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Autism is a neurodevelopmental disorder that affects the everyday life of people who have this lifelong condition. Robots hold great promise for uplifting therapy and care of the affected population. We searched Scopus, Medline, ScienceDirect, Web of Science, and PubMed databases for randomized controlled trials that had evaluated robot use in the therapy of people with autism, to see how effective social robots have been incorporated in autism care. Out of 240 papers initially identified, 19 satisfied the inclusion criteria and were fully evaluated. Overall, 10 different robots were utilized in the trials, out of which, four were non-humanoids. The number of papers with positive results for using robots on the main and secondary parameters was 11 and 5, respectively. Three papers reported that robot groups did not achieve better results than others. Robots in the papers included here were mainly added as the “entertainment agent” to elicit greater engagement from the participants, which is understandable, as robots at this stage might not be ready yet to deliver high-end care.

Previous reviews have specifically looked at computer-based or Internet-based approaches. However, there has been no systematic review focused upon electronic communication based interventions for hazardous young drinkers. Out of 3298 relevant citations, 13 papers consisting of 11 studies met the inclusion criteria. Effectiveness of intervention delivery was assessed using behavioural outcomes. Eight papers delivered interventions using the Web, three implemented text messaging, one used a mobile phone app and the remaining paper used a social networking site. The ability to provide personalized electronic feedback resulted in a reduction in alcohol consumption, frequency of binge drinking, and drinking in a non-risky way. However, intervention length did not appear to have an impact on overall effectiveness. Usage of text messaging and Social Network Sites (SNS) increased accessibility and ease of engaging in an intervention that is appealing and acceptable for young adults.

Oral somatosensory awareness refers to the somatic sensations arising within the mouth, and to the information these sensations provide about the state and structure of the mouth itself, and objects in the mouth. Because the oral tissues have a strong somatosensory innervation, they are the locus of some of our most intense and vivid bodily experiences. The salient pain of toothache, or the habit of running one's tongue over one's teeth when someone mentions “dentist”, provide two very different indications of the power of oral somatosensory awareness in human experience and behaviour. This paper aims to review the origins and structure of oral somatosensory awareness, focussing on quantitative, mechanistic studies in humans. We first extend a model of levels of bodily awareness to the specific case of the mouth. We then briefly summarise the sensory innervation of oral tissues, and their projections in the brain. We next describe how these peripheral inputs give rise to perceptions of objects in the mouth, such as foods, liquids and oral devices, and also of the mouth tissues themselves. Finally, we consider the concept of a conscious mouth image, and the somatosensory basis of “mouth feel”. The theoretical framework outlined in this paper is intended to facilitate scientific studies of this important site of human experience.

This paper presents a behavioral ecologist's view on adaptive responses to early stress. I first summarize two approaches to this topic drawn from other papers in this Special Issue: the 'inoculation model' and the 'adaptive calibration model'. I then describe three relevant modeling approaches from behavioral and evolutionary ecology: models of adaptive plasticity, models of adaptive prey behavior under uncertainty about risk, and models of state-dependent adaptive behavioral syndromes. These models generate some novel predictions on factors that explain variation in how organisms might respond adaptively to early stress. In particular, the state-dependent models of adaptive behavioral syndromes emphasize the importance of feedback loops between behavior and state variables in explaining the long-term persistence of effects of early experiences. State variables can include aspects of physiology, morphology or life history, differences among individuals in information state or skill, or even in social state (e.g., social rank). The feedbacks between behavior and individual state suggest a framework for an integrative approach to understanding responses to stress. The behavioral syndrome approach also emphasizes the importance of understanding stress carryovers - e.g., situations where effects of one kind of stressor (e.g., early social stress) carry over to influence other stress responses (e.g., response to danger) later in life. Finally, I discuss how responses to early stress might relate to variation in the ability of animals to cope well with novel conditions associated with human-induced rapid environmental change, a ubiquitous problem that animals face in the modern world.

This paper provides a selective review of controlled memory retrieval, i.e., processes, that operate on long-term stored information in the service of current goals and task demands. Binding mechanisms that combine fragments of long-term stored information in response to a retrieval cue, are central for the understanding of the interaction between a retrieval cue and memory-stored information. The paper summarizes empirical evidence showing that ERP slow waves are highly sensitive to the initiation and maintenance of retrieval orientations. It is argued that similar mechanisms of controlled memory retrieval operate in the service of successful remembering and the suppression of unwanted memories (forgetting). The mechanisms can be grouped into two classes: those that enhance retrieval cue processing (cue bias) and those that directly act on memory representations and modulate their accessibility (target bias). From a neuroanatomical point of view, the former class of processes reflects selection mechanisms for internal actions that rely on the integrity of the prefrontal cortex (PFC), whereas the second class of processes can be identified with selective attention mechanisms for which the posterior parietal cortex (PPC) plays an important role.

In Italy, little is known about the spectrum of adverse fetal effects related to maternal alcohol use during pregnancy. In this paper, we report on the phenotype of Italian children with fetal alcohol spectrum disorders (FASD). These data were gathered as part of a field study assessing the prevalence of FASD in children in an in-school study in a rural area near Rome. The purposes of this paper are: (1) to completely characterize the clinical phenotype of a large cohort of Italian children with FASD; (2) to correlate and contrast the phenotype of this population with that observed in other populations and reported in the medical literature; (3) to discuss the drinking habits of Italian women, before, during and after pregnancy; and (4) to suggest mechanisms for intervention and prevention of FASD based on data gathered from this study.

