Only cortical prediction error signals are involved in visual learning, despite availability of subcortical prediction error signals.

Both the midbrain systems, encompassing the ventral striatum (VS), and the cortical systems, including the dorsal anterior cingulate cortex (dACC), play roles in reinforcing and enhancing learning. However, the specific contributions of signals from these regions in learning remains unclear. To investigate this, we examined how VS and dACC are involved in visual perceptual learning (VPL) through an orientation discrimination task. In the primary experiment, subjects fasted for 5 hours before each of 14 days of training sessions and 3 days of test sessions. Subjects were rewarded with water for accurate trial responses. During the test sessions, BOLD signals were recorded from regions including VS and dACC. Although BOLD signals in both areas were associated with positive and negative RPEs, only those in dACC associated with negative RPE showed a significant correlation with performance improvement. Additionally, no significant correlation was observed between BOLD signals associated with RPEs in VS and dACC. These results suggest that although signals associated with positive and negative RPEs from both midbrain and cortical systems are readily accessible, only RPE signals in the prefrontal system, generated without linking to RPE signals in VS, are utilized for the enhancement of VPL.

Association between arginine vasopressin receptor 1A (AVPR1A) polymorphism and inequity aversion.

Although numerous studies have focused on brain functions related to inequity aversion, few have examined its genetic basis. Here, we show the association between estimated inequity aversion and polymorphisms in three genes associated with human sociality. Non-student adult participants took part in five economic game experiments on different days. Disadvantageous inequity aversion (DIA) and advantageous inequity aversion (AIA) were calculated from behavioural responses using Bayesian estimation. We investigated the association between genetic polymorphisms in the oxytocin receptor (OXTR rs53576), arginine vasopressin receptor 1A (AVPR1A RS3) and opioid receptor mu 1 (OPRM1 rs1799971) and inequity aversion. Regarding AVPR1A RS3, participants with the SS genotype had higher AIA than those with the SL or LL genotypes, but no association was found for DIA. Moreover, we observed no aversion associations for OXTR rs53576 or OPRM1 rs1799971. The results suggest that AVPR1A plays an important role in aversion when one's own gain is greater than that of others. Our findings may provide a solid theoretical basis for future studies on the relationship between genetic polymorphisms and inequity aversion.

Proselfs depend more on model-based than model-free learning in a non-social probabilistic state-transition task.

Humans form complex societies in which we routinely engage in social decision-making regarding the allocation of resources among ourselves and others. One dimension that characterizes social decision-making in particular is whether to prioritize self-interest or respect for others-proself or prosocial. What causes this individual difference in social value orientation? Recent developments in the social dual-process theory argue that social decision-making is characterized by its underlying domain-general learning systems: the model-free and model-based systems. In line with this "learning" approach, we propose and experimentally test the hypothesis that differences in social preferences stem from which learning system is dominant in an individual. Here, we used a non-social state transition task that allowed us to assess the balance between model-free/model-based learning and investigate its relation to the social value orientations. The results showed that proselfs depended more on model-based learning, whereas prosocials depended more on model-free learning. Reward amount and reaction time analyses showed that proselfs learned the task structure earlier in the session than prosocials, reflecting their difference in model-based/model-free learning dependence. These findings support the learning hypothesis on what makes differences in social preferences and have implications for understanding the mechanisms of prosocial behavior.

Right dorsolateral prefrontal cortex regulates default prosociality preference.

The dorsolateral prefrontal cortex has been shown to be associated with prosocial behavior. However, the direction of this relationship remains controversial. To resolve inconsistencies in the existing literature, we introduced the concept of default prosociality preference and hypothesized that this preference moderates the relationship between gray matter volume in the dorsolateral prefrontal cortex and prosocial behavior. This study analyzed the data of 168 participants obtained from voxel-based morphometry, 4 types of economic games, and 3 different measures of social value orientation that represent default prosociality preference. Here we show that, in individuals who were consistently classified as proself on the 3 social value orientation measures, gray matter volume in the right dorsolateral prefrontal cortex was positively associated with prosocial behavior. However, in individuals who were consistently classified as prosocial, the direction of this association was vice versa. These results indicate that the right dorsolateral prefrontal cortex regulates default prosociality preference.

The neuroanatomy of social trust predicts depression vulnerability.

