The caudal primate prefrontal cortex (PFC) is involved in target selection and visually-guided saccades through both covert attention and overt orienting eye movements (Passingham and Wise 2012). Unilateral damage to the caudal PFC often leads to decreased awareness of a contralesional target alone, referred to as 'neglect', or when it is presented simultaneously with an ipsilesional target, referred to as 'extinction'. Here, we examined whether deficits in contralesional target selection were due to contralesional oculomotor deficits, such as slower reaction times. We experimentally-induced a focal ischemic lesion in the right caudal PFC of four male macaque monkeys using the vasoconstrictor endothelin-1 and measured saccade choice and reaction times on double stimulus free-choice and single stimulus trials before and after the lesion. We found that (1) endothelin-1-induced lesions in the caudal PFC produced contralesional target selection deficits that varied in severity and duration based on lesion volume and location; (2) contralesional neglect-like deficits were transient and recovered by week 4 post-lesion; (3) contralesional extinction-like deficits were longer lasting and recovered by weeks 8-16 post-lesion; (4) contralesional reaction time returned to baseline well before the contralesional choice deficit had recovered; and (5) neither the mean reaction times or the reaction time distributions could account for the degree of contralesional extinction on the free-choice task throughout recovery. These findings demonstrate that the saccade choice bias observed after a right caudal PFC lesion is not exclusively due to contralesional motor deficits but instead reflects a combination of impaired motor and attentional processing.

Cognitive control often requires suppression of prepotent stimulus-driven responses in favour of less potent alternatives. Suppression of prepotent saccades has been shown to require proactive inhibition in the frontoparietal saccade network. Electrophysiological evidence in macaque monkeys has revealed neural correlates of such inhibition in this network, however the interlaminar instantiation of inhibitory processes remains poorly understood as these areas lie deep within sulci in macaques, rendering them inaccessible to laminar recordings. Here we addressed this gap by exploiting the mostly lissencephalic cortex of the common marmoset (Callithrix jacchus). We inserted linear electrode arrays into areas 8Ad - the putative marmoset frontal eye field - and lateral intraparietal area (LIP) of two male marmosets, and recorded neural activity during performance of a task comprised of alternating blocks of trials requiring a saccade either toward a large, high-luminance stimulus or the inhibition of this prepotent response in favour of a saccade toward a small, low-luminance stimulus. We observed prominent task-dependent activity in both alpha/gamma bands of the local field potential and discharge rates of single neurons in area 8Ad during a prestimulus task epoch in which the animals had been instructed which of these two tasks to perform but prior to peripheral stimulus onset. These data are consistent with a model in which rhythmic alpha-band activity in deeper layers inhibits spiking in upper layers to support proactive inhibitory saccade control.

In primates, both the dorsal anterior cingulate cortex (dACC) and the dorsolateral prefrontal cortex (dlPFC) are key regions of the frontoparietal cognitive control network. To study the role of the dACC and its communication with the dlPFC in cognitive control, we recorded local field potentials (LFPs) from the dlPFC before and during the reversible deactivation of the dACC, in macaque monkeys engaging in uncued switches between 2 stimulus-response rules, namely prosaccade and antisaccade. Cryogenic dACC deactivation impaired response accuracy during maintenance of-but not the initial switching to-the cognitively demanding antisaccade rule, which coincided with a reduction in task-related theta activity and the correct-error (C-E) difference in dlPFC beta-band power. During both rule switching and maintenance, dACC deactivation prolonged the animals' reaction time and reduced task-related alpha power in the dlPFC. Our findings support a role of the dACC in prefrontal oscillatory activities that are involved the maintenance of a new, challenging task rule.

PI: Stefan EverlinG

Recent Papers from the lab

Recovery of contralesional saccade choice and reaction time deficits after a unilateral endothelin-1-induced lesion in the macaque caudal prefrontal cortex.
Adam R, Johnston K, Everling S  (2019) J Neurophysiol.

Alpha-oscillations modulate preparatory activity in marmoset area 8Ad. Johnst​on K, Ma L, Schaeffer L, Everling S (2019) J Neurosci. 2019 Jan 16. pii: 2703-18.

Laboratory for Neural Circuits and Cognitive Control

Last updated: 15.7..2019