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  • Fairness, fast and slow: A review of dual process models of fairness
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2018-02-24
    Bjørn G. Hallsson, Hartwig R. Siebner, Oliver J. Hulme

    Fairness, the notion that people deserve or have rights to certain resources or kinds of treatment, is a fundamental dimension of moral cognition. Drawing on recent evidence from economics, psychology, and neuroscience, we ask whether self-interest is always intuitive, requiring self-control to override with reasoning-based fairness concerns, or whether fairness itself can be intuitive. While we find strong support for rejecting the notion that self-interest is always intuitive, the literature has reached conflicting conclusions about the neurocognitive systems underpinning fairness. We propose that this disagreement can largely be resolved in light of an extended Social Heuristics Hypothesis. Divergent findings may be attributed to the interpretation of behavioral effects of ego depletion or neurostimulation, reverse inference from brain activity to the underlying psychological process, and insensitivity to social context and inter-individual differences. To better dissect the neurobiological basis of fairness, we outline how future research should embrace cross-disciplinary methods that combine psychological manipulations with neuroimaging, and that can probe inter-individual, and cultural heterogeneities.

  • The Role of the Cerebellum in Multiple Sclerosis – 150 years after Charcot
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2018-02-23
    Katrin Parmar, Christine Stadelmann, Maria A. Rocca, Dawn Langdon, Egidio D'Angelo, Marcus D’Souza, Jessica Burggraaff, Christiane Wegner, Jaume Sastre-Garriga, Alonso Barrantes-Freer, Jonas Dorn, Bernard M.J. Uitdehaag, Xavier Montalban, Jens Wuerfel, Christian Enzinger, Alex Rovira, Mar Tintore, Massimo Filippi, Ludwig Kappos, Till Sprenger

    Despite its functional importance and well known clinical impact in Multiple Sclerosis (MS), the cerebellum has only received significant attention over the past few years. It is now established that the cerebellum plays a key role not only in various sensory-motor networks, but also in cognitive-behavioural processes, domains primarily affected in patients with MS. Evidence from histopathological and magnetic resonance imaging (MRI) studies on cerebellar involvement in MS is increasingly available, however linking these pathological findings with clinical dysfunction remains challenging. There are promising advances in technology that are likely to improve the detection of pathological changes within the cerebellum, which may elucidate how pathology relates to disability.

  • Subliminal (Latent) Processing of Pain and its Evolution to Conscious Awareness
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2018-02-21
    David Borsook, Andrew M. Youssef, Nadia Barakat, Christine B. Sieberg, Igor Elman
  • Assessment of Intradimensional/Extradimensional Attentional Set-Shifting in Rats
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2018-02-21
    David S. Tait, Eric M. Bowman, Lorenz S. Neuwirth, Verity J. Brown

    The rat intradimensional/extradimensional (ID/ED) task, first described by Birrell and Brown 18 years ago, has become the predominant means by which attentional set-shifting is investigated in rodents: the use of rats in the task has been described in over 135 publications by researchers from nearly 90 universities and pharmaceutical companies. There is variation in the protocols used by different groups, including differences in apparatus, stimuli (both stimulus dimensions and exemplars within), and also the methodology. Nevertheless, most of these variations seem to be of little consequence: there is remarkable similarity in the profile of published data, with consistency of learning rates and in the size and reliability of the set-shifting and reversal ‘costs’. However, we suspect that there may be inconsistent data that is unpublished or perhaps ‘failed experiments’ that may have been caused by unintended deviations from effective protocols. The purpose of this review is to describe our approach and the rationale behind certain aspects of the protocol, including common pitfalls that are encountered when establishing an effective local protocol.

  • Moderate effects of noninvasive brain stimulation of the frontal cortex for improving negative symptoms in schizophrenia: meta-analysis of controlled trials
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2018-02-19
    André Aleman, Stefanie Enriquez-Geppert, Henderikus Knegtering, Jozarni J. Dlabac-de Lange

    Background Negative symptoms in schizophrenia concern a clinically relevant reduction of goal-directed behavior that strongly and negatively impacts daily functioning. Existing treatments are of marginal effect and novel approaches are needed. Noninvasive neurostimulation by means of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are novel approaches that may hold promise. Objectives To provide a quantitative integration of the published evidence regarding effects of rTMS and tDCS over the frontal cortex on negative symptoms, including an analysis of effects of sham stimulation. Methods Meta-analysis was applied, using a random effects model, to calculate mean weighted effect sizes (Cohen's d). Heterogeneity was assessed by using Cochrans Q and I2 tests. Results For rTMS treatment, the mean weighted effect size compared to sham stimulation was 0.64 (0.32 - 0.96; k=22, total N=827). Studies with younger participants showed stronger effects as compared to studies with older participants. For tDCS studies a mean weighted effect size of 0.50 (-0.07 - 1.07; k=5, total N=134) was found. For all frontal noninvasive neurostimulation studies together (i.e., TMS and tDCS studies combined) active stimulation was superior to sham, the mean weighted effect size was 0.61 (24 studies, 27 comparisons, 95% confidence interval 0.33 - 0.89; total N=966). Sham rTMS (baseline - posttreatment comparison) showed a significant improvement of negative symptoms, d=0.31 (0.09 - 0.52; k=16, total N=333). Whereas previous meta-analyses were underpowered, our meta-analysis had a power of 0.87 to detect a small effect. Conclusions The available evidence indicates that noninvasive prefrontal neurostimulation can improve negative symptoms. This finding suggests a causal role for the lateral frontal cortex in self-initiated goal-directed behavior. The evidence is stronger for rTMS than for tDCS, although this may be due to the small number of studies as yet with tDCS. More research is needed to establish moderator variables that may affect response to neurostimulation and to optimize treatment parameters in order to achieve stable and durable (and thus clinically relevant) effects.

  • Predicting neurodevelopmental outcome in preterm born infants using auditory event-related potentials: A systematic review
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2018-02-17
    Antoinette Depoorter, Julia Früh, Katharina Herrmann, Davide Zanchi, Peter Weber

    Prematurity is a known risk factor for later cognitive deficits. At present there are neither behavioral nor neurological tests available to detect those preterm infants who would benefit most from early interventions. Neurophysiologic methods, and more specifically, auditory event-related potentials (AERPs) are convenient tools to investigate early cognitive functioning. However, the capability of AERPs as a prognostic factor for mental development in preterm infants remains unclear. The present systematic search of the literature yielded 1016 articles, out of which 13 were included. Both prospective and cross-sectional studies reported a relationship between AERPs and cognitive outcome. Our results show that larger amplitudes and shorter latencies of late AERPs are related to better cognitive outcomes. Additional studies are needed to corroborate our findings regarding this potential use of AERPs in the individual evaluation of preterm born infants.

  • Blood biomarkers in paediatric mild traumatic brain injury: a systematic review
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2018-02-17
    Micaela Lugones, Georgia Parkin, Stefan Bjelosevic, Michael Takagi, Cathriona Clarke, Vicki Anderson, Vera Ignjatovic

    Objective To summarize all current studies focusing on blood biomarkers in paediatric mild traumatic brain injury (mTBI) and to outline the possible use of blood biomarkers for diagnostic, prognostic and monitoring purposes within this setting. Methods A systematic review following the PRISMA guidelines was conducted using the MEDLINE, PubMed and EMBASE databases. Results: A total of 21 studies were included in the review, encompassing a total of 14 different biomarkers. Seventeen (81%) of these studies found a significant association between biomarker concentration and mTBI characteristics, however results from studies to date are diverse and at times conflicting. Conclusion GFAP appears to be a promising blood biomarker for the prognosis and monitoring of mTBI, whereas UCH-L1 appears more promising at mTBI diagnosis. Despite this, the overall heterogeneity in assessed biomarkers, study design and measurement tools has made drawing specific conclusions challenging. Future research will require more uniform study design and methodological approaches to allow for the comparison, corroboration and validation of blood biomarkers within the context of paediatric mTBI.

