Social context and drug cues modulate inhibitory control in cocaine addiction: involvement of the STN evidenced through functional MRI.

Addictions often develop in a social context, although the influence of social factors did not receive much attention in the neuroscience of addiction. Recent animal studies suggest that peer presence can reduce cocaine intake, an influence potentially mediated, among others, by the subthalamic nucleus (STN). However, there is to date no neurobiological study investigating this mediation in humans. This study investigated the impact of social context and drug cues on brain correlates of inhibitory control in individuals with and without cocaine use disorder (CUD) using functional Magnetic Resonance Imaging (fMRI). Seventeen CUD participants and 17 healthy controls (HC) performed a novel fMRI "Social" Stop-Signal Task (SSST) in the presence or absence of an observer while being exposed to cocaine-related (vs. neutral) cues eliciting craving in drug users. The results showed that CUD participants, while slower at stopping with neutral cues, recovered control level stopping abilities with cocaine cues, while HC did not show any difference. During inhibition (Stop Correct vs Stop Incorrect), activity in the right STN, right inferior frontal gyrus (IFG), and bilateral orbitofrontal cortex (OFC) varied according to the type of cue. Notably, the presence of an observer reversed this effect in most areas for CUD participants. These findings highlight the impact of social context and drug cues on inhibitory control in CUD and the mediation of these effects by the right STN and bilateral OFC, emphasizing the importance of considering the social context in addiction research. They also comfort the STN as a potential addiction treatment target.

Interpretable prediction of brain activity during conversations from multimodal behavioral signals.

We present an analytical framework aimed at predicting the local brain activity in uncontrolled experimental conditions based on multimodal recordings of participants' behavior, and its application to a corpus of participants having conversations with another human or a conversational humanoid robot. The framework consists in extracting high-level features from the raw behavioral recordings and applying a dynamic prediction of binarized fMRI-recorded local brain activity using these behavioral features. The objective is to identify behavioral features required for this prediction, and their relative weights, depending on the brain area under investigation and the experimental condition. In order to validate our framework, we use a corpus of uncontrolled conversations of participants with a human or a robotic agent, focusing on brain regions involved in speech processing, and more generally in social interactions. The framework not only predicts local brain activity significantly better than random, it also quantifies the weights of behavioral features required for this prediction, depending on the brain area under investigation and on the nature of the conversational partner. In the left Superior Temporal Sulcus, perceived speech is the most important behavioral feature for predicting brain activity, regardless of the agent, while several features, which differ between the human and robot interlocutors, contribute to the prediction in regions involved in social cognition, such as the TemporoParietal Junction. This framework therefore allows us to study how multiple behavioral signals from different modalities are integrated in individual brain regions during complex social interactions.

Perceived facial happiness during conversation correlates with insular and hypothalamus activity for humans, not robots.

Emotional contagion, in particular of happiness, is essential to creating social bonds. The somatic marker hypothesis posits that embodied physiological changes associated with emotions and relayed to the brain by the autonomous nervous system influence behavior. Perceiving others' positive emotions should thus be associated with activity in brain regions relaying information from and to the autonomic nervous system. Here, we address this question using a unique corpus of brain activity recorded during unconstrained conversations between participants and a human or a humanoid robot. fMRI recordings are used to test whether activity in key brain regions of the autonomic system, the amygdala, hypothalamus, and insula, is differentially affected by the level of happiness expressed by the human and robot agents. Results indicate that for the hypothalamus and the insula, in particular the anterior agranular region strongly involved in processing social emotions, activity in the right hemisphere increases with the level of happiness expressed by the human but not the robot. Perceiving positive emotions in social interactions induces local brain responses predicted by the contagion of somatic markers of emotions only when the interacting agent is a fellow human.

Precuneus brain response changes differently during human-robot and human-human dyadic social interaction.

