UC Davis

Despite many observations of anterior cingulate cortex (ACC) activity related to cognition and affect in humans and nonhuman animals, little is known about the causal role of the ACC in psychological processes. Here, we investigate the causal role of the ACC in affective responding to threat in rhesus monkeys (Macaca mulatta), a species with an ACC largely homologous to humans in structure and connectivity. Male adult monkeys received bilateral ibotenate axon-sparing lesions to the ACC (sulcus and gyrus of areas 24, 32, and 25) and were tested in two classic tasks of monkey threat processing: the human intruder and object responsiveness tasks. Monkeys with ACC lesions did not significantly differ from controls in their overall mean reactivity toward threatening or novel stimuli. However, while control monkeys maintained their reactivity across test days, monkeys with ACC lesions reduced their reactivity toward stimuli as days advanced. Critically, this attenuated reactivity was found even when the stimuli presented each day were novel, suggesting that ACC lesions did not simply cause accelerated adaptation to stimuli as they became less novel over repeated presentations. Rather, these results imply that the primate ACC is necessary for maintaining appropriate affective responses toward potentially harmful and/or novel stimuli. These findings therefore have implications for mood disorders in which responding to threat and novelty is disrupted.SIGNIFICANCE STATEMENT Decades of research in humans and nonhuman animals have investigated the role of the anterior cingulate cortex in a huge number and variety of psychological processes spanning cognition and affect, as well as in psychological and neurologic diseases. The structure is broadly implicated in psychological processes and mental and neurologic health, yet its causal role in these processes has largely gone untested, particularly in primates. Here we demonstrate that when anterior cingulate cortex is completely eliminated, rhesus monkeys are initially responsive to threats, but these responses attenuate rather than persist, resembling a pattern of behavior commonly seen in patients diagnosed with mood disorders.