  • Phosphodiesterase inhibition and modulation of corticostriatal and hippocampal circuits: Clinical overview and translational considerations
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2018-02-15
    P.R.A. Heckman, A. Blokland, E.P.P. Bollen, J. Prickaerts

    The corticostriatal and hippocampal circuits contribute to the neurobiological underpinnings of several neuropsychiatric disorders, including Alzheimer’s disease, Parkinson’s disease and schizophrenia. Based on biological function, these circuits can be clustered into motor circuits, associative/cognitive circuits and limbic circuits. Together, dysfunctions in these circuits produce the wide range of symptoms observed in related neuropsychiatric disorders. Intracellular signaling in these circuits is largely mediated through the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway with an additional role for the cyclic guanosine monophosphate (cGMP)/ protein kinase G (PKG) pathway, both of which can be regulated by phosphodiesterase inhibitors (PDE inhibitors). Through their effects on cAMP response element-binding protein (CREB) and Dopamine- and cAMP-Regulated PhosphoProtein MR 32 kDa (DARPP-32), cyclic nucleotide pathways are involved in synaptic transmission, neuron excitability, neuroplasticity and neuroprotection. In this clinical review, we provide an overview of the current clinical status, discuss the general mechanism of action of PDE inhibitors in relation to the corticostriatal and hippocampal circuits and consider several translational challenges.

  • ATP-activated P2X7 receptor in the pathophysiology of mood disorders and as an emerging target for the development of novel antidepressant therapeutics
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2018-02-14
    Linyu Wei, Sharifah A Syed Mortadza, Jing Yan, Libin Zhang, Lu Wang, Yaling Yin, Chaokun Li, Sylvie Chalon, Patrick Emond, Catherine Belzung, Dongliang Li, Chengbiao Lu, Sebastien Roger, Lin-Hua Jiang

    Mood disorders are a group of psychiatric conditions that represent leading global disease burdens. Increasing evidence from clinical and preclinical studies supports that innate immune system dysfunction plays an important part in the pathophysiology of mood disorders. P2X7 receptor, belonging to the ligand-gated ion channel P2X subfamily of purinergic P2 receptors for extracellular ATP, is highly expressed in immune cells including microglia in the central nervous system (CNS) and has a vital role in mediating innate immune response. The P2X7 receptor is also important in neuron-glia signalling in the CNS. The gene encoding human P2X7 receptor is located in a locus of susceptibility to mood disorders. In this review, we will discuss the recent progress in understanding the role of the P2X7 receptor in the pathogenesis and development of mood disorders and in discovering CNS-penetrable P2X7 antagonists for potential uses in in vivo imaging to monitor brain inflammation and antidepressant therapeutics.

  • Are sleep disturbances causally linked to the presence and severity of psychotic-like, dissociative and hypomanic experiences in non-clinical populations? A Systematic Review
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2018-02-13
    Jack Barton, Simon D. Kyle, Filippo Varese, Steven H. Jones, Gillian Haddock

    The present review aimed to 1) identify what sleep disturbances co-occur alongside psychotic-like, dissociative and hypomanic experiences; 2) assess the strength of potential associations between the severity of sleep disturbances and of the experiences studied; and 3) appraise evidence for a causal link. MedLine and PsycInfo were searched and 44 studies were deemed eligible. Results showed that insomnia was associated with all individual psychotic-like, dissociative and hypomanic experiences reviewed (effect size range: small-to-large). Parasomnias were associated with all psychotic-like experiences; however, there was evidence of variation in magnitude between individual experiences. An eveningness chronotype was associated with dissociative and hypomanic experiences, and circadian dysrhythmia was found alongside hypomania but not the other experiences reviewed. Finally, experimental sleep manipulation studies revealed a potential causal link between sleep loss and psychotic-like and dissociative experiences with a large effect size. However, this was not the case for experiences such as paranoia. Future research, using experimental manipulations of sleep to address putative mechanisms, will enable questions of causality to be answered with more confidence.

  • Serotonergic psychedelics and personality: a systematic review of contemporary research
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2018-02-13
    José Carlos Bouso, Rafael G. dos Santos, Miguel Ángel Alcázar-Córcoles, Jaime E.C. Hallak

    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 to 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.

  • Cognitive and Neuromodulation Strategies for Unhealthy Eating and Obesity: Systematic Review and Discussion of Neurocognitive Mechanisms
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2018-02-09
    Laura Forcano, Fernanda Mata, Rafael de la Torre, Antonio Verdejo-Garcia

    We systematically reviewed research on cognitive training and neuromodulation interventions for reducing food craving/intake, unhealthy diet and weight, and discussed their mechanisms of action. We reviewed 50 studies involving six cognitive trainings: Approach and Attentional Bias Modification, Implementation Intentions, Response Inhibition, Episodic Future Thinking and Working Memory; and four neuromodulation approaches: Transcranial Magnetic Stimulation (TMS), transcranial Direct Current Stimulation (tDCS), Deep Brain Stimulation (DBS) and Neurofeedback. Response Inhibition and Implementation Intentions have shown to reduce unhealthy diet and weight in people with overweight/obesity. Attentional Bias Modification has shown promising results in healthy-weight participants. Brain stimulation of the Dorsolateral Prefrontal Cortex via tDCS and the Hypothalamus via DBS showed benefits for reducing food craving and weight in people with overweight/obesity. Studies quality was generally high, but most trials were short-term and many conducted in healthy-weight samples. Modification of cognitive control and motivational processes/circuits are common mechanisms of beneficial training and neuromodulation interventions, and thus a promising approach for overweight/obesity treatment. Longer duration trials in clinical populations are needed to confirm benefits.

  • Reactivity to interpersonal stress in patients with eating disorders: A systematic review and meta-analysis of studies using an experimental paradigm
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2018-02-08
    Alessio Maria Monteleone, Janet Treasure, Carol Kan, Valentina Cardi

    Reactivity to interpersonal stress in patients with eating disorders: A systematic review and meta-analysis of studies using an experimental paradigm. NEUROSCI BIOBEHAV REV XXX-XXX, 2018.- Social difficulties have been implicated in the development and maintenance of eating disorder symptoms. The aim of this work was to conduct a systematic review and meta-analysis of experimental studies testing patients' reactivity to interpersonal stress, compared to healthy controls. Thirty-four studies were included. Meta-analyses were conducted on 16 studies and on following outcomes: attention bias and interference to threatening faces and cortisol, heart rate and negative affect before and after exposure to interpersonal stress. Patients show heightened attention bias and interference to threatening faces. Lower heart rate after exposure to interpersonal stress and greater negative affect before and after interpersonal stress are observed in the clinical group compared to controls. Surprisingly, only a small minority of studies included measures of abnormal eating behaviour and attitudes. This seems a missed opportunity for testing the causal and maintaining role that abnormalities in interpersonal stress response play in eating disorders. Nonetheless, findings corroborate the hypothesis that patients' response to interpersonal stress overall differs from that of healthy controls.

  • 更新日期:2018-02-08
  • Frontoparietal areas link impairments of large-scale intrinsic brain networks with aberrant fronto-striatal interactions in OCD: a meta-analysis of resting-state functional connectivity
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2018-02-03
    Deniz A. Gürsel, Mihai Avram, Christian Sorg, Felix Brandl, Kathrin Koch

    Neuroimaging studies report evidence for two distinct pathophysiological models of obsessive-compulsive disorder (OCD): disrupted fronto-striatal circuits and impaired large-scale fronto-parietal-limbic intrinsic brain networks, defined by functionally connected (FC) infra-slow oscillations in ongoing brain activity. To synthesize this literature and overcome inconsistencies, we conducted a coordinate-based meta-analysis of 18 whole-brain resting-state functional magnetic resonance imaging (fMRI) studies (541 patients, 572 healthy controls) comparing seed-based FC between OCD patients and healthy controls. In patients, the meta-analysis revealed (1) consistent hypoconnectivity within frontoparietal and salience network, and between salience, frontoparietal and default-mode network, and (2) consistent general dysconnectivity (no specific direction of connectivity change) within default-mode and frontoparietal network, as well as between frontoparietal, default-mode, and salience networks. Between-network hypoconnectivity provides evidence for the triple-network model in OCD, while aberrant within-network connectivity of frontoparietal and striatal regions supports reports of aberrant fronto-striatal circuitry. Therefore, results corroborate both models of OCD pathophysiology and link them by underlining the importance of intrinsic connectivity of frontoparietal regions which are common to both models.