Human-human interactions (HHI) and human-robot interactions (HRI) are compared to identify differences between cognitive processes reflecting bonding in social interactions with natural and artificial agents. We capitalize on a unique corpus of neuroimaging data (fMRI) recorded while participants freely discussed with another human or a conversational robotic head, in order to study a crucial parameter of human social cognition, namely that social interactions are adaptive bidirectional processes that evolve over time. We used linear statistics to identify regions of the brain where activity changes differently when participants carry out twelve one-minute conversations, alternating between a human and a robotic interlocutor. Results show that activity in the posterior cingulate cortex, a key region associated with social cognition, increases over time in HHI but not in HRI. These results are interpreted as reflecting a process of strengthening social bonding during repeated exchanges when the interacting agent is a human, but not a robot.

Going Beyond the "Synthetic Method": New Paradigms Cross-Fertilizing Robotics and Cognitive Neuroscience.

In so-called ethorobotics and robot-supported social cognitive neurosciences, robots are used as scientific tools to study animal behavior and cognition. Building on previous epistemological analyses of biorobotics, in this article it is argued that these two research fields, widely differing from one another in the kinds of robots involved and in the research questions addressed, share a common methodology, which significantly differs from the "synthetic method" that, until recently, dominated biorobotics. The methodological novelty of this strategy, the research opportunities that it opens, and the theoretical and technological challenges that it gives rise to, will be discussed with reference to the peculiarities of the two research fields. Some broad methodological issues related to the generalization of results concerning robot-animal interaction to theoretical conclusions on animal-animal interaction will be identified and discussed.

Causal Analysis of Activity in Social Brain Areas During Human-Agent Conversation.

This article investigates the differences in cognitive and neural mechanisms between human-human and human-virtual agent interaction using a dataset recorded in an ecologically realistic environment. We use Convergent Cross Mapping (CCM) to investigate functional connectivity between pairs of regions involved in the framework of social cognitive neuroscience, namely the fusiform gyrus, superior temporal sulcus (STS), temporoparietal junction (TPJ), and the dorsolateral prefrontal cortex (DLPFC)-taken as prefrontal asymmetry. Our approach is a compromise between investigating local activation in specific regions and investigating connectivity networks that may form part of larger networks. In addition to concording with previous studies, our results suggest that the right TPJ is one of the most reliable areas for assessing processes occurring during human-virtual agent interactions, both in a static and dynamic sense.

The measurement, evolution, and neural representation of action grammars of human behavior.

Human behaviors from toolmaking to language are thought to rely on a uniquely evolved capacity for hierarchical action sequencing. Testing this idea will require objective, generalizable methods for measuring the structural complexity of real-world behavior. Here we present a data-driven approach for extracting action grammars from basic ethograms, exemplified with respect to the evolutionarily relevant behavior of stone toolmaking. We analyzed sequences from the experimental replication of ~ 2.5 Mya Oldowan vs. ~ 0.5 Mya Acheulean tools, finding that, while using the same "alphabet" of elementary actions, Acheulean sequences are quantifiably more complex and Oldowan grammars are a subset of Acheulean grammars. We illustrate the utility of our complexity measures by re-analyzing data from an fMRI study of stone toolmaking to identify brain responses to structural complexity. Beyond specific implications regarding the co-evolution of language and technology, this exercise illustrates the general applicability of our method to investigate naturalistic human behavior and cognition.

Cracking the EMDR code: Recruitment of sensory, memory and emotional networks during bilateral alternating auditory stimulation.

INTRODUCTION: The inability to extinguish a conditioned fear is thought to be at the core of post-traumatic stress disorder. Eye movement desensitization and reprocessing therapy has been efficacious for post-traumatic stress disorder, but the brain mechanisms underlying the effect are still unknown. The core effect of eye movement desensitization and reprocessing therapy seems to rely on the simultaneous association of bilateral alternating stimulation and the recall of the traumatic memory. To shed light on how eye movement desensitization and reprocessing therapy functions, we aimed to highlight the structures activated by bilateral alternating stimulation during fear extinction and its recall. METHODS: We included 38 healthy participants in this study. Participants were examined twice in functional magnetic resonance imaging, over 2 consecutive days. On the first day, they performed two fear conditioning and extinction procedures, one with and one without the bilateral alternating stimulation during the fear extinction learning phase in a counter-balanced order across the participants. On the second day, participants completed the fear extinction recall procedure, in the same order as the previous day. Statistical significance of maps was set at p < 0.05 after correction for family-wise error at the cluster level. RESULTS: The analysis revealed significant activation with versus without bilateral alternating stimulation at the early extinction in the bilateral auditory areas, the right precuneus, and the left medial frontal gyrus. The same pattern was found in the early recall on the second day. The connectivity analysis found a significant increase in connectivity during bilateral alternating stimulation versus without bilateral alternating stimulation in the early extinction and recall between the two superior temporal gyri, the precuneus, the middle frontal gyrus and a set of structures involved in multisensory integration, executive control, emotional processing, salience and memory. CONCLUSION: We show for the first time that in the eye movement desensitization and reprocessing therapy the bilateral alternating stimulation is not a simple sensory signal and can activate large emotional neural networks.

