Western News article about Ramina

Last updated: 11.1.2016

Ketamine-induced changes in the signal and noise of rule representation in working memory by lateral prefrontal neurons​
Ma L, Skoblenick KS, Seamans JK, Everling S (2015).J. Neurosci. 35: 11612-11622 

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

Optimized parallel transmit and receive radiofrequency coil for ultrahigh-field MRI of monkeys.
Gilbert KM, Gati JS, Barker K, Everling S, Menon RS  (i2015) Neuroimage 125:153-161

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.

Working memory dysfunction is an especially debilitating symptom in schizophrenia. The NMDA antagonist ketamine has been successfully used to model working memory deficits in both rodents and nonhuman primates, but how it affects the strength and the consistency of working memory representations remains unclear. Here we recorded single-neuron activity in the lateral prefrontal cortex of macaque monkeys before and after the administration of subanesthetic doses of ketamine in a rule-based working memory task. The rule was instructed with a color cue before each delay period and dictated the correct prosaccadic or antisaccadic response to a peripheral stimulus appearing after the delay. We found that acute ketamine injections both weakened the rule signal across all delay periods and amplified the trial-to-trial variance in neural activities (i.e., noise), both within individual neurons and at the ensemble level, resulting in impaired performance. In the minority of postinjection trials when the animals responded correctly, the preservation of the signal strength during the delay periods was predictive of their subsequent success. Our findings suggest that NMDA receptor function may be critical for establishing the optimal signal-to-noise ratio in information representation by ensembles of prefrontal cortex neurons..

Laboratory for Neural Circuits and Cognitive Control

Recent Papers from the lab

Monkeys are a valuable model for investigating the structure and function of the brain. To attain the requisite resolution to resolve fine anatomical detail and map localized brain activation requires radiofrequency (RF) coils that produce high signal-to-noise ratios (SNRs) both spatially (image SNR) and temporally. Increasing the strength of the static magnetic field is an effective method to improve SNR, yet this comes with commensurate challenges in RF coil design. First, at ultrahigh field strengths, the magnetic field produced by a surface coil in a dielectric medium is asymmetric. In neuroimaging of rhesus macaques, this complex field pattern is compounded by the heterogeneous structure of the head. The confluence of these effects results in a non-uniform flip angle, but more markedly, a suboptimal circularly polarized mode with reduced transmit efficiency. Secondly, susceptibility-induced geometric distortions are exacerbated when performing echo-planar imaging (EPI), which is a standard technique in functional studies. This requires receive coils capable of parallel imaging with low noise amplification during image reconstruction. To address these challenges at 7T, this study presents a parallel (8-channel) transmit coil developed for monkey imaging, along with a highly parallel (24-channel) receive coil. RF shimming with the parallel-transmit coil produced significant advantages-the transmit field was 38% more uniform than a traditional circularly polarized mode and 54% more power-efficient, demonstrating that parallel-transmit coils should be used for monkey imaging at ultrahigh field strengths. The receive coil had the ability to accelerate along an arbitrary axis with at least a three-fold reduction factor, thereby reducing geometric distortions in whole-brain EPI..