  • Preclinical models of conduct disorder – principles and pharmacologic perspectives
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2016-05-26
    Jozsef Haller

    The translational value of preclinical research was recently enhanced by abnormal aggression models, which focus on deviant behaviors induced by the exposure of rodents to etiological factors of aggression-related psychopathologies. Prompted by similar trials in other psychiatric disorders, here we investigate models of abnormal aggression from the perspective of DSM5 criteria. After proposing principles based on which analogies can be established between psychopathology symptoms and rodent behavioral dysfunctions, we show that rodents submitted to abnormal aggression models fulfill basic criteria of aggression-related psychopathologies; moreover, some models can be considered specific to particular disorders e.g. conduct disorder. We also show that abnormal and species-typical aggressions differ in terms of both brain mechanisms and pharmacological responsiveness, which mimics differences observed in psychiatric disorders. We conclude that evaluating abnormal aggression models from a DSM5 perspective is not only possible but also worthwhile, and such models may contribute to the development of novel treatment strategies not only for aggression as a symptom but also for specific aggression-related disorders or multi-symptom clusters at least.

  • Behavioral and mechanistic insight into rodent empathy
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2016-06-14
    Sivaani Sivaselvachandran, Erinn L. Acland, Salsabil Abdallah, Loren J. Martin

    Empathy is a psychological construct that allows individuals to understand and share the emotions of others. The ability to share emotional states relies on basic social mechanisms, such as mimicry and emotional contagion, which are considered building blocks for empathy. Mimicking another’s emotional or physical state is essential for successful social interactions and is found in a number of animal species. For the current review we focus on emotional state sharing in rodents, a core feature of empathy that is often measured using pain and fear as proxies; we also discuss prosociality in rodents. The evidence for empathy in rodents shows that rats and mice consistently imitate arousal states and behaviors of conspecifics and will even sacrifice personal gain to relieve the distress of a conspecific. These behaviors support basic processes that are crucial for the survival of individual animals and give us insight into the neural mechanisms that govern empathy-related behaviors.

  • Genetic influences on conduct disorder
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2016-06-24
    Jessica E. Salvatore, Danielle M. Dick

    Conduct disorder (CD) is a moderately heritable psychiatric disorder of childhood and adolescence characterized by aggression toward people and animals, destruction of property, deceitfulness or theft, and serious violation of rules. Genome-wide scans using linkage and association methods have identified a number of suggestive genomic regions that are pending replication. A small number of candidate genes (e.g., GABRA2, MAOA, SLC6A4, AVPR1A) are associated with CD related phenotypes across independent studies; however, failures to replicate also exist. Studies of gene-environment interplay show that CD genetic predispositions also contribute to selection into higher-risk environments, and that environmental factors can alter the importance of CD genetic factors and differentially methylate CD candidate genes. The field’s understanding of CD etiology will benefit from larger, adequately powered studies in gene identification efforts; the incorporation of polygenic approaches in gene-environment interplay studies; attention to the mechanisms of risk from genes to brain to behavior; and the use of genetically informative data to test quasi-causal hypotheses about purported risk factors.

  • Gene x environment interactions in conduct disorder: Implications for future treatments
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2016-08-18
    Nathalie E. Holz, Katrin Zohsel, Manfred Laucht, Tobias Banaschewski, Sarah Hohmann, Daniel Brandeis

    Conduct disorder (CD) causes high financial and social costs, not only in affected families but across society, with only moderately effective treatments so far. There is consensus that CD is likely caused by the convergence of many different factors, including genetic and adverse environmental factors. There is ample evidence of gene-environment interactions in the etiology of CD on a behavioral level regarding genetically sensitive designs and candidate gene-driven approaches, most prominently and consistently represented by MAOA. However, conclusive indications of causal GxE patterns are largely lacking. Inconsistent findings, lack of replication and methodological limitations remain a major challenge. Likewise, research addressing the identification of affected brain pathways which reflect plausible biological mechanisms underlying GxE is still very sparse. Future research will have to take multilevel approaches into account, which combine genetic, environmental, epigenetic, personality, neural and hormone perspectives. A better understanding of relevant GxE patterns in the etiology of CD might enable researchers to design customized treatment options (e.g. biofeedback interventions) for specific subgroups of patients.

  • Psychiatric evaluation of youths with Disruptive Behavior Disorders and psychopathic traits: A critical review of assessment measures
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2016-09-25
    Gabriele Masi, Annarita Milone, Paola Brovedani, Simone Pisano, Pietro Muratori

    Disruptive Behavior Disorders (DBDs) are stable and impairing disorders, heterogeneous in presentation, developmental pathways, and treatment needs. Disentangling subtypes according to psychopathological dimensions is helpful for timely diagnoses, precise prognoses and tailored interventions. Psychopathic traits are relevant in subtyping DBDs with severe antisocial and aggressive behaviors. Three psychopathy dimensions have been found: 1) an affective dimension, the callous-unemotional (CU) trait, with lack of empathy and remorse, and with short-lived emotions; 2) an interpersonal dimension, the narcissistic domain, with manipulative abilities, superficial charm, egocentricity and grandiosity; 3) a behavioral dimension, the impulsivity or impulsive-irresponsibility, with irresponsibility, proneness to boredom, and novelty seeking. Recently, research suggests that youth with CU traits, similarly to adults with psychopathy, can present a low-anxious “primary” and high-anxious “secondary” variants. Our aim is to critically review the main measures of psychopathic traits, including the three main dimensions (with specific emphasis on CU traits), and the “primary/secondary” distinction, focusing on the assessment in clinical settings. An assessment procedure is proposed, based on previous literature and personal clinical experience.

  • Understanding heterogeneity in conduct disorder: A review of psychophysiological studies
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2016-09-28
    Kostas A. Fanti

    The present review is concerned with the role of different physiological systems (e.g., skin conductance, heart rate, electromyography, and the eye-bling startle reflex) in understanding heterogeneity in conduct disorder (CD). Four subtyping approaches are considered: age of onset, comorbid psychopathology, callous-unemotional traits, and proactive/reactive aggression. Empirical findings are discussed in terms of distinct theoretical perspectives that aim to explain CD behaviors based on physiological over-arousal, under-arousal, and empathy deficits. According to the studies reviewed, the callous-unemotional (CD + CU) and internalizing (CD + Internalizing) sub-types can best inform CD heterogeneity. Findings indicated that children in the CD + CU and CD + Internalizing subtypes score on opposite extremes on heart rate, skin conductance and startle reactivity measures. Heart rate variability and respiratory sinus arrhythmia dysfunctions, associated with emotional dysregulation, were more evident among children in the CD + Internalizing group, while dysfunctional facial electromyography activity, which has been linked with reduced empathy, with the CD + CU group. In conclusion, it might be important to redefine CD diagnostic criteria based on physiological heterogeneity to enable the identification of distinct subtypes of CD.

  • The link between aberrant hypothalamic–pituitary–adrenal axis activity during development and the emergence of aggression—Animal studies
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2016-10-14
    Sophie E. Walker, Aurélie Papilloud, Damien Huzard, Carmen Sandi

    Aggressive behavior is not uniform, including proactive and reactive forms of aggression. Aberrant functioning of the hypothalamic–pituitary–adrenal (HPA) axis is frequently associated with abnormal aggression. Here, we review the rodent literature in order to assess whether developmental abnormalities in the HPA axis can be causally linked with the emergence of abnormal aggression. We examine studies that involve genetic models and life challenges (e.g., early life stress, drug exposure) that course with developmental alterations in the HPA axis. Although the lack of systematic studies hinders development of an integrated model, existing evidence supports a U-shaped function regarding differences in HPA axis functioning during development and the emergence of aggressive phenotypes. Thus, developmentally low or high HPA axis reactivity are typically found to be aligned with the emergence of aggressive phenotypes; however, existing information is insufficient to causally link divergent HPA axis aberration with specific types of aggression. Progress in this field is needed to support interventions in children aimed at ameliorating social dysfunctions associated with aberrations in HPA axis function.

