Impaired Auditory Temporal Selectivity in the Inferior Colliculus of Aged Mongolian Gerbils

Aged humans show severe difficulties in temporal auditory processing tasks (e.g., speech recognition in noise, low-frequency sound localization, gap detection). A degradation of auditory function with age is also evident in experimental animals. To investigate age-related changes in temporal processing, we compared extracellular responses to temporally variable pulse trains and human speech in the inferior colliculus of young adult (3 month) and aged (3 years) Mongolian gerbils. We observed a significant decrease of selectivity to the pulse trains in neuronal responses from aged animals. This decrease in selectivity led, on the population level, to an increase in signal correlations and therefore a decrease in heterogeneity of temporal receptive fields and a decreased efficiency in encoding of speech signals. A decrease in selectivity to temporal modulations is consistent with a downregulation of the inhibitory transmitter system in aged animals. These alterations in temporal processing could underlie declines in the aging auditory system, which are unrelated to peripheral hearing loss. These declines cannot be compensated by traditional hearing aids (that rely on amplification of sound) but may rather require pharmacological treatment

Population Coding of Interaural Time Differences in Gerbils and Barn Owls

Interaural time differences (ITDs) are the primary cue for the localization of low-frequency sound sources in the azimuthal plane. For decades, it was assumed that the coding of ITDs in the mammalian brain was similar to that in the avian brain, where information is sparsely distributed across individual neurons, but recent studies have suggested otherwise. In this study, we characterized the representation of ITDs in adult male and female gerbils. First, we performed behavioral experiments to determine the acuity with which gerbils can use ITDs to localize sounds. Next, we used different decoders to infer ITDs from the activity of a population of neurons in central nucleus of the inferior colliculus. These results show that ITDs are not represented in a distributed manner, but rather in the summed activity of the entire population. To contrast these results with those from a population where the representation of ITDs is known to be sparsely distributed, we performed the same analysis on activity from the external nucleus of the inferior colliculus of adult male and female barn owls. Together, our results support the idea that, unlike the avian brain, the mammalian brain represents ITDs in the overall activity of a homogenous population of neurons within each hemisphere

Trapping and observing single atoms in the dark

A single atom strongly coupled to a cavity mode is stored by three-dimensional confinement in blue-detuned cavity modes of different longitudinal and transverse order. The vanishing light intensity at the trap center reduces the light shift of all atomic energy levels. This is exploited to detect a single atom by means of a dispersive measurement with 95% confidence in 0.010 ms, limited by the photon-detection efficiency. As the atom switches resonant cavity transmission into cavity reflection, the atom can be detected while scattering about one photon

Scanning tunneling spectroscopy of superconducting LiFeAs single crystals: Evidence for two nodeless energy gaps and coupling to a bosonic mode

The superconducting compound, LiFeAs, is studied by scanning tunneling microscopy and spectroscopy. A gap map of the unreconstructed surface indicates a high degree of homogeneity in this system. Spectra at 2 K show two nodeless superconducting gaps with $\Delta_1=5.3\pm0.1$ meV and $\Delta_2=2.5\pm0.2$ meV. The gaps close as the temperature is increased to the bulk $T_c$ indicating that the surface accurately represents the bulk. A dip-hump structure is observed below $T_c$ with an energy scale consistent with a magnetic resonance recently reported by inelastic neutron scattering

Reduced [¹⁸F]flortaucipir retention in white matter hyperintensities compared to normal-appearing white matter

PURPOSE: Recent research has suggested the use of white matter (WM) reference regions for longitudinal tau-PET imaging. However, tau tracers display affinity for the β-sheet structure formed by myelin, and thus WM lesions might influence tracer retention. Here, we explored whether the tau-sensitive tracer [18F]flortaucipir shows reduced retention in WM hyperintensities (WMH) and how this retention changes over time. METHODS: We included 707 participants from the Alzheimer's Disease Neuroimaging Initiative with available [18F]flortaucipir-PET and structural and FLAIR MRI scans. WM segments and WMH were automatically delineated in the structural MRI and FLAIR scans, respectively. [18F]flortaucipir standardized uptake value ratios (SUVR) of WMH and normal-appearing WM (NAWM) were calculated using the inferior cerebellar grey matter as reference region, and a 3-mm erosion was applied to the combined NAWM and WMH masks to avoid partial volume effects. Longitudinal [18F]flortaucipir SUVR changes in NAWM and WMH were estimated using linear mixed models. The percent variance of WM-referenced cortical [18F]flortaucipir SUVRs explained by longitudinal changes in the WM reference region was estimated with the R2 coefficient. RESULTS: Compared to NAWM, WMH areas displayed significantly reduced [18F]flortaucipir SUVR, independent of cognitive impairment or Aβ status (mean difference = 0.14 SUVR, p < 0.001). Older age was associated with lower [18F]flortaucipir SUVR in both NAWM (- 0.002 SUVR/year, p = 0.005) and WMH (- 0.004 SUVR/year, p < 0.001). Longitudinally, [18F]flortaucipir SUVR decreased in NAWM (- 0.008 SUVR/year, p = 0.03) and even more so in WMH (- 0.02 SUVR/year, p < 0.001). Between 17% and 66% of the variance of longitudinal changes in cortical WM-referenced [18F]flortaucipir SUVRs were explained by longitudinal changes in the reference region. CONCLUSIONS: [18F]flortaucipir retention in the WM decreases over time and is influenced by the presence of WMH, supporting the hypothesis that [18F]flortaucipir retention in the WM is partially myelin-dependent. These findings have implications for the use of WM reference regions for [18F]flortaucipir-PET imaging

Differential associations of APOE-epsilon 2 and APOE-epsilon 4 alleles with PET-measured amyloid-beta and tau deposition in older individuals without dementia

Purpose: To examine associations between the APOE-ε2 and APOE-ε4 alleles and core Alzheimer’s disease (AD) pathological hallmarks as measured by amyloid-β (Aβ) and tau PET in older individuals without dementia. Methods: We analyzed data from 462 ADNI participants without dementia who underwent Aβ ([18F]florbetapir or [18F]florbetaben) and tau ([18F]flortaucipir) PET, structural MRI, and cognitive testing. Employing APOE-ε3 homozygotes as the reference group, associations between APOE-ε2 and APOE-ε4 carriership with global Aβ PET and regional tau PET measures (entorhinal cortex (ERC), inferior temporal cortex, and Braak-V/VI neocortical composite regions) were investigated using linear regression models. In a subset of 156 participants, we also investigated associations between APOE genotype and regional tau accumulation over time using linear mixed models. Finally, we assessed whether Aβ mediated the cross-sectional and longitudinal associations between APOE genotype and tau. Results: Compared to APOE-ε3 homozygotes, APOE-ε2 carriers had lower global Aβ burden (βstd [95% confidence interval (CI)]: − 0.31 [− 0.45, − 0.16], p = 0.034) but did not differ on regional tau burden or tau accumulation over time. APOE-ε4 participants showed higher Aβ (βstd [95%CI]: 0.64 [0.42, 0.82], p < 0.001) and tau burden (βstd range: 0.27-0.51, all p < 0.006). In mediation analyses, APOE-ε4 only retained an Aβ-independent effect on tau in the ERC. APOE-ε4 showed a trend towards increased tau accumulation over time in Braak-V/VI compared to APOE-ε3 homozygotes (βstd [95%CI]: 0.10 [− 0.02, 0.18], p = 0.11), and this association was fully mediated by baseline Aβ. Conclusion: Our data suggest that the established protective effect of the APOE-ε2 allele against developing clinical AD is primarily linked to resistance against Aβ deposition rather than tau pathology