Limits...
Localized microstimulation of primate pregenual cingulate cortex induces negative decision-making.

Amemori K, Graybiel AM - Nat. Neurosci. (2012)

Bottom Line: In healthy individuals, the pACC is involved in cost-benefit evaluation.We found that the macaque pACC has an opponent process-like organization of neurons representing motivationally positive and negative subjective value.This cortical zone could be critical for regulating negative emotional valence and anxiety in decision-making.

View Article: PubMed Central - PubMed

Affiliation: McGovern Institute for Brain Research, and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

ABSTRACT
The pregenual anterior cingulate cortex (pACC) has been implicated in human anxiety disorders and depression, but the circuit-level mechanisms underlying these disorders are unclear. In healthy individuals, the pACC is involved in cost-benefit evaluation. We developed a macaque version of an approach-avoidance decision task used to evaluate anxiety and depression in humans and, with multi-electrode recording and cortical microstimulation, we probed pACC function as monkeys performed this task. We found that the macaque pACC has an opponent process-like organization of neurons representing motivationally positive and negative subjective value. Spatial distribution of these two neuronal populations overlapped in the pACC, except in one subzone, where neurons with negative coding were more numerous. Notably, microstimulation in this subzone, but not elsewhere in the pACC, increased negative decision-making, and this negative biasing was blocked by anti-anxiety drug treatment. This cortical zone could be critical for regulating negative emotional valence and anxiety in decision-making.

Show MeSH

Related in: MedlinePlus

Evidence suggesting potential negative affective state changes induced by microstimulation. (a) Effects of the anxiolytic, diazepam (0.25 mg/kg, IM), on the stimulation-induced change in the approach-avoidance decisions. Orange lines indicate the results of stimulation at site previously identified as an effective site A (square terminals: 80 µA, 2 sessions; circle terminals: 150 µA, 1 session) before and after diazepam treatment. Black line shows the result of diazepam treatment at ineffective site B, where stimulation (80 µA) did not induce a change in decision. Locations of sites A and B are shown in b. (b) Percent changes in the cost-benefit ratio defined by the ratio of sensitivities to offered airpuff and offered reward. The two sensitivities were derived from coefficients of the logistic behavioral model. Left panel: Ap-Av task (red-orange hues, increased sensitivity to aversive airpuff relative to reward; blue hues, increased sensitivity to reward relative to airpuff; black, no effect). Right panel: Ap-Ap task (yellow, increase in placing more value in square target; black, no effect).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3369110&req=5

Figure 8: Evidence suggesting potential negative affective state changes induced by microstimulation. (a) Effects of the anxiolytic, diazepam (0.25 mg/kg, IM), on the stimulation-induced change in the approach-avoidance decisions. Orange lines indicate the results of stimulation at site previously identified as an effective site A (square terminals: 80 µA, 2 sessions; circle terminals: 150 µA, 1 session) before and after diazepam treatment. Black line shows the result of diazepam treatment at ineffective site B, where stimulation (80 µA) did not induce a change in decision. Locations of sites A and B are shown in b. (b) Percent changes in the cost-benefit ratio defined by the ratio of sensitivities to offered airpuff and offered reward. The two sensitivities were derived from coefficients of the logistic behavioral model. Left panel: Ap-Av task (red-orange hues, increased sensitivity to aversive airpuff relative to reward; blue hues, increased sensitivity to reward relative to airpuff; black, no effect). Right panel: Ap-Ap task (yellow, increase in placing more value in square target; black, no effect).

Mentions: These results in turn raised the possibility that such a persistent state could be influenced by anxiolytic treatment. We tested this possibility in another set of experiments by asking whether anxiolytics could reduce the stimulation effects (Fig. 8a). We divided Ap-Av sessions into three successive 200-trial blocks: stimulation-off, stimulation-on and stimulation-on after drug administration. Between the second and third blocks, we administered the anxiolytic, diazepam (0.25 mg/kg, IM). We represented the effect of microstimulation by the change in the decision matrix between the first and second blocks (Fisher’s exact test, P < 0.05), and the effect of stimulation plus drug by the change in decision between the first and third blocks. In two experiments, we stimulated an effective ventral bank site with 80 µA current (site A; orange lines with square terminals in Fig. 8a; location marked in Fig. 8b). We consistently observed an increase in avoidance decisions, especially for high-conflict regions, and in each session, this stimulation effect was fully blocked by the diazepam administration. In a third experiment (Supplementary Fig. 13), we stimulated the same site with a higher current amplitude (150 µA), and obtained a larger effect of the microstimulation. This effect was not only blocked by the anxiolytic, but reversed: now the microstimulation produced increased approach decisions (Fig. 8a, orange line with circle terminals). Finally, in a fourth experiment, we stimulated at a site previously identified as non-effective (80 µA; site B; location marked in Fig. 8b). We found no change in the monkey’s decisions (black line in Fig. 8a), but confirmed an increase in approach by diazepam administration.