  • Classification and treatment of antisocial individuals: From behavior to biocognition
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2016-10-17
    I.A. Brazil, J.D.M. van Dongen, J.H.R. Maes, R.B. Mars, A.R. Baskin-Sommers

    Antisocial behavior is a heterogeneous construct that can be divided into subtypes, such as antisocial personality and psychopathy. The adverse consequences of antisocial behavior produce great burden for the perpetrators, victims, family members, and for society at-large. The pervasiveness of antisocial behavior highlights the importance of precisely characterizing subtypes of antisocial individuals and identifying specific factors that are etiologically related to such behaviors to inform the development of targeted treatments. The goals of the current review are (1) to briefly summarize research on the operationalization and assessment of antisocial personality and psychopathy; (2) to provide an overview of several existing treatments with the potential to influence antisocial personality and psychopathy; and (3) to present an approach that integrates and uses biological and cognitive measures as starting points to more precisely characterize and treat these individuals. A focus on integrating factors at multiple levels of analysis can uncover person-specific characteristics and highlight potential targets for treatment to alleviate the burden caused by antisocial behavior.

  • Neuro-cognitive system dysfunction and symptom sets: A review of fMRI studies in youth with conduct problems
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2016-10-26
    R.J.R. Blair, K. Veroude, J.K. Buitelaar

    In this paper, we review fMRI work on neuro-cognitive systems that are considered to be dysfunctional in individuals with conduct problems (i.e., individuals with Conduct Disorder (CD), Oppositional Defiant Disorder (ODD) or antisocial behavior without formal clinical diagnosis). These are: empathy, the acute threat response, reinforcement-based decision-making, response inhibition and the Default Mode Network. Evidence regarding the Default Mode Network is somewhat inconsistent and its functional role/the symptom sets consequent on its dysfunction remain underspecified. However, dysfunctions in the other four neuro-cognitive systems are associated with symptom sets seen in individuals with conduct problems.

  • The impact of chronic stress during adolescence on the development of aggressive behavior: A systematic review on the role of the dopaminergic system in rodents
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2016-11-05
    Jorim J Tielbeek, Zeineb Al-Itejawi, Josjan Zijlmans, Tinca JC Polderman, Joshua W Buckholtz, Arne Popma

    Pathological aggression, frequently observed in psychiatric patients and criminal subjects, poses a major burden on the health care and criminal justice system, necessitating better aetiological models to inform targets for prevention and intervention. Emerging evidence suggests that adverse experiences during development can cause long-lasting brain alterations associated with maladaptive behaviors, such as aggression. The present review discusses, mainly based on studies in rodents, whether disruption of the mesocorticolimbic dopamine system through chronic stress-exposure during adolescence predisposes to adult aggression. Our findings suggest that chronic stress in adolescence induces prefrontal cortex (PFC) hyperdopaminergia and ultimately leads to blunted prefrontal dopamine transmission in adulthood. This, in turn, disrupts the ability of the PFC to guide adaptive, long-term focused action selection by regulating mesolimbic dopamine signaling. We propose that, especially during the dynamic and transitional period of adolescence, exposure to chronic stress could lead to excessive adaptive change, which may result in an increased vulnerability to maladaptive aggression in adulthood. We discuss how these findings in rodents may translate to humans.

  • Clock genes, ADHD and aggression
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2016-11-09
    Floriana Mogavero, Amanda Jager, Jeffrey C. Glennon

    Attention deficit/hyperactivity disorder (ADHD) is frequently associated with comorbid aggression and sleep disturbances. The sleep/wake cycle is under the control of the circadian system which is moderated by clock genes. Clock genes can regulate the transcription of monoamine oxidase A, which is involved in the degradation of monoamines. Disturbances in monoamine interaction with clock genes in those with monoamine gene polymorphisms may regulate susceptibility of ADHD and comorbid aggression/sleep disturbances. While monoamines influence circadian rhythm and clock gene expression, circadian rhythm components modulate aggressive behavior, and altered clock genes expression have been associated with ADHD. We propose a mechanism by which circadian rhythm and clock gene expression may influence ADHD and comorbid aggression through the modulation of neurotransmitters. The role of clock genes in ADHD patients with comorbid aggression awaits further research; therefore we also indicate directions for future studies to help increase understanding of the underlying mechanisms in ADHD with comorbid aggression and sleep disturbances.

  • Comparative studies of social buffering: A consideration of approaches, terminology, and pitfalls
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2017-12-06
    Yasushi Kiyokawa, Michael B. Hennessy

    KIYOKAWA, Y. and HENNESSY, M.B. Comparative studies of social buffering: A consideration of approaches, terminology, and pitfalls…NEUROSCI BIOBEHAV REV XXX–XXX, .- Over the past decades, there has been an increasing number of investigations of the impact of social variables on neural, endocrine, and immune outcomes. Among these are studies of “social buffering”—or the phenomenon by which affiliative social partners mitigate the response to stressors. Yet, as social buffering studies have become more commonplace, the variety of approaches taken, definitions employed, and divergent results obtained in different species can lead to confusion and miscommunication. The aim of the present paper, therefore, is to address terminology and approaches and to highlight potential pitfalls to the study of social buffering across nonhuman species. We review and categorize variables currently being employed in social buffering studies and provide an overview of responses measured, mediating sensory modalities and underlying mechanisms. It is our hope that the paper will be useful to those contemplating examination of social buffering in the context of their own research.

  • Verbal learning and hippocampal dysfunction in schizophrenia: A meta-analysis
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2017-12-06
    Mathilde Antoniades, Tabea Schoeler, Joaquim Radua, Isabel Valli, Paul Allen, Matthew J. Kempton, Philip McGuire

    This meta-analysis summarizes research examining whether deficits in verbal learning are related to bilateral hippocampal volume reductions in patients with or at risk for schizophrenia and in healthy controls. 17 studies with 755 patients with schizophrenia (SCZ), 232 Genetic High Risk (GHR) subjects and 914 healthy controls (HC) were included. Pooled correlation coefficients were calculated between hemisphere (left, right or total) and type of recall (immediate or delayed) for each diagnostic group individually (SCZ, GHR and HC). In SCZ, left and right hippocampal volume positively correlated with immediate (r = 0.256, 0.230) and delayed (r = 0.132, 0.231) verbal recall. There was also a correlation between total hippocampal volume and delayed recall (r = 0.233). None of these correlations were significant in healthy controls. There was however, a positive correlation between left hippocampal volume and immediate recall in the GHR group (r = 0.356). The results suggest that hippocampal volume affects immediate and delayed verbal learning capacity in schizophrenia and provides further evidence of hippocampal dysfunction in the pathophysiology of schizophrenia.

  • Obstructive sleep apnoea and Alzheimer’s disease: In search of shared pathomechanisms
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2017-12-07
    D. Polsek, N. Gildeh, D. Cash, R. Winsky-Sommerer, S.C.R. Williams, F. Turkheimer, G.D. Leschziner, M.J. Morrell, I. Rosenzweig

    Alzheimer’s disease (AD) is a significant public health concern. The incidence continues to rise, and it is set to be over one million in the UK by 2025. The processes involved in the pathogenesis of AD have been shown to overlap with those found in cognitive decline in patients with Obstructive Sleep Apnoea (OSA). Currently, the standard treatment for OSA is Continuous Positive Airway Pressure. Adherence to treatment can, however, be an issue, especially in patients with dementia. Also, not all patients respond adequately, necessitating the use of additional treatments. Based on the body of data, we here suggest that excessive and prolonged neuronal activity might contribute to genesis and acceleration of both AD and OSA in the absence of appropriately structured sleep. Further, we argue that external factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain, and further promote disease progression. If this hypothesis is proven in future studies, it could have far-reaching clinical translational implications, as well as implications for future treatment strategies in OSA.

