelination similar to multiple sclerosis (MS). Hence, current evidence warrants further evaluation and long-term follow-up of possible neurologic sequelae in COVID-19 patients. It may be particularly relevant to evaluate brainstem integrity in recovered patients, as it is suspected that this cerebral area may particularly be dysfunctional following SARS-CoV-2 infection. Because CoV infection can potentially lead to chronic neuroinflammation and progressive demyelination, neuroimaging features and signs of MS may also be evaluated in the long term in recovered COVID-19 patients., Highlights • Acute neurologic symptoms are observed in one third of COVID-19 patients • Neurotropism of SARS-CoV-2 is highly suspected • Brainstem damage may be a crucial driver for COVID-19-associated respiratory failure • COVID-19 is likely to trigger demyelination similarly to multiple sclerosis • Monitoring patients using Auditory Brainstem Responses and neuroimaging is warranted

In a multi-talker situation, spatial separation between talkers reduces cognitive processing load: this is the “spatial release of cognitive load”. The present study investigated the role played by the relative levels of the talkers on this spatial release of cognitive load. During the experiment, participants had to report the speech emitted by a target talker in the presence of a concurrent masker talker. The spatial separation (0° and 120° angular distance in azimuth) and the relative levels of the talkers (adverse, intermediate, and favorable target-to-masker ratio) were manipulated. The cognitive load was assessed with a prefrontal functional near-infrared spectroscopy. Data from 14 young normal- hearing listeners revealed that the target-to-masker ratio had a direct impact on the spatial release of cognitive load. Spatial separation significantly reduced the prefrontal activity only for the intermediate target-to-masker ratio and had no effect on prefrontal activity for the favorable and the adverse target-to-masker ratios. Therefore, the relative levels of the talkers might be a key point to determine the spatial release of cognitive load and more specifically the prefrontal activity induced by spatial cues in multi- talker environments.

Human sound localization abilities rely on binaural and spectral cues. Spectral cues arise from interactions between the sound wave and the listener's body (head-related transfer function, HRTF). Large individual differences were reported in localization abilities, even in young normal-hearing adults. Several studies have attempted to determine whether localization abilities depend mostly on acoustical cues or on perceptual processes involved in the analysis of these cues. These studies have yielded inconsistent findings, which could result from methodological issues. In this study, we measured sound localization performance with normal and modified acoustical cues (i.e., with individual and non-individual HRTFs, respectively) in 20 naive listeners. Test conditions were chosen to address most methodological issues from past studies. Procedural training was provided prior to sound localization tests. The results showed no direct relationship between behavioral results and an acoustical metrics (spectral-shape prominence of individual HRTFs). Despite uncertainties due to technical issues with the normalization of the HRTFs, large acoustical differences between individual and non-individual HRTFs appeared to be needed to produce behavioral effects. A subset of 15 listeners then trained in the sound localization task with individual HRTFs. Training included either visual correct-answer feedback (for the test group) or no feedback (for the control group), and was assumed to elicit perceptual learning for the test group only. Few listeners from the control group, but most listeners from the test group, showed significant training-induced learning. For the test group, learning was related to pre-training performance (i.e., the poorer the pre-training performance, the greater the learning amount) and was retained after 1 month. The results are interpreted as being in favor of a larger contribution of perceptual factors than of acoustical factors to sound localization abilities with virtual sources.

The mammalian auditory system contains descending neural pathways, some of which project onto the cochlea via the medial olivocochlear (MOC) system. The function of this efferent auditory system is not entirely clear. Behavioral studies in animals with olivocochlear (OC) lesions suggest that the MOC serves to facilitate sound localization in noise. In the current work, noise-induced OC activity (the OC reflex) and sound-localization performance in noise were measured in normal-hearing humans. Consistent with earlier studies, both measures were found to vary substantially across individuals. Importantly, significant correlations were observed between OC-reflex strength and the effect of noise on sound-localization performance; the stronger the OC reflex, the less marked the effect of noise. These results suggest that MOC activation by noise helps to counteract the detrimental effects of background noise on neural representations of direction-dependent spectral features, which are especially important for accurate localization in the up/down and front/back dimensions.

The activity of the medial olivocochlear bundle (MOCB) can be studied in humans through variations in the level of evoked otoacoustic emissions (EOAEs) elicited by contralateral acoustic stimuli (CAS). The present study sought to investigate how the activity of the MOC system at a given frequency, as measured through the contralateral suppression of tone-pip EOAEs, depends on the bandwidth of the contralateral stimulus. EOAEs were recorded in 155 normal-hearing subjects, successively with and without contralateral stimuli whose bandwidth, center frequency and level were systematically varied. We showed a clear dependence of contralateral EOAE suppression on bandwidth demonstrating increased suppression with increased bandwidth over about two octaves around the center frequency of the noise. This effect was obtained irrespective of whether contralateral noise energy was kept constant independently of bandwidth or not, which indicates a role of bandwidth per se in contralateral EOAE suppression. Results are interpreted in terms of a simple model of MOCB activation mechanisms including peripheral bandpass filtering, within-channel compression and across-channel spatial summation by the afferent paths. Complementary experiments suggested a greater effectiveness of increases in bandwidth on the upper than on the lower side and of frequency components akin to or remote from the test frequency than of intermediate bands. Finally, these results were complemented by detailed spectrum analyses of the EOAE level variations induced by the different noises, which revealed that whilst noise components close to or remote from the center frequency generally attenuated EOAE level, intermediate components could in some cases lead to a relative increase in EOAE level. These results can further be explained by assuming different positive and negative weights on the inputs to the spatial summation process depending on their position relative to the center frequency.