Trust attitude is a social personality trait linked with the estimation of others' trustworthiness. Trusting others, however, can have substantial negative effects on mental health, such as the development of depression. Despite significant progress in understanding the neurobiology of trust, whether the neuroanatomy of trust is linked with depression vulnerability remains unknown. To investigate a link between the neuroanatomy of trust and depression vulnerability, we assessed trust and depressive symptoms and employed neuroimaging to acquire brain structure data of healthy participants. A high depressive symptom score was used as an indicator of depression vulnerability. The neuroanatomical results observed with the healthy sample were validated in a sample of clinically diagnosed depressive patients. We found significantly higher depressive symptoms among low trusters than among high trusters. Neuroanatomically, low trusters and depressive patients showed similar volume reduction in brain regions implicated in social cognition, including the dorsolateral prefrontal cortex (DLPFC), dorsomedial PFC, posterior cingulate, precuneus, and angular gyrus. Furthermore, the reduced volume of the DLPFC and precuneus mediated the relationship between trust and depressive symptoms. These findings contribute to understanding social- and neural-markers of depression vulnerability and may inform the development of social interventions to prevent pathological depression.

Social impact and governance of AI and neurotechnologies.

Advances in artificial intelligence (AI) and brain science are going to have a huge impact on society. While technologies based on those advances can provide enormous social benefits, adoption of new technologies poses various risks. This article first reviews the co-evolution of AI and brain science and the benefits of brain-inspired AI in sustainability, healthcare, and scientific discoveries. We then consider possible risks from those technologies, including intentional abuse, autonomous weapons, cognitive enhancement by brain-computer interfaces, insidious effects of social media, inequity, and enfeeblement. We also discuss practical ways to bring ethical principles into practice. One proposal is to stop giving explicit goals to AI agents and to enable them to keep learning human preferences. Another is to learn from democratic mechanisms that evolved in human society to avoid over-consolidation of power. Finally, we emphasize the importance of open discussions not only by experts, but also including a diverse array of lay opinions.

Dissecting the Prefrontal Network With Pathway-Selective Manipulation in the Macaque Brain-A Review.

Macaque monkeys are prime animal models for studying the neural mechanisms of decision-making because of their close kinship with humans. Manipulation of neural activity during decision-making tasks is essential for approaching the causal relationship between the brain and its functions. Conventional manipulation methods used in macaque studies are coarse-grained, and have worked indiscriminately on mutually intertwined neural pathways. To systematically dissect neural circuits responsible for a variety of functions, it is essential to analyze changes in behavior and neural activity through interventions in specific neural pathways. In recent years, an increasing number of studies have applied optogenetics and chemogenetics to achieve fine-grained pathway-selective manipulation in the macaque brain. Here, we review the developments in macaque studies involving pathway-selective operations, with a particular focus on applications to the prefrontal network. Pathway selectivity can be achieved using single viral vector transduction combined with local light stimulation or ligand administration directly into the brain or double-viral vector transduction combined with systemic drug administration. We discuss the advantages and disadvantages of these methods. We also highlight recent technological developments in viral vectors that can effectively infect the macaque brain, as well as the development of methods to deliver photostimulation or ligand drugs to a wide area to effectively manipulate behavior. The development and dissemination of such pathway-selective manipulations of macaque prefrontal networks will enable us to efficiently dissect the neural mechanisms of decision-making and innovate novel treatments for decision-related psychiatric disorders.

Association Between Polymorphism (5-HTTLPR) of the Serotonin Transporter Gene and Behavioral Response to Unfair Distribution.

Behavioral responses to unfair distribution have been measured mainly using the Ultimatum Game (UG). Recent studies examining the biological basis of behavioral responses to unfair distribution have focused attention on the role of the serotonin transporter gene. However, studies, to date, have been conducted on non-Asians, and it has not been confirmed whether similar results can be seen in other ethnic groups. It has also been shown that behavioral responses to unfair distribution are not only seen in the case of victims themselves but also in the case of third parties not directly affected. This study aimed to determine whether the results of the previous study would be replicated in an Asian population and whether the serotonin transporter gene would also be associated with behavior toward unfair distribution by third parties. We examined the association between polymorphisms (5-HTTLPR) of the serotonin transporter gene and participants' behavior in the UG and the third-party punishment game (TPPG). The results did not show an association between punishment for unfair proposals in the TPPG and genetic polymorphisms, while participants with the SL/LL genotype were more likely to reject unfair offers in the UG than those with the SS genotype. These results indicate that 5-HTTLPR is associated with behavior when unfair intentions are directed at oneself.

