Through-polymer,via technology-enabled,flexible,lightweight,and integrated devices for implantable neural probes

In implantable electrophysiological recording systems,the headstage typically comprises neural probes that interface with brain tissue and integrated circuit chips for signal processing.While advancements in MEMS and CMOS technology have significantly improved these components,their interconnection still relies on conventional printed circuit boards and sophisticated adapters.This conventional approach adds considerable weight and volume to the package,especially for high channel count systems.To address this issue,we developed a through-polymer via(TPV)method inspired by the through-silicon via(TSV)technique in advanced three-dimensional packaging.This innovation enables the vertical integration of flexible probes,amplifier chips,and PCBs,realizing a flexible,lightweight,and integrated device(FLID).The total weight of the FLIDis only 25%that of its conventional counterparts relying on adapters,which significantly increased the activity levels of animals wearing the FLIDs to nearly match the levels of control animals without implants.Furthermore,by incorporating a platinum-iridium alloy as the top layer material for electrical contact,the FLID realizes exceptional electrical performance,enabling in vivo measurements of both local field potentials and individual neuron action potentials.These findings showcase the potential of FLIDs in scaling up implantable neural recording systems and mark a significant advancement in the field of neurotechnology.

Dynamic Organization of Large-scale Functional Brain Networks Supports Interactions Between Emotion and Executive Control

Emotion and executive control are often conceptualized as two distinct modes of human brain functioning.Little,however,is known about how the dynamic organization of large-scale functional brain networks that support flexible emotion processing and executive control,especially their interactions.The amygdala and prefrontal systems have long been thought to play crucial roles in these processes.Recent advances in human neuroimaging studies have begun to delineate functional organization principles among the large-scale brain networks underlying emotion,executive control,and their interactions.Here,we propose a dynamic brain network model to account for interactive competition between emotion and executive control by reviewing recent resting-state and task-related neuroimaging studies using network-based approaches.In this model,dynamic interactions among the executive control network,the salience network,the default mode network,and sensorimotor networks enable dynamic processes of emotion and support flexible executive control of multiple processes;neural oscillations across multiple frequency bands and the locus coeruleus−norepinephrine pathway serve as communicational mechanisms underlying dynamic synergy among large-scale functional brain networks.This model has important implications for understanding how the dynamic organization of complex brain systems and networks empowers flexible cognitive and affective functions.

MAL2 DNA methylation serves as a biomarker for the diagnosis and prognosis of glioma

Glioma is a common and malignant brain tumor,and molecular diagnostics for glioma have received increasing attention.1,2 Previous studies have suggested that the MAL2 gene may be involved in the transcytosis of various cancers.3 This study aimed to investigate the potential of MAL2 as a biomarker for glioma.The candidate MAL2 CpG sites were validated by pyrosequencing and used to construct a diagnostic model for glioma.Survival analysis was also conducted to determine the relationship between highly methylated MAL2-specific CpG sites and the prognosis of glioma.The findings also showed that MAL2 was more highly methylated in glioma than in other cancers.The constructed diagnostic model can distinguish glioma from other cancers with high sensitivity(93.3%)and specificity(86.5%).Additionally,a risk score model was built based on MAL2 methylation to assess the prognosis of glioma。

Microglia modulation with 1070-nm light attenuates Aβ burden and cognitive impairment in Alzheimer’s disease mouse model

Photobiomodulation,by utilizing low-power light in the visible and near-infrared spectra to trigger biological responses in cells and tissues,has been considered as a possible therapeutic strategy for Alzheimer’s disease(AD),while its specific mechanisms have remained elusive.Here,we demonstrate that cognitive and memory impairment in an AD mouse model can be ameliorated by 1070-nm light via reducing cerebralβ-amyloid(Aβ)burden,the hallmark of AD.The glial cells,including microglia and astrocytes,play important roles in Aβclearance.Our results show that 1070-nm light pulsed at 10 Hz triggers microglia rather than astrocyte responses in AD mice.The 1070-nm lightinduced microglia responses with alteration in morphology and increased colocalization with Aβare sufficient to reduce Aβload in AD mice.Moreover,1070-nm light pulsed at 10 Hz can reduce perivascular microglia and promote angiogenesis to further enhance Aβclearance.Our study confirms the important roles of microglia and cerebral vessels in the use of 1070-nm light for the treatment of AD mice and provides a framework for developing a novel therapeutic approach for AD.

A mosquito mouthpart-like bionic neural probe

Advancements in microscale electrode technology have revolutionized the field of neuroscience and clinicalapplications by offering high temporal and spatial resolution of recording and stimulation. Flexible neural probes, withtheir mechanical compliance to brain tissue, have been shown to be superior to rigid devices in terms of stability andlongevity in chronic recordings. Shuttle devices are commonly used to assist flexible probe implantation;however, theprotective membrane of the brain still makes penetration difficult. Hidden damage to brain vessels duringimplantation is a significant risk. Inspired by the anatomy of the mosquito mouthparts, we present a biomimeticneuroprobe system that integrates high-sensitivity sensors with a high-fidelity multichannel flexible electrode array.This customizable system achieves distributed and minimally invasive implantation across brain regions. Mostimportantly, the system’s nonvisual monitoring capability provides an early warning detection for intracranial softtissues, such as vessels, reducing the potential for injury during implantation. The neural probe system demonstratesexceptional sensitivity and adaptability to environmental stimuli, as well as outstanding performance in postoperativeand chronic recordings. These findings suggest that our biomimetic neural-probe device offers promising potential forfuture applications in neuroscience and brain-machine interfaces.

A silk-based self-adaptive flexible opto-electro neural probe

The combination of optogenetics and electrophysiological recording enables high-precision bidirectional interactions between neural interfaces and neural circuits,which provides a promising approach for the study of progressive neurophysiological phenomena.Opto-electrophysiological neural probes with sufficient flexibility and biocompatibility are desirable to match the low mechanical stiffness of brain tissue for chronic reliable performance.However,lack of rigidity poses challenges for the accurate implantation of flexible neural probes with less invasiveness.Herein,we report a hybrid probe(Silk-Optrode)consisting of a silk protein optical fiber and multiple flexible microelectrode arrays.The Silk-Optrode can be accurately inserted into the brain and perform synchronized optogenetic stimulation and multichannel recording in freely behaving animals.Silk plays an important role due to its high transparency,excellent biocompatibility,and mechanical controllability.Through the hydration of the silk optical fiber,the Silk-Optrode probe enables itself to actively adapt to the environment after implantation and reduce its own mechanical stiffness to implant into the brain with high fidelity while maintaining mechanical compliance with the surrounding tissue.The probes with 128 recording channels can detect high-yield well-isolated single units while performing intracranial light stimulation with low optical losses,surpassing previous work of a similar type.Two months of post-surgery results suggested that as-reported Silk-Optrode probes exhibit better implant-neural interfaces with less immunoreactive glial responses and tissue lesions.