Modularity of auditory spatial representations

Abstract : Auditory spatial functions are of crucial importance in everyday life. Determining the origin of sound sources in space plays a key role in a variety of tasks including orientation of attention, disentangling of complex acoustic patterns reaching our ears in noisy environments. Following brain damage, auditory spatial processing can be disrupted, resulting in severe handicaps. Complaints of patients with sound localization deficits include the inability to locate their crying child or being over-loaded by sounds in crowded public places. Yet, the brain bears a large capacity for reorganization following damage and/or learning. This phenomenon is referred as plasticity and is believed to underlie post-lesional functional recovery as well as learning-induced improvement. The aim of this thesis was to investigate the organization and plasticity of different aspects of auditory spatial functions. Overall, we report the outcomes of three studies: In the study entitled "Learning-induced plasticity in auditory spatial representations" (Spierer et al., 2007b), we focused on the neurophysiological and behavioral changes induced by auditory spatial training in healthy subjects. We found that relatively brief auditory spatial discrimination training improves performance and modifies the cortical representation of the trained sound locations, suggesting that cortical auditory representations of space are dynamic and subject to rapid reorganization. In the same study, we tested the generalization and persistence of training effects over time, as these are two determining factors in the development of neurorehabilitative intervention. In "The path to success in auditory spatial discrimination" (Spierer et al., 2007c), we investigated the neurophysiological correlates of successful spatial discrimination and contribute to the modeling of the anatomo-functional organization of auditory spatial processing in healthy subjects. We showed that discrimination accuracy depends on superior temporal plane (STP) activity in response to the first sound of a pair of stimuli. Our data support a model wherein refinement of spatial representations occurs within the STP and that interactions with parietal structures allow for transformations into coordinate frames that are required for higher-order computations including absolute localization of sound sources. In "Extinction of auditory stimuli in hemineglect: space versus ear" (Spierer et al., 2007a), we investigated auditory attentional deficits in brain-damaged patients. This work provides insight into the auditory neglect syndrome and its relation with neglect symptoms within the visual modality. Apart from contributing to a basic understanding of the cortical mechanisms underlying auditory spatial functions, the outcomes of the studies also contribute to develop neurorehabilitation strategies, which are currently being tested in clinical populations.

Airway surface liquid volume regulation determines different airway phenotypes in liddle compared with betaENaC-overexpressing mice.

Studies in cystic fibrosis patients and mice overexpressing the epithelial Na(+) channel beta-subunit (betaENaC-Tg) suggest that raised airway Na(+) transport and airway surface liquid (ASL) depletion are central to the pathogenesis of cystic fibrosis lung disease. However, patients or mice with Liddle gain-of-function betaENaC mutations exhibit hypertension but no lung disease. To investigate this apparent paradox, we compared the airway phenotype (nasal versus tracheal) of Liddle with CFTR-null, betaENaC-Tg, and double mutant mice. In mouse nasal epithelium, the region that functionally mimics human airways, high levels of CFTR expression inhibited Liddle epithelial Nat channel (ENaC) hyperfunction. Conversely, in mouse trachea, low levels of CFTR failed to suppress Liddle ENaC hyperfunction. Indeed, Na(+) transport measured in Ussing chambers ("flooded" conditions) was raised in both Liddle and betaENaC-Tg mice. Because enhanced Na(+) transport did not correlate with lung disease in these mutant mice, measurements in tracheal cultures under physiologic "thin film" conditions and in vivo were performed. Regulation of ASL volume and ENaC-mediated Na(+) absorption were intact in Liddle but defective in betaENaC-Tg mice. We conclude that the capacity to regulate Na(+) transport and ASL volume, not absolute Na(+) transport rates in Ussing chambers, is the key physiologic function protecting airways from dehydration-induced lung disease.

High Altitude Increases Alteration in Maximal Torque but Not in Rapid Torque Development in Knee Extensors after Repeated Treadmill Sprinting.

We assessed knee extensor neuromuscular adjustments following repeated treadmill sprints in different normobaric hypoxia conditions, with special reference to rapid muscle torque production capacity. Thirteen team- and racquet-sport athletes undertook 8 × 5-s "all-out" sprints (passive recovery = 25 s) on a non-motorized treadmill in normoxia (NM; FiO2 = 20.9%), at low (LA; FiO2 = 16.8%) and high (HA; FiO2 = 13.3%) normobaric hypoxia (simulated altitudes of ~1800 m and ~3600 m, respectively). Explosive (~1 s; "fast" instruction) and maximal (~5 s; "hard" instruction) voluntary isometric contractions (MVC) of the knee extensors (KE), with concurrent electromyographic (EMG) activity recordings of the vastus lateralis (VL) and rectus femoris (RF) muscles, were performed before and 1-min post-exercise. Rate of torque development (RTD) and EMG (i.e., Root Mean Square or RMS) rise from 0 to 30, -50, -100, and -200 ms were recorded, and were also normalized to maximal torque and EMG values, respectively. Distance covered during the first 5-s sprint was similar (P > 0.05) in all conditions. A larger (P < 0.05) sprint decrement score and a shorter (P < 0.05) cumulated distance covered over the eight sprints occurred in HA (-8 ± 4% and 178 ± 11 m) but not in LA (-7 ± 3% and 181 ± 10 m) compared to NM (-5 ± 2% and 183 ± 9 m). Compared to NM (-9 ± 7%), a larger (P < 0.05) reduction in MVC torque occurred post-exercise in HA (-14 ± 9%) but not in LA (-12 ± 7%), with no difference between NM and LA (P > 0.05). Irrespectively of condition (P > 0.05), peak RTD (-6 ± 11%; P < 0.05), and normalized peak RMS activity for VL (-8 ± 11%; P = 0.07) and RF (-14 ± 11%; P < 0.01) muscles were reduced post-exercise, whereas reductions (P < 0.05) in absolute RTD occurred within the 0-100 (-8 ± 9%) and 0-200 ms (-10 ± 8%) epochs after contraction onset. After normalization to MVC torque, there was no difference in RTD values. Additionally, the EMG rise for VL muscle was similar (P > 0.05), whereas it increased (P < 0.05) for RF muscle during all epochs post-exercise, independently of the conditions. In summary, alteration in repeated-sprint ability and post-exercise MVC decrease were greater at high altitude than in normoxia or at low altitude. However, the post-exercise alterations in RTD were similar between normoxia and low-to-high hypoxia.