Background: Amnestic mild cognitive impairment (aMCI) is a heterogeneous condition. Based on clinical symptoms, aMCI could be categorized into single-domain aMCI (SD-aMCI, only memory deficit) and multi-domain aMCI (MD-aMCI, one or more cognitive domain deficit). As core intrinsic functional architecture, inter-hemispheric connectivity maintains many cognitive abilities. However, few studies investigated whether SD-aMCI and MD-aMCI have different inter-hemispheric connectivity pattern. Methods: We evaluated inter-hemispheric connection pattern using fluorine-18 positron emission tomography – fluorodeoxyglucose (¹⁸F PET-FDG), resting-state functional MRI and structural T1 in 49 controls, 32 SD-aMCI, and 32 MD-aMCI patients. Specifically, we analyzed the 18^F PET-FDG (intensity normalized by cerebellar vermis) in a voxel-wise manner. Then, we estimated inter-hemispheric functional and structural connectivity by calculating the voxel-mirrored homotopic connectivity (VMHC) and corpus callosum (CC) subregions volume. Further, we correlated inter-hemispheric indices with the behavioral score and pathological biomarkers. Results: We found that MD-aMCI exhibited more several inter-hemispheric connectivity damages than SD-aMCI. Specifically, MD-aMCI displayed hypometabolism in the bilateral middle temporal gyrus (MTG), inferior parietal lobe, and left precuneus (PCu) (p < 0.001, corrected). Correspondingly, MD-aMCI showed decreased VMHC in MTG, PCu, calcarine gyrus, and postcentral gyrus, as well as smaller mid-posterior CC than the SD-aMCI and controls (p < 0.05, corrected). Contrary to MD-aMCI, there were no neuroimaging indices with significant differences between SD-aMCI and controls, except reduced hypometabolism in bilateral MTG. Within aMCI patients, hypometabolism and reduced inter-hemispheric connectivity correlated with worse executive ability. Moreover, hypometabolism indices correlated to increased amyloid deposition. Conclusion: In conclusion, patients with MD-aMCI exhibited the more severe deficit in inter-hemispheric communication than SD-aMCI. This long-range connectivity deficit may contribute to cognitive profiles and potentially serve as a biomarker to estimate disease progression of aMCI patients.

Rapid eye movement (REM) sleep behavior disorder (RBD) could develop preceding or come after motor symptoms during Parkinson's disease (PD). It remains unknown that whether PD with different timing of RBD onset relative to motor symptoms suggests different spatiotemporal sequence of neurodegeneration. This study aimed to explore the sequence of disease progression in crucially involved brain regions in PD with different timing of RBD onset. We recruited 157 PD, 16 isolated RBD (iRBD), and 78 healthy controls. PD patients were identified as (1) PD with RBD preceding motor symptoms (PD-preRBD, n = 50), (2) PD with RBD posterior to motor symptoms (PD-postRBD, n = 31), (3) PD without RBD (PD-nonRBD, n = 75). The volumes of crucial brain regions, including the basal ganglia and limbic structures in T1-weighted imaging, and the contrast-noise-ratios of locus coeruleus (LC) and substantia nigra (SN) in neuromelanin-sensitive magnetic resonance imaging, were extracted. To simulate the sequence of disease progression for cross-sectional data, an event-based model was introduced to estimate the maximum likelihood sequence of regions' involvement for each group. Then, a statistical parameter, the Bhattacharya coefficient (BC), was used to evaluate the similarity of the sequence. The model predicted that SN occupied the highest likelihood in the maximum likelihood sequence of disease progression in the all PD subgroups, while LC was specifically positioned earlier to SN in iRBD, a prodromal phase of PD. Subsequent early involvement of LC was observed in the both PD-preRBD and PD-postRBD. In contrast, atrophy in the para-hippocampal gyrus but relatively intact LC in the early stage was demonstrated in PD-nonRBD. Then, the similarity comparisons indicated higher BC between PD-postRBD and PD-preRBD (BC = 0.76) but lower BC between PD-postRBD and PD-nonRBD group (BC = 0.41). iRBD had higher BC against PD-preRBD (BC = 0.66) and PD-postRBD (BC = 0.63) but lower BC against PD- nonRBD (BC = 0.48). The spatiotemporal sequence of neurodegeneration between PD-pre and PD-post were similar but distinct from PD-nonRBD. The presence of RBD may be the essential factor for differentiating the degeneration patterns of PD, but the timing of RBD onset has currently proved to be not.

