A role for primate subgenual cingulate cortex in sustaining autonomic arousal

Abstract

The subgenual anterior cingulate cortex (subgenual ACC) plays an important role in regulating emotion, and degeneration in this area correlates with depressed mood and anhedonia. Despite this understanding, it remains unknown how this part of the prefrontal cortex causally contributes to emotion, especially positive emotions. Using Pavlovian conditioning procedures in macaque monkeys, we examined the contribution of the subgenual ACC to autonomic arousal associated with positive emotional events. After such conditioning, autonomic arousal increases in response to cues that predict rewards, and monkeys maintain this heightened state of arousal during an interval before reward delivery. Here we show that although monkeys with lesions of the subgenual ACC show the initial, cue-evoked arousal, they fail to sustain a high level of arousal until the anticipated reward is delivered. Control procedures showed that this impairment did not result from differences in autonomic responses to reward delivery alone, an inability to learn the association between cues and rewards, or to alterations in the light reflex. Our data indicate that the subgenual ACC may contribute to positive affect by sustaining arousal in anticipation of positive emotional events. A failure to maintain positive affect for expected pleasurable events could provide insight into the pathophysiology of psychological disorders in which negative emotions dominate a patient's affective experience.Area 25 | infralimbic | pupil size | anticipatory arousal T he ability to regulate emotion and arousal in response to pleasurable and aversive situations is essential for adapting to our environment and, ultimately, for our mental health. The anterior cingulate cortex (ACC), specifically its subgenual part, has been implicated in a number of psychiatric disorders, including major depressive disorder (1). Dysfunction and degeneration in the subgenual ACC have been reported in patients suffering from depression (2, 3), and the degree of activation in this area correlates with anhedonia, the loss of positive emotions (4). Based on these findings, new approaches for treatmentresistant depression target the subgenual ACC with deep brain stimulation (5). Determining the causal role of subgenual ACC in the regulation of affect and arousal would advance our understanding of emotional regulation and could provide insight into the pathophysiology of depression.A long history of research implicates the ACC as a whole in the control of autonomic arousal, emotional responses, and behavior (6)(7)(8). Much of what is known about the function of the ACC, however, relates to the more dorsal parts of the ACC and its role in higher cognition and arousal (9-11). Less is known about the function of the ventral ACC, especially the subgenual ACC, in part because lesions of the ventromedial prefrontal cortex often include the subgenual ACC as well as adjacent portions of orbitofrontal cortex and the dorsal ACC (12-14). Where research has focused on the primate subgenual ACC, it has emphas...

Opposing pupil responses to offered and anticipated reward values

“…This length of time was chosen because it was the shortest length of the ITI, and therefore the longest normalization window that could be applied to the beginning of all trials. This normalization method was based on previously published approaches (Geng et al, 2015; Rudebeck et al, 2014), and also served the purpose of controlling for the luminance of the tokens present on the screen (we also controlled for this possibility through checking and showing no relationship, see below). During the ITI, tokens were the only object on the screen, and they remained visible on the screen throughout each trial.…”

“…Specifically, pupil size increases in anticipation of rewards and increases more in anticipation of larger primary rewards (Rudebeck et al, 2014). The positive relationship between pupil size and anticipated rewards is also observed in anticipation of conditioned reinforcers (Rudebeck et al, 2014; Varazzani et al, 2015). These results suggest that there may be a positive relationship between pupil size and reward amount that is observed for types of rewards other than anticipated ones.…”

Using pupil size and heart rate to infer affective states during behavioral neurophysiology and neuropsychology experiments

“…The experimental aims, methods, and results of our original studies have been described in detail elsewhere (45, 46). Here we present unpublished data from these same studies to provide guidance for acquisition of autonomic measures in NHP.…”

“…Although neuroanatomical differences exist between humans and, for example, rhesus monkeys, the two species are remarkably similar when comparing autonomic responses and brain activity (e.g., (51) vs (45)). Phasic pupil responses are associated with the P300 event-related scalp potential (52), which is driven by cortical projections of the locus coeruleus norepinephrine system(53, 54).…”

“…In our recent NHP work (45, 55), we used at least one set of monochrome stimuli that are of relative equal luminance instead of generating separate color sensitivity curves. However, color sensitivity curves can be determined using random luminance modulation (40, 56).…”