Intracortical microelectrode arrays (MEAs) are tools for recording and stimulating neural activity, with potential applications in prosthetic control and treatment of neurological disorders. However, when chronically implanted, the long-term functionality of MEAs is hindered by the foreign body response (FBR), characterized by gliosis, neuronal loss, and the formation of a glial scar encapsulating layer. This response begins immediately after implantation and is exacerbated by factors such as brain micromotion and the mechanical mismatch between stiff electrodes and soft brain tissue, leading to signal degradation. Despite progress in mitigating these issues, the underlying mechanisms of the brain’s response to MEA implantation remain unclear, particularly regarding how cells sense and respond to the associated mechanical forces. Mechanosensitive ion channels, such as the Piezo family, are key mediators of cellular responses to mechanical stimuli. In this study, silicon-based NeuroNexus MEAs consisting of four shanks were implanted in the rat somatosensory cortex for sixteen weeks. Weekly neural recordings were conducted to assess signal quality over time, revealing a decline in active electrode yield and signal amplitude. Immunohistochemical analysis showed an increase in GFAP intensity and decreased neuronal density near the implant site. Furthermore, Piezo1—but not Piezo2—was strongly expressed in GFAP-positive astrocytes within 25 µm of the implant. Piezo2 expression appeared relatively uniform within each brain slice, both in and around the MEA implantation site across cortical layers. Our study builds on previous work by demonstrating a potential role of Piezo1 in the chronic FBR induced by MEA implantation over a 16-week period. Our findings highlight Piezo1 as the primary mechanosensitive channel driving chronic FBR, suggesting it may be a target for improving MEA design and long-term functionality.

Ruthenium oxide has emerged as a promising electrode coating material for intracortical microstimulation applications due to its favorable electrochemical properties. However, its long-term in vivo stimulation performance has not been well characterized. Using a go/no-go behavioral paradigm, we show that ruthenium oxide-coated microelectrode arrays support functionally relevant intracortical microstimulation-induced percepts for up to 25 wk postimplantation in rat somatosensory cortex, highlighting stable electrochemical properties and the utility of ruthenium oxide for chronic applications.

This study reveals that locomotion speed is encoded in mouse primary motor cortex through a sigmoidal state-transition mechanism carried by two functionally distinct spiking populations with a shared speed threshold. Using high-density laminar recordings and markerless motion tracking, we show that this framework extends to local field potentials and enables accurate, generalizable decoding. These findings establish a push-pull sigmoidal architecture and highlight implications for stable, calibration-light brain-machine interface design.

Rett syndrome is a neurodevelopmental disorder caused by mutations in the X-linked transcriptional regulator MECP2, which causes widespread abnormalities in cortical network activity and sensory processing. In rodent models, Mecp2^+/- rats recapitulate key clinical features of Rett syndrome, including disrupted auditory cortical responses and impaired spike timing fidelity. Given its potential to normalize abnormal cortical activity, vagus nerve stimulation (VNS) may offer a promising therapeutic approach. This study examined auditory local field potential (LFP) responses in Mecp2^+/- rats and assesses the modulatory effects of VNS. Auditory cortical LFPs were recorded in response to speech, noise, and tone stimuli in Mecp2^+/- rats, VNS-treated Mecp2^+/- rats, and wild-type littermates. LFP component latency, amplitude, trial-to-trial variability, and oscillatory band power were quantitatively analyzed across groups. Mecp2^+/- rats were characterized by delayed and weakened LFP responses, widespread increases in trial-to-trial variability of latency, amplitude, and power, and stimulus-dependent changes in spectral power, with the most pronounced abnormalities for speech, followed by tones and then noise. VNS partially normalized these abnormalities by improving speech-evoked latency and variability and reducing noise-evoked power variability. However, tone-evoked responses were largely unchanged with VNS, indicating a selective rescue of specific components and stimulus classes rather than a global restoration of auditory function. These findings demonstrate robust auditory cortical processing deficits in a preclinical model of Rett syndrome and highlight the potential of VNS to partially restore cortical function. The results support further development of targeted neuromodulatory interventions to ameliorate sensory processing abnormalities in Rett syndrome.