Orbitofrontal high-gamma reflects spike-dissociable value and decision mechanisms.

The orbitofrontal cortex (OFC) plays a crucial role in value-based decision-making. While previous research has focused on spiking activity in OFC neurons, the role of OFC local field potentials (LFPs) in decision-making remains unclear. LFPs are important because they can reflect synaptic and subthreshold activity not directly coupled to spiking, and because they are potential targets for less invasive forms of brain-machine interface (BMI). We recorded LFPs and spiking activity using multi-channel vertical probes while monkeys performed a two-option value-based decision-making task. We compared the value- and decision-coding properties of high-gamma range LFPs (HG, 50-150 Hz) to the coding properties of spiking multi-unit activity (MUA) recorded concurrently on the same electrodes. Results show that HG and MUA both represent the values of decision targets, and that their representations have similar temporal profiles in a trial. However, we also identified value-coding properties of HG that were dissociable from the concurrently-measured MUA. On average across channels, HG amplitude increased monotonically with value, whereas the average value encoding in MUA was net neutral. HG also encoded a signal consistent with a comparison between the values of the two targets, a signal which was much weaker in MUA. In individual channels, HG was better able to predict choice outcomes than MUA; however, when simultaneously recorded channels were combined in population-based decoder, MUA provided more accurate predictions than HG. Interestingly, HG value representations were accentuated in channels in or near shallow cortical layers, suggesting a dissociation between neuronal sources of HG and MUA. In summary, we find that HG signals are dissociable from MUA with respect to cognitive variables encoded in prefrontal cortex, evident in the monotonic encoding of value, stronger encoding of value comparisons, and more accurate predictions about behavior. High-frequency LFPs may therefore be a viable - or even preferable - target for BMIs to assist cognitive function, opening the possibility for less invasive access to mental contents that would otherwise be observable only with spike-based measures.

Behavioral read-out from population value signals in primate orbitofrontal cortex.

The primate orbitofrontal cortex (OFC) has long been recognized for its role in value-based decisions; however, the exact mechanism linking value representations in the OFC to decision outcomes has remained elusive. Here, to address this question, we show, in non-human primates, that trial-wise variability in choices can be explained by variability in value signals decoded from many simultaneously recorded OFC neurons. Mechanistically, this relationship is consistent with the projection of activity within a low-dimensional value-encoding subspace onto a potentially higher-dimensional, behaviorally potent output subspace. Identifying this neural-behavioral link answers longstanding questions about the role of the OFC in economic decision-making and suggests population-level read-out mechanisms for the OFC similar to those recently identified in sensory and motor cortex.

Monkeys exhibit human-like gaze biases in economic decisions.

In economic decision-making individuals choose between items based on their perceived value. For both humans and nonhuman primates, these decisions are often carried out while shifting gaze between the available options. Recent studies in humans suggest that these shifts in gaze actively influence choice, manifesting as a bias in favor of the items that are viewed first, viewed last, or viewed for the overall longest duration in a given trial. This suggests a mechanism that links gaze behavior to the neural computations underlying value-based choices. In order to identify this mechanism, it is first necessary to develop and validate a suitable animal model of this behavior. To this end, we have created a novel value-based choice task for macaque monkeys that captures the essential features of the human paradigms in which gaze biases have been observed. Using this task, we identified gaze biases in the monkeys that were both qualitatively and quantitatively similar to those in humans. In addition, the monkeys' gaze biases were well-explained using a sequential sampling model framework previously used to describe gaze biases in humans-the first time this framework has been used to assess value-based decision mechanisms in nonhuman primates. Together, these findings suggest a common mechanism that can explain gaze-related choice biases across species, and open the way for mechanistic studies to identify the neural origins of this behavior.

When we choose between two items, we might expect to spend more time looking at the one we have a pre-existing preference for. For example, at the grocery store, you might assume that someone who likes grapes better than bananas would spend a longer time looking at the grapes. Surprisingly, a series of studies on human decision-making have shown that the opposite relationship is also true: the more time we spend looking at an item, the more likely we are to pick it. This 'gaze bias' occurs in many real-life and laboratory decision settings, and it is especially evident for choices between two equally preferred options. However, examining the brain circuits that underpin this behavior has so far been difficult due to a lack of animal models in which to study them. In response, Lupkin and McGinty proposed that rhesus macaques may be the ideal species in which to study gaze biases, as these animals likely rely on the same brain regions as humans when gazing and making decisions. To test this hypothesis, a computer-based decision game similar to the ones used for humans was designed for the monkeys. It involved the animals having to choose between two icons that were associated with different amounts of a juice reward. Analysing how long the macaques had spent looking at each icon before making their choice revealed that they indeed tended to select the icon they had looked at for longer ­ including when the two icons indicated equal rewards. Other types of gaze biases present in humans were also detected, such as choosing the icon that was viewed first or last in a trial. Additional analyses using computer simulations confirmed that the gaze biases of humans and monkeys were comparable and, critically, that they could be explained by similar underlying brain processes. These strong similarities suggest that rhesus macaques could be used to study the neural basis for decision-making in both humans and nonhuman primates, potentially making it easier to examine the harmful changes in decision-making that occur in conditions like substance abuse or depression.

