Motivation and Affective Judgments Differentially Recruit Neurons in the Primate Dorsolateral Prefrontal and Anterior Cingulate Cortex

The judgment of whether to accept or to reject an offer is determined by positive and negative affect related to the offer, but affect also induces motivational responses. Rewarding and aversive cues influence the firing rates of many neurons in primate prefrontal and cingulate neocortical regions, but it still is unclear whether neurons in these regions are related to affective judgment or to motivation. To address this issue, we recorded simultaneously the neuronal spike activities of single units in the dorsolateral prefrontal cortex (dlPFC) and the anterior cingulate cortex (ACC) of macaque monkeys as they performed approach–avoidance (Ap–Av) and approach–approach (Ap–Ap) decision-making tasks that can behaviorally dissociate affective judgment and motivation. Notably, neurons having activity correlated with motivational condition could be distinguished from neurons having activity related to affective judgment, especially in the Ap–Av task. Although many neurons in both regions exhibited similar, selective patterns of task-related activity, we found a larger proportion of neurons activated in low motivational conditions in the dlPFC than in the ACC, and the onset of this activity was significantly earlier in the dlPFC than in the ACC. Furthermore, the temporal onsets of affective judgment represented by neuronal activities were significantly slower in the low motivational conditions than in the other conditions. These findings suggest that motivation and affective judgment both recruit dlPFC and ACC neurons but with differential degrees of involvement and timing.National Institutes of Health (U.S.) (Grant R01 NS025529)United States. Office of Naval Research (Grant N00014-07-1-0903)Cure Huntington’s Disease Initiative, Inc. (Grant A-5552)Massachusetts Institute of Technology. Simons Center for the Social BrainNational Parkinson Foundation (U.S.) (Lynn Diamond Fellowship

Striatal Beta Oscillation and Neuronal Activity in the Primate Caudate Nucleus Differentially Represent Valence and Arousal Under Approach-Avoidance Conflict

An approach-avoidance (Ap–Av) conflict arises when an individual has to decide whether to accept or reject a compound offer that has features indicating both reward and punishment. During value judgments of likes and dislikes, arousal responses simultaneously emerge and influence reaction times and the frequency of behavioral errors. In Ap–Av decision-making, reward and punishment differentially influence valence and arousal, allowing us to dissociate their neural processing. The primate caudate nucleus (CN) has been implicated in affective judgment, but it is still unclear how neural responses in the CN represent decision-related variables underlying choice. To address this issue, we recorded spikes and local field potentials (LFPs) from the CN while macaque monkeys performed an Ap–Av decision-making task. We analyzed 450 neuronal units and 667 beta oscillatory activities recorded during the performance of the task. To examine how these activities represented valence, we focused on beta-band responses and unit activities that encoded the chosen value (ChV) of the compound offer as derived from an econometric model. Unit activities exhibited either positive (65.0% = 26/40) or negative (35.0% = 14/40) correlations with the ChV, whereas beta responses exhibited almost exclusively positive correlations with the ChV (98.4% = 62/63). We examined arousal representation by focusing on beta responses and unit activities that encoded the frequency of omission errors (FOE), which were negatively correlated with arousal. The unit activities were either positively (65.3% = 17/26) or negatively (34.6% = 9/26) correlated with the FOE, whereas the beta responses were almost entirely positively correlated with the FOE (95.8% = 23/24). We found that the temporal onset of the beta-band responses occurred sequentially across conditions: first, the negative-value, then low-arousal, and finally, high-value conditions. These findings suggest the distinctive roles of CN beta oscillations that were sequentially activated for the valence and arousal conditions. By identifying dissociable groups of CN beta-band activity responding in relation to valence and arousal, we demonstrate that the beta responses mainly exhibited selective activation for the high-valence and low-arousal conditions, whereas the unit activities simultaneously recorded in the same experiments responded to chosen value and other features of decision-making under approach-avoidance conflict

Habit Learning by Naive Macaques Is Marked by Response Sharpening of Striatal Neurons Representing the Cost and Outcome of Acquired Action Sequences

