Decades of research have shown that global brain states such as arousal can be indexed by measuring the properties of the eyes. The spiking responses of neurons throughout the brain have been associated with the pupil, small fixational saccades, and vigor in eye movements, but it has been difficult to isolate how internal states affect the eyes, and vice versa. While recording from populations of neurons in the visual and prefrontal cortex (PFC), we recently identified a latent dimension of neural activity called “slow drift,” which appears to reflect a shift in a global brain state. Here, we asked if slow drift is correlated with the action of the eyes in distinct behavioral tasks. We recorded from visual cortex (V4) while monkeys performed a change detection task, and PFC, while they performed a memory-guided saccade task. In both tasks, slow drift was associated with the size of the pupil and the microsaccade rate, two external indicators of the internal state of the animal. These results show that metrics related to the action of the eyes are associated with a dominant and task-independent mode of neural activity that can be accessed in the population activity of neurons across the cortex.

Long-range interactions between cortical areas are undoubtedly a key to the computational power of the brain. For healthy human subjects, the premier method for measuring brain activity on fast timescales is electroencephalography (EEG), and coherence between EEG signals is often used to assay functional connectivity between different brain regions. However, the nature of the underlying brain activity that is reflected in EEG coherence is currently the realm of speculation, because seldom have EEG signals been recorded simultaneously with intracranial recordings near cell bodies in multiple brain areas. Here, we take the early steps towards narrowing this gap in our understanding of EEG coherence by measuring local field potentials with microelectrode arrays in two brain areas (extrastriate visual area V4 and dorsolateral prefrontal cortex) simultaneously with EEG at the nearby scalp in rhesus macaque monkeys. Although we found inter-area coherence at both scales of measurement, we did not find that scalp-level coherence was reliably related to coherence between brain areas measured intracranially on a trial-to-trial basis, despite that scalp-level EEG was related to other important features of neural oscillations, such as trial-to-trial variability in overall amplitudes. This suggests that caution must be exercised when interpreting EEG coherence effects, and new theories devised about what aspects of neural activity long-range coherence in the EEG reflects.

Separating neural signals from noise can improve brain-computer interface performance and stability. However, most algorithms for separating neural action potentials from noise are not suitable for use in real time and have shown mixed effects on decoding performance. With the goal of removing noise that impedes online decoding, we sought to automate the intuition of human spike-sorters to operate in real time with an easily tunable parameter governing the stringency with which spike waveforms are classified. We trained an artificial neural network with one hidden layer on neural waveforms that were hand-labeled as either spikes or noise. The network output was a likelihood metric for each waveform it classified, and we tuned the network’s stringency by varying the minimum likelihood value for a waveform to be considered a spike. Using the network’s labels to exclude noise waveforms, we decoded remembered target location during a memory-guided saccade task from electrode arrays implanted in prefrontal cortex of rhesus macaque monkeys. The network classified waveforms in real time, and its classifications were qualitatively similar to those of a human spike-sorter. Compared with decoding with threshold crossings, in most sessions we improved decoding performance by removing waveforms with low spike likelihood values. Furthermore, decoding with our network’s classifications became more beneficial as time since array implantation increased. Our classifier serves as a feasible preprocessing step, with little risk of harm, that could be applied to both off-line neural data analyses and online decoding. NEW & NOTEWORTHY Although there are many spike-sorting methods that isolate well-defined single units, these methods typically involve human intervention and have inconsistent effects on decoding. We used human classified neural waveforms as training data to create an artificial neural network that could be tuned to separate spikes from noise that impaired decoding. We found that this network operated in real time and was suitable for both off-line data processing and online decoding.

SummaryDecades of research have shown that global brain states such as arousal can be indexed by measuring the properties of the eyes. Neural signals from individual neurons, populations of neurons, and field potentials measured throughout much of the brain have been associated with the size of the pupil, small fixational eye movements, and vigor in saccadic eye movements. However, precisely because the eyes have been associated with modulation of neural activity across the brain, and many different kinds of measurements of the eyes have been made across studies, it has been difficult to clearly isolate how internal states affect the behavior of the eyes, and vice versa. Recent work in our laboratory identified a latent dimension of neural activity in macaque visual cortex on the timescale of minutes to tens of minutes. This ‘slow drift’ was associated with perceptual performance on an orientation-change detection task, as well as neural activity in visual and prefrontal cortex (PFC), suggesting it might reflect a shift in a global brain state. This motivated us to ask if the neural signature of this internal state is correlated with the action of the eyes in different behavioral tasks. We recorded from visual cortex (V4) while monkeys performed a change detection task, and the prefrontal cortex, while they performed a memory-guided saccade task. On both tasks, slow drift was associated with a pattern that is indicative of changes in arousal level over time. When pupil size was large, and the subjects were in a heighted state of arousal, microsaccade rate and reaction time decreased while saccade velocity increased. These results show that the action of the eyes is associated with a dominant mode of neural activity that is pervasive and task-independent, and can be accessed in the population activity of neurons across the cortex.