A sub-anesthetic dose of the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine is known to induce a schizophrenia-like phenotype in humans and non-human primates alike. The transient behavioural changes mimic the positive, negative, and cognitive symptoms of the disease but the neural mechanisms behind these changes are poorly understood. A growing body of evidence indicates that the cognitive control processes associated with prefrontal cortex regions relies on groups of neurons synchronizing at narrow-band burst frequencies measurable in the local field potential (LFP). Here, we recorded LFPs from the caudo-lateral prefrontal cortex of two macaque monkeys performing an anti-saccade task, which requires the suppression of an automatic saccade towards a stimulus and the initiation of a goal-directed saccade in the opposite direction. Pre-ketamine injection activity showed significant differences in a narrow 20-30 Hz beta frequency band between correct and error trials in the post-saccade response epoch. Ketamine significantly impaired the animals’ performance and was associated with a loss of the differences in outcome-specific beta-band power. Instead, we observed a large increase in high gamma-band activity. Our results suggest that the prefrontal cortex employs beta-band synchronization to prepare for top-down cognitive control of saccades and the monitoring of task outcome.

Last updated:27.8.2015

PI: Stefan EverlinG

Spontaneous brain activity is ubiquitous across brain structures and states. Determining the role of these metabolically costly intrinsic events may be critical for understanding the brain's fundamental physiological principles that govern cognition and behavior. To date, most investigations of large-scale fluctuations and their coupling have been conducted using electro- or magneto-encephalography, modalities that are limited in their ability to spatially resolve the origin of the signals. Invasive, electrophysiological local field potential (LFP) recordings are limited in their spatial range and studies combining the approach with functional imaging have been primarily relegated to sensory/motor areas with little basis in which to extrapolate findings to evolutionarily newer prefrontal cortical regions. Here, we acquired spontaneous fMRI data in two anesthetized macaque monkeys (Macaca fascicularis) at 7T together with simultaneous recordings of intracortical LFPs recorded bilaterally from the prefrontal cortex (area 9/46d). High (beta-low gamma) and low (delta-theta) band-limited power (BLP) ranges of the LFP frequencies were anticorrelated in the absence of any explicit stimuli. Beyond the high LFP-BLP signal being correlated with BOLD activity at the recording site, the high and low LFP-BLP envelopes were shown to be significantly correlated with spontaneous BOLD activity recorded from positively and negatively connected prefrontal network regions, respectively. The results suggest that complementary changes in low and high frequency bands may be an intrinsic property of LFPs, that local prefrontal cortical activity is related to spontaneous BOLD fluctuations, and further, that LFP-BLPs may be correlated at a network level.

Recent Papers from the lab

Cognitive control requires the selection and maintenance of task-relevant stimulus-response associations, or rules. The dorsolateral prefrontal cortex (DLPFC) has been implicated by lesion, functional imaging, and neurophysiological studies to be involved in encoding rules, but the mechanisms by which it modulates other brain areas are poorly understood. Here, the functional relationship of the DLPFC with the superior colliculus (SC) was investigated by bilaterally deactivating the DLPFC while recording local field potentials (LFPs) in the SC in monkeys performing an interleaved pro- and antisaccade task. Event-related LFPs showed differences between pro- and antisaccades and responded prominently to stimulus presentation. LFP power after stimulus onset was higher for correct saccades than erroneous saccades. Deactivation of the DLPFC did not affect stimulus onset related LFP activity, but reduced high beta (20-30 Hz) and high gamma (60-150 Hz) power during the preparatory period for both pro- and antisaccades. Spike rate during the preparatory period was positively correlated with gamma power and this relationship was attenuated by DLPFC deactivation. These results suggest that top-down control of the SC by the DLPFC may be mediated by beta oscillations.

Electrophysiological signatures of spontaneous BOLD fluctuations in macaque prefrontal cortex.
Hutchison RM, Hashemi N, Gati JS, Menon RS, Everling S (2015) . Neuroimage 113:257-267

Ketamine alters outcome-related local field potentials in monkey prefrontal cortex.​
Skoblenick KS, Womelsdorf T, Everling S (in press) Cerebral Cortex

Dorsolateral Prefrontal Cortex Deactivation in Monkeys Reduces Preparatory Beta and Gamma Power in the Superior Colliculus.
Chan JL, Koval MJ, Womelsdorf T, Lomber SG, Everling S.Cereb Cortex. 2014 Jul 17. pii: bhu154.

Laboratory for Neural Circuits and Cognitive Control