Overt Attention toward Appetitive Cues Enhances Their Subjective Value, Independent of Orbitofrontal Cortex Activity.

Neural representations of value underlie many behaviors that are crucial for survival. Previously, we found that value representations in primate orbitofrontal cortex (OFC) are modulated by attention, specifically, by overt shifts of gaze toward or away from reward-associated visual cues (McGinty et al., 2016). Here, we investigate the influence of overt attention on behavior by asking how gaze shifts correlate with reward anticipatory responses and whether activity in OFC mediates this correlation. Macaque monkeys viewed pavlovian conditioned appetitive cues on a visual display, while the fraction of time they spent looking toward or away from the cues was measured using an eye tracker. Also measured during cue presentation were the reward anticipation, indicated by conditioned licking responses (CRs), and single-neuron activity in OFC. In general, gaze allocation predicted subsequent licking responses: the longer the monkeys spent looking at a cue at a given time point in a trial, the more likely they were to produce an anticipatory CR later in that trial, as if the subjective value of the cue were increased. To address neural mechanisms, mediation analysis measured the extent to which the gaze-CR correlation could be statistically explained by the concurrently recorded firing of OFC neurons. The resulting mediation effects were indistinguishable from chance. Therefore, while overt attention may increase the subjective value of reward-associated cues (as revealed by anticipatory behaviors), the underlying mechanism remains unknown, as does the functional significance of gaze-driven modulation of OFC value signals.

How the Midbrain Helps Us Decide.

In an elegant synthesis of behavior, modeling, and neurophysiology, Crapse et al. (2018) show that neurons of the superior colliculus influence choice behavior by encoding choice criterion, a quantitative measure of decision bias integral to signal detection theory.

Limbic-motor integration by neural excitations and inhibitions in the nucleus accumbens.

The nucleus accumbens (NAc) has often been described as a "limbic-motor interface," implying that the NAc integrates the value of expected rewards with the motor planning required to obtain them. However, there is little direct evidence that the signaling of individual NAc neurons combines information about predicted reward and behavioral response. We report that cue-evoked neural responses in the NAc form a likely physiological substrate for its limbic-motor integration function. Across task contexts, individual NAc neurons in behaving rats robustly encode the reward-predictive qualities of a cue, as well as the probability of behavioral response to the cue, as coexisting components of the neural signal. In addition, cue-evoked activity encodes spatial and locomotor aspects of the behavioral response, including proximity to a reward-associated target and the latency and speed of approach to the target. Notably, there are important limits to the ability of NAc neurons to integrate motivational information into behavior: in particular, updating of predicted reward value appears to occur on a relatively long timescale, since NAc neurons fail to discriminate between cues with reward associations that change frequently. Overall, these findings suggest that NAc cue-evoked signals, including inhibition of firing (as noted here for the first time), provide a mechanism for linking reward prediction and other motivationally relevant factors, such as spatial proximity, to the probability and vigor of a reward-seeking behavioral response.NEW & NOTEWORTHY The nucleus accumbens (NAc) is thought to link expected rewards and action planning, but evidence for this idea remains sparse. We show that, across contexts, both excitatory and inhibitory cue-evoked activity in the NAc jointly encode reward prediction and probability of behavioral responding to the cue, as well as spatial and locomotor properties of the response. Interestingly, although spatial information in the NAc is updated quickly, fine-grained updating of reward value occurs over a longer timescale.

Orbitofrontal Cortex Value Signals Depend on Fixation Location during Free Viewing.

In the natural world, monkeys and humans judge the economic value of numerous competing stimuli by moving their gaze from one object to another, in a rapid series of eye movements. This suggests that the primate brain processes value serially, and that value-coding neurons may be modulated by changes in gaze. To test this hypothesis, we presented monkeys with value-associated visual cues and took the unusual step of allowing unrestricted free viewing while we recorded neurons in the orbitofrontal cortex (OFC). By leveraging natural gaze patterns, we found that a large proportion of OFC cells encode gaze location and, that in some cells, value coding is amplified when subjects fixate near the cue. These findings provide the first cellular-level mechanism for previously documented behavioral effects of gaze on valuation and suggest a major role for gaze in neural mechanisms of valuation and decision-making under ecologically realistic conditions.