According to the dual origin hypothesis, the cerebral cortex of higher mammals evolved from two primordial brain structures, the amygdala and hippocampal formation. This developmental process defines the orderly principles of cortical connectivity and gives rise to functionally distinct ventral and dorsal systems within the cerebrum. This paper reviews the basic features of the dual origin theory. This model is then applied to understanding symptom production in a number of psychiatric illnesses, with particular reference to recent structural and functional imaging studies. In this paper I propose that psychiatric symptoms can be conceptualized as arising from abnormal processing within dorsal (time-space-motility) or ventral (meaning-motivation) systems, or from a disturbance in the functional interaction/balance between them. Within this framework, one can identify symptom-specific correlations that cross-traditional diagnostic boundaries, as well as potential mechanisms that may explain biologically valid diagnostic entities. Integrating evolutionary, connectional and functional bases across multiple species, the dual origin hypothesis offers a powerful neural systems model to help organize our understanding of psychiatric illness, therein suggesting novel approaches to diagnosis, prevention and treatment.

Variation in the risk for and severity of substance use disorders (SUD) in the population is caused by multiple organismic (genetic, biochemical, psychological) and environmental factors. Whereas drug- or drug-class-specific liability mechanisms exist, a substantial proportion of variance in the risk is shared between specific liabilities, reflecting mechanisms that determine common liability to SUD. Data from epidemiologic, clinical, psychological, physiological, biochemical, and family and genetic studies reviewed in this paper indicate the existence of mechanisms and characteristics shared in common by liabilities to SUD related to different drugs. These mechanisms can be conceptualized as common liability to SUD, a latent trait accounting for a substantial portion of variation in SUD risk and severity and determined by all factors influencing the probability of SUD development. An accompanying paper describes an approach to the quantitative estimation of this trait.

Liabilities to complex disorders, discussed in the accompanying paper, present difficulties in measurement related to the arbitrariness of diagnostic threshold definitions and problems with discrimination between trait values, especially within the 'normal' individuals. The inability to quantitatively estimate the risk for a disorder, such as substance use disorders (SUD), is an obstacle for studying etiological (e.g. genetic) mechanisms and developing efficient prevention and treatment measures. Based on the concept of common liability to SUD, this paper delineates an application of the longitudinal family/high-risk design and item response theory to the development of a continuous index of liability. The method has been tested in both simulation study and empirical data. The approach described affords the opportunity to quantitatively estimate the risk for SUD at an early age and before any drug exposure. This method is also applicable to measuring liabilities to other complex disorders, especially those with relatively late onset.

This paper reviews evidence demonstrating a bidirectional relationship between memory and eating in humans and rodents. In humans, amnesia is associated with impaired processing of hunger and satiety cues, disrupted memory of recent meals, and overconsumption. In healthy participants, meal-related memory limits subsequent ingestive behavior and obesity is associated with impaired memory and disturbances in the hippocampus. Evidence from rodents suggests that dorsal hippocampal neural activity contributes to the ability of meal-related memory to control future intake, that endocrine and neuropeptide systems act in the ventral hippocampus to provide cues regarding energy status and regulate learned aspects of eating, and that consumption of hypercaloric diets and obesity disrupt these processes. Collectively, this evidence indicates that diet-induced obesity may be caused and/or maintained, at least in part, by a vicious cycle wherein excess intake disrupts hippocampal functioning, which further increases intake. This perspective may advance our understanding of how the brain controls eating, the neural mechanisms that contribute to eating-related disorders, and identify how to treat diet-induced obesity.

Background There has been much speculation about untoward effects of the Covid-19 pandemic on psychological symptoms. OCD may be expected to be especially impacted. Our aim was to distil the current evidence base on relationships between the pandemic and obsessive-compulsive symptoms, in patients, and general population samples. Methods We conducted a rapid scoping review, in the form of a systematic literature search, coupled with narrative review. 32 relevant papers were identified. Results and interpretation (1) A sizable proportion of people with OCD (but not all) experienced/reported symptom worsening during the pandemic, especially during initial restrictions (approximately 20–65 % of cases in longitudinal studies); (2) contamination/washing symptoms appeared particularly susceptible; and (3) OCD symptoms in general population samples were associated with trait compulsivity and pandemic-related-stress. The literature was heterogeneous with various methodological issues being commonplace. Future directions The review identified important unaddressed issues: how should exposure based therapy be adapted during pandemics? How can we minimise harm from exacerbation of OCD in vulnerable individuals arising from public health messaging? Why do some but not all OCD patients experience worsening? And does Covid-19 infection affect (or lead to) OCD symptoms?

Although obesity is a result of processes operating at multiple levels, most forms result from decision-making behavior. The aim of this review was to examine the candidacy of temporal discounting (TD) (i.e. the reduction in the value of a reinforcer as a function of the delay to its receipt) as a behavioral marker of obesity. For this purpose, we assessed whether TD has the ability to: identify risk for obesity development, diagnose obesity, track obesity progression, predict treatment prognosis/outcomes, and measure treatment effectiveness. Three databases (Pubmed, PsycINFO, and Web of Science) were searched using a combination of terms related to TD and obesity. A total of 153 papers were reviewed. Several areas show strong evidence of TD's predictive utility as a behavioral marker of obesity (e.g., distinguishing obese from non obese). However, other areas have limited and/or mixed evidence (e.g., predicting weight change). Given the positive relationship for TD in the majority of domains examined, further consideration for TD as a behavioral marker of obesity is warranted.

Statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) treat dyslipidaemia and cardiovascular disease by inhibiting cholesterol biosynthesis. They also have immunomodulatory and anti-inflammatory properties. Beyond cardiovascular disease, cholesterol and inflammation appear to be components of the pathogenesis and pathophysiology of neuropsychiatric disorders. Statins may therefore afford some therapeutic benefit in mood disorders. In this paper, we review the pathophysiology of mood disorders with a focus on pharmacologically relevant pathways, using major depressive disorder and bipolar disorder as exemplars. Statins are discussed in the context of these disorders, with particular focus on the putative mechanisms involved in their anti-inflammatory and immunomodulatory effects. Recent clinical data suggest that statins may have antidepressant properties, however given their interactions with many known biological pathways, it has not been fully elucidated which of these are the major determinants of clinical outcomes in mood disorders. Moreover, it remains unclear what the appropriate dose, or appropriate patient phenotype for adjunctive treatment may be. High quality randomised control trials in concert with complementary biological investigations are needed if the potential clinical effects of statins on mood disorders, as well as their biological correlates, are to be better understood.

This paper outlines a brain model of mental imaging abilities by reviewing neuropsychological evidence of the association and dissociation between mental imaging processes and known perceptual mechanisms; differentiating between visual-mode and auditory-mode thought systems; pointing to brain arousal systems involved in waking and dream imaging; and exploring pre-frontal involvement in deliberate imaging and cognitive state monitoring. In the process, the paper develops an emerging distinction between objective-imagery and subjective-imagery abilities. It ends by suggesting possible brain models for in-born and clinical loss of subjective imaging abilities.

PALINKAS, L.A., and P. SUEDFELD. Psychosocial Issues in Isolated and Confined Extreme Environments. NEUROSCI BIOBEHAV REV (1) XXX-XXX, 2020. Psychosocial elements of behavior and performance will significantly impact the outcomes of long duration missions in space, ranging from individual and team decrements to positive benefits associated with successful adaptation. This paper reviews our current understanding of the individual, interpersonal and organizational issues related to living and working in isolated and confined extreme (ICE) environments. Individual issues include changes in emotions and cognitive performance; seasonal syndromes linked to changes in the physical environment; and positive effects of adapting to ICE environments. Interpersonal issues include processes of crew cohesion, tension and conflict; interpersonal relations and social support; the impact of group diversity and leadership styles on small group dynamics; and crew-mission control interactions. Organizational issues include the influence of organizational culture and mission duration on individual and group performance, crew autonomy, and managerial requirements for long duration missions. Improved screening and selection, leadership, coping and interpersonal skills training, and organizational change are key elements to optimizing adjustment to the environment and preventing decrements during and after long duration missions.

In humans and other vertebrates, the range of disturbances and behavioural changes induced by spaceflight conditions are well known. Sensory organs and the central nervous system (CNS) are forced to adapt to new environmental conditions of weightlessness. In comparison with peripheral vestibular organs and behavioural disturbances in weightlessness conditions, the CNS vestibular centres of vertebrates, including the cerebellum, have been poorly examined in orbital experiments, as well as in experimental micro- and hypergravity. However, the cerebellum serves as a critical control centre for learning and sensory system integration during space-flight. Thus, it is referred to as a principal brain structure for adaptation to gravity and the entire sensorimotor adaptation and learning during weightlessness. This paper is focused on the prolonged spaceflight effects on the vestibular cerebellum evidenced from animal models used in the Bion-M1 project. The changes in the peripheral vestibular apparatus and brainstem primary vestibular centres with appropriate behavioural disorders after altered gravity exposure are briefly reviewed. The cerebellum studies in space missions and altered gravity are discussed.

Benzodiazepine agonists stimulate feeding in animals. This paper reviews evidence which indicates that benzodiazepine-induced feeding is due to a specific enhancement of the perceived palatability of food and fluids, and is not a mere secondary consequence of anxiety reduction. In studies of the effect of benzodiazepines on affective reactions that are naturally elicited from rats by tastes, we have shown that (a) benzodiazepines enhance hedonic taste palatability in a receptor-specific fashion; (b) the relevant receptors and the minimal neural circuitry required to mediate benzodiazepine-induced palatability enhancement both exist complete in the decerebrate brain stem; and (c) even in normal brains, receptors in the brain stem, not forebrain, are the primary substrate for the benzodiazepine-induced enhancement of taste palatability. We conclude that a 'benzodiazepine-GABA' neural system in the brain stem constitutes an important component of the neural hierarchy responsible for taste pleasure. The reason why benzodiazepine tranquilizers have not been reported to enhance palatability for humans may be that the appropriate studies have not yet been done, that human doses are low, and that the brain stem palatability system is less responsive to commonly prescribed agonists that are anxiety/arousal benzodiazepine systems. Finally, in keeping with the purpose of the symposium in which this paper was originally presented, we discuss a number of issues regarding the measurement and interpretation of taste reactivity data.