A whole brain probabilistic generative model: Toward realizing cognitive architectures for developmental robots.

Building a human-like integrative artificial cognitive system, that is, an artificial general intelligence (AGI), is the holy grail of the artificial intelligence (AI) field. Furthermore, a computational model that enables an artificial system to achieve cognitive development will be an excellent reference for brain and cognitive science. This paper describes an approach to develop a cognitive architecture by integrating elemental cognitive modules to enable the training of the modules as a whole. This approach is based on two ideas: (1) brain-inspired AI, learning human brain architecture to build human-level intelligence, and (2) a probabilistic generative model (PGM)-based cognitive architecture to develop a cognitive system for developmental robots by integrating PGMs. The proposed development framework is called a whole brain PGM (WB-PGM), which differs fundamentally from existing cognitive architectures in that it can learn continuously through a system based on sensory-motor information. In this paper, we describe the rationale for WB-PGM, the current status of PGM-based elemental cognitive modules, their relationship with the human brain, the approach to the integration of the cognitive modules, and future challenges. Our findings can serve as a reference for brain studies. As PGMs describe explicit informational relationships between variables, WB-PGM provides interpretable guidance from computational sciences to brain science. By providing such information, researchers in neuroscience can provide feedback to researchers in AI and robotics on what the current models lack with reference to the brain. Further, it can facilitate collaboration among researchers in neuro-cognitive sciences as well as AI and robotics.

Chemogenetic inactivation reveals the inhibitory control function of the prefronto-striatal pathway in the macaque brain.

The lateral prefrontal cortex (LPFC) has a strong monosynaptic connection with the caudate nucleus (CdN) of the striatum. Previous human MRI studies have suggested that this LPFC-CdN pathway plays an important role in inhibitory control and working memory. We aimed to validate the function of this pathway at a causal level by pathway-selective manipulation of neural activity in non-human primates. To this end, we trained macaque monkeys on a delayed oculomotor response task with reward asymmetry and expressed an inhibitory type of chemogenetic receptors selectively to LPFC neurons that project to the CdN. Ligand administration reduced the inhibitory control of impulsive behavior, as well as the task-related neuronal responses observed in the local field potentials from the LPFC and CdN. These results show that we successfully suppressed pathway-selective neural activity in the macaque brain, and the resulting behavioral changes suggest that the LPFC-CdN pathway is involved in inhibitory control.

Microendoscopic calcium imaging of the primary visual cortex of behaving macaques.

In vivo calcium imaging with genetically encoded indicators has recently been applied to macaque brains to monitor neural activities from a large population of cells simultaneously. Microendoscopic calcium imaging combined with implantable gradient index lenses captures neural activities from deep brain areas with a compact and convenient setup; however, this has been limited to rodents and marmosets. Here, we developed miniature fluorescent microscopy to image neural activities from the primary visual cortex of behaving macaques. We found tens of clear fluorescent signals from three of the six brain hemispheres. A subset of these neurons showed clear retinotopy and orientation tuning. Moreover, we successfully decoded the stimulus orientation and tracked the cells across days. These results indicate that microendoscopic calcium imaging is feasible and reasonable for investigating neural circuits in the macaque brain by monitoring fluorescent signals from a large number of neurons.

How do we generalize?

Humans and animals are able to generalize or transfer information from previous experience so that they can behave appropriately in novel situations. What mechanisms-computations, representations, and neural systems-give rise to this remarkable ability? The members of this Generative Adversarial Collaboration (GAC) come from a range of academic backgrounds but are all interested in uncovering the mechanisms of generalization. We started out this GAC with the aim of arbitrating between two alternative conceptual accounts: (1) generalization stems from integration of multiple experiences into summary representations that reflect generalized knowledge, and (2) generalization is computed on-the-fly using separately stored individual memories. Across the course of this collaboration, we found that-despite using different terminology and techniques, and although some of our specific papers may provide evidence one way or the other-we in fact largely agree that both of these broad accounts (as well as several others) are likely valid. We believe that future research and theoretical synthesis across multiple lines of research is necessary to help determine the degree to which different candidate generalization mechanisms may operate simultaneously, operate on different scales, or be employed under distinct conditions. Here, as the first step, we introduce some of these candidate mechanisms and we discuss the issues currently hindering better synthesis of generalization research. Finally, we introduce some of our own research questions that have arisen over the course of this GAC, that we believe would benefit from future collaborative efforts.

