Dopamine D1 and D2 Receptors Make Dissociable Contributions to Dorsolateral Prefrontal Cortical Regulation of Rule-Guided Oculomotor Behavior.
Vijayraghavan S, MAjor A,, Everling S (2016)
Cell Reports 16, 1–12
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.
In contrast to the well established macaque monkey, little is known about functional connectivity patterns of common marmoset monkey (Callithrix jacchus) that is poised to become the leading transgenic primate model. Here, we used resting-state ultra-high-field fMRI data collected from anesthetized marmosets and macaques along with awake human subjects, to examine and compare the brain's functional organization, with emphasis on the saccade system. Exploratory independent component analysis revealed eight resting-state networks in marmosets that greatly overlapped with corresponding macaque and human networks including a distributed frontoparietal network. Seed-region analyses of the superior colliculus (SC) showed homolog areas in macaques and marmosets. The marmoset SC displayed the strongest frontal functional connectivity with area 8aD at the border to area 6DR. Functional connectivity of this frontal region revealed a similar functional connectivity pattern as the frontal eye fields in macaques and humans. Furthermore, areas 8aD, 8aV, PG,TPO, TE2, and TE3 were identified as major hubs based on region-wise evaluation of betweeness centrality, suggesting that these cortical regions make up the functional core of the marmoset brain. The results support an evolutionarily preserved frontoparietal system and provide a starting point for invasive neurophysiological studies in the marmoset saccade and visual systems.
Frontoparietal Functional Connectivity in the Common Marmoset.
Ghahremani M, Hutchison RM, Menon RS, Everling S (2016) Cerebral Cortex
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 hypoth- esized 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 selec- tivity. 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.
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Unilateral Deactivation of Macaque Dorsolateral Prefrontal Cortex Induces Biases in Stimulus Selection.
Johnston K, Lomber SG, Everling S (2016) . J Neurophysiol. 115: 1468-1476