Disruption of corticocortical information transfer during ketamine anesthesia in the primate brain.

The neural mechanisms of anesthetic-induced unconsciousness have yet to be fully elucidated, in part because of the diverse molecular targets of anesthetic agents. We demonstrate, using intracortical recordings in macaque monkeys, that information transfer between structurally connected cortical regions is disrupted during ketamine anesthesia, despite preserved primary sensory representation. Furthermore, transfer entropy, an information-theoretic measure of directed connectivity, decreases significantly between neuronal units in the anesthetized state. This is the first direct demonstration of a general anesthetic disrupting corticocortical information transfer in the primate brain. Given past studies showing that more commonly used GABAergic drugs inhibit surrogate measures of cortical communication, this finding suggests the potential for a common network-level mechanism of anesthetic-induced unconsciousness.

Data-driven model comparing the effects of glial scarring and interface interactions on chronic neural recordings in non-human primates.

OBJECTIVE: We characterized electrode stability over twelve weeks of impedance and neural recording data from four chronically-implanted Utah arrays in two rhesus macaques, and investigated the effects of glial scarring and interface interactions at the electrode recording site on signal quality using a computational model. APPROACH: A finite-element model of a Utah array microelectrode in neural tissue was coupled with a multi-compartmental model of a neuron to quantify the effects of encapsulation thickness, encapsulation resistivity, and interface resistivity on electrode impedance and waveform amplitude. The coupled model was then reconciled with the in vivo data. Histology was obtained seventeen weeks post-implantation to measure gliosis. MAIN RESULTS: From week 1-3, mean impedance and amplitude increased at rates of 115.8 kΩ/week and 23.1 µV/week, respectively. This initial ramp up in impedance and amplitude was observed across all arrays, and is consistent with biofouling (increasing interface resistivity) and edema clearing (increasing tissue resistivity), respectively, in the model. Beyond week 3, the trends leveled out. Histology showed that thin scars formed around the electrodes. In the model, scarring could not match the in vivo data. However, a thin interface layer at the electrode tip could. Despite having a large effect on impedance, interface resistivity did not have a noticeable effect on amplitude. SIGNIFICANCE: This study suggests that scarring does not cause an electrical problem with regard to signal quality since it does not appear to be the main contributor to increasing impedance or significantly affect amplitude unless it displaces neurons. This, in turn, suggests that neural signals can be obtained reliably despite scarring as long as the recording site has sufficiently low impedance after accumulating a thin layer of biofouling. Therefore, advancements in microelectrode technology may be expedited by focusing on improvements to the recording site-tissue interface rather than elimination of the glial scar.