  • Rhythmic facilitation of sensory processing: A critical review
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2017-12-07
    Saskia Haegens, Elana Zion Golumbic

    Here we review the role of brain oscillations in sensory processing. We examine the idea that neural entrainment of intrinsic oscillations underlies the processing of rhythmic stimuli in the context of simple isochronous rhythms as well as in music and speech. This has been a topic of growing interest over recent years; however, many issues remain highly controversial: how do fluctuations of intrinsic neural oscillations—both spontaneous and entrained to external stimuli—affect perception, and does this occur automatically or can it be actively controlled by top-down factors? Some of the controversy in the literature stems from confounding use of terminology. Moreover, it is not straightforward how theories and findings regarding isochronous rhythms generalize to more complex, naturalistic stimuli, such as speech and music. Here we aim to clarify terminology, and distinguish between different phenomena that are often lumped together as reflecting “neural entrainment” but may actually vary in their mechanistic underpinnings. Furthermore, we discuss specific caveats and confounds related to making inferences about oscillatory mechanisms from human electrophysiological data.

  • Photopigments and the dimensionality of animal color vision
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2017-12-07
    Gerald H. Jacobs

    Early color-matching studies established that normal human color vision is trichromatic. Subsequent research revealed a causal link between trichromacy and the presence in the retina of three classes of cone photopigments. Over the years, measurements of the photopigment complements of other species have expanded greatly and these are frequently used to predict the dimensionality of an animal’s color vision. This review provides an account of how the linkage between the number of active photopigments and the dimensions of human color vision developed, summarizes the various mechanisms that can impact photopigment spectra and number, and provides an across-species survey to examine cases where the photopigment link to the dimensionality of color vision has been claimed. The literature reveals numerous instances where the human model fails to account for the ways in which the visual systems of other animals exploit information obtained from the presence of multiple photopigments in support of their behavior.

  • A quantitative approach to neuropsychiatry: The why and the how
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2017-12-12
    Martien J. Kas, Brenda Penninx, Bernd Sommer, Alessandro Serretti, Celso Arango, Hugh Marston

    The current nosology of neuropsychiatric disorders allows for a pragmatic approach to treatment choice, regulation and clinical research. However, without a biological rationale for these disorders, drug development has stagnated. The recently EU-funded PRISM project aims to develop a quantitative biological approach to the understanding and classification of neuropsychiatric diseases to accelerate the discovery and development of better treatments. By combining clinical data sets from major worldwide disease cohorts and by applying innovative technologies to deeply phenotype stratified patient groups, we will define a set of quantifiable biological parameters for social withdrawal and cognitive deficits common to Schizophrenia (SZ), Major Depression (MD), and Alzheimer’s Disease (AD). These studies aim to provide new classification and assessment tools for social and cognitive performance across neuropsychiatric disorders, clinically relevant substrates for treatment development, and predictive, preclinical animal systems. With patients and regulatory agencies, we seek to provide clear routes for the future translation and regulatory approval for new treatments and provide solutions to the growing public health challenges of psychiatry and neurology.

  • The infant brain in the social world: moving toward interactive social neuroscience with functional near-infrared spectroscopy
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2018-01-31
    Nicole M. McDonald, Katherine L. Perdue

    Typically developing infants rapidly acquire a sophisticated array of social skills within the first year of life. These social skills are largely learned within the context of day-to-day interactions with caregivers. While social neuroscience has made great gains in our knowledge of the underlying neural circuitry of social cognition and behavior, much of this work has focused on experiments that sacrifice ecological validity for experimental control. Functional near-infrared spectroscopy (fNIRS) is a promising methodology for measuring brain activity in the context of naturalistic social interactions. Here, we review what we have learned from fNIRS studies that have used traditional experimental stimuli to study social development during infancy. We then discuss recent infant fNIRS studies that have utilized more naturalistic social stimuli, followed by a discussion of applications of this methodology to the study of atypical social development, with a focus on infants at risk for autism spectrum disorder. We end with recommendations for applying fNIRS to studies of typically developing and at-risk infants in naturalistic social situations.

  • The Vicious Cycle of Itch and Anxiety
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2018-01-31
    Kristen M. Sanders, Tasuku Akiyama

    Chronic itch is associated with increased stress, anxiety, and other mood disorders. In turn, stress and anxiety exacerbate itch, leading to a vicious cycle that affects patient behavior (scratching) and worsens disease prognosis and quality of life. This cycle persists across chronic itch conditions of different etiologies and even to some extent in healthy individuals, suggesting that the final common pathway for itch processing (the central nervous system) plays a major role in the relationship between itch and anxiety. Pharmacological and nonpharmacological treatments that reduce anxiety have shown promising anti-itch effects. Further research is needed to establish specific central mechanisms of the itch-anxiety cycle and provide new targets for treatment.

  • The Neurobiological Basis of Sleep: Insights from Drosophila
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2018-01-31
    Sarah Ly, Allan I. Pack, Nirinjini Naidoo

    Sleep is a biological enigma that has raised numerous questions about the inner workings of the brain. The fundamental question of why our nervous systems have evolved to require sleep remains a topic of ongoing scientific deliberation. This question is largely being addressed by research using animal models of sleep. Drosophila melanogaster, also known as the common fruit fly, exhibits a sleep state that shares common features with many other species. Drosophila sleep studies have unearthed an immense wealth of knowledge about the neuroscience of sleep. Given the breadth of findings published on Drosophila sleep, it is important to consider how all of this information might come together to generate a more holistic understanding of sleep. This review provides a comprehensive summary of the neurobiology of Drosophila sleep and explores the broader insights and implications of how sleep is regulated across species and why it is necessary for the brain.

  • Reproducibility and replicability of rodent phenotyping in preclinical studies
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2018-01-31
    Neri Kafkafi, Joseph Agassi, Elissa J. Chesler, John C. Crabbe, Wim E. Crusio, David Eilam, Robert Gerlai, Ilan Golani, Alex Gomez-Marin, Ruth Heller, Fuad Iraqi, Iman Jaljuli, Natasha A. Karp, Hugh Morgan, George Nicholson, Donald W. Pfaff, S. Helene Richter, Philip B. Stark, Oliver Stiedl, Victoria Stodden, Lisa M. Tarantino, Valter Tucci, William Valdar, Robert W. Williams, Hanno Würbel, Yoav Benjamini

    The scientific community is increasingly concerned with the proportion of published “discoveries” that are not replicated in subsequent studies. The field of rodent behavioral phenotyping was one of the first to raise this concern, and to relate it to other methodological issues: the complex interaction between genotype and environment; the definitions of behavioral constructs; and the use of laboratory mice and rats as model species for investigating human health and disease mechanisms. In January 2015, researchers from various disciplines gathered at Tel Aviv University to discuss these issues. The general consensus was that the issue is prevalent and of concern, and should be addressed at the statistical, methodological and policy levels, but is not so severe as to call into question the validity and the usefulness of model organisms as a whole. Well-organized community efforts, coupled with improved data and metadata sharing, have a key role in identifying specific problems and promoting effective solutions. Replicability is closely related to validity, may affect generalizability and translation of findings, and has important ethical implications.

  • Structure of the alexithymic brain: A parametric coordinate-based meta-analysis
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2018-01-31
    Pengfei Xu, Esther M. Opmeer, Marie-José van Tol, Katharina S. Goerlich, André Aleman

    Alexithymia refers to deficiencies in identifying and expressing emotions. This might be related to changes in structural brain volumes, but its neuroanatomical basis remains uncertain as studies have shown heterogeneous findings. Therefore, we conducted a parametric coordinate-based meta-analysis. We identified seventeen structural neuroimaging studies (including a total of 2,586 individuals with different levels of alexithymia) investigating the association between gray matter volume and alexithymia. Volumes of the left insula, left amygdala, orbital frontal cortex and striatum were consistently smaller in people with high levels of alexithymia. These areas are important for emotion perception and emotional experience. Smaller volumes in these areas might lead to deficiencies in appropriately identifying and expressing emotions. These findings provide the first quantitative integration of results pertaining to the structural neuroanatomical basis of alexithymia.