Localized microstimulation of primate pregenual cingulate cortex induces negative decision-making.

Amemori K, Graybiel AM - Nat. Neurosci. (2012)

Evidence suggesting potential negative affective state changes induced by microstimulation. (a) Effects of the anxiolytic, diazepam (0.25 mg/kg, IM), on the stimulation-induced change in the approach-avoidance decisions. Orange lines indicate the results of stimulation at site previously identified as an effective site A (square terminals: 80 µA, 2 sessions; circle terminals: 150 µA, 1 session) before and after diazepam treatment. Black line shows the result of diazepam treatment at ineffective site B, where stimulation (80 µA) did not induce a change in decision. Locations of sites A and B are shown in b. (b) Percent changes in the cost-benefit ratio defined by the ratio of sensitivities to offered airpuff and offered reward. The two sensitivities were derived from coefficients of the logistic behavioral model. Left panel: Ap-Av task (red-orange hues, increased sensitivity to aversive airpuff relative to reward; blue hues, increased sensitivity to reward relative to airpuff; black, no effect). Right panel: Ap-Ap task (yellow, increase in placing more value in square target; black, no effect).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3369110&req=5

Figure 8: Evidence suggesting potential negative affective state changes induced by microstimulation. (a) Effects of the anxiolytic, diazepam (0.25 mg/kg, IM), on the stimulation-induced change in the approach-avoidance decisions. Orange lines indicate the results of stimulation at site previously identified as an effective site A (square terminals: 80 µA, 2 sessions; circle terminals: 150 µA, 1 session) before and after diazepam treatment. Black line shows the result of diazepam treatment at ineffective site B, where stimulation (80 µA) did not induce a change in decision. Locations of sites A and B are shown in b. (b) Percent changes in the cost-benefit ratio defined by the ratio of sensitivities to offered airpuff and offered reward. The two sensitivities were derived from coefficients of the logistic behavioral model. Left panel: Ap-Av task (red-orange hues, increased sensitivity to aversive airpuff relative to reward; blue hues, increased sensitivity to reward relative to airpuff; black, no effect). Right panel: Ap-Ap task (yellow, increase in placing more value in square target; black, no effect).
Mentions: These results in turn raised the possibility that such a persistent state could be influenced by anxiolytic treatment. We tested this possibility in another set of experiments by asking whether anxiolytics could reduce the stimulation effects (Fig. 8a). We divided Ap-Av sessions into three successive 200-trial blocks: stimulation-off, stimulation-on and stimulation-on after drug administration. Between the second and third blocks, we administered the anxiolytic, diazepam (0.25 mg/kg, IM). We represented the effect of microstimulation by the change in the decision matrix between the first and second blocks (Fisher’s exact test, P < 0.05), and the effect of stimulation plus drug by the change in decision between the first and third blocks. In two experiments, we stimulated an effective ventral bank site with 80 µA current (site A; orange lines with square terminals in Fig. 8a; location marked in Fig. 8b). We consistently observed an increase in avoidance decisions, especially for high-conflict regions, and in each session, this stimulation effect was fully blocked by the diazepam administration. In a third experiment (Supplementary Fig. 13), we stimulated the same site with a higher current amplitude (150 µA), and obtained a larger effect of the microstimulation. This effect was not only blocked by the anxiolytic, but reversed: now the microstimulation produced increased approach decisions (Fig. 8a, orange line with circle terminals). Finally, in a fourth experiment, we stimulated at a site previously identified as non-effective (80 µA; site B; location marked in Fig. 8b). We found no change in the monkey’s decisions (black line in Fig. 8a), but confirmed an increase in approach by diazepam administration.

Bottom Line: In healthy individuals, the pACC is involved in cost-benefit evaluation.We found that the macaque pACC has an opponent process-like organization of neurons representing motivationally positive and negative subjective value.This cortical zone could be critical for regulating negative emotional valence and anxiety in decision-making.

View Article: PubMed Central - PubMed

Affiliation: McGovern Institute for Brain Research, and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

ABSTRACT
The pregenual anterior cingulate cortex (pACC) has been implicated in human anxiety disorders and depression, but the circuit-level mechanisms underlying these disorders are unclear. In healthy individuals, the pACC is involved in cost-benefit evaluation. We developed a macaque version of an approach-avoidance decision task used to evaluate anxiety and depression in humans and, with multi-electrode recording and cortical microstimulation, we probed pACC function as monkeys performed this task. We found that the macaque pACC has an opponent process-like organization of neurons representing motivationally positive and negative subjective value. Spatial distribution of these two neuronal populations overlapped in the pACC, except in one subzone, where neurons with negative coding were more numerous. Notably, microstimulation in this subzone, but not elsewhere in the pACC, increased negative decision-making, and this negative biasing was blocked by anti-anxiety drug treatment. This cortical zone could be critical for regulating negative emotional valence and anxiety in decision-making.

Show MeSH
Related in: MedlinePlus