Over a century of scientific work has focused on defining the factors motivating behavioral learning. Observations in animals and humans trained on a wide range of tasks support reinforcement learning (RL) algorithms as accounting for the learning. Still unknown, however, are the signals that drive learning in naive, untrained subjects. Here, we capitalized on a sequential saccade task in which macaque monkeys acquired repetitive scanning sequences without instruction. We found that spike activity in the caudate nucleus after each trial corresponded to an integrated cost-benefit signal that was highly correlated with the degree of naturalistic untutored learning by the monkeys. Across learning, neurons encoding both cost and outcome gradually acquired increasingly sharp phasic trial-end responses that paralleled the development of the habit-like, repetitive saccade sequences. Our findings demonstrate an integrated cost-benefit signal by which RL and its neural correlates could drive naturalistic behaviors in freely behaving primates. Video Abstract: Feedback about the costs and benefits of our actions is an essential part of how we learn. Desrochers et al. show that neurons in the striatum of monkeys develop combined cost-benefit signals marking movement sequences that they acquire without explicit training.National Institutes of Health (U.S.) (Grant R01 EY012848)National Institutes of Health (U.S.) (Grant R01 NS025529)United States. Defense Advanced Research Projects Agency (Grant NBCHC070105)United States. Office of Naval Research (Grant N00014-07-1-0903

Habit Learning by Naive Macaques Is Marked by Response Sharpening of Striatal Neurons Representing the Cost and Outcome of Acquired Action Sequences

SummaryOver a century of scientific work has focused on defining the factors motivating behavioral learning. Observations in animals and humans trained on a wide range of tasks support reinforcement learning (RL) algorithms as accounting for the learning. Still unknown, however, are the signals that drive learning in naive, untrained subjects. Here, we capitalized on a sequential saccade task in which macaque monkeys acquired repetitive scanning sequences without instruction. We found that spike activity in the caudate nucleus after each trial corresponded to an integrated cost-benefit signal that was highly correlated with the degree of naturalistic untutored learning by the monkeys. Across learning, neurons encoding both cost and outcome gradually acquired increasingly sharp phasic trial-end responses that paralleled the development of the habit-like, repetitive saccade sequences. Our findings demonstrate an integrated cost-benefit signal by which RL and its neural correlates could drive naturalistic behaviors in freely behaving primates.Video Abstrac

Long-term dopamine neurochemical monitoring in primates

Many debilitating neuropsychiatric and neurodegenerative disorders are characterized by dopamine neurotransmitter dysregulation. Monitoring subsecond dopamine release accurately and for extended, clinically relevant timescales is a critical unmet need. Especially valuable has been the development of electrochemical fast-scan cyclic voltammetry implementing microsized carbon fiber probe implants to record fast millisecond changes in dopamine concentrations. Nevertheless, these well-established methods have only been applied in primates with acutely (few hours) implanted sensors. Neurochemical monitoring for long timescales is necessary to improve diagnostic and therapeutic procedures for a wide range of neurological disorders. Strategies for the chronic use of such sensors have recently been established successfully in rodents, but new infrastructures are needed to enable these strategies in primates. Here we report an integrated neurochemical recording platform for monitoring dopamine release from sensors chronically implanted in deep brain structures of nonhuman primates for over 100 days, together with results for behavior-related and stimulation-induced dopamine release. From these chronically implanted probes, we measured dopamine release from multiple sites in the striatum as induced by behavioral performance and reward-related stimuli, by direct stimulation, and by drug administration. We further developed algorithms to automate detection of dopamine. These algorithms could be used to track the effects of drugs on endogenous dopamine neurotransmission, as well as to evaluate the long-term performance of the chronically implanted sensors. Our chronic measurements demonstrate the feasibility of measuring subsecond dopamine release from deep brain circuits of awake, behaving primates in a longitudinally reproducible manner. Keywords: striatum; voltammetry; neurotransmitters; chronic implantsNational Institute of Neurological Diseases and Stroke (U.S.) (Grant R01 NS025529)National Institute of Neurological Diseases and Stroke (U.S.) (Grant F32 NS093897)United States. Army Research Office (Contract W911NF-16-1-0474)National Institute of Biomedical Imaging and Bioengineering (U.S.) (Grant R01 EB016101

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

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.National Institutes of Health (U.S.) (Javits Merit Grant R01 NS025529)United States. Office of Naval Research (N000140710903)National Parkinson Foundation (U.S.) (Lynn Diamond Fellowship