Thin flexible arrays for long-term multi-electrode recordings in macaque primary visual cortex.

Objective.Basic, translational and clinical neuroscience are increasingly focusing on large-scale invasive recordings of neuronal activity. However, in large animals such as nonhuman primates and humans-in which the larger brain size with sulci and gyri imposes additional challenges compared to rodents, there is a huge unmet need to record from hundreds of neurons simultaneously anywhere in the brain for long periods of time. Here, we tested the electrical and mechanical properties of thin, flexible multi-electrode arrays (MEAs) inserted into the primary visual cortex of two macaque monkeys, and assessed their magnetic resonance imaging (MRI) compatibility and their capacity to record extracellular activity over a period of 1 year.Approach.To allow insertion of the floating arrays into the visual cortex, the 20 by 100µm2shafts were temporarily strengthened by means of a resorbable poly(lactic-co-glycolic acid) coating.Main results. After manual insertion of the arrays, theex vivoandin vivoMRI compatibility of the arrays proved to be excellent. We recorded clear single-unit activity from up to 50% of the electrodes, and multi-unit activity (MUA) on 60%-100% of the electrodes, which allowed detailed measurements of the receptive fields and the orientation selectivity of the neurons. Even 1 year after insertion, we obtained significant MUA responses on 70%-100% of the electrodes, while the receptive fields remained remarkably stable over the entire recording period.Significance.Thus, the thin and flexible MEAs we tested offer several crucial advantages compared to existing arrays, most notably in terms of brain tissue compliance, scalability, and brain coverage. Future brain-machine interface applications in humans may strongly benefit from this new generation of chronically implanted MEAs.

Neural effects of continuous theta-burst stimulation in macaque parietal neurons.

Theta-burst transcranial magnetic stimulation (TBS) has become a standard non-invasive technique to induce offline changes in cortical excitability in human volunteers. Yet, TBS suffers from a high variability across subjects. A better knowledge about how TBS affects neural activity in vivo could uncover its mechanisms of action and ultimately allow its mainstream use in basic science and clinical applications. To address this issue, we applied continuous TBS (cTBS, 300 pulses) in awake behaving rhesus monkeys and quantified its after-effects on neuronal activity. Overall, we observed a pronounced, long-lasting, and highly reproducible reduction in neuronal excitability after cTBS in individual parietal neurons, with some neurons also exhibiting periods of hyperexcitability during the recovery phase. These results provide the first experimental evidence of the effects of cTBS on single neurons in awake behaving monkeys, shedding new light on the reasons underlying cTBS variability.

Behavioral effects of continuous theta-burst stimulation in macaque parietal cortex.

The neural mechanisms underlying the effects of continuous Theta-Burst Stimulation (cTBS) in humans are poorly understood. Animal studies can clarify the effects of cTBS on individual neurons, but behavioral evidence is necessary to demonstrate the validity of the animal model. We investigated the behavioral effect of cTBS applied over parietal cortex in rhesus monkeys performing a visually-guided grasping task with two differently sized objects, which required either a power grip or a pad-to-side grip. We used Fitts' law, predicting shorter grasping times (GT) for large compared to small objects, to investigate cTBS effects on two different grip types. cTBS induced long-lasting object-specific and dose-dependent changes in GT that remained present for up to two hours. High-intensity cTBS increased GTs for a power grip, but shortened GTs for a pad-to-side grip. Thus, high-intensity stimulation strongly reduced the natural GT difference between objects (i.e. the Fitts' law effect). In contrast, low-intensity cTBS induced the opposite effects on GT. Modifying the coil orientation from the standard 45-degree to a 30-degree angle induced opposite cTBS effects on GT. These findings represent behavioral evidence for the validity of the nonhuman primate model to study the neural underpinnings of non-invasive brain stimulation.