Dopamine firing plays a dual role in coding reward prediction errors and signaling motivation in a working memory task

Little is known about how dopamine (DA) neuron firing rates behave in cognitively demanding decision-making tasks. Here, we investigated midbrain DA activity in monkeys performing a discrimination task in which the animal had to use working memory (WM) to report which of two sequentially applied vibrotactile stimuli had the higher frequency. We found that perception was altered by an internal bias, likely generated by deterioration of the representation of the first frequency during the WM period. This bias greatly controlled the DA phasic response during the two stimulation periods, confirming that DA reward prediction errors reflected stimulus perception. In contrast, tonic dopamine activity during WM was not affected by the bias and did not encode the stored frequency. More interestingly, both delay-period activity and phasic responses before the second stimulus negatively correlated with reaction times of the animals after the trial start cue and thus represented motivated behavior on a trial-by-trial basis. During WM, this motivation signal underwent a ramp-like increase. At the same time, motivation positively correlated with accuracy, especially in difficult trials, probably by decreasing the effect of the bias. Overall, our results indicate that DA activity, in addition to encoding reward prediction errors, could at the same time be involved in motivation and WM. In particular, the ramping activity during the delay period suggests a possible DA role in stabilizing sustained cortical activity, hypothetically by increasing the gain communicated to prefrontal neurons in a motivation-dependent way.

Dopamine D2Rs Coordinate Cue-Evoked Changes in Striatal Acetylcholine Levels

In the striatum, acetylcholine (ACh) neuron activity is modulated co-incident with dopamine (DA) release in response to unpredicted rewards and reward predicting cues and both neuromodulators are thought to regulate each other. While this co-regulation has been studied using stimulation studies, the existence of this mutual regulation in vivo during natural behavior is still largely unexplored. One long-standing controversy has been whether striatal DA is responsible for the induction of the cholinergic pause or whether D2R modulate a pause that is induced by other mechanisms. Here, we used genetically encoded sensors in combination with pharmacological and genetic inactivation of D2Rs from cholinergic interneurons (CINs) to simultaneously measure ACh and DA levels after CIN D2R inactivation. We found that CIN D2Rs are not necessary for the induction of cue induced dips in ACh levels but regulate dip lengths and rebound ACh levels. Importantly, D2R inactivation strongly decreased the temporal correlation between DA and Ach signals not only at cue presentation but also during the intertrial interval. This points to a general mechanism by which D2Rs coordinate both signals. At the behavioral level D2R antagonism increased the latency to lever press, which was not observed in CIN-selective D2R knock out mice. This latency correlated with the cue evoked dip length supporting a role of the ACh dip and it’s regulation by D2Rs in motivated behavior. Overall, our data indicate that striatal DA coordinate phasic ACh and DA signals via CIN D2Rs which is important for the regulation of motivated behavior.

Correlates of real-world goal-directed behavior in schizophrenia

Background Deficits in goal-directed behavior (i.e. behavior conducted to achieve a specific goal or outcome) are core to schizophrenia, difficult to treat, and associated with poor functional outcomes. Factors such as negative symptoms, effort-cost decision-making, cognition, and functional skills have all been associated with goal-directed behavior in schizophrenia as indexed by clinical interviews or laboratory-based tasks. However, little work has examined whether these factors relate to the real-world pursuit of goal-directed activities in this population. Methods This study aimed to fill this gap by using Ecological Momentary Assessment (four survey prompts per day for 1 week) to test hypotheses about symptom, effort allocation, cognitive, and functional measures associated with planned and completed goal-directed behavior in the daily lives of 63 individuals with schizophrenia. Results Individuals with schizophrenia completed more goal-directed activities than they planned [t(62) = −4.01, p < 0.001]. Motivation and pleasure (i.e. experiential) negative symptoms, controlling for depressive symptoms, negatively related to planned goal-directed behavior [odds ratio (OR) 0.92, p = 0.005]. Increased effort expenditure for high probability rewards (planned: OR 1.01, p = 0.034, completed: OR 1.01, p = 0.034) along with performance on a daily functional skills task (planned: OR 1.04, p = 0.002, completed: OR 1.03, p = 0.047) negatively related to both planned and completed goal-directed activity. Conclusions Our results present correlates of real-world goal-directed behavior that largely align with impaired ability to make future estimations in schizophrenia. This insight could help identify targeted treatments for the elusive motivated behavior deficits in this population.

Neurocomputational mechanism of controllability inference under a multi-agent setting

Controllability perception significantly influences motivated behavior and emotion and requires an estimation of one’s influence on an environment. Previous studies have shown that an agent can infer controllability by observing contingency between one’s own action and outcome if there are no other outcome-relevant agents in an environment. However, if there are multiple agents who can influence the outcome, estimation of one’s genuine controllability requires exclusion of other agents’ possible influence. Here, we first investigated a computational and neural mechanism of controllability inference in a multi-agent setting. Our novel multi-agent Bayesian controllability inference model showed that other people’s action-outcome contingency information is integrated with one’s own action-outcome contingency to infer controllability, which can be explained as a Bayesian inference. Model-based functional MRI analyses showed that multi-agent Bayesian controllability inference recruits the temporoparietal junction (TPJ) and striatum. Then, this inferred controllability information was leveraged to increase motivated behavior in the vmPFC. These results generalize the previously known role of the striatum and vmPFC in single-agent controllability to multi-agent controllability, and this generalized role requires the TPJ in addition to the striatum of single-agent controllability to integrate both self- and other-related information. Finally, we identified an innate positive bias toward the self during the multi-agent controllability inference, which facilitated behavioral adaptation under volatile controllability. Furthermore, low positive bias and high negative bias were associated with increased daily feelings of guilt. Our results provide a mechanism of how our sense of controllability fluctuates due to other people in our lives, which might be related to social learned helplessness and depression.

