The neurophysiological mechanisms of medial prefrontal-perirhinal cortex circuit mediating temporal order memory decline in early stage of AD rats.

The temporal component of episodic memory has been recognized as a sensitive behavioral marker in early stage of Alzheimer's disease (AD) patients. However, parallel studies in AD animals are currently lacking, and the underlying neural circuit mechanisms remain poorly understood. Using a novel AppNL-G-F knock-in (APP-KI) rat model, the developmental changes of temporal order memory (TOM) and the relationship with medial prefrontal cortex and perirhinal cortex (mPFC-PRH) circuit were determined through in vivo electrophysiology and microimaging technique. We observed a deficit in TOM performance during the object temporal order memory task (OTOMT) in APP-KI rats at 6 month old, which was not evident at 3 or 4 months of age. Alongside behavioral changes, we identified a gradually extensive and aggravated regional activation and functional alterations in the mPFC and PRH during the performance of OTOMT, which occurred prior to the onset of TOM deficits. Moreover, coherence analysis showed that the functional connectivity between the mPFC and PRH could predict the extent of future behavioral performance. Further analysis revealed that the aberrant mPFC-PRH interaction mainly attributed to the progressive deterioration of synaptic transmission, information flow and network coordination from mPFC to PRH, suggesting the mPFC dysfunction maybe the key area of origin underlying the early changes of TOM. These findings identify a pivotal role of the mPFC-PRH circuit in mediating the TOM deficits in the early stage of AD, which holds promising clinical translational value and offers potential early biological markers for predicting AD memory progression.

The Changes of Histone Methylation Induced by Adolescent Social Stress Regulate the Resting-State Activity in mPFC.

Early-life stress can lead to sustained alterations in regional resting-state brain functions, but the underlying molecular mechanism remains unclear. Stress can also induce sustained changes in epigenetic modifications across brain regions, which are not limited to a few genes; rather, they often tend to produce global levels of change. The functional implication of these changes also remains to be elucidated. We hypothesize that global epigenetic changes may partly modulate the resting-state functions of brain regions to influence behavior. To test this hypothesis, we used an adolescent social stress (ASS) model in mice and examined the relationship between epigenetic modifications and regional resting-state brain activity using resting-state functional magnetic resonance imaging (rs-fMRI). The results showed that, compared to the control mice, the stressed mice showed increased anxiety and social avoidance behaviors and greater levels of dimethylation of histone H3 at lysine 9 (H3K9me2) in the medial prefrontal cortex (mPFC). In addition, the resting-state activity represented by the amplitude of low-frequency fluctuation (ALFF) was significantly lower in the mPFC of stressed mice. To verify the relationship of H3K9me2 and ALFF, the specific inhibition of H3Kme2 was performed by using the drug UNC0642, which reversed the anxiety behavior induced by ASS and significantly increase the ALFF value of mPFC in both normal and ASS animals. Our study is the first to report an association between histone modifications and rs-fMRI findings, providing a new perspective for understanding of the significance of regional brain epigenetic changes and a possible molecular explanation for rs-fMRI findings.

Intonation trajectories within tones in unaccompanied soprano, alto, tenor, bass quartet singing.

Unlike fixed-pitch instruments, the voice requires careful regulation during each note in order to maintain a steady pitch. Previous studies have investigated aspects of singing performance such as intonation accuracy and pitch drift, treating pitch as fixed within notes, while the pitch trajectory within notes has hardly been investigated. The aim of this paper is to study pitch variation within vocal notes and ascertain what factors influence the various parts of a note. The authors recorded five soprano, alto, tenor, bass quartets singing two pieces of music in three different listening conditions, according to whether the singers can hear the other participants or not. After analysing all of the individual notes and extracting pitch over time, the authors observed the following regularities: (1) There are transient parts of approximately 120 ms duration at both the beginning and end of a note, where the pitch varies rapidly; (2) the shapes of transient parts differ significantly according to the adjacent pitch, although all singers tend to have a descending transient at the end of a note; (3) the trajectory shapes of female singers differ from those of male singers at the beginnings of notes; (4) between vocal parts, there is a tendency to expand harmonic intervals (by about 8 cents between adjacent voices); (5) the listening condition had no significant effect on within-note pitch trajectories.

Singing together: Pitch accuracy and interaction in unaccompanied unison and duet singing.

This paper investigates singing interaction by analysis of the factors influencing pitch accuracy of unaccompanied pairs of singers. Eight pairs of singers sang two excerpts either in unison or two-part harmony. The experimental condition varied which singers could hear singing partners. After semi-automatic pitch-tracking and manual checking, this paper calculated the pitch error (PE) and interval error and tested the factors of influence using a one-way analysis of variance and a linear mixed-effects model. The results indicate that: (1) singing with the same vocal part is more accurate than singing with a different vocal part; (2) singing solo has less pPE than singing with a partner; (3) PEs are correlated, as singers adjust pitch to mitigate a partner's error and preserve harmonic intervals at the expense of melodic intervals and absolute pitch; (4) other factors influence the pitch accuracy, including: score pitch, score harmonic interval, score melodic interval, musical background, vocal part, and individual differences.