Prediction error, defined by the discrepancy between real and expected outcomes, lies at the core of associative learning. Behavioural investigations have provided evidence that prediction error up- and down-regulates associative relationships, and allocates attention to stimuli to enable learning. These behavioural advances have recently been followed by investigations into the neurobiological substrates of prediction error. In the present paper, we review neuroscience data obtained using causal and recording neural methods from a variety of key behavioural designs. We explore the neurobiology of both appetitive (reward) and aversive (fear) prediction error with a focus on the mesolimbic dopamine system, the amygdala, ventrolateral periaqueductal gray, hippocampus, cortex and locus coeruleus noradrenaline. New questions and avenues for research are considered.

The maternal behavior decline is important for the normal development of the young and the wellbeing of the mother. This paper reviews limited research on the factors and mechanisms involved in the rat maternal behavior decline and proposes a multi-level model. Framed in the parent-offspring conflict theory (an ultimate cause) and the approach-withdrawal model (a proximate cause), the maternal behavior decline is viewed as an active and effortful process, reflecting the dynamic interplay between the mother and her offspring. It is instigated by the waning of maternal motivation, coupled with the increased maternal aversion by the mother in responding to the changing sensory and motoric patterns of pup stimuli. In the decline phase, the neural circuit that mediates the inhibitory ("withdrawal") responses starts to increase activity and gain control of behavioral outputs, while the excitatory ("approach") maternal neural circuit is being inhibited or reorganized. Various hormones and certain monoamines may play a critical role in tipping the balance between the excitatory and inhibitory neural circuits to synchronize the mother-infant interaction.

Bipolar disorders have an onset in late adolescence or early adulthood and patients may experience alternating episodes of mania and depression, with euthymic periods interspersed between these extremes of mood. Clinical research studies have shown that bipolar disorder patients exhibit disruptions in circadian and seasonal rhythms, even when they are symptom free. In addition, some bipolar patients display pronounced seasonal patterns in occurrence of manic and depressive episodes, time of year for disease onset, and age of onset. Several groups have emphasized the impact of seasonal changes in sunlight intensity on bipolar disorder, especially in locations farther from the equator. In this paper, we examine rate of change of solar insolation during the spring and fall in locations that vary in their distance from the equator and propose that seasonal changes in sunlight intensity may be tracked by the suprachiasmatic nucleus and affect disease onset and progression in seasonally susceptible bipolar patients.

Music-based interventions have emerged as a promising tool in stroke motor rehabilitation as they integrate most of the principles of motor training and multimodal stimulation. This paper aims to review the use of music in the rehabilitation of upper extremity motor function after stroke. First, we review the evidence supporting current music-based interventions including Music-supported Therapy, Music glove, group music therapy, Rhythm- and music-based intervention, and Musical sonification. Next, we describe the mechanisms that may be responsible for the effectiveness of these interventions, focusing on motor learning aspects, how multimodal stimulation may boost motor performance, and emotional and motivational aspects related to music. Then, we discuss methodological concerns in music therapy research related to modifications of therapy protocols, evaluation of patients and study designs. Finally, we highlight clinical considerations for the implementation of music-based interventions in clinical settings.

A search of the PubMed and Web of Science databases for articles on skin picking in PWS was undertaken identifying case studies; trials of specific treatments; and descriptions of when skin picking occurs, what sites are chosen, and what initiates and sustains this behaviour. Published papers have also considered how skin picking might link to the PWS genotype and whether it is best considered to be part of the repetitive and ritualistic behaviours characteristic of the syndrome. To answer specific questions raised as a result of the review additional analysis was undertaken using data from our earlier population-based study of PWS. We consider this behaviour of skin picking using the framework of the Research Domains Criteria that is cross diagnostic and focuses on the identification of specific neurobiological, psychological and cognitive processes. PWS illustrates the likely interplay between different processes that first initiate and then maintain such behaviour. Treatment development depends on better understanding these mechanisms and their relative contribution to the behaviour.

Endometriosis, a condition in which uterine tissue grows outside the uterus, is a debilitating disease, affecting millions of women and costing the United States approximately $78 billion annually in pain- related disability. It is also the leading cause of chronic pelvic pain (CPP), which is often unresponsive to existing treatments. Adolescent women with the disease are at particular risk as there are often significant diagnostic delays, which in turn can exacerbate pain. Research and treatment guidelines for adolescents with endometriosis are largely based on studies for adult women due to the limited number of studies focusing on adolescents. The current paper critically reviews the literature as it pertains to endometriosis pathophysiology, mechanisms contributing to CPP, and treatment implications and recommendations with a focus on gaps related to adolescents.

Social cognition refers to the mental operations governing social interactions. Recent research has highlighted the importance of social cognition in determining functional outcome in patients with schizophrenia and in psychosis risk populations. The aim of this review is to investigate the neural correlates of social cognition in different psychosis risk populations, potentially representing different levels of risk i.e. high schizotypy (SR), familial risk (FR) and clinical high risk (CHR). PsychINFO, Web of Science and PubMed were systematically searched, and 39 papers were included in the final review. Results in FR samples were highly inconclusive. In SR samples, findings showed a tendency towards increased task related activity in frontal cortex regions. The most consistent results come from CHR samples, where findings suggest increased task related activity in frontal and cingulate cortices. Interestingly, all studies of CHR populations also report increased activity in temporal cortex and abnormal response to neutral stimuli during emotional processing tasks. These findings are discussed in relation to dopamine models of psychosis due to temporal cortex abnormality.