  • Reprint of Reframing autism as a behavioral syndrome and not a specific mental disorder: Perspectives from a literature review
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2018-01-31
    S. Tordjman, D. Cohen, N. Coulon, G.M. Anderson, M. Botbol, P.L. Roubertoux

    Clinical and molecular genetics have advanced current knowledge on genetic disorders associated with autism. A review of diverse genetic disorders associated with autism is presented and for the first time discussed extensively with regard to possible common underlying mechanisms leading to a similar cognitive-behavioral phenotype of autism. The possible role of interactions between genetic and environmental factors, including epigenetic mechanisms, is in particular examined. Finally, the pertinence of distinguishing non-syndromic autism (isolated autism) from syndromic autism (autism associated with genetic disorders) will be reconsidered. Given the high genetic and etiological heterogeneity of autism, autism can be viewed as a behavioral syndrome related to known genetic disorders (syndromic autism) or currently unknown disorders (apparent non-syndromic autism), rather than a specific categorical mental disorder. It highlights the need to study autism phenotype and developmental trajectory through a multidimensional, non-categorical approach with multivariate analyses within autism spectrum disorder but also across mental disorders, and to conduct systematically clinical genetic examination searching for genetic disorders in all individuals (children but also adults) with autism.

  • Metabolic/inflammatory/vascular comorbidity in psychiatric disorders; soluble epoxide hydrolase (sEH) as a possible new target
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2018-02-02
    W. Swardfager, M. Hennebelle, D. Yu, B.D. Hammock, A.J. Levitt, K. Hashimoto, A.Y. Taha

    The common and severe psychiatric disorders, including major depressive disorder (MDD) and bipolar disorder (BD), are associated with inflammation, oxidative stress and changes in lipid metabolism. Those pathways are implicated in the premature development of vascular and metabolic comorbidities, which account for considerable morbidity and mortality, including increased dementia risk. During endoplasmic reticulum stress, the soluble epoxide hydrolase (sEH) enzyme converts anti-inflammatory fatty acid epoxides generated by cytochrome p450 enzymes into their corresponding and generally less anti-inflammatory, or even pro-inflammatory, diols, slowing the resolution of inflammation. The sEH enzyme and its oxylipin products are elevated post-mortem in MDD, BD and schizophrenia. Preliminary clinical data suggest that oxylipins increase with symptoms in seasonal MDD and anorexia nervosa, requiring confirmation in larger studies and other cohorts. In rats, a soluble sEH inhibitor mitigated the development of depressive-like behaviors. We discuss sEH inhibitors under development for cardiovascular diseases, post-ischemic brain injury, neuropathic pain and diabetes, suggesting new possibilities to address the mood and cognitive symptoms of psychiatric disorders, and their most common comorbidities.

  • 更新日期:2018-02-03
  • Prenatal antidepressant exposure and the risk of attention-deficit hyperactivity disorder in children: A systematic review and meta-analysis
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2017-12-13
    Kenneth K.C. Man, Esther W. Chan, Patrick Ip, David Coghill, Emily Simonoff, Phyllis K.L. Chan, Wallis C.Y. Lau, Martijn J. Schuemie, Miriam C.J.M. Sturkenboom, Ian C.K. Wong

    This systematic review assesses the association between prenatal antidepressant exposure and risk of ADHD in children. Electronic databases were searched up to 25 July 2017. Observational studies examining this association were included in the review and meta-analysis was conducted where appropriate. Eight relevant studies were identified. The seven studies included in the meta-analysis comprised a total of 2,886,502 children. The pooled estimates comparing prenatal exposure to non-exposure showed an adjusted rate ratio (aRR) of 1.39 (95%CI 1.21-1.61). Similarly, an increased risk was found comparing previous antidepressant users and non-users: aRR = 1.56 (95%CI 1.25-1.95). The relationship between maternal psychiatric conditions and ADHD in children yielded an aRR of 1.90 (95%CI 1.47-2.45). Three studies conducted sibling-matched analyses with aRR of 0.94 (95%CI 0.75-1.16). These data suggest that the observed association between prenatal use of antidepressants and risk of ADHD in offspring can be partially explained by confounding by indication because the results from sibling-matched analyses do not support an increased risk of ADHD in discordant exposed siblings.

  • Assessing cerebellar brain inhibition (CBI) via transcranial magnetic stimulation (TMS): A systematic review
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2017-12-05
    Lara Fernandez, Brendan P. Major, Wei-Peng Teo, Linda K. Byrne, Peter G. Enticott

    The inhibitory tone that the cerebellum exerts on the primary motor cortex (M1) is known as cerebellar brain inhibition (CBI). Studies show CBI to be relevant to several motor functions, including adaptive motor learning and muscle control. CBI can be assessed noninvasively via transcranial magnetic stimulation (TMS) using a double-coil protocol. Variability in parameter choice and controversy surrounding the protocol’s ability to isolate the cerebellothalamocortical pathway casts doubt over its validity in neuroscience research. This justifies a systematic review of both the protocol, and its application. The following review examines studies using the double-coil protocol to assess CBI in healthy adults. Parameters and CBI in relation to task-based studies, other non-invasive protocols, over different muscles, and in clinical samples are reviewed. Of the 1398 studies identified, 24 met selection criteria. It was found that methodological design and selection of parameters in several studies may have reduced the validity of outcomes. Further systematic testing of CBI protocols is warranted, both from a parameter and task-based perspective.

  • Embodiment in the aging mind
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2017-11-22
    Esther Kuehn, Mario Borja Perez-Lopez, Nadine Diersch, Juliane Döhler, Thomas Wolbers, Martin Riemer

    Bodily awareness is a central component of human sensation, action, and cognition. The human body is subject to profound changes over the adult lifespan. We live in an aging society: the mean age of people living in industrialized countries is currently over 40 years, and further increases are expected. Nevertheless, there is a lack of comprehensive knowledge that links changes in embodiment that occur with age to neuronal mechanisms and associated sensorimotor and cognitive deficits in the elderly. Here, we synthesize existing evidence and introduce the NFL Framework of Embodied Aging, which links basic neuronal (N) mechanisms of age-related sensorimotor decline to changes in functional (F) bodily impairments, including deficits in higher-level cognitive functions, and impairments in daily life (L). We argue that cognitive and daily life impairments associated with old age are often due to deficits in embodiment, which can partly be linked to neuronal degradation at the sensorimotor level. The framework may encourage the development of novel approaches to improve autonomous living for the elderly.

  • Hypothesis for cognitive effects of transcranial direct current stimulation: Externally- and internally-directed cognition
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2017-11-15
    Pamela M. Greenwood, Eric J. Blumberg, Melissa R. Scheldrup

    A comprehensive explanation is lacking for the broad array of cognitive effects modulated by transcranial direct current stimulation (tDCS). We advanced the testable hypothesis that tDCS to the default mode network (DMN) increases processing of goals and stored information at the expense of external events. We further hypothesized that tDCS to the dorsal attention network (DAN) increases processing of external events at the expense of goals and stored information. A literature search (PsychINFO) identified 42 empirical studies and 3 meta-analyses examining effects of prefrontal and/or parietal tDCS on tasks that selectively required external and/or internal processing. Most, though not all, of the studies that met our search criteria supported our hypothesis. Three meta-analyses supported our hypothesis. The hypothesis we advanced provides a framework for the design and interpretation of results in light of the role of large-scale intrinsic networks that govern attention.

  • Epigenetic regulation of motivated behaviors by histone deacetylase inhibitors
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2017-10-08
    Lindsay Elvir, Florian Duclot, Zuoxin Wang, Mohamed Kabbaj

    Growing evidence has begun to elucidate the contribution of epigenetic mechanisms in the modulation and maintenance of gene expression and behavior. Histone acetylation is one such epigenetic mechanism, which has been shown to profoundly alter gene expression and behaviors. In this review, we begin with an overview of the major epigenetic mechanisms including histones acetylation. We next focus on recent evidence about the influence of environmental stimuli on various motivated behaviors through histone acetylation and highlight how histone deacetylase inhibitors can correct some of the pathologies linked to motivated behaviors including substance abuse, feeding and social attachments. Particularly, we emphasize that the effects of histone deacetylase inhibitors on motivated behaviors are time and context-dependent.

