Within-trial effects of stimulus-reward associations

While a globally energizing influence of motivation has long been appreciated in psychological research, a series of more recent studies has described motivational influences on specific cognitive operations ranging from visual attention, to cognitive control, to memory formation. In the majority of these studies, a cue predicts the potential to win money in a subsequent task, thus allowing for modulations of proactive task preparation. Here we describe some recent studies using tasks that communicate reward availability without such cues by directly associating specific task features with reward. Despite abolishing the cue-based preparation phase, these studies show similar performance benefits. Given the clear difference in temporal structure, a central question is how these behavioral effects are brought about, and in particular whether control processes can rapidly be enhanced reactively. We present some evidence in favor of this notion. Although additional influences, for example sensory prioritization of reward-related features, could contribute to the reward-related performance benefits, those benefits seem to strongly rely on enhancements of control processes during task execution. Still, for a better mechanistic understanding of reward benefits in these two principal paradigms (cues vs. no cues), more work is needed that directly compares the underlying processes. We anticipate that reward benefits can be brought about in a very flexible fashion depending on the exact nature of the reward manipulation and task, and that a better understanding of these processes will not only be relevant for basic motivation research, but that it can also be valuable for educational and psychopathological contexts

Cannabinoid Transmission in the Basolateral Amygdala Modulates Prefrontal Cortex and Ventral Hippocampal Activity

The cannabinoid system is important for maintaining neuron-to-neuron communication within the mammalian brain. One of the most commonly used substances to alter the cannabinoid system is cannabis. Individuals who are exposed to cannabis report having dissociable effects; both positive and negative. High amounts of THC have been commonly associated with the negative effects of cannabis, whereas CBD can be used to counter these. Pre-clinical evidence suggests that the combination of the two compounds can produce a therapeutic benefit for individuals who are susceptible to the effects of THC. The present study investigates whether the combination of THC+CBD can prevent electrophysiological changes induced by THC. Using In Vivo electrophysiology, simultaneous recordings of single unit activity both in the ventral hippocampal and prefrontal cortex were compared after infusions of cannabinoids into the basolateral amygdala. THC induced changes in the PFC to increase overall activity whereas the combined dose of THC+CBD returned cortical activity to baseline and introduced a potential benefit in reduced hippocampal activity

Humor Modulates the Mesolimbic Reward Centers

AbstractHumor plays an essential role in many facets of human life including psychological, social, and somatic functioning. Recently, neuroimaging has been applied to this critical human attribute, shedding light on the affective, cognitive, and motor networks involved in humor processing. To date, however, researchers have failed to demonstrate the subcortical correlates of the most fundamental feature of humor—reward. In an effort to elucidate the neurobiological substrate that subserves the reward components of humor, we undertook a high-field (3 Tesla) event-related functional MRI study. Here we demonstrate that humor modulates activity in several cortical regions, and we present new evidence that humor engages a network of subcortical regions including the nucleus accumbens, a key component of the mesolimbic dopaminergic reward system. Further, the degree of humor intensity was positively correlated with BOLD signal intensity in these regions. Together, these findings offer new insight into the neural basis of salutary aspects of humor

Independent circuits in basal ganglia and cortex for the processing of reward and precision feedback

In order to understand human decision making it is necessary to understand how the brain uses feedback to guide goal-directed behavior. The ventral striatum (VS) appears to be a key structure in this function, responding strongly to explicit reward feedback. However, recent results have also shown striatal activity following correct task performance even in the absence of feedback. This raises the possibility that, in addition to processing external feedback, the dopamine-centered reward circuit might regulate endogenous reinforcement signals, like those triggered by satisfaction in accurate task performance. Here we use functional magnetic resonance imaging (fMRI) to test this idea. Participants completed a simple task that garnered both reward feedback and feedback about the precision of performance. Importantly, the design was such that we could manipulate information about the precision of performance within different levels of reward magnitude. Using parametric modulation and functional connectivity analysis we identified brain regions sensitive to each of these signals. Our results show a double dissociation: frontal and posterior cingulate regions responded to explicit reward but were insensitive to task precision, whereas the dorsal striatum - and putamen in particular - was insensitive to reward but responded strongly to precision feedback in reward-present trials. Both types of feedback activated the VS, and sensitivity in this structure to precision feedback was predicted by personality traits related to approach behavior and reward responsiveness. Our findings shed new light on the role of specific brain regions in integrating different sources of feedback to guide goal-directed behavior

P2 receptors are involved in the mediation of motivation-related behavior

The importance of purinergic signaling in the intact mesolimbic–mesocortical circuit of the brain of freely moving rats is reviewed. In the rat, an endogenous ADP/ATPergic tone reinforces the release of dopamine from the axon terminals in the nucleus accumbens as well as from the somatodendritic region of these neurons in the ventral tegmental area, as well as the release of glutamate, probably via P2Y1 receptor stimulation. Similar mechanisms may regulate the release of glutamate in both areas of the brain. Dopamine and glutamate determine in concert the activity of the accumbal GABAergic, medium-size spiny neurons thought to act as an interface between the limbic cortex and the extrapyramidal motor system. These neurons project to the pallidal and mesencephalic areas, thereby mediating the behavioral reaction of the animal in response to a motivation-related stimulus. There is evidence that extracellular ADP/ATP promotes goal-directed behavior, e.g., intention and feeding, via dopamine, probably via P2Y1 receptor stimulation. Accumbal P2 receptor-mediated glutamatergic mechanisms seem to counteract the dopaminergic effects on behavior. Furthermore, adaptive changes of motivation-related behavior, e.g., by chronic succession of starvation and feeding or by repeated amphetamine administration, are accompanied by changes in the expression of the P2Y1 receptor, thought to modulate the sensitivity of the animal to respond to certain stimuli