Animals engage in intricately woven and choreographed action sequences that are constructed from trial-and-error learning. The mechanisms by which the brain links together individual actions which are later recalled as fluid chains of behavior are not fully understood, but there is broad consensus that the basal ganglia play a crucial role in this process. This paper presents a comprehensive review of the role of the basal ganglia in action sequencing, with a focus on whether the computational framework of reinforcement learning can capture key behavioral features of sequencing and the neural mechanisms that underlie them. While a simple neurocomputational model of reinforcement learning can capture key features of action sequence learning, this model is not sufficient to capture goal-directed control of sequences or their hierarchical representation. The hierarchical structure of action sequences, in particular, poses a challenge for building better models of action sequencing, and it is in this regard that further investigations into basal ganglia information processing may be informative.

In recent years, an increasing number of studies employed the full body illusion paradigm (i.e., the experimentally induced illusory ownership over a fake/virtual body) to investigate the role of body ownership in higher-level cognition. However, to date, no systematic review of this topic is present. To fill this gap, here we identified 102 papers classifiable in 4 cognitive domains and 12 subdomains. Overall, they manipulated the identity of the fake body, and/or its spatial perspective, and/or the kind of multisensory stimulation, and/or its spatiotemporal congruency. The effects were measured through implicit and/or explicit indices. In summary, results showed that participants' behavior shifted away from the self and/or towards that of the embodied fake/virtual body. The findings have been interpreted within various exploratory frameworks, with the most common being the Proteus effect, the cortical body matrix and the inverse model of motor control. Future studies should focus on building a unitary theoretical explanation of the effects, gaining solid neural evidence, creating standard experimental procedures, and exploring the practical applications.

Brain imaging studies on eating disorders (EDs) often reported volumetric and functional changes involving the cerebellum. Nevertheless, few studies performed in-depth examinations and suggested a cerebellar role in the EDs' pathophysiology.A systematic literature search on volumetric changes and functional alterations involving the cerebellum in individuals with EDs was conducted using PubMed, PsychInfo and Web of Science. This review was conducted according to the Preferred Reporting Items for Systematic Reviews (PRISMA) statement and Rayyan web application for screening studies.Twenty-four papers reporting cerebellar alterations in individuals with EDs were included in the study: 9 assessing brain volumetric changes, 9 investigating task-based functional brain activation and 6 investigating brain functional connectivity at rest. Most studies focused on anorectic-type EDs (n.22), while fewer involved bulimic-type EDs (n.9) and eating disorders not otherwise specified (n.2), revealing subtypes-specific patterns of altered cerebellar volume and functionality.This review proposes critical arguments to consider the cerebellum as a key structure in the pathophysiology of EDs that requires further forthcoming exploration.

Psychosis-a cardinal symptom of schizophrenia-has been associated with a failure to appropriately create or use stored regularities about past states of the world to guide the interpretation of incoming information, which leads to abnormal perceptions and beliefs. The visual system provides a test bed for investigating the role of prior experience and prediction, as accumulated knowledge of the world informs our current perception. More specifically, the strength of visual aftereffects, illusory percepts that arise after prolonged viewing of a visual stimulus, can serve as a valuable measure of the influence of prior experience on current visual processing. In this paper, we review findings from a largely older body of work on visual aftereffects in schizophrenia, attempt to reconcile discrepant findings, highlight the role of antipsychotic medication, consider mechanistic interpretations for behavioral effects, and propose directions for future research.

Schizophrenia and Alzheimer’s disease impacts on various sensory processings are extensively reviewed in the present publication. This article describes aspects of a research project whose aim is to delineate the neurobiology that may underlie Social Withdrawal in Alzheimer’s disease, Schizophrenia and Major Depression. This is a European-funded IMI 2 project, identified as PRISM (Psychiatric Ratings using Intermediate Stratified Markers). This paper focuses specifically on the selected electrophysiological paradigms chosen based on a comprehensive review of all relevant literature and practical constraints. The choice of the electrophysiological biomarkers were fundamentality based their metrics and capacity to discriminate between populations. The selected electrophysiological paradigms are resting state EEG, auditory mismatch negativity, auditory and visual based oddball paradigms, facial emotion processing ERP’s and auditory steady-state response. The primary objective is to study the effect of social withdrawal on various biomarkers and endophenotypes found altered in the target populations. This has never been studied in relationship to social withdrawal, an important component of CNS diseases.

Sensory preconditioned and second-order conditioned responding are each well-documented. The former occurs in subjects (typically rats) exposed to pairings of two relatively neutral stimuli, S2 and S1, and then to pairings of S1 and a motivationally significant event [an unconditioned stimulus (US)]; the latter occurs when the order of these experiences is reversed with rats being exposed to S1-US pairings and then to S2-S1 pairings. In both cases, rats respond when tested with S2 in a manner appropriate to the affective nature of the US, e.g., approach when the US is appetitive and withdrawal when it is aversive. This paper reviews the neural substrates of sensory preconditioning and second-order conditioning. It identifies commonalities and differences in the substrates of these so-called higher-order conditioning protocols and discusses these commonalities/differences in relation to what is learned. In so doing, the review highlights ways in which these types of conditioning enhance our understanding of how the brain encodes and retrieves different types of information to generate appropriate behavior.