  • Dopamine, the antipsychotic molecule: A perspective on mechanisms underlying antipsychotic response variability
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2017-09-29
    Davide Amato, Anthony C. Vernon, Francesco Papaleo

    All antipsychotics bind to the dopamine D2 receptor. An “optimal” level of D2 receptor blockade with antipsychotics is thought to ameliorate the positive symptoms of schizophrenia. However, persistent D2 receptor blockade is associated with a deteriorating clinical response in a subset of patients. Interestingly, antipsychotics with a weaker D2 receptor binding profile appear somewhat superior in this respect. This evidence challenges the hypothesis that D2 receptor blockade is the sole mechanism of antipsychotic efficacy and points to consistent inter-individual responses to antipsychotic treatment. Here, we hypothesize that clinically effective doses of antipsychotics would lead to the formation of a D2 receptor “reserve” that is likely composed of presynaptic dopamine D2 autoreceptors. The majority of the remaining postsynaptic dopamine receptors are instead occupied by antipsychotics. Endogenous dopamine would then mainly interact with this D2 autoreceptor reserve, thereby reducing the presynaptic synthesis and release of dopamine and resulting in an indirect antipsychotic effect. This new proposal reconciles conceptual and empirical gaps encountered when clinical outcomes are compared to the pharmacology of antipsychotics.

  • The role of central and medial amygdala in normal and abnormal aggression: A review of classical approaches
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2017-09-14
    Jozsef Haller

    The involvement of the amygdala in aggression is supported by overwhelming evidence. Frequently, however, the amygdala is studied as a whole, despite its complex internal organization. To reveal the role of various subdivisions, here we review the involvement of the central and medial amygdala in male rivalry aggression, maternal aggression, predatory aggression, and models of abnormal aggression where violent behavior is associated with increased or decreased arousal. We conclude that: (1) rivalry aggression is controlled by the medial amygdala; (2) predatory aggression is controlled by the central amygdala; (3) hypoarousal-associated violent aggression recruits both nuclei, (4) a specific upregulation of the medial amygdala was observed in hyperarousal-driven aggression. These patterns of amygdala activation were used to build four alternative models of the aggression circuitry, each being specific to particular forms of aggression. The separate study of the roles of amygdala subdivisions may not only improve our understanding of aggressive behavior, but also the differential control of aggression and violent behaviors of various types, including those associated with various psychopathologies.

  • Reconciling the different faces of hippocampal theta: The role of theta oscillations in cognitive, emotional and innate behaviors
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2017-09-05
    Tatiana Korotkova, Alexey Ponomarenko, Caitlin K. Monaghan, Steven L. Poulter, Francesca Cacucci, Tom Wills, Michael E. Hasselmo, Colin Lever

    The theta oscillation (5–10 Hz) is a prominent behavior-specific brain rhythm. This review summarizes studies showing the multifaceted role of theta rhythm in cognitive functions, including spatial coding, time coding and memory, exploratory locomotion and anxiety-related behaviors. We describe how activity of hippocampal theta rhythm generators − medial septum, nucleus incertus and entorhinal cortex, links theta with specific behaviors. We review evidence for functions of the theta-rhythmic signaling to subcortical targets, including lateral septum. Further, we describe functional associations of theta oscillation properties − phase, frequency and amplitude – with memory, locomotion and anxiety, and outline how manipulations of these features, using optogenetics or pharmacology, affect associative and innate behaviors. We discuss work linking cognition to the slope of the theta frequency to running speed regression, and emotion-sensitivity (anxiolysis) to its y-intercept. Finally, we describe parallel emergence of theta oscillations, theta-mediated neuronal activity and behaviors during development. This review highlights a complex interplay of neuronal circuits and synchronization features, which enables an adaptive regulation of multiple behaviors by theta-rhythmic signaling.

  • Substance P and neurotensin in the limbic system: Their roles in reinforcement and memory consolidation
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2017-09-05
    L. Lénárd, K. László, E. Kertes, T. Ollmann, L. Péczely, A. Kovács, V. Kállai, O. Zagorácz, R. Gálosi, Z. Karádi

    Substance P (SP) and neurotensin (NT) are neuropeptides isolated in the periphery and in the central nervous system. They are involved in various regulatory processes in the gastrointestinal tract, in the circulatory and respiratory systems, kidney and endocrine system. In addition to the peripheral effects, SP and NT act as neurotransmitters and neuromodulators in the central nervous system, regulating various behavioural actions, such as general and motor activity, pain, food and water intake, anxiety, reward/reinforcement and memory consolidation. In the limbic system SPergic and NTergic pathways, terminals and related receptors have been identified. According to several data of literature and to our recently published results, SP and NT have rewarding/reinforcing effects and facilitate memory consolidation in various limbic regions. In this report evidences are provided about the interaction of these neuropeptides with dopaminergic and acetylcholinergic systems. A hypothesis is presented that rewarding/reinforcing effects of SP and NT develop by modulating the mesencephalic dopaminergic system, while their mnemonic effects are mediated via the mesencephalic dopaminergic and the basal forebrain cholinergic systems.

  • The zebrafish as a promising tool for modeling human brain disorders: A review based upon an IBNS Symposium
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2017-09-05
    Soaleha Shams, Jason Rihel, Jose G. Ortiz, Robert Gerlai

    The zebrafish represents an excellent compromise between system complexity and practical simplicity, features that make it useful for modeling and mechanistic analysis of complex brain disorders. Also promising are screens for psychoactive drugs with effects on larval and adult zebrafish behavior. This review, based upon a recent symposium held at the 2016 IBNS Congress, provides different perspectives on how the zebrafish may be utilized to advance research into human central nervous system disorders. It starts with a discussion on an important bottleneck in zebrafish research, measuring the behavior of this species (specifically shoaling), and continues with examples on research on autism spectrum disorder in larval zebrafish, on screening natural products for compounds with psychoactive properties in adult zebrafish, and on the development of a zebrafish model of fetal alcohol spectrum disorders. By providing information on a broad spectrum of brain disorders, experimental methods, and scientific approaches using both larval and adult zebrafish, the review is intended to showcase this underutilized laboratory species for behavioral neuroscience and psychopharmacology research.

  • Transgenerational effects of early environmental insults on aging and disease incidence
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2017-08-12
    Mirela Ambeskovic, Tessa J. Roseboom, Gerlinde A.S. Metz

    Adverse early life experiences are major influences on developmental trajectories with potentially life-long consequences. Prenatal or early postnatal exposure to stress, undernutrition or environmental toxicants may reprogram brain development and increase risk of behavioural and neurological disorders later in life. Not only experience within a single lifetime, but also ancestral experience affects health trajectories and chances of successful aging. The central mechanism in transgenerational programming of a disease may be the formation of epigenetic memory. This review explores transgenerational effects of early adverse experience on health and disease incidence in older age. First, we address mechanisms of developmental and transgenerational programming of disease and inheritance. Second, we discuss experimental and clinical findings linking early environmental determinants to adverse aging trajectories in association with possible parental contributions and sex-specific effects. Third, we outline the main mechanisms of age-related functional decline and suggest potential interventions to reverse negative effects of transgenerational programming. Thus, strategies that support healthy development and successful aging should take into account the potential influences of transgenerational inheritance.

  • Prenatal developmental origins of behavior and mental health: The influence of maternal stress in pregnancy
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2017-07-28
    Bea R.H. Van den Bergh, Marion I. van den Heuvel, Marius Lahti, Marijke Braeken, Susanne R. de Rooij, Sonja Entringer, Dirk Hoyer, Tessa Roseboom, Katri Räikkönen, Suzanne King, Matthias Schwab

    Accumulating research shows that prenatal exposure to maternal stress increases the risk for behavioral and mental health problems later in life. This review systematically analyzes the available human studies to identify harmful stressors, vulnerable periods during pregnancy, specificities in the outcome and biological correlates of the relation between maternal stress and offspring outcome. Effects of maternal stress on offspring neurodevelopment, cognitive development, negative affectivity, difficult temperament and psychiatric disorders are shown in numerous epidemiological and case-control studies. Offspring of both sexes are susceptible to prenatal stress but effects differ. There is not any specific vulnerable period of gestation; prenatal stress effects vary for different gestational ages possibly depending on the developmental stage of specific brain areas and circuits, stress system and immune system. Biological correlates in the prenatally stressed offspring are: aberrations in neurodevelopment, neurocognitive function, cerebral processing, functional and structural brain connectivity involving amygdalae and (pre)frontal cortex, changes in hypothalamo-pituitary-adrenal (HPA)-axis and autonomous nervous system.

