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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.

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Effects of pACC microstimulation on decision-making. Microstimulation (70 µA) was delivered during cue period at a single site (indicated by asterisk in Fig. 7a) in monkey S as she performed single Ap-Av (a–c) and Ap-Ap (d–f) task-sessions on consecutive days. (a, b, d, e) Left panels show scatter plots of each decision for stimulation-off (a and d) and stimulation-on (b and e) trials. Blue cross and red square indicate choice of cross and square targets, respectively. Black line indicates the session’s decision boundary estimated by logistic regression analysis. Light blue and orange lines indicate the 90% and 10% levels, respectively, for choices of cross target, estimated by the modeled data produced by the logistic regression. Right panels show the mean choices for these stimulation-off (a and d) and stimulation-on (b and e) trials, with decision boundaries shown as dotted lines (black: stimulation-off, white: stimulation-on). Data were smoothed by a square window (20% by 20% of the decision matrix). Black outlines enclose decisions with 5% to 95% probability of cross target choices. (c,f) Matrix plots of t-scores demonstrating significant stimulation-induced increase in avoidance in the Ap-Av task (c), and lack of significant stimulation effect in the Ap-Ap task (f). Region outlined in black in c indicates zone with significant effects (Fisher’s exact test, P < 0.05), which covered 16.6% of the entire data matrix.
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Figure 6: Effects of pACC microstimulation on decision-making. Microstimulation (70 µA) was delivered during cue period at a single site (indicated by asterisk in Fig. 7a) in monkey S as she performed single Ap-Av (a–c) and Ap-Ap (d–f) task-sessions on consecutive days. (a, b, d, e) Left panels show scatter plots of each decision for stimulation-off (a and d) and stimulation-on (b and e) trials. Blue cross and red square indicate choice of cross and square targets, respectively. Black line indicates the session’s decision boundary estimated by logistic regression analysis. Light blue and orange lines indicate the 90% and 10% levels, respectively, for choices of cross target, estimated by the modeled data produced by the logistic regression. Right panels show the mean choices for these stimulation-off (a and d) and stimulation-on (b and e) trials, with decision boundaries shown as dotted lines (black: stimulation-off, white: stimulation-on). Data were smoothed by a square window (20% by 20% of the decision matrix). Black outlines enclose decisions with 5% to 95% probability of cross target choices. (c,f) Matrix plots of t-scores demonstrating significant stimulation-induced increase in avoidance in the Ap-Av task (c), and lack of significant stimulation effect in the Ap-Ap task (f). Region outlined in black in c indicates zone with significant effects (Fisher’s exact test, P < 0.05), which covered 16.6% of the entire data matrix.

Mentions: The effects of the microstimulation on the monkeys’ decision-making were remarkably selective. Stimulation was effective almost exclusively during performance of the Ap-Av task, it produced almost exclusively an increase in avoidance decisions, and it produced this effect almost exclusively for stimulation applied to the ventral bank of the cingulate sulcus (Figs. 6 and 7). Fig. 6 shows the results from a single stimulation site in the ventral bank region. Compared to the stimulation-off trials (Fig. 6a), the slope of the decision boundary during the stimulation-on trials was shifted rightward, and the number of avoidance decisions was increased (Fig. 6b). To quantify the effect of the stimulation, we introduced a spatial smoothing method and used Fisher’s exact probability test (Methods). We defined effective sites as those for which stimulation changed the monkey’s decisions significantly (P < 0.05) for at least 5% of all combinations of the two cues. Microstimulation in the ventral bank of the cingulate sulcus significantly increased avoidance choices for 16.6% of all cue combinations, most strongly for those indicating high airpuff strengths (Fig. 6c). Identically applied stimulation at the same site during Ap-Ap task performance did not induce any change in decision (Fig. 6d–f).


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

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

Effects of pACC microstimulation on decision-making. Microstimulation (70 µA) was delivered during cue period at a single site (indicated by asterisk in Fig. 7a) in monkey S as she performed single Ap-Av (a–c) and Ap-Ap (d–f) task-sessions on consecutive days. (a, b, d, e) Left panels show scatter plots of each decision for stimulation-off (a and d) and stimulation-on (b and e) trials. Blue cross and red square indicate choice of cross and square targets, respectively. Black line indicates the session’s decision boundary estimated by logistic regression analysis. Light blue and orange lines indicate the 90% and 10% levels, respectively, for choices of cross target, estimated by the modeled data produced by the logistic regression. Right panels show the mean choices for these stimulation-off (a and d) and stimulation-on (b and e) trials, with decision boundaries shown as dotted lines (black: stimulation-off, white: stimulation-on). Data were smoothed by a square window (20% by 20% of the decision matrix). Black outlines enclose decisions with 5% to 95% probability of cross target choices. (c,f) Matrix plots of t-scores demonstrating significant stimulation-induced increase in avoidance in the Ap-Av task (c), and lack of significant stimulation effect in the Ap-Ap task (f). Region outlined in black in c indicates zone with significant effects (Fisher’s exact test, P < 0.05), which covered 16.6% of the entire data matrix.
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Related In: Results  -  Collection

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Figure 6: Effects of pACC microstimulation on decision-making. Microstimulation (70 µA) was delivered during cue period at a single site (indicated by asterisk in Fig. 7a) in monkey S as she performed single Ap-Av (a–c) and Ap-Ap (d–f) task-sessions on consecutive days. (a, b, d, e) Left panels show scatter plots of each decision for stimulation-off (a and d) and stimulation-on (b and e) trials. Blue cross and red square indicate choice of cross and square targets, respectively. Black line indicates the session’s decision boundary estimated by logistic regression analysis. Light blue and orange lines indicate the 90% and 10% levels, respectively, for choices of cross target, estimated by the modeled data produced by the logistic regression. Right panels show the mean choices for these stimulation-off (a and d) and stimulation-on (b and e) trials, with decision boundaries shown as dotted lines (black: stimulation-off, white: stimulation-on). Data were smoothed by a square window (20% by 20% of the decision matrix). Black outlines enclose decisions with 5% to 95% probability of cross target choices. (c,f) Matrix plots of t-scores demonstrating significant stimulation-induced increase in avoidance in the Ap-Av task (c), and lack of significant stimulation effect in the Ap-Ap task (f). Region outlined in black in c indicates zone with significant effects (Fisher’s exact test, P < 0.05), which covered 16.6% of the entire data matrix.
Mentions: The effects of the microstimulation on the monkeys’ decision-making were remarkably selective. Stimulation was effective almost exclusively during performance of the Ap-Av task, it produced almost exclusively an increase in avoidance decisions, and it produced this effect almost exclusively for stimulation applied to the ventral bank of the cingulate sulcus (Figs. 6 and 7). Fig. 6 shows the results from a single stimulation site in the ventral bank region. Compared to the stimulation-off trials (Fig. 6a), the slope of the decision boundary during the stimulation-on trials was shifted rightward, and the number of avoidance decisions was increased (Fig. 6b). To quantify the effect of the stimulation, we introduced a spatial smoothing method and used Fisher’s exact probability test (Methods). We defined effective sites as those for which stimulation changed the monkey’s decisions significantly (P < 0.05) for at least 5% of all combinations of the two cues. Microstimulation in the ventral bank of the cingulate sulcus significantly increased avoidance choices for 16.6% of all cue combinations, most strongly for those indicating high airpuff strengths (Fig. 6c). Identically applied stimulation at the same site during Ap-Ap task performance did not induce any change in decision (Fig. 6d–f).

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