This paper aims to review the limitations of the current classification of insomnia of early childhood and propose a new conceptual model allowing a better understanding of its pathophysiology. Our hypothesis is that chronic insomnia of childhood has different phenotypical expressions, associated to different pathophysiological mechanisms. Based on a long-lasting experience in evaluating a very large number of children with specific insomnia symptoms (nocturnal awakenings, difficulty in falling asleep, nocturnal restlessness, early morning awakenings) and on published data, we hypothesize that different phenotypes of insomnia might exist with different therapeutic implications. We describe three phenotypes of insomnia in early childhood: a) insomnia with motor restlessness; b) insomnia characterized without difficulties in falling asleep but with long-lasting early morning awakenings; c) insomnia with multiple night awakenings and falling asleep difficulty. This type of categorization might have important implications for treatment, based on the different hypothetical neurotransmitter dysfunctions. The early identification of a phenotype of insomnia might guide to specific behavioral and/or pharmacological interventions with the aim to prevent chronic insomnia.

Survival requires the implementation of adaptive changes that demand energy resources. The efficient regulation of energetic resources thus plays a critical role in enabling systems to adapt to the demands of their internal and external environments. The framework of active inference explains how living organisms can build probabilistic models that enable them to predict, track, and regulate energy expenditure in the short and long run. The aim of the paper is to characterize the physiological changes that accompany stress, and the relationship between these changes and the loss of confidence in a system's predictions about its internal and external milieu—ultimately manifesting as depressive symptomatology. We identify the systems that underwrite goal-directed behavior, and the neuroendocrine and immunological systems, as the hierarchical controller that regulates energy resources. In doing so, we establish an etiological pathway from allostatic overload to depression via active inference.

Tryptophan hydroxylase 2 (TPH2) plays a crucial role in the human brain. Although the association between the TPH2 gene and depression has been suggested in previous meta-analyses, studies based on Chinese subjects are often neglected. Therefore, we included some previous studies based on Chinese subjects to explore the relationship between TPH2 polymorphisms and depression via conducting an extensive meta-analysis. We reviewed 40 research papers that included data on TPH2 gene single nucleotide polymorphisms (SNPs) from 5766 patients with depression and 5988 healthy subjects. The analysis showed an association between polymorphisms in the TPH2 gene and depression, and some results were significant in 24 studies that included Chinese Han study participants. The results of our meta-analysis showed that rs4570625, rs17110747, rs120074175, rs4290270, rs120074175, and rs4290270 may be significantly associated with depression, and that rs11178997 (A/A genotype) may be a significant risk factor for depression in the Chinese subjects. Based on the results of this study, biological experiments should be performed in the future to explore how different SNPs affect depression.

Virtual Reality (VR) is an increasingly widespread tool for research as it allows the creation of experiments taking place in multimodal and daily-life-like environments, while keeping a strong experimental control. Adding neuroimaging to VR leads to a better understanding of the underlying brain networks activated during a naturalistic task, whether for research purposes or rehabilitation. The present paper focuses on the specific use of concurrent VR and fMRI and its technical challenges and feasibility, with a brief examination of the general existing solutions. Following the PRISMA guidelines, the review investigates the particular case of how VR-fMRI has explored episodic memory so far, with a comparison of object- and place-based episodic memory. This review confirms the involvement of cerebral regions well-known to be implicated in episodic memory and unravels other regions devoted to bodily and narrative aspects of the self, promoting new avenues of research in the domain of naturalistic episodic memory. Future studies should develop more immersive and interactive virtual neuroimaging features to increase ecological and embodied neurocognition aspects.

We are entering a new era of understanding human development with the ability to perform studies at the earliest time points possible. There is a substantial body of evidence to support the concept that early motor behaviour originates from supraspinal motor centres, reflects neurological integrity, and that altered patterns of behaviour may precede clinical manifestation of disease. Cine Magnetic Resonance Imaging (cineMRI) has established its value as a novel method to visualise motor behaviour in the human fetus, building on the wealth of knowledge gleaned from ultrasound sonography based studies. This paper presents a state of the art review incorporating findings from human and preclinical models, the insights from which, we propose, can proceed a reconceptualisation of fetal motor behaviour using advanced imaging techniques. Foremost is the need to better understand the role of the intrauterine environment, and its inherent unique set of stimuli that activate sensorimotor pathways and shape early brain development. Finally, an improved model of early motor development, combined with multimodal imaging, will provide a novel source of in utero biomarkers predictive of neurodevelopmental disorders.

Problem solving is a complex skill engaging multi-stepped reasoning processes to find unknown solutions. The breadth of real-world contexts requiring problem solving is mirrored by a similarly broad, yet unfocused neuroimaging literature, and the domain-general or context-specific brain networks associated with problem solving are not well understood. To more fully characterize those brain networks, we performed activation likelihood estimation meta-analysis on 280 neuroimaging problem solving experiments reporting 3,166 foci from 1,919 individuals across 131 papers. The general map of problem solving revealed broad fronto-cingulo-parietal convergence, regions similarly identified when considering separate mathematical, verbal, and visuospatial problem solving domain-specific analyses. Conjunction analysis revealed a common network supporting problem solving across diverse contexts, and difference maps distinguished functionally-selective sub-networks specific to task type. Our results suggest cooperation between representationally specialized sub-network and whole-brain systems provide a neural basis for problem solving, with the core network contributing general purpose resources to perform cognitive operations and manage problem demand. Further characterization of cross-network dynamics could inform neuroeducational studies on problem solving skill development.

