Pertrubed affective processing is a defining symptom of a host of psychiatric disorders, such as depression where it is a primary symptom, and disorders where affective disturbances are secondary symptoms, for example, schizophrenia. Studies of healthy individuals and those with depressed mood implicate a network of areas centering on ventral anterior cingulate cortex (ACC) and amygdala in the control of long-term changes in affect. Despite this understanding, the neural mechanisms that generate and regulate affective experiences are unclear. One reason for this lack of clarity stems from the fact that studies of affect in animals typically only assess instantaneous and short-lived behavioral and neural responses to discrete aversive or positive stimuli. These stimuli typically last less than a second and generally belonging to a small class (e.g., juice) that are not particularly ecologically relevant. To date, no studies in non-human primates have probed the neural basis of affective states that extend over minutes or hours, durations typical of mood states in humans. Such studies would form the foundation for understanding how mood is controlled at the level of brain circuits and single neurons. The objective of this proposal is to determine how the circuit connecting ventral ACC and amygdala functions before, during, and after the induction of either negative or positive affective states in non-human primates. We hypothesize that negative and positive temporally extended affective states will be associated with unique patterns of local and circuit-level neural activity within ventral ACC and amygdala during affect induction and the selection (or regulation) of affective state. We will test our hypothesis by first determining how local and circuit level activity within ventral ACC and amygdala encodes the valence of dynamic, ecologically relevant stimuli that generate unique affective states (Aim 1). We will record both single neurons and local field potentials in both ventral ACC and amygdala and analyze the timing of the neural responses and LFP coherence among these areas to gain circuit-level understanding. Then, using a translationally- relevant affect induction technique that mirrors affect induction paradigms used in humans, we will establish how affect-related neural activity within the ventral ACC-amygdala circuit is altered when temporally extended changes in affective state, both positive and negative, are induced (Aim 2). The induction of affective state will be confirmed using both behavioral (i.e., response selection) and cardiac correlates of parasympathetic and sympathetic activity, measures of affective state that are well validated in humans. Once the neural mechanisms, the specific patterns of neural activity within the ventral ACC-amygdala circuit that control affective states are known, we anticipate being able to either increase or decrease activity in this circuit to influence affective states. This project marks a significant departure from standard approaches to studying affective non-human primates and has the potential to provide vital knowledge for treating mood disorders.
Perturbed affective processing is a defining symptom of a host of psychiatric disorders, such as depression, but the neural mechanisms that generate and regulate affective experiences are unclear, hindering the development of effective treatments. In this project, we use a translationally-relevant affect induction technique that mirrors affect induction paradigms used in humans to investigate the neural circuitry that supports affective regulation. Specifically, we will establish how affect-related neural activity within a circuit connecting ventral anterior cingulate cortex and amygdala in macaque monkeys is altered when mood-like affective states, both positive and negative, are induced.