Inter-subject pattern analysis: A straightforward and powerful scheme for group-level MVPA.

Multivariate pattern analysis (MVPA) has become vastly popular for analyzing functional neuroimaging data. At the group level, two main strategies are used in the literature. The standard one is hierarchical, combining the outcomes of within-subject decoding results in a second-level analysis. The alternative one, inter-subject pattern analysis, directly works at the group-level by using, e.g. a leave-one-subject-out cross-validation. This study provides a thorough comparison of these two group-level decoding schemes, using both a large number of artificial datasets where the size of the multivariate effect and the amount of inter-individual variability are parametrically controlled, as well as two real fMRI datasets comprising 15 and 39 subjects, respectively. We show that these two strategies uncover distinct significant regions with partial overlap, and that inter-subject pattern analysis is able to detect smaller effects and to facilitate the interpretation. The core source code and data are openly available, allowing to fully reproduce most of these results.

Posttraumatic Stress Disorder is associated with altered reward mechanisms during the anticipation and the outcome of monetary incentive cues.

BACKGROUND: Recent studies suggest that Posttraumatic Stress Disorder (PTSD) might be associated with dysfunctional reward circuitry. However, further research is needed to understand the key role of the reward system in PTSD symptomatology. METHODS: Twenty participants with PTSD and 21 Trauma-Exposed matched Controls (TECs) completed the Monetary Incentive Delay (MID) task during an MRI session. Reaction times (RTs) and hit rates were recorded. Brain activity was investigated during the anticipation and the outcome of monetary gains and losses. RESULTS: During the anticipation of monetary loss, PTSD participants had higher RTs than TECs. However, the groups did not differ at the neurofunctional level. During successful avoidance of monetary loss, PTSD patients showed higher activation than TECs in the left caudate nucleus. During the anticipation of monetary gains, no differences in RTs were found between groups. PTSD patients had specific activations in the right amygdala, nucleus accumbens, putamen, and middle frontal gyrus (p < 0.05 family-wise error (FWE)-corrected), while TECs had specific activation in the anterior cingulate cortex. When obtaining monetary gains, PTSD patients had specific activation in the caudate nucleus, while TECs had specific activations in the right hypothalamus, subthalamic nucleus, and left inferior frontal gyrus. CONCLUSION: For the first time, functional brain activation during both the anticipation and the outcome of monetary rewards is reported altered in PTSD patients. These alterations might be associated with the complex symptomatology of PTSD.

Brain activity during reciprocal social interaction investigated using conversational robots as control condition.

We present a novel functional magnetic resonance imaging paradigm for second-person neuroscience. The paradigm compares a human social interaction (human-human interaction, HHI) to an interaction with a conversational robot (human-robot interaction, HRI). The social interaction consists of 1 min blocks of live bidirectional discussion between the scanned participant and the human or robot agent. A final sample of 21 participants is included in the corpus comprising physiological (blood oxygen level-dependent, respiration and peripheral blood flow) and behavioural (recorded speech from all interlocutors, eye tracking from the scanned participant, face recording of the human and robot agents) data. Here, we present the first analysis of this corpus, contrasting neural activity between HHI and HRI. We hypothesized that independently of differences in behaviour between interactions with the human and robot agent, neural markers of mentalizing (temporoparietal junction (TPJ) and medial prefrontal cortex) and social motivation (hypothalamus and amygdala) would only be active in HHI. Results confirmed significantly increased response associated with HHI in the TPJ, hypothalamus and amygdala, but not in the medial prefrontal cortex. Future analysis of this corpus will include fine-grained characterization of verbal and non-verbal behaviours recorded during the interaction to investigate their neural correlates. This article is part of the theme issue 'From social brains to social robots: applying neurocognitive insights to human-robot interaction'.