  • Dual-transmitter systems regulating arousal, attention, learning and memory
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2017-07-27
    Sherie Ma, Balázs Hangya, Christopher S. Leonard, William Wisden, Andrew L. Gundlach

    An array of neuromodulators, including monoamines and neuropeptides, regulate most behavioural and physiological traits. In the past decade, dramatic progress has been made in mapping neuromodulatory circuits, in analysing circuit dynamics, and interrogating circuit function using pharmacogenetic, optogenetic and imaging methods This review will focus on several distinct neural networks (acetylcholine/GABA/glutamate; histamine/GABA; orexin/glutamate; and relaxin-3/GABA) that originate from neural hubs that regulate wakefulness and related attentional and cognitive processes, and highlight approaches that have identified dual transmitter roles in these behavioural functions. Modulation of these different neural networks might be effective treatments of diseases related to arousal/sleep dysfunction and of cognitive dysfunction in psychiatric and neurodegenerative disorders.

  • Basic and functional effects of transcranial Electrical Stimulation (tES)—An introduction
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2017-07-06
    Fatemeh Yavari, Asif Jamil, Mohsen Mosayebi Samani, Liliane Pinto Vidor, Michael A. Nitsche

    Non-invasive brain stimulation (NIBS) has been gaining increased popularity in human neuroscience research during the last years. Among the emerging NIBS tools is transcranial electrical stimulation (tES), whose main modalities are transcranial direct, and alternating current stimulation (tDCS, tACS). In tES, a small current (usually less than 3 mA) is delivered through the scalp. Depending on its shape, density, and duration, the applied current induces acute or long-lasting effects on excitability and activity of cerebral regions, and brain networks. tES is increasingly applied in different domains to (a) explore human brain physiology with regard to plasticity, and brain oscillations, (b) explore the impact of brain physiology on cognitive processes, and (c) treat clinical symptoms in neurological and psychiatric diseases. In this review, we give a broad overview of the main mechanisms and applications of these brain stimulation tools.

  • Elucidating opportunities and pitfalls in the treatment of experimental traumatic brain injury to optimize and facilitate clinical translation
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2017-05-30
    Patricia B. de la Tremblaye, Darik A. O’Neil, Megan J. LaPorte, Jeffrey P. Cheng, Joshua A. Beitchman, Theresa Currier Thomas, Corina O. Bondi, Anthony E. Kline

    The aim of this review is to discuss the research presented in a symposium entitled “Current progress in characterizing therapeutic strategies and challenges in experimental CNS injury” which was presented at the 2016 International Behavioral Neuroscience Society annual meeting. Herein we discuss diffuse and focal traumatic brain injury (TBI) and ensuing chronic behavioral deficits as well as potential rehabilitative approaches. We also discuss the effects of stress on executive function after TBI as well as the response of the endocrine system and regulatory feedback mechanisms. The role of the endocannabinoids after CNS injury is also discussed. Finally, we conclude with a discussion of antipsychotic and antiepileptic drugs, which are provided to control TBI-induced agitation and seizures, respectively. The review consists predominantly of published data.

  • Shaping vulnerability to addiction – the contribution of behavior, neural circuits and molecular mechanisms
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2017-05-29
    Gabor Egervari, Roberto Ciccocioppo, J. David Jentsch, Yasmin L. Hurd

    Substance use disorders continue to impose increasing medical, financial and emotional burdens on society in the form of morbidity and overdose, family disintegration, loss of employment and crime, while advances in prevention and treatment options remain limited. Importantly, not all individuals exposed to abused substances effectively develop the disease. Genetic factors play a significant role in determining addiction vulnerability and interactions between innate predisposition, environmental factors and personal experiences are also critical. Thus, understanding individual differences that contribute to the initiation of substance use as well as on long-term maladaptations driving compulsive drug use and relapse propensity is of critical importance to reduce this devastating disorder. In this paper, we discuss current topics in the field of addiction regarding individual vulnerability related to behavioral endophenotypes, neural circuits, as well as genetics and epigenetic mechanisms. Expanded knowledge of these factors is of importance to improve and personalize prevention and treatment interventions in the future.

  • Experience-induced transgenerational (re-)programming of neuronal structure and functions: Impact of stress prior and during pregnancy
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2017-05-29
    Katharina Braun, Jörg Bock, Tamar Wainstock, Emmanuel Matas, Inna Gaisler-Salomon, Jörg Fegert, Ute Ziegenhain, Menahem Segal

    This review focuses on the inter- and transgenerational effects of stress experience prior to and during gestation. We provide an overview of findings from studies in humans as well as in animal models on brain structural and physiological functions and on the development of cognitive and executive functions. We also discuss the concept of stress-induced (re-)programming in more detail by highlighting epigenetic mechanisms and particularly those affecting the development of monoaminergic transmitter systems, which constitute the braińs reward system. As the majority of studies have focused on male individuals we will emphasize sex-specific differences in stress vulnerability and resilience. Finally, we offer some perspectives on the development of protective and therapeutic interventions in cognitive and emotional disturbances resulting from pre-conception and prenatal stress.

  • Prenatal stress and epigenetics
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2017-05-18
    L. Cao-Lei, S.R. de Rooij, S. King, S.G. Matthews, G.A.S. Metz, T.J. Roseboom, M. Szyf

    In utero exposure to environmental stress in both animals and humans could result in long-term epigenome alterations which further lead to consequences for adaptation and development in the offspring. Epigenetics, especially DNA methylation, is considered one of the most widely studied and well-characterized mechanisms involved in the long-lasting effects of in utero stress exposure. In this review, we outlined evidence from animal and human prenatal research supporting the view that prenatal stress could lead to lasting, broad and functionally organized signatures in DNA methylation which, in turn, could mediate exposure-phenotype associations. We also emphasized the advantage of using stressor from quasi-randomly assigned experiments. Furthermore, we discuss challenges that still need to be addressed in this field in the future.

  • High times for cannabis: Epigenetic imprint and its legacy on brain and behavior
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2017-05-12
    Henrietta Szutorisz, Yasmin L. Hurd

    Extensive debates continue regarding marijuana (Cannabis spp), the most commonly used illicit substance in many countries worldwide. There has been an exponential increase of cannabis studies over the past two decades but the drug’s long-term effects still lack in-depth scientific data. The epigenome is a critical molecular machinery with the capacity to maintain persistent alterations of gene expression and behaviors induced by cannabinoids that have been observed across the individual’s lifespan and even into the subsequent generation. Though mechanistic investigations regarding the consequences of developmental cannabis exposure remain sparse, human and animal studies have begun to reveal specific epigenetic disruptions in the brain and the periphery. In this article, we focus attention on long-term disturbances in epigenetic regulation in relation to prenatal, adolescent and parental germline cannabinoid exposure. Expanding knowledge about the protracted molecular memory could help to identify novel targets to develop preventive strategies and treatments for behaviors relevant to neuropsychiatric risks associated with developmental cannabis exposure.

  • Perinatal selective serotonin reuptake inhibitor medication (SSRI) effects on social behaviors, neurodevelopment and the epigenome
    Neurosci. Biobehav. Rev. (IF 8.299) Pub Date : 2017-05-01
    Mary Gemmel, Eszter Bögi, Christina Ragan, Mariah Hazlett, Michal Dubovicky, Daniel L. van den Hove, Tim F. Oberlander, Thierry D. Charlier, Jodi L. Pawluski

    Recent research has linked early life exposure to selective serotonin reuptake inhibitor medications (SSRIs) to modifications of social behaviors in children. Serotonin is a key regulator of neurodevelopment, social behaviors and mental health, and with the growing use of SSRIs to treat maternal affective disorders during the perinatal period, questions have been raised about the benefits and risks of perinatal SSRI exposure on the developing child. This review will highlight how perinatal SSRIs affect maternal care and neurodevelopmental outcomes related to social affiliative behaviors in offspring; such as play behaviors, social interactions, reproductive behaviors, and maternal care of the next generation. We will also review how early life exposure to SSRIs can alter related neurobiology, and the epigenome. Both clinical research and findings from animal models will be discussed. Understanding the impact of perinatal SSRIs on neurobehavioral outcomes will improve the health and well-being of subsequent generations.

Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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