Invigoration of reward seeking by cue and proximity encoding in the nucleus accumbens.

A key function of the nucleus accumbens is to promote vigorous reward seeking, but the corresponding neural mechanism has not been identified despite many years of research. Here, we study cued flexible approach behavior, a form of reward seeking that strongly depends on the accumbens, and we describe a robust, single-cell neural correlate of behavioral vigor in the excitatory response of accumbens neurons to reward-predictive cues. Well before locomotion begins, this cue-evoked excitation predicts both the movement initiation latency and the speed of subsequent flexible approach responses, but not those of stereotyped, inflexible responses. Moreover, the excitation simultaneously signals the subject's proximity to the approach target, a signal that appears to mediate greater response vigor on trials that begin with the subject closer to the target. These results demonstrate a neural mechanism for response invigoration whereby accumbens neuronal encoding of reward availability and target proximity together drive the onset and speed of reward-seeking locomotion.

Emerging, reemerging, and forgotten brain areas of the reward circuit: Notes from the 2010 Motivational Neural Networks conference.

On April 24-27, 2010, the Motivational Neuronal Networks meeting took place in Wrightsville Beach, North Carolina. The conference was devoted to "Emerging, re-emerging, and forgotten brain areas" of the reward circuit. A central feature of the conference was four scholarly discussions of cutting-edge topics related to the conference's theme. These discussions form the basis of the present review, which summarizes areas of consensus and controversy, and serves as a roadmap for the next several years of research.

Timing-dependent regulation of evoked spiking in nucleus accumbens neurons by integration of limbic and prefrontal cortical inputs.

Single nucleus accumbens (NAcc) neurons receive excitatory synaptic input from cortical and limbic structures, and the integration of converging goal- and motivation-related signals in these neurons influences reward-directed actions. While limbic/cortical synaptic input summation has been characterized at subthreshold intensities, the manner in which multiple inputs govern NAcc neuron spike discharge has not been measured and is poorly understood. Single NAcc neurons were recorded in urethane-anesthetized rats, and spiking was evoked by coincident stimulation of two major NAcc afferent regions: the basolateral amygdala (BLA) and medial prefrontal cortex (mPFC). BLA input increased NAcc spiking elicited by mPFC stimulation depending on the timing of the stimulation pulses, consistent with the summation of monosynaptically evoked excitatory activity. When mPFC input intensity was below threshold for evoked spiking, the addition of BLA input produced the largest facilitation of evoked spiking, and the latency of the evoked spikes reflected the latency of the individual inputs. When mPFC inputs were stimulated at higher intensities, BLA-mediated facilitation was weaker, and the spike latency reflected only the mPFC input. Thus NAcc neurons integrate both the magnitude and timing of afferent synaptic activity, suggesting that NAcc neuron output is strongly dependent on the comparative magnitude of synaptic activity in its afferent structures. These interactions may be crucial integrative mechanisms that allow motivational and cognitive information to produce appropriate reward-directed actions.

Selective activation of medial prefrontal-to-accumbens projection neurons by amygdala stimulation and Pavlovian conditioned stimuli.

Medial prefrontal cortex (mPFC) neurons respond to Pavlovian conditioned stimuli, and these responses depend on input from the basolateral amygdala (BLA). In this study, we examined the mPFC efferent circuits mediating conditioned responding by testing whether specific subsets of mPFC projection neurons receive BLA input and respond to conditioned stimuli. In urethane-anesthetized rats, we identified mPFC neurons that projected to the nucleus accumbens (NAcc) or to the contralateral mPFC (cmPFC) using antidromic activation. Stimulation of the BLA and Pavlovian conditioned odors selectively activated a subpopulation of ventral mPFC neurons that projected to NAcc, but elicited virtually no activation in mPFC neurons that projected to cmPFC. BLA stimulation typically evoked inhibitory responses among nonactivated neurons projecting to either site. These results suggest that the ventral mPFC-to-NAcc pathway may support behavioral responses to conditioned cues. Furthermore, because projections from the BLA (which also encode affective information) and the mPFC converge within the NAcc, the BLA may recruit the mPFC to drive specific sets of NAcc neurons, and thereby exert control over prefrontal cortical-striato-thalamocortical information flow.