A transparent and penetrable cranial window is essential for neuroimaging, transcranial injection and comprehensive understanding of cortical functions. For these applications, cranial windows made from glass coverslip, polydimethylsiloxane (PDMS), polymethylmethacrylate, crystal and silicone hydrogel have offered remarkable convenience. However, there is a lack of high-strength, high-transparency, penetrable cranial window with clinical application potential. We engineer high-strength hybrid Titanium-PDMS (Ti-PDMS) cranial windows, which allow large transparent area for in vivo two-photon imaging, and provide a soft window for transcranial injection. Laser scanning and 3D printing techniques are used to match the hybrid cranial window to different skull morphology. A multi-cycle degassing pouring process ensures a good combination of PDMS and Ti frame. Ti-PDMS cranial windows have a high fracture strength matching human skull bone, excellent light transmittance up to 94.4%, and refractive index close to biological tissue. Ti-PDMS cranial windows show excellent bio-compatibility during 21-week implantation in mice. Dye injection shows that the PDMS window has a “self-sealing” to keep liquid from leaking out. Two-photon imaging for brain tissues could be achieved up to 450 µm in z-depth. As a novel brain-computer-interface, this Ti-PDMS device offers an alternative choice for in vivo drug delivery, optical experiments, ultrasonic treatment and electrophysiology recording.

Monitoring the thermal responses of individual cells to external stimuli is essential for studies of cell metabolism, organelle function, and drug screening. Fluorescent temperature probes are usually employed to measure the temperatures of individual cells; however, they have some unavoidable problems, such as, poor stability caused by their sensitivity to the chemical composition of the solution and the limitation in their measurement time due to the short fluorescence lifetime. Here, we demonstrate a stable, non-interventional, and high-precision temperature-measurement chip that can monitor the temperature fluctuations of individual cells subject to external stimuli and over a normal cell life cycle as long as several days. To improve the temperature resolution, we designed temperature sensors made of Pd–Cr thin-film thermocouples, a freestanding Si₃N₄ platform, and a dual-temperature control system. Our experimental results confirm the feasibility of using this cellular temperature-measurement chip to detect local temperature fluctuations of individual cells that are 0.3–1.5 K higher than the ambient temperature for HeLa cells in different proliferation cycles. In the future, we plan to integrate this chip with other single-cell technologies and apply it to research related to cellular heat-stress response.

Temperature is a significant factor in determining and characterizing cellular metabolism and other biochemical activities. In this study, we provide a brief overview of two important technologies used to monitor the local temperatures of individual living cells: fluorescence nano-thermometry and an array of micro-/nano-sized thin-film thermocouples. We explain some key technical issues that must be addressed and optimised for further practical applications, such as in cell biology, drug selection, and novel antitumor therapy. We also offer a method for combining them into a hybrid measuring system.

We review the experimental and computational data about the propagation of neural signals in myelinated axons in mice, cats, rabbits, and frogs published in the past five decades. In contrast to the natural assumption that neural signals occur one by one in time and in space, we figure out that neural signals are highly overlapped in time between neighboring nodes. This phenomenon was occasionally illustrated in some early reports, but seemed to have been overlooked for some time. The shift in time between two successive neural signals from neighboring nodes, defined as relay time τ, was calculated to be only 16.3 μs–87.0 μs, i.e., 0.8 %–4.4 % of the average duration of an action potential peak (roughly 2 ms). We present a clearer picture of the exact physical process about how the information transmits along a myelinated axon, rather than a whole action potential peak, what is transmitted is only a rising electric field caused by transmembrane ion flows. Here in the paper, τ represents the waiting time until the neighboring node senses an attenuated electric field reaching the threshold to trigger the open state. The mechanisms addressed in this work have the potential to be universal, and may hold clues to revealing the exact triggering processes of voltage-gated ion channels and various brain functions.