[Stimulus and reward information encoded by population neurons in the primate prefrontal cortex and striatum].

It has been reported that single-unit activity in the prefrontal cortex (PFC) and striatum represented visual stimulus and reward information. But how to encode these pieces of information is quite complex from the view of single-neuron activity. Different neurons represented stimulus or reward information in different task epochs with increasing or decreasing their activities relative to their baseline firing rates. The present paper was aimed to study whether population neurons in the two brain areas could stably encode task-relevant parameters in a whole trial period. We recorded single-unit activities in the lateral PFC (LPFC) and striatum while the monkey was performing a stimulus- reward prediction task, and analyzed the neuronal activities by the method of a multi-variable regression model and the linear support vector machine. The results showed that, although proportions of task-related neurons in the two areas varied largely in the whole trial period, LPFC population neurons encoded reward and stimulus information stably and reliably. Population neurons in the striatum encoded only reward information, not stimulus information. A group of neurons in the two areas represented combined information of stimulus and reward. Further analysis showed that LPFC neurons encoded reward information for a group of relevant stimuli, while striatal neurons encoded reward information for a specific stimulus. These results suggest that both LPFC and striatal population neurons are able to stably represent task-relevant information, but from different aspects of the task. The different strategies to encode information in the LPFC and striatum suggest their different contributions in reward-based decision making.

The cost of obtaining rewards enhances the reward prediction error signal of midbrain dopamine neurons.

Midbrain dopamine neurons are known to encode reward prediction errors (RPE) used to update value predictions. Here, we examine whether RPE signals coded by midbrain dopamine neurons are modulated by the cost paid to obtain rewards, by recording from dopamine neurons in awake behaving monkeys during performance of an effortful saccade task. Dopamine neuron responses to cues predicting reward and to the delivery of rewards were increased after the performance of a costly action compared to a less costly action, suggesting that RPEs are enhanced following the performance of a costly action. At the behavioral level, stimulus-reward associations are learned faster after performing a costly action compared to a less costly action. Thus, information about action cost is processed in the dopamine reward system in a manner that amplifies the following dopamine RPE signal, which in turn promotes more rapid learning under situations of high cost.

Association of Polymorphism of Arginine-Vasopressin Receptor 1A (AVPR1a) Gene With Trust and Reciprocity.

Oxytocin (OXT) is known to play an important role in trust, whereas the involvement of other peptide hormones has not been evaluated. In this study, we focused on microsatellite polymorphisms in the intron of the arginine-vasopressin receptor 1a (AVPR1a) gene and examined whether the association between the repeat lengths in the intron of AVPR1a is associated with trust and reciprocity in humans. Four-hundred and thirty-three participants played the trust game, answered the attitudinal trust question, and their buccal cells were collected. Results showed that men with a short form of AVPR1a tend to send more money to the opponent, even if there is a possibility of being betrayed by the opponent. Additionally, people with a short form of AVPR1a tended to return money to the opponent who trusts them. However, attitudinal trust was not associated with AVPR1a. These results indicate that arginine-vasopressin receptor 1a plays an important role in trust and reciprocal behaviors.

Psychosocial Twin Cohort Studies in Japan: The Keio Twin Research Center (KoTReC).

The Keio Twin Research Center (KoTReC) was established in 2009 at Keio University to combine two longitudinal cohort projects - the Keio Twin Study (KTS) for adolescence and adulthood and the Tokyo Twin Cohort Project (ToTCoP) for infancy and childhood. KoTReC also conducted a two-time panel study of self-control and psychopathology in twin adolescence in 2012 and 2013 and three independent anonymous cross-sectional twin surveys (ToTcross) before 2012 - the ToTCross, the Junior and Senior High School Survey and the High School Survey. This article introduces the recent research designs of KoTReC and its publications.

Association of the oxytocin receptor gene with attitudinal trust: role of amygdala volume.