Fear extinction learning improvement in PTSD after EMDR therapy: an fMRI study.

Objective: Neurobiological models of Posttraumatic Stress Disorder (PTSD) implicate fear processing impairments in the maintenance of the disorder. Eye Movement Desensitization and Reprocessing (EMDR) is one of the most efficient psychotherapies to treat PTSD. We aimed at exploring the brain mechanisms of the fear circuitry involved in PTSD patients' symptom remission after EMDR therapy. Method: Thirty-six PTSD participants were randomly assigned to either EMDR group receiving EMDR therapy or Wait-List (WL) group receiving supportive therapy. Participants underwent a behavioural fear conditioning and extinction paradigm during functional magnetic resonance (fMRI). In the EMDR group, patients were scanned at baseline, before EMDR and one week after remission. In the WL group, patients were scanned at baseline and within the same time interval as the EMDR group. Results: In the EMDR group after treatment, fear responses in the late extinction were significantly lower than before therapy. In parallel, significant functional activity and connectivity changes were found in the EMDR group versus the WL during the late extinction. These changes involve the fear circuit (amygdalae, left hippocampus), the right inferior frontal gyrus, the right frontal eye field and insula (pFWE < .05). Conclusion: These functional modifications underlie a significant improvement of fear extinction learning in PTSD patients after EMDR therapy.

Objetivo: Los modelos neurobiológicos del TEPT implican deficiencias en el procesamiento del miedo en el mantenimiento del trastorno. EMDR es una de las psicoterapias más eficaces para tratar el TEPT. Nuestro objetivo fue explorar los mecanismos cerebrales de los circuitos de miedo implicados en la remisión de los síntomas de los pacientes con el TEPT después de la terapia EMDR.Método: Treinta y seis participantes con el TEPT fueron asignados aleatoriamente a un grupo EMDR que recibió terapia EMDR o un grupo de Lista de Espera (LE) que recibió terapia de apoyo. Los participantes se sometieron a un paradigma de condicionamiento y extinción del miedo conductual durante la resonancia magnética funcional (fMRI). En el grupo EMDR, los pacientes fueron escaneados al inicio del estudio, antes de EMDR y una semana después de la remisión. En el grupo LE, los pacientes fueron escaneados al inicio y en el mismo intervalo de tiempo que el grupo EMDR.Resultados: En el grupo EMDR después del tratamiento, las respuestas de miedo en la extinción tardía fueron significativamente más bajas que antes de la terapia. En paralelo, se encontraron cambios significativos en la actividad funcional y en la conectividad en el grupo EMDR v/s el grupo LE durante la extinción tardía. Estos cambios involucran el circuito de miedo (amígdala, hipocampo izquierdo), el giro frontal inferior derecho, los campos del ojo frontal derecho y la ínsula (pFWE < .05).Conclusión: Estas modificaciones funcionales subyacen a una mejora significativa del aprendizaje de extinción del miedo en pacientes con el TEPT después de la terapia EMDR.

Functional connectivity within the voice perception network and its behavioural relevance.

Recognizing who is speaking is a cognitive ability characterized by considerable individual differences, which could relate to the inter-individual variability observed in voice-elicited BOLD activity. Since voice perception is sustained by a complex brain network involving temporal voice areas (TVAs) and, even if less consistently, extra-temporal regions such as frontal cortices, functional connectivity (FC) during an fMRI voice localizer (passive listening of voices vs non-voices) has been computed within twelve temporal and frontal voice-sensitive regions ("voice patches") individually defined for each subject (N = 90) to account for inter-individual variability. Results revealed that voice patches were positively co-activated during voice listening and that they were characterized by different FC pattern depending on the location (anterior/posterior) and the hemisphere. Importantly, FC between right frontal and temporal voice patches was behaviorally relevant: FC significantly increased with voice recognition abilities as measured in a voice recognition test performed outside the scanner. Hence, this study highlights the importance of frontal regions in voice perception and it supports the idea that looking at FC between stimulus-specific and higher-order frontal regions can help understanding individual differences in processing social stimuli such as voices.