Culture of collaboration

Purpose: The purpose of this article is to report the results from a research project which focused on understanding how motivation to read is manifested and maintained in children with learning impairments. The participants were enrolled in a specialized university literacy program with graduate student clinicians. Method: An interpretative, qualitative study utilizing components of ethnography and microanalysis was employed to analyze video transcripts of recorded therapy sessions of speech-language pathology student clinicians and children with language disorders. These interactions were coded for the nature of their role in motivating children to read. Results and conclusions: This study revealed that a culture of collaboration was a hallmark of treatment that facilitated motivation in the participants. Two key characteristics of motivated behavior that emerged as a result of this culture of collaboration are identified and described. Additionally, three specific, collaborative, therapeutic strategies found to sustain motivation to read are described.

The SEEKING Drive and Its Fixation: A Neuro-Psycho-Evolutionary Approach to the Pathology of Addiction

Neuro-ethological studies conducted by Panksepp and his colleagues have provided an understanding of how the activity of the mesolimbic dopaminergic (ML DA) system leads to the emotional disposition to SEEK/Explore, which is involved in all appetitive motivated behavior and mental activity. In pathological addiction phenomena, this emotional disposition “fixes” itself on certain obsessive-compulsive habits, losing its versatility and its natural predisposition to spontaneous and unconditioned activation. Overall, the result is a consistent disinterest in everything that is not the object of addiction. From a neuro-psycho-evolutionary point of view, the predisposition to develop addictive behavior can be attributed to a loss of “functional autonomy” of the SEEKING/Explorative disposition. Indeed, as shown by animal and human studies, the tendency to be conditioned by situations and contexts that provide an immediate reward can be closely related to a deficit in the tonic endogenous activity of the ML DA-SEEKING system.

Motivational learning biases are differentially modulated by genetic determinants of striatal and prefrontal dopamine function

Dopaminergic neurotransmission plays a pivotal role in appetitively motivated behavior in mammals, including humans. Notably, action and valence are not independent in motivated tasks, and it is particularly difficult for humans to learn the inhibition of an action to obtain a reward. We have previously observed that the carriers of the DRD2/ANKK1 TaqIA A1 allele, that has been associated with reduced striatal dopamine D2 receptor expression, showed a diminished learning performance when required to learn response inhibition to obtain rewards, a finding that was replicated in two independent cohorts. With our present study, we followed two aims: first, we aimed to replicate our finding on the DRD2/ANKK1 TaqIA polymorphism in a third independent cohort (N = 99) and to investigate the nature of the genetic effects more closely using trial-by-trial behavioral analysis and computational modeling in the combined dataset (N = 281). Second, we aimed to assess a potentially modulatory role of prefrontal dopamine availability, using the widely studied COMT Val108/158Met polymorphism as a proxy. We first report a replication of the above mentioned finding. Interestingly, after combining all three cohorts, exploratory analyses regarding the COMT Val108/158Met polymorphism suggest that homozygotes for the Met allele, which has been linked to higher prefrontal dopaminergic tone, show a lower learning bias. Our results corroborate the importance of genetic variability of the dopaminergic system in individual learning differences of action–valence interaction and, furthermore, suggest that motivational learning biases are differentially modulated by genetic determinants of striatal and prefrontal dopamine function.

RFamide peptides, the novel regulators of mammalian HPG axis: A review

The RFamide-related peptides (RFRPs) are the group of neuropeptides synthesized predominantly from the hypothalamus that negatively affects the hypothalamo-hypophyseal-gonadal (hypothalamic–pituitary–gonadal [HPG]) axis. These peptides are first identified in quail brains and emerged as the mammalian orthologs of avian gonadotropin inhibitory hormones. The RFRP-3 neurons in the hypothalamus are present in several mammalian species. The action of RFRP-3 is mediated through a G-protein-coupled receptor called OT7T022. The predominant role of RFRP-3 is the inhibition of HPG axis with several other effects such as the regulation of metabolic activity, stress regulation, controlling of non-sexual motivated behavior, and sexual photoperiodicity in concert with other neuropeptides such as kisspeptin, neuropeptide-Y (NPY), pro-opiomelanocortin, orexin, and melanin. RFamide peptides synthesized in the granulosa cells, interstitial cells, and seminiferous tubule regulate steroidogenesis and gametogenesis in the gonads. The present review is intended to provide the recent findings that explore the role of RFRP-3 in regulating HPG axis and its potential applications in the synchronization of reproduction and its therapeutic interventions to prevent stress-induced amenorrhea.

Impact of Sports Education Model in Physical Education on Students’ Motivation: A Systematic Review

Background: Research has suggested that applying the Sport Education Model (SEM) in Physical Education (PE) increases students’ motivation. However, it is important to systematize this evidence to have a clearer idea. Therefore, this study aimed to analyze the impact of the SEM on the students’ motivation. Methods: A systematic review with a narrative synthesis was performed. In March 2021, an articles search was conducted in PubMed, Scopus, and Web of Science. Eligibility criteria were: longitudinal or experimental study design; outcomes included PE settings; results reported the relationship between the SEM and students’ motivation. Results: Fourteen studies were included, totaling 2146 students. The majority of the studies indicated a significant association between the SEM and motivation, particularly in autonomy and more enjoyment toward PE. Conclusions: This review supports that the SEM has a positive impact on motivation. The SEM offers a wide range of opportunities for students to develop more self-determined motivated behavior in PE classes. Therefore, the SEM should be considered when developing or adapting existing PE programs to promote students’ intrinsic motivation to engage in physical activity.