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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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Task procedures and recording regions. (a) Task flow diagram of the approach-avoidance (Ap-Av) task. The task started when the monkey put the hand on the home position. After 1.5-s fixation period, two bars appeared on the screen as a visual cue. The lengths of red and yellow bars indicated, respectively, the amount of liquified food and airpuff delivered after approach choice. After the 1.5-s cue period, the monkey could move the joystick to choose one target. Cross target indicated approach, and square target indicated avoidance. The locations of two targets were randomized across trials. After approach decisions, both airpuff and food were delivered in the indicated amounts. After avoidance decision, the monkey did not receive the indicated airpuff and food. (b) Task flow diagram of the approach-approach (Ap-Ap) task. The lengths of red and yellow bars corresponded to the amount of reward that the monkey could obtain after choosing cross and square targets, respectively. (c) Stimulation procedure. Daily sessions consisted of stimulation-off and stimulation-on blocks, each with 250 trials. In stimulation-on trials, microstimulation (a train of biphasic pluses; frequency: 200 Hz, current amplitude: 70–80µA) was applied for 1 s, starting at the onset of the visual cue. (d) Sagittal (left) and coronal (right) magnetic resonance images of the pregenual recording region. Red lines indicate estimated tracks of recording and stimulation electrodes ranging from AP 32 to AP 36. To the right, a schematic diagram of the pACC is shown with cingulate sulcus (Cgs).
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Figure 1: Task procedures and recording regions. (a) Task flow diagram of the approach-avoidance (Ap-Av) task. The task started when the monkey put the hand on the home position. After 1.5-s fixation period, two bars appeared on the screen as a visual cue. The lengths of red and yellow bars indicated, respectively, the amount of liquified food and airpuff delivered after approach choice. After the 1.5-s cue period, the monkey could move the joystick to choose one target. Cross target indicated approach, and square target indicated avoidance. The locations of two targets were randomized across trials. After approach decisions, both airpuff and food were delivered in the indicated amounts. After avoidance decision, the monkey did not receive the indicated airpuff and food. (b) Task flow diagram of the approach-approach (Ap-Ap) task. The lengths of red and yellow bars corresponded to the amount of reward that the monkey could obtain after choosing cross and square targets, respectively. (c) Stimulation procedure. Daily sessions consisted of stimulation-off and stimulation-on blocks, each with 250 trials. In stimulation-on trials, microstimulation (a train of biphasic pluses; frequency: 200 Hz, current amplitude: 70–80µA) was applied for 1 s, starting at the onset of the visual cue. (d) Sagittal (left) and coronal (right) magnetic resonance images of the pregenual recording region. Red lines indicate estimated tracks of recording and stimulation electrodes ranging from AP 32 to AP 36. To the right, a schematic diagram of the pACC is shown with cingulate sulcus (Cgs).

Mentions: We first recorded behavior and neural spike activity in the pACC in two macaque monkeys (S and A) as they performed a novel approach-avoidance (Ap-Av) task in which they made decisions to approach or to avoid combinations of positive (food) and negative (airpuff) outcomes cued in advance by visual stimuli during a decision period (Fig. 1a; Methods). The monkeys looked at a cue composed of contiguous red and yellow bars whose lengths linearly corresponded to the amount of food (red bar) and the strength of the airpuff (yellow bar) that would be delivered at the end of the trial. They could then choose to approach or to avoid the combinations by moving a cursor. After approach decisions, both food and airpuff were delivered in the indicated amounts. After avoidance decisions, the monkeys did not receive the indicated food and airpuff, but only a standard minimum food amount, necessary to maintain motivation to perform the task.


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

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

Task procedures and recording regions. (a) Task flow diagram of the approach-avoidance (Ap-Av) task. The task started when the monkey put the hand on the home position. After 1.5-s fixation period, two bars appeared on the screen as a visual cue. The lengths of red and yellow bars indicated, respectively, the amount of liquified food and airpuff delivered after approach choice. After the 1.5-s cue period, the monkey could move the joystick to choose one target. Cross target indicated approach, and square target indicated avoidance. The locations of two targets were randomized across trials. After approach decisions, both airpuff and food were delivered in the indicated amounts. After avoidance decision, the monkey did not receive the indicated airpuff and food. (b) Task flow diagram of the approach-approach (Ap-Ap) task. The lengths of red and yellow bars corresponded to the amount of reward that the monkey could obtain after choosing cross and square targets, respectively. (c) Stimulation procedure. Daily sessions consisted of stimulation-off and stimulation-on blocks, each with 250 trials. In stimulation-on trials, microstimulation (a train of biphasic pluses; frequency: 200 Hz, current amplitude: 70–80µA) was applied for 1 s, starting at the onset of the visual cue. (d) Sagittal (left) and coronal (right) magnetic resonance images of the pregenual recording region. Red lines indicate estimated tracks of recording and stimulation electrodes ranging from AP 32 to AP 36. To the right, a schematic diagram of the pACC is shown with cingulate sulcus (Cgs).
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Related In: Results  -  Collection

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Figure 1: Task procedures and recording regions. (a) Task flow diagram of the approach-avoidance (Ap-Av) task. The task started when the monkey put the hand on the home position. After 1.5-s fixation period, two bars appeared on the screen as a visual cue. The lengths of red and yellow bars indicated, respectively, the amount of liquified food and airpuff delivered after approach choice. After the 1.5-s cue period, the monkey could move the joystick to choose one target. Cross target indicated approach, and square target indicated avoidance. The locations of two targets were randomized across trials. After approach decisions, both airpuff and food were delivered in the indicated amounts. After avoidance decision, the monkey did not receive the indicated airpuff and food. (b) Task flow diagram of the approach-approach (Ap-Ap) task. The lengths of red and yellow bars corresponded to the amount of reward that the monkey could obtain after choosing cross and square targets, respectively. (c) Stimulation procedure. Daily sessions consisted of stimulation-off and stimulation-on blocks, each with 250 trials. In stimulation-on trials, microstimulation (a train of biphasic pluses; frequency: 200 Hz, current amplitude: 70–80µA) was applied for 1 s, starting at the onset of the visual cue. (d) Sagittal (left) and coronal (right) magnetic resonance images of the pregenual recording region. Red lines indicate estimated tracks of recording and stimulation electrodes ranging from AP 32 to AP 36. To the right, a schematic diagram of the pACC is shown with cingulate sulcus (Cgs).
Mentions: We first recorded behavior and neural spike activity in the pACC in two macaque monkeys (S and A) as they performed a novel approach-avoidance (Ap-Av) task in which they made decisions to approach or to avoid combinations of positive (food) and negative (airpuff) outcomes cued in advance by visual stimuli during a decision period (Fig. 1a; Methods). The monkeys looked at a cue composed of contiguous red and yellow bars whose lengths linearly corresponded to the amount of food (red bar) and the strength of the airpuff (yellow bar) that would be delivered at the end of the trial. They could then choose to approach or to avoid the combinations by moving a cursor. After approach decisions, both food and airpuff were delivered in the indicated amounts. After avoidance decisions, the monkeys did not receive the indicated food and airpuff, but only a standard minimum food amount, necessary to maintain motivation to perform the task.

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