Are friends really the family we choose? Local variations of hypothalamus activity when viewing personally known faces.

Sibling and friend relationships have significant impact on individuals' socio-emotional development. Hypothalamic supraoptic nucleus (SON) and paraventricular nucleus (PVN) synthesize and secrete neuropeptides, including oxytocin, associated with attachment behaviors. Here, using fMRI, we investigate the implication of these two hypothalamic nuclei in the visual processing of personally known faces.  Faces of same-sex sibling, best friend, celebrity, and unknown person appear in the middle of the screen while participants perform a task requiring a button click each time a central white dot turns red. Ratings of familiarity (time spent together) and emotionality (feelings toward individual) toward the four individuals are recorded. Local activation within the hypothalamus is assessed via two complementary methods: (1) voxel-based analyses within inclusive mask of the hypothalamus; (2) region-of-interest (ROI) analysis of partial hypothalamic volumes using SON and PVN as center of mass coordinates, with percent signal change extracted and analyzed within these ROIs. Results suggest that the SON responds to all familiar individuals while the PVN has increased response to sibling compared to friend faces and is correlated to familiarity but not emotionality. These findings support differential involvement of local hypothalamic substructures SON and PVN in response to faces of individuals with different social relationships.

Embodied artificial agents for understanding human social cognition.

In this paper, we propose that experimental protocols involving artificial agents, in particular the embodied humanoid robots, provide insightful information regarding social cognitive mechanisms in the human brain. Using artificial agents allows for manipulation and control of various parameters of behaviour, appearance and expressiveness in one of the interaction partners (the artificial agent), and for examining effect of these parameters on the other interaction partner (the human). At the same time, using artificial agents means introducing the presence of artificial, yet human-like, systems into the human social sphere. This allows for testing in a controlled, but ecologically valid, manner human fundamental mechanisms of social cognition both at the behavioural and at the neural level. This paper will review existing literature that reports studies in which artificial embodied agents have been used to study social cognition and will address the question of whether various mechanisms of social cognition (ranging from lower- to higher-order cognitive processes) are evoked by artificial agents to the same extent as by natural agents, humans in particular. Increasing the understanding of how behavioural and neural mechanisms of social cognition respond to artificial anthropomorphic agents provides empirical answers to the conundrum 'What is a social agent?'

Focal atrophy of the hypothalamus associated with third ventricle enlargement in autism spectrum disorder.

The hypothalamus is a brain structure containing multiple nuclei that mediate essential behavioral, autonomic, and endocrine functions including oxytocin synthesis. Oxytocin is a neuropeptide linked to complex social cognition and behaviors necessary for an effective social interaction. Oxytocinergic system dysfunction has been linked to social deficits in autism spectrum disorders (ASD). Limited studies have been carried out on the hypothalamus because of its small size and methodological constraints in current technologies. This neuroimaging study examines hypothalamic atrophy in ASD in comparison with a typically developing population (a) by directly measuring gray matter (GM) density with a region-of-interest analysis using voxel-based morphometry in a homogenous sample of participants controlled for age and intelligence quotient; (b) for generalization, by measuring third ventricular volume, on the basis of its position bilaterally surrounded by the hypothalamus, using Freesurfer in a heterogeneous sample of participants. A voxel-based morphometry analysis of cerebrospinal fluid density on the first sample provides a link between GM density and third ventricle volume. Our results show decreased hypothalamic GM density and increased third ventricle volume in ASD compared with typically developing patients. Our findings provide neuroanatomical insights into social deficits in ASD within the hypothalamus that might be relevant for other psychiatric conditions.

Cognitive demands of lower paleolithic toolmaking.