The role of the preoptic area in response to cocaine

The preoptic area of the hypothalamus is ideally suited to modulate the behavioral and neural response to drugs of abuse such as cocaine. The preoptic area is broken up into two major subregions the medial preoptic area (mPOA) and the lateral preoptic area (LPO), both of which send dense projections to mesolimbic dopamine system. Specifically, both project to the ventral tegmental area (VTA), a brain region implicated in drug-associated reward. Previous work has demonstrated the mPOA is involved in the behavioral and neural response to cocaine in female rats, however the mechanism through which the mPOA modulates response to cocaine is unclear. Whether or not the mPOA also plays a role in response to cocaine in male rats is still not clear. Furthermore the role of the adjacent LPO in response to cocaine is unexplored, despite its anatomical relationship to the VTA and involvement in intracranial self-stimulation. Here I demonstrate that estradiol acts in the mPOA of female rats to modulate response to cocaine. Specifically, microinjections of estradiol directly into the mPOA one day prior to cocaine administration increase cocaine-induced dopamine levels in the nucleus accumbens. The mPOA is also involved in the behavioral regulation of response to cocaine in male rats, as mPOA lesions enhanced cocaine-induced locomotion and reward. Finally, activation of the LPO, with pharmacology or chemogenetics, potentiates reinstatement of cocaine seeking, an animal model of drug relapse. Together these results demonstrate that the preoptic area as a whole is involved in the regulation of the neural and behavioral response to cocaine and shed light on underlying regulatory mechanisms.Psycholog

The Melanin-Concentrating Hormone (MCH) System Modulates Behaviors Associated with Psychiatric Disorders

Deficits in sensorimotor gating measured by prepulse inhibition (PPI) of the startle have been known as characteristics of patients with schizophrenia and related neuropsychiatric disorders. PPI disruption is thought to rely on the activity of the mesocorticolimbic dopaminergic system and is inhibited by most antipsychotic drugs. These drugs however act also at the nigrostriatal dopaminergic pathway and exert adverse locomotor responses. Finding a way to inhibit the mesocorticolimbic- without affecting the nigrostriatal-dopaminergic pathway may thus be beneficial to antipsychotic therapies. The melanin-concentrating hormone (MCH) system has been shown to modulate dopamine-related responses. Its receptor (MCH1R) is expressed at high levels in the mesocorticolimbic and not in the nigrostriatal dopaminergic pathways. Interestingly a genomic linkage study revealed significant associations between schizophrenia and markers located in the MCH1R gene locus. We hypothesize that the MCH system can selectively modulate the behavior associated with the mesocorticolimbic dopamine pathway. Using mice, we found that central administration of MCH potentiates apomorphine-induced PPI deficits. Using congenic rat lines that differ in their responses to PPI, we found that the rats that are susceptible to apomorphine (APO-SUS rats) and exhibit PPI deficits display higher MCH mRNA expression in the lateral hypothalamic region and that blocking the MCH system reverses their PPI deficits. On the other hand, in mice and rats, activation or inactivation of the MCH system does not affect stereotyped behaviors, dopamine-related responses that depend on the activity of the nigrostriatal pathway. Furthermore MCH does not affect dizocilpine-induced PPI deficit, a glutamate related response. Thus, our data present the MCH system as a regulator of sensorimotor gating, and provide a new rationale to understand the etiologies of schizophrenia and related psychiatric disorders

The Feedback-Related Negativity is a Time-Dependent Brain Mechanism that Facilitates Aversive Learning: Implications for the Reinforcement Learning FRN Hypothesis

Organisms encode rewarding and aversive experiences through reinforcement learning, capitalizing on prediction errors (PEs), which adapt action strategies over time. Computational theories are explicit that PE signals should update action weights continuously over the course of a behavioral task, an important time-dependent variation that is eschewed in traditional neuroscience studies that average over large numbers of trials. I examined variation in reaction times and feedback-locked cortical activity over time as a function of PE to critically examine theories indicating that PE signals drive time-dependent learning. We recorded EEG while participants completed a novel reinforcement task that varied prediction error on a trial-by-trial basis. I applied a computational framework that modeled reaction time changes over the task as a function of prediction error and time. In positive reinforcement conditions, reaction times improved over the course of the task regardless of the PE. For negative reinforcement, learning effects were moderated by PE. For better than expected outcomes, more positive prediction errors (further from expectation) drove faster reaction times over the course of the task, and for worse than expected outcomes, more negative prediction errors (further from expectation) drove faster reaction times over the course of the task. Behavioral analyses were supplemented by single-trial robust regression of feedback-locked EEG. The feedback-related negativity (FRN), a mediofrontal ERP component thought to convey a PE signal, showed robust changes in activation over time but did not respond to trial-by-trial magnitude of prediction errors. This time-dependent change was evident only for reward delivery and aversive stimulus delivery, which represent on average the most salient outcomes in the task. Mediofrontal brain activity during this same time window and at the same scalp location drove subsequent reaction time improvements over the course of the task following aversive stimulus delivery. I suggest that the standard approach of examining the ERP as an average across conditions obscures important adaptation effects of the FRN that reflect reinforcement learning as outcomes are learned