Previous studies have shown that genetic variations in rs53576, a common variant of the oxytocin receptor gene (OXTR) resulting from a single nucleotide polymorphism involving an adenine (A)/guanine (G) transition, are associated with attitudinal trust in men. However, the pathway from gene to behaviour has not been elucidated. We conducted the present study to determine whether amygdala volume mediates the association between OXTR rs53576 genotypes and attitudinal trust. Our results revealed that the left amygdala volume was significantly smaller in GG men than in AA and AG men, whereas it was significantly smaller in AA and AG women than in GG women. In addition, the left amygdala volume was negatively associated with attitudinal trust in men, whereas there was no such association in women. We also found a significant mediation effect of the left amygdala volume on the association between OXTR rs53576 genotypes and attitudinal trust in men. The results of our study suggest that the left amygdala volume plays a pivotal role in the association between OXTR rs53576 genotypes and attitudinal trust in men.

Differences in reward processing between putative cell types in primate prefrontal cortex.

Single-unit studies in monkeys have demonstrated that neurons in the prefrontal cortex predict the reward type, reward amount or reward availability associated with a stimulus. To examine contributions of pyramidal cells and interneurons in reward processing, single-unit activity was extracellularly recorded in prefrontal cortices of four monkeys performing a reward prediction task. Based on their shapes of spike waveforms, prefrontal neurons were classified into broad-spike and narrow-spike units that represented putative pyramidal cells and interneurons, respectively. We mainly observed that narrow-spike neurons showed higher firing rates but less bursty discharges than did broad-spike neurons. Both narrow-spike and broad-spike cells selectively responded to the stimulus, reward and their interaction, and the proportions of each type of selective neurons were similar between the two cell classes. Moreover, the two types of cells displayed equal reliability of reward or stimulus discrimination. Furthermore, we found that broad-spike and narrow-spike cells showed distinct mechanisms for encoding reward or stimulus information. Broad-spike neurons raised their firing rate relative to the baseline rate to represent the preferred reward or stimulus information, whereas narrow-spike neurons inhibited their firing rate lower than the baseline rate to encode the non-preferred reward or stimulus information. Our results suggest that narrow-spike and broad-spike cells were equally involved in reward and stimulus processing in the prefrontal cortex. They utilized a binary strategy to complementarily represent reward or stimulus information, which was consistent with the task structure in which the monkeys were required to remember two reward conditions and two visual stimuli.

Behavioural Differences and Neural Substrates of Altruistic and Spiteful Punishment.

Altruistic punishment following social norm violations promotes human cooperation. However, experimental evidence indicates that some forms of punishment are spiteful rather than altruistic. Using two types of punishment games and seven non-strategic games, we identified strong behavioural differences between altruistic and spiteful punishers. Altruistic punishers who rejected unfair offers in the ultimatum game and punished norm violators in the third-party punishment game behaved pro-socially in various non-strategic games. Spiteful punishers who rejected unfair offers in the ultimatum game but did not punish norm violators in the third-party punishment game behaved selfishly in non-strategic games. In addition, the left caudate nucleus was larger in spiteful punishers than in altruistic punishers. These findings are in contrast to the previous assumption that altruistic punishers derive pleasure from enforcement of fairness norms, and suggest that spiteful punishers derive pleasure from seeing the target experience negative consequences.

[Reward information encoded by power of local field potentials in the primate prefrontal cortex and striatum].

Prefrontal cortex and striatum are two major areas in the brain. Some research reports suggest that both areas are involved in many advanced cognitive processes, such as learning and memory, reward processing, and behavioral decision. Single-unit recording experiments have found that neurons in the prefrontal cortex and striatum can represent reward information, but it remains elusive whether and how local field potentials (LFPs) in the two areas encode reward information. To investigate these issues, we recorded LFPs simultaneously in the prefrontal cortex and striatum of two monkeys by performing a reward prediction task (a large amount reward vs a small amount reward). Recorded LFP signals were transformed from the time domain to the time and frequency domain using the method of short-time Fourier transform (STFT). We calculated the power in each frequency and time, and examined whether they were different in the two reward conditions. The results showed that power of LFPs in both the prefrontal cortex and striatum distinguished one reward condition from the other one. And the power in small reward trials was greater than that in large reward trials. Furthermore, it was found that the LFPs better encoded reward information in the beta band (14-30 Hz) rather than other frequency bands. Our results suggest that the LFPs in the prefrontal cortex and striatum effectively represent reward information, which would help to further understand functional roles of LFPs in reward processing.