Stone tools provide some of the most abundant, continuous, and high resolution evidence of behavioral change over human evolution, but their implications for cognitive evolution have remained unclear. We investigated the neurophysiological demands of stone toolmaking by training modern subjects in known Paleolithic methods ("Oldowan", "Acheulean") and collecting structural and functional brain imaging data as they made technical judgments (outcome prediction, strategic appropriateness) about planned actions on partially completed tools. Results show that this task affected neural activity and functional connectivity in dorsal prefrontal cortex, that effect magnitude correlated with the frequency of correct strategic judgments, and that the frequency of correct strategic judgments was predictive of success in Acheulean, but not Oldowan, toolmaking. This corroborates hypothesized cognitive control demands of Acheulean toolmaking, specifically including information monitoring and manipulation functions attributed to the "central executive" of working memory. More broadly, it develops empirical methods for assessing the differential cognitive demands of Paleolithic technologies, and expands the scope of evolutionary hypotheses that can be tested using the available archaeological record.

Attachment style impacts behavior and early oculomotor response to positive, but not negative, pictures.

The present study investigated whether oculomotor behavior is influenced by attachment styles. The Relationship Scales Questionnaire was used to assess attachment styles of forty-eight voluntary university students and to classify them into attachment groups (secure, preoccupied, fearful, and dismissing). Eye-tracking was recorded while participants engaged in a 3-seconds free visual exploration of stimuli presenting either a positive or a negative picture together with a neutral picture, all depicting social interactions. The task consisted in identifying whether the two pictures depicted the same emotion. Results showed that the processing of negative pictures was impermeable to attachment style, while the processing of positive pictures was significantly influenced by individual differences in insecure attachment. The groups highly avoidant regarding to attachment (dismissing and fearful) showed reduced accuracy, suggesting a higher threshold for recognizing positive emotions compared to the secure group. The groups with higher attachment anxiety (preoccupied and fearful) showed differences in automatic capture of attention, in particular an increased delay preceding the first fixation to a picture of positive emotional valence. Despite lenient statistical thresholds induced by the limited sample size of some groups (p < 0.05 uncorrected for multiple comparisons), the current findings suggest that the processing of positive emotions is affected by attachment styles. These results are discussed within a broader evolutionary framework.

Anthropomorphic bias found in typically developing children is not found in children with autistic spectrum disorder.

The anthropomorphic bias describes the finding that the perceived naturalness of a biological motion decreases as the human-likeness of a computer-animated agent increases. To investigate the anthropomorphic bias in autistic children, human or cartoon characters were presented with biological and artificial motions side by side on a touchscreen. Children were required to touch one that would grow while the other would disappear, implicitly rewarding their choice. Only typically developing controls depicted the expected preference for biological motion when rendered with human, but not cartoon, characters. Despite performing the task to report a preference, children with autism depicted neither normal nor reversed anthropomorphic bias, suggesting that they are not sensitive to the congruence of form and motion information when observing computer-animated agents' actions.

Comparing the effect of humanoid and human face for the spatial orientation of attention.

The current study was designed to investigate how the automatic spatial orientation of attention induced by the perception of another agent's orientation of attention is modulated by the social nature of the other agent. Modified versions of the Posner task, using a real or schematic face with eyes or head looking toward the left or the right before a to-be-detected target appears on one side of the screen have been used to demonstrate a reduction of reaction time (RT) for target detection when the gaze is directed toward the target, even though the cue is not informative. We compared the effect of two agents, the humanoid robotic platform Nao and a real human, using head turn to cue the spatial orientation of attention. Our results reproduced the typical Posner effect, with reduced RT to valid compared to invalid spatial cues. RT increased when no spatial information was provided, interpreted as an increased difficulty to disengage from a direct gaze. RT was also increased when the robot was used instead of the human face and when the eyes of the stimuli were blacked out. Both effects were interpreted as resulting from an increased difficulty to disengage attention from the central stimulus because of its novelty. In all experiments, there was no interaction between cue validity and cue agent, implying that the exact nature of the human-like agent didn't have an effect on the automatic spatial orientation of attention. Altogether, our results imply that a humanoid face is as potent as a human face to trigger an automatic orientation of spatial attention.