For centuries, scholars have been puzzled by the distinct human prosociality. A variety of explanations have been proposed to unveil the mystery of it and nearly all these explanations have focused on the role of complex cognitive processes. In this paper, we propose a novel hypothesis that human prosociality is touch-scaffolded. We argue that early tactile stimulation such as maternal touch serves as the basic component that enables the emergence of nascent human prosociality. During this process, C-tactile afferents along with many neuropeptides, such as oxytocin and endogenous opioids, play pivotal roles in the touch - prosociality connection by facilitating the formation of an intimate caregiver-infant bond and the development of a positive social schema. Our model provides a different perspective on the development of human prosociality and builds a bridge between the human tactile system and high-level psychology - human prosociality.

Background Children and adolescents with conduct disorder (CD) show repetitive and persistent patterns of aggressive behaviour and the more severe forms are often associated with callous-unemotional (CU) traits. Objectives To systematically review and, where data are adequate, conduct meta-analyses on the efficacy of medication on aggression in children and adolescent with CD considering the impact of CU traits. Results Few studies have investigated patients with CD as primary diagnosis, and few of these have discriminated between different types of aggression or reported measures of CU traits. Methylphenidate and risperidone showed the largest effects on aggression in randomized controlled trials; other antipsychotics showed clinical efficacy on CD but this evidence is mainly revealed by open label trials. There is some low quality evidence to support a small effect of mood stabilizers and other agents. There were only two papers describing the effects of CU traits thus providing inconclusive results. Conclusion Considering heterogeneity of the disorder, more proof-of-concept clinical studies are needed to define effects of medication and role of CU traits.

Recent years have witnessed the proliferation of neuroimaging studies of neurodevelopmental disorders (NDDs), particularly of children with autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and Tourette's syndrome (TS). Neuroimaging offers immense potential in understanding the biology of these disorders, and how it relates to clinical symptoms. Neuroimaging techniques, in the long run, may help identify neurobiological markers to assist clinical diagnosis and treatment. However, methodological challenges have affected the progress of clinical neuroimaging. This paper reviews the methodological challenges involved in imaging children with NDDs. Specific topics include correcting for head motion, normalization using pediatric brain templates, accounting for psychotropic medication use, delineating complex developmental trajectories, and overcoming smaller sample sizes. The potential of neuroimaging-based biomarkers and the utility of implementing neuroimaging in a clinical setting are also discussed. Data-sharing approaches, technological advances, and an increase in the number of longitudinal, prospective studies are recommended as future directions. Significant advances have been made already, and future decades will continue to see innovative progress in neuroimaging research endeavors of NDDs.

Serotonergic psychedelics act as agonists at cortical 5-HT2A receptors and seem to induce personality changes. We conducted a systematic review of studies assessing the effects of these drugs on personality. Papers published from 1985-2016 were included from PubMed, LILACS, and SciELO databases. Three hundred and sixty-nine studies were identified, and 18 were included. Specific personality traits, such as Absorption and Self-Transcendence, seem to influence the effects of psychedelics, and psychedelic drug users and nonusers appear to differ in some personality traits. Psychedelics administered in controlled settings may induce personality changes, such as increased Openness and Self-Transcendence. Increases in global brain entropy induced by acute psychedelic administration predicted changes in Openness, and Self-Transcendence was negatively correlated with cortical thinning of the posterior cingulate cortex in long-term religious ayahuasca users. Acute and long-term use of psychedelics is associated with personality changes that appear to be modulated by 5-HT2A receptors. These changes seem to induce therapeutic effects that should be further explored in randomized controlled studies.

There is a wealth of data indicating that de novo protein S-nitrosylation in general and protein transnitrosylation in particular mediates the bulk of nitric oxide signalling. These processes enable redox sensing and facilitate homeostatic regulation of redox dependent protein signalling, function, stability and trafficking. Increased S-nitrosylation in an environment of increasing oxidative and nitrosative stress (O&NS) is initially a protective mechanism aimed at maintaining protein structure and function. When O&NS becomes severe, mechanisms governing denitrosylation and transnitrosylation break down leading to the pathological state referred to as hypernitrosylation (HN). Such a state has been implicated in the pathogenesis and pathophysiology of several neuropsychiatric and neurodegenerative diseases and we investigate its potential role in the development and maintenance of neuroprogressive disorders. In this paper, we propose a model whereby the hypernitrosylation of a range of functional proteins and enzymes lead to changes in activity which conspire to produce at least some of the core abnormalities contributing to the development and maintenance of pathology in these illnesses.

Work stress can increase the risk of cardiovascular disease by 50%, with increasing research focusing on the underlying mechanisms responsible for these associations. Our meta-analysis assessed the associations of the effort-reward imbalance (ERI) workplace stress model with indices of cardiovascular disease. The search term 'effort*reward*imbalance' produced 22 papers (129 associations, N=93,817) meeting inclusion criteria. Greater ERI was most associated with increased hypertension (r=0.26, p

The locus coeruleus (LC), the major origin of noradrenergic modulation of the central nervous system, innervates extensive areas throughout the brain and is implicated in a variety of autonomic and cognitive functions. Alterations in the LC-noradrenergic system have been associated with healthy ageing and neuropsychiatric disorders including Parkinson's disease, Alzheimer's disease and depression. The last decade has seen advances in imaging the structure and function of the LC, and this paper systematically reviews the methodology and outcomes of sixty-nine structural and functional MRI studies of the LC in humans. Structural MRI studies consistently showed lower LC signal intensity and volume in clinical groups compared to healthy controls. Within functional studies, the LC was activated by a variety of tasks/stimuli and had functional connectivity to a range of brain regions. However, reported functional LC location coordinates were widely distributed compared to previously published neuroanatomical locations. Methodological and demographic factors potentially contributing to these differences are discussed, together with recommendations to optimize the reliability and validity of future LC imaging studies.

