Implanted neural electrodes cause chronic, local inflammation that is correlated with local neurodegeneration

Abstract

Prosthetic devices that are controlled by intracortical electrodes recording one's 'thoughts' are a reality today, and no longer merely in the realm of science fiction. However, widespread clinical use of implanted electrodes is hampered by a lack of reliability in chronic recordings, independent of the type of electrodes used. One major hypothesis has been that astroglial scar electrically impedes the electrodes. However, there is a temporal discrepancy between stabilization of scar's electrical properties and recording failure with recording failure lagging by 1 month. In this study, we test a possible explanation for this discrepancy: the hypothesis that chronic inflammation, due to the persistent presence of the electrode, causes a local neurodegenerative state in the immediate vicinity of the electrode. Through modulation of chronic inflammation via stab wound, electrode geometry and age-matched control, we found that after 16 weeks, animals with an increased level of chronic inflammation were associated with increased neuronal and dendritic, but not axonal, loss. We observed increased neuronal and dendritic loss 16 weeks after implantation compared to 8 weeks after implantation, suggesting that the local neurodegenerative state is progressive. After 16 weeks, we observed axonal pathology in the form of hyperphosphorylation of the protein tau in the immediate vicinity of the microelectrodes (as observed in Alzheimer's disease and other tauopathies). The results of this study suggest that a local, late onset neurodegenerative disease-like state surrounds the chronic electrodes and is a potential cause for chronic recording failure. These results also inform strategies to enhance our capability to attain reliable long-term recordings from implantable electrodes in the CNS.

A new type of recording chamber with an easy-to-exchange microdrive array for chronic recordings in macaque monkeys

“…A challenging problem in chronic recordings is long-term stability of electrodes and recording sites, i.e., obtaining single-and multiunit activity even several months or years following implantation (Hatsopoulos and Donoghue 2009; Polikov et al 2005;Zhong and Bellamkonda 2008). Within cortical tissue, chronically implanted electrodes are likely to induce foreign body reactions like local inflammation processes (Biran et al 2005;McConnell et al 2009), encapsulation of the recording surface (Schmidt et al 1976;Szarowski et al 2003;Turner et al 1999), and formation of glial scars (Griffith and Humphrey 2006), thereby increasing electrode impedance (Grill and Mortimer 1994;Newbold et al 2004;Williams et al 2007) and the distance between electrode tips and nearby neurons (Liu et al 1999). Strategies to minimize these tissue reactions include use of biocompatible materials such as polymers (Musallam et al 2007;Rousche et al 2001;Schmidt et al 1988;Suner et al 2005) and ceramics (Moxon et al 2004;Singh et al 2003) for electrode insulation as well as coating electrodes with antiinflammatory agents (Kim and Martin 2006;Bellamkonda 2005, 2007).…”

Neural origin of evoked potentials during thalamic deep brain stimulation

“…electrode with reference to a stereotactic atlas of the cat brain (Snider and Niemer 1961) was determined from Nissl-stained sections of formalin-fixed brain samples (McConnell et al 2009). For all experiments, we verified that the ECAP was indeed a biological response by recording the neural activity at several time points after euthanasia and confirming that the ECAP was eventually abolished.…”

Soft, Flexible Freestanding Neural Stimulation and Recording Electrodes Fabricated from Reduced Graphene Oxide

“…In other words, the initial "stab wound" will heal eventually, but it is the longterm irritation, and subsequent cellular activation, at the implant site that leads to loss of the electrode-neuron interface. [10] However, 2-photon imaging has been used to show an immediate microglial response to electrode insertion whereby microglial cells extended processes toward the electrode within 30-45 minutes and began the transition to their "frustrated" phenotype (T-cell mode) after 6 hours. [11] Initial damage sends the signal for microglial activation and migration to the implantation site, which, if tissue irritation continues, progresses until microglia form the dense glial sheath that is a familiar detriment to chronic neural communication.…”