Muscarinic Attenuation of Mnemonic Rule Representation in Macaque Dorsolateral Prefrontal Cortex during a Pro- and Anti-Saccade Task.
Major AJ, Vijayraghavan S, Everling S (2015).J. Neurosci. 35: 16064-16076
Unilateral Deactivation of Macaque Dorsolateral Prefrontal Cortex Induces Biases in Stimulus Selection.
Johnston K, Lomber SG, Everling S (2016) . J Neurophysiol. 115: 1468-1476
Optimized parallel transmit and receive radiofrequency coil for ultrahigh-field MRI of monkeys.
Gilbert KM, Gati JS, Barker K, Everling S, Menon RS (2015) Neuroimage 125:153-161
Following unilateral brain injury, patients are often unable to detect a stimulus presented in the contralesional field when another is presented simultaneously ipsilesionally. This phenomenon has been referred to as extinction, and conceptualized as a deficit in selective attention. Although most commonly observed following damage to posterior parietal areas, extinction has been observed following lesions of prefrontal cortex (PFC) in both humans and non-human primates. Most studies in non-human primates have examined lesions of multiple PFC subregions, including the frontal eye fields (FEF). Theoretical accounts of attentional disturbances from human patients, however, also implicate other PFC areas including the middle frontal gyrus (MFG). Here, we investigated the effects of deactivating PFC areas anterior to the FEF on stimulus selection using a free-choice task. Macaque monkeys were presented with two peripheral stimuli appearing either simultaneously, or at varying stimulus onset asynchronies, and their performance was evaluated during unilateral cryogenic deactivation of part of dorsolateral prefrontal cortex (DPC) or the cortex lining the caudal principal sulcus (cPS), the likely homologue of the human MFG. A decreased proportion of saccades was made to stimuli presented in the hemifield contralateral to the deactivated PFC. We also observed increases in reaction times to contralateral stimuli, and decreases for stimuli presented in the hemifield ipsilateral to the deactivated hemisphere. In both cases, these results were greatest when both PFC subregions were deactivated. These findings demonstrate that selection biases result from PFC deactivation, and support a role of dorsolateral prefrontal subregions anterior to FEF in stimulus selection.
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..
Maintenance of context is necessary for execution of appropriate responses to diverse environmental stimuli. The dorsolateral prefrontal cortex (DLPFC) plays a pivotal role in executive function, including working memory and representation of abstract rules. DLPFC activity is modulated by the ascending cholinergic system through nicotinic and muscarinic receptors. Although muscarinic receptors have been implicated in executive performance and gating of synaptic signals, their effect on local primate DLPFC neuronal activity in vivo during cognitive tasks remains poorly understood. Here, we examined the effects of muscarinic receptor blockade on rule-related activity in the macaque prefrontal cortex by combining iontophoretic application of the general muscarinic receptor antagonist scopolamine with single-cell recordings while monkeys performed a mnemonic rule-guided saccade task. We found that scopolamine reduced overall neuronal firing rate and impaired rule discriminability of task-selective cells. Saccade and visual direction selectivity measures were also reduced by muscarinic antagonism. These results demonstrate that blockade of muscarinic receptors in DLPFC creates deficits in working memory representation of rules in primates.
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