A ubiquitous spectrolaminar motif of local field potential power across the primate cortex.

The mammalian cerebral cortex is anatomically organized into a six-layer motif. It is currently unknown whether a corresponding laminar motif of neuronal activity patterns exists across the cortex. Here we report such a motif in the power of local field potentials (LFPs). Using laminar probes, we recorded LFPs from 14 cortical areas across the cortical hierarchy in five macaque monkeys. The laminar locations of recordings were histologically identified by electrolytic lesions. Across all areas, we found a ubiquitous spectrolaminar pattern characterized by an increasing deep-to-superficial layer gradient of high-frequency power peaking in layers 2/3 and an increasing superficial-to-deep gradient of alpha-beta power peaking in layers 5/6. Laminar recordings from additional species showed that the spectrolaminar pattern is highly preserved among primates-macaque, marmoset and human-but more dissimilar in mouse. Our results suggest the existence of a canonical layer-based and frequency-based mechanism for cortical computation.

Propofol-mediated loss of consciousness disrupts predictive routing and local field phase modulation of neural activity.

Predictive coding is a fundamental function of the cortex. The predictive routing model proposes a neurophysiological implementation for predictive coding. Predictions are fed back from deep-layer cortex via alpha/beta (8-30Hz) oscillations. They inhibit the gamma (40-100Hz) and spiking that feed sensory inputs forward. Unpredicted inputs arrive in circuits unprepared by alpha/beta, resulting in enhanced gamma and spiking. To test the predictive routing model and its role in consciousness, we collected data from intracranial recordings of macaque monkeys during passive presentation of auditory oddballs (e.g., AAAAB) before and after propofol-mediated loss of consciousness (LOC). In line with the predictive routing model, alpha/beta oscillations in the awake state served to inhibit the processing of predictable stimuli. Propofol-mediated LOC eliminated alpha/beta modulation by a predictable stimulus in sensory cortex and alpha/beta coherence between sensory and frontal areas. As a result, oddball stimuli evoked enhanced gamma power, late (> 200 ms from stimulus onset) period spiking, and superficial layer sinks in sensory cortex. Therefore, auditory cortex was in a disinhibited state during propofol-mediated LOC. However, despite these enhanced feedforward responses in auditory cortex, there was a loss of differential spiking to oddballs in higher order cortex. This may be a consequence of a loss of within-area and inter-area spike-field coupling in the alpha/beta and gamma frequency bands. These results provide strong constraints for current theories of consciousness. Significance statement: Neurophysiology studies have found alpha/beta oscillations (8-30Hz), gamma oscillations (40-100Hz), and spiking activity during cognition. Alpha/beta power has an inverse relationship with gamma power/spiking. This inverse relationship suggests that gamma/spiking are under the inhibitory control of alpha/beta. The predictive routing model hypothesizes that alpha/beta oscillations selectively inhibit (and thereby control) cortical activity that is predictable. We tested whether this inhibitory control is a signature of consciousness. We used multi-area neurophysiology recordings in monkeys presented with tone sequences that varied in predictability. We recorded brain activity as the anesthetic propofol was administered to manipulate consciousness. Compared to conscious processing, propofol-mediated unconsciousness disrupted alpha/beta inhibitory control during predictive processing. This led to a disinhibition of gamma/spiking, consistent with the predictive routing model.

Muscarinic M1 Receptor Overstimulation Disrupts Working Memory Activity for Rules in Primate Prefrontal Cortex.

Acetylcholine release in the prefrontal cortex (PFC), acting through muscarinic receptors, has an essential role in regulating flexible behavior and working memory (WM). General muscarinic receptor blockade disrupts PFC WM representations, while selective stimulation of muscarinic receptor subtypes is of great interest for the treatment of cognitive dysfunction in Alzheimer's disease. Here, we tested selective stimulation and blockade of muscarinic M1 receptors (M1Rs) in macaque PFC, during performance of a cognitive control task in which rules maintained in WM specified saccadic responses. We hypothesized that M1R blockade and stimulation would disrupt and enhance rule representation in WM, respectively. Unexpectedly, M1R blockade did not consistently affect PFC neuronal rule selectivity. Moreover, M1R stimulation suppressed PFC activity, and at higher doses, degraded rule representations. Our results suggest that, in primates, the deleterious effects of general muscarinic blockade on PFC WM activity are not mediated by M1Rs, while their overstimulation deteriorates PFC rule maintenance.

Dopamine D1 and D2 Receptors Make Dissociable Contributions to Dorsolateral Prefrontal Cortical Regulation of Rule-Guided Oculomotor Behavior.

Studies of neuromodulation of spatial short-term memory have shown that dopamine D1 receptor (D1R) stimulation in dorsolateral prefrontal cortex (DLPFC) dose-dependently modulates memory activity, whereas D2 receptors (D2Rs) selectively modulate activity related to eye movements hypothesized to encode movement feedback. We examined localized stimulation of D1Rs and D2Rs on DLPFC neurons engaged in a task involving rule representation in memory to guide appropriate eye movements toward or away from a visual stimulus. We found dissociable effects of D1R and D2R on DLPFC physiology. D1R stimulation degrades memory activity for the task rule and increases stimulus-related selectivity. In contrast, D2R stimulation affects motor activity tuning only when eye movements are made to the stimulus. Only D1R stimulation degrades task performance and increases impulsive responding. Our results suggest that D1Rs regulate rule representation and impulse control, whereas D2Rs selectively modulate eye-movement-related dynamics and not rule representation in the DLPFC.