The use of proper names enables us to designate entities, including people, at a very specific level of categorization: the unique entity or the individual. The paper presents a general overview of psychological/cognitive and neuroscientific studies that have compared the production of proper names, in particular people's names, with the production of common nouns during the last thirty years. The search for specific brain correlates of proper naming included single-case and group studies of patients with brain lesions, and studies utilizing functional neuroimaging or brain electrical stimulation with healthy participants. These studies have led neuroscientists to hypothesize that the recall of proper names involves a rather complex network including mainly left frontal and temporal regions. Behavioural evidence supports the view that proper names are more difficult to recall than common names, and scientists have proposed different explanations for this relative difficulty. Finally, several new directions for future research are proposed to improve our understanding of both cognitive processes and their brain correlates involved during proper name recall.

Several recent research findings indicate that schizophrenia (SCZ) may begin with an abnormal neuro-genesis from embryonic Neural Stem Cells (NSCs) and that this process may be particularly vulnerable to a number of genetic and/or environmental disturbances of early brain development. Since it is now well known that neurogenesis is not confined to the womb, but is a protracted process continuing in postnatal life well into adolescence and beyond, and since in the majority of subjects diagnosed with SCZ the first psychotic break occurs in late adolescence or early adulthood, the aim of our paper is to summarize the main findings supporting a possible link between changes in developmental postnatal neurogenesis and SCZ, with a specific focus on the critical period of adolescence and associated environmental risk factors. Establishing a significant role of adult neurogenesis in the emergence of psychosis will help us not only to better understand the pathogenesis of this neuopsychiatric disorder, but also to provide the key to potential strategies toward possible treatments and/or early corrective interventions.

Despite it has not been formally included in DSM-5 as a disorder, 'Internet addiction (IA)' has become a worldwide issue. It can be broadly defined as a non-chemical, behavioral addiction, which involves human-machine interaction. We pinpoint it as an "instrumental" form of social interaction (i.e. mediated by machines), a notion that appears useful for the sake of possible preclinical modeling. The features of Internet use reveals as addictive when this comes at the expense of genuine real-life sociability, with an overlap towards the hikikomori phenomenon (i.e., extreme retreat to one's own room). Due to the specific neuro-developmental plasticity in adolescence, IA poses risks to youths' mental health, and may likely produce negative consequences in everyday life. The thwarted development of adolescents' identity, self-image and adaptive social relationships is discussed: the IA adolescents often suffer loss of control, feelings of anger, symptoms of distress, social withdrawal, and familial conflicts. Further, more severe clinical conditions are also associated to IA, such as dysthymic, bipolar, affective, social-anxiety disorders, as well as major depression. This paper overviews the literature on IA, from neuro-biological, psycho-social and clinical standpoints, taking into account recent debates on diagnostic criteria, nosographic label and assessment tools. Neuroimaging data and neurochemical regulations are illustrated with links to pathogenetic hypotheses, which are amenable to validation through innovative preclinical modeling.

There is not a consensus as to whether neuropsychological profiling can distinguish depressive subtypes. We aimed to systematically review and critically analyse the literature on cognitive function in patients with melancholic and atypical depression. We searched in databases PubMed, SCOPUS, Web of Knowledge and PsycInfo for papers comparing the neuropsychological performance of melancholic patients (MEL) to non-melancholic depressive patients (NMEL), including atypical depressives, and healthy controls (HC). All studies were scrutinised to determine the main methodological characteristics and particularly possible sources of bias influencing the results reported, using the STROBE statement checklist. We also provide effect size of the results reported for contrasts between MEL; patients and NMEL patients. Seventeen studies were included; most of them demonstrated higher neuropsychological impairments of MEL patients compared to both NMEL patients and HC on tasks requiring memory, executive function, attention and reaction time. Detailed analysis of the methodologies used in the studies revealed significant variability especially regarding the participants' sociodemographic characteristics, clinical characteristics of patients and differences in neuropsychological assessment. These findings suggest that MEL may have a distinct and impaired cognitive performance compared to NMEL depressive patients on tasks involving verbal and visual memory, executive function, sustained attention and span, as well as psychomotor speed, this last especially when cognitive load is increased. Additional studies with adequate control of potentially confounding variables will help to clarify further differences in the neuropsychological functioning of depressive subtypes.

Gene-environment (G×E) interactions have largely been regarded as the root of many complex disorders, including several psychiatric disorders. In this regard, it has been hypothesized that epigenetic mechanisms may be the main mediators of such interactions. Of particular interest is the previously described interaction between psychosocial stress and genetic variability of the serotonin transporter gene (SLC6A4) in its polymorphic region 5-HTTLPR. Here we review the literature concerning SLC6A4 methylation in association with environmental, clinical or genetic variables. While SLC6A4 hypermethylation has typically been described to be independently associated with both early life stress and depressive disorders, only a few papers address whether methylation could mediate the interaction between stress and 5-HTTLPR in predicting psychopathological risk. Nevertheless, research preliminarily indicates a methylation-driven increased vulnerability of carriers of the short allele of 5-HTTLPR to psychiatric disorders when exposed to early stress or soon after exposure to stress.