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The brainstem nuclei of the reticular formation (RF) are critical for regulating homeostasis, behavior, and cognition. RF degenerates in tauopathies including Alzheimer disease (AD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). Although the burden of phopho-tau inclusion is high across these diseases, suggesting a similar vulnerability pattern, a distinct RF-associated clinical phenotype in these diseases indicates the opposite. To compare patterns of RF selective vulnerability to tauopathies, we analyzed 5 RF nuclei in tissue from 14 AD, 14 CBD, 10 PSP, and 3 control cases. Multidimensional quantitative analysis unraveled discernable differences on how these nuclei are vulnerable to AD, CBD, and PSP. For instance, PSP and CBD accrued more tau inclusions than AD in locus coeruleus, suggesting a lower vulnerability to AD. However, locus coeruleus neuronal loss in AD was so extreme that few neurons remained to develop aggregates. Likewise, tau burden in gigantocellular nucleus was low in AD and high in PSP, but few GABAergic neurons were present in AD. This challenges the hypothesis that gigantocellular nucleus neuronal loss underlies REM behavioral disorders because REM behavioral disorders rarely manifests in AD. This study provides foundation for characterizing the clinical consequences of RF degeneration in tauopathies and guiding customized treatment., (© 2018 American Association of Neuropathologists, Inc. All rights reserved.)

Congenital amusia is a neurogenetic condition, characterized by a deficit in music perception and production, not explained by hearing loss, brain damage or lack of exposure to music. Despite inferior musical performance, amusics exhibit normal auditory cortical responses, with abnormal neural correlates suggested to lie beyond auditory cortices. Here we show, using auditory brainstem responses to complex sounds in humans, that fine-grained automatic processing of sounds is impoverished in amusia. Compared with matched non-musician controls, spectral amplitude was decreased in amusics for higher harmonic components of the auditory brainstem response. We also found a delayed response to the early transient aspects of the auditory stimulus in amusics. Neural measures of spectral amplitude and response timing correlated with participants' behavioral assessments of music processing. We demonstrate, for the first time, that amusia affects how complex acoustic signals are processed in the auditory brainstem. This neural signature of amusia mirrors what is observed in musicians, such that the aspects of the auditory brainstem responses that are enhanced in musicians are degraded in amusics. By showing that gradients of music abilities are reflected in the auditory brainstem, our findings have implications not only for current models of amusia but also for auditory functioning in general., (© 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Clarifying the mechanisms connecting neurofibrillary tangle (NFT) neurotoxicity to neuronal dysfunction in humans is likely to be pivotal for developing effective treatments for Alzheimer's disease (AD). To model the temporal progression of AD in humans, we used a collection of brains with controls and individuals from each Braak stage to quantitatively investigate the correlation between intraneuronal caspase activation or macroautophagy markers, NFT burden, and neuronal loss, in the dorsal raphe nucleus and locus coeruleus, the earliest vulnerable areas to NFT accumulation. We fit linear regressions with each count as outcomes, with Braak score and age as the predictors. In progressive Braak stages, intraneuronal active caspase-6 positivity increases both alone and overlapping with NFTs. Likewise, the proportion of NFT-bearing neurons showing autophagosomes increases. Overall, caspases may be involved in upstream cascades in AD and are associated with higher NFTs. Macroautophagy changes correlate with increasing NFT burden from early AD stages. [ABSTRACT FROM AUTHOR]

Neurons in the auditory cortex synchronize their responses to temporal regularities in sound input. This coupling or “entrainment” is thought to facilitate beat extraction and rhythm perception in temporally structured sounds, such as music. As a consequence of such entrainment, the auditory cortex responds to an omitted (silent) sound in a regular sequence. Although previous studies suggest that the auditory brainstem frequency-following response (FFR) exhibits some of the beat-related effects found in the cortex, it is unknown whether omissions of sounds evoke a brainstem response. We simultaneously recorded cortical and brainstem responses to isochronous and irregular sequences of consonant–vowel syllable /da/ that contained sporadic omissions. The auditory cortex responded strongly to omissions, but we found no evidence of evoked responses to omitted stimuli from the auditory brainstem. However, auditory brainstem responses in the isochronous sound sequence were more consistent across trials than in the irregular sequence. These results indicate that the auditory brainstem faithfully encodes short-term acoustic properties of a stimulus and is sensitive to sequence regularity, but does not entrain to isochronous sequences sufficiently to generate overt omission responses, even for sequences that evoke such responses in the cortex. These findings add to our understanding of the processing of sound regularities, which is an important aspect of human cognitive abilities like rhythm, music and speech perception. [ABSTRACT FROM AUTHOR]

Abstract: A three-dimensional stereotaxic atlas of the human brainstem based on high resolution ex vivo diffusion tensor imaging (DTI) is introduced. The atlas consists of high resolution (125–255μm isotropic) three-dimensional DT images of the formalin-fixed brainstem acquired at 11.7T. The DTI data revealed microscopic neuroanatomical details, allowing three-dimensional visualization and reconstruction of fiber pathways including the decussation of the pyramidal tract fibers, and interdigitating fascicles of the corticospinal and transverse pontine fibers. Additionally, strong gray-white matter contrasts in the apparent diffusion coefficient (ADC) maps enabled precise delineation of gray matter nuclei in the brainstem, including the cranial nerve and the inferior olivary nuclei. Comparison with myelin-stained histology shows that at the level of resolution achieved in this study, the structural details resolved with DTI contrasts in the brainstem were comparable to anatomical delineation obtained with histological sectioning. Major neural structures delineated from DTI contrasts in the brainstem are segmented and three-dimensionally reconstructed. Further, the ex vivo DTI data are nonlinearly mapped to a widely-used in vivo human brain atlas, to construct a high-resolution atlas of the brainstem in the Montreal Neurological Institute (MNI) stereotaxic coordinate space. The results demonstrate the feasibility of developing a 3D DTI based atlas for detailed characterization of brainstem neuroanatomy with high resolution and contrasts, which will be a useful resource for research and clinical applications. [Copyright &y& Elsevier]

The cuneiform nucleus (CN) and the pedunculopontine nucleus (PPN) in the midbrain control coordinated locomotion in vertebrates, but whether similar mechanisms exist in humans remain to be elucidated. Using functional magnetic resonance imaging, we found that simulated gait evoked activations in the CN, PPN, and other brainstem regions in humans. Brain networks were constructed for each condition using functional connectivity. Bilateral CN–PPN and the four pons–medulla regions constituted two separate modules under all motor conditions, presenting two brainstem functional units for locomotion control. Outside- and inside-brainstem nodes were connected more densely although the links between the two groups were sparse. Functional connectivity and network analysis revealed the role of brainstem circuits in dual-task walking and walking automaticity. Together, our findings indicate that the CN, PPN, and other brainstem regions participate in locomotion control in humans. [ABSTRACT FROM AUTHOR]