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  • Cannabis use and human retina: The path for the study of brain synaptic transmission dysfunctions in cannabis users
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-02-14
    Thomas Schwitzer, Raymund Schwan, Karine Angioi-Duprez, Laurence Lalanne, Anne Giersch, Vincent Laprevote

    Owing to the difficulty of obtaining direct access to the functioning brain, new approaches are needed for the indirect exploration of brain disorders in neuroscience research. Due to its embryonic origin, the retina is part of the central nervous system and is well suited to the investigation of neurological functions in psychiatric and addictive disorders. In this review, we focus on cannabis use, which is a crucial public health challenge, since cannabis is one of the most widely used addictive drugs in industrialized countries. We first explain why studying retinal function is relevant when exploring the effects of cannabis use on brain function. Next, we describe both the retinal electrophysiological measurements and retinal dysfunctions observed after acute and regular cannabis use. We then discuss how these retinal dysfunctions may inform brain synaptic transmission abnormalities. Finally, we present various directions for future research on the neurotoxic effects of cannabis use.

  • The Arc gene: Retroviral heritage in cognitive functions
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-02-14
    Alexander V. Kedrov, Mikhail Durymanov, Konstantin V. Anokhin

    Stabilization of neuronal plastic changes is mediated by transient gene expression, including transcription of the activity-regulated cytoskeleton-associated gene (Arc), also known as Arg 3.1. Arc is implicated in several types of synaptic plasticity, including synaptic scaling, long-term potentiation, and long-term depression. However, the precise mechanisms by which Arc mediates these forms of long-term plasticity are unclear. It was recently found that Arc protein is capable of forming capsid-like structures and of transferring its own mRNA to neighboring cells. Moreover, Arc mRNA undergoes activity-dependent translation in these “transfected” cells. These new data raise unexpected possibilities for the mechanisms of the Arc action, and many intriguing questions concerning the role of Arc transcellular traffic in neuronal plasticity. In this mini-review, we discuss a possible link between the role of Arc in learning and memory and the virus-like properties of this protein. Additionally, we highlight some of the emerging questions for future neurobiological studies and translational applications of Arc transsynaptic effects.

  • Extrinsic and default mode networks in psychiatric conditions: Relationship to excitatory-inhibitory transmitter balance and early trauma
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-02-12
    Paul Allen, Iris E. Sommer, Renaud Jardri, Michael W. Eysenck, Kenneth Hugdahl

    Over the last three decades there has been an accumulation of Magnetic Resonance Imaging (MRI) studies reporting that aberrant functional networks may underlie cognitive deficits and other symptoms across a range of psychiatric diagnoses. The use of pharmacological MRI and 1H-Magnetic Resonance Spectroscopy (1H-MRS) has allowed researchers to investigate how changes in network dynamics are related to perturbed excitatory and inhibitory neurotransmission in individuals with psychiatric conditions. More recently, changes in functional network dynamics and excitatory/inhibitory (E/I) neurotransmission have been linked to early childhood trauma, a major antecedents for psychiatric illness in adulthood. Here we review studies investigating whether perturbed network dynamics seen across psychiatric conditions are related to changes in E/I neurotransmission, and whether such changes could be linked to childhood trauma. Whilst there is currently a paucity of studies relating early traumatic experiences to altered E/I balance and network function, the research discussed here lead towards a plausible mechanistic hypothesis, linking early traumatic experiences to cognitive dysfunction and symptoms mediated by E/I neurotransmitter imbalances.

  • Motor Imagery in children with DCD: a systematic and meta-analytic review of hand-rotation task performance
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-02-10
    Pamela Barhoun, Ian Fuelscher, Emily Jane Kothe, Jason L. He, George J. Youssef, Peter G. Enticott, Jacqueline Williams, Christian Hyde

    This is the first review to quantitatively summarise evidence evaluating MI functioning in children with DCD compared to controls, based on the hand rotation task (HRT). Specifically, MI performance was assessed using three different behavioural performance measures on the HRT (i.e., reaction time, accuracy and efficiency). Eight studies were included for quantitative analysis, yielding data for 176 and 198 children with and without DCD respectively. While children with DCD consistently used MI across all measures of the task, they continually demonstrated reductions in HRT performance relative to controls. Additionally, group differences appeared to be strongest and more commonly detected when using the IES (mean inverse efficiency-IES) metric on the HRT. These effects did not differ statistically as a function of instruction type. In support of the internal modelling deficit hypothesis, group effects suggested children with DCD demonstrate broad reductions in HRT performance relative to controls. However, consideration of effect size and study level analysis showed the ability for an individual study to detect these effects differs considerably depending on the outcome metric adopted.

  • Non-invasive neurophysiological measures of learning: A meta-analysis
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-02-06
    Angelica M. Tinga, Tycho T. de Back, Max M. Louwerse

    In a meta-analysis of 113 experiments we examined neurophysiological outcomes of learning, and the relationship between neurophysiological and behavioral outcomes of learning. Findings showed neurophysiology yielding large effect sizes, with the majority of studies examining electroencephalography and eye-related outcome measures. Effect sizes on neurophysiological outcomes were smaller than effect sizes on behavioral outcomes, however, neurophysiological outcomes were, but behavioral outcomes were not, influenced by several modulating factors. These factors included the sensory system in which learning took place, number of learning days, whether feedback on performance was provided, and age of participants. Controlling for these factors resulted in the effect size differences between behavior and neurophysiology to disappear. The findings of the current meta-analysis demonstrate that neurophysiology is an appropriate measure in assessing learning, particularly when taking into account factors that could have an influence on neurophysiology. We propose a first model to aid further studies that are needed to examine the exact interplay between learning, neurophysiology, behavior, individual differences, and task-related aspects.

  • Circadian modulation of human reward function: Is there an evidentiary signal in existing neuroimaging studies?
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-02-02
    Jamie E.M. Byrne, Hailey Tremain, Nuwan D. Leitan, Charlotte Keating, Sheri L. Johnson, Greg Murray

    Reward functioning in animals is modulated by the circadian system, but such effects are poorly understood in the human case. The aim of this study was to address this deficit via a systematic review of human fMRI studies measuring one or more proxies for circadian function and a neural reward outcome. A narrative synthesis of 15 studies meeting inclusion criteria identified 13 studies that show a circadian impact on the human reward system, with four types of proxy (circadian system biology, downstream circadian rhythms, circadian challenge, and time of day) associated with neural reward activation. Specific reward-related regions/networks subserving this effect included the medial prefrontal cortex, ventral striatum, putamen and default mode network. The circadian effect was observed in measures of both reward anticipation and reward receipt, with more consistent evidence for the latter. Findings are limited by marked heterogeneity across study designs. We encourage a systematic program of research investigating circadian-reward interactions as an adapted biobehavioural feature and as an aetiological mechanism in reward-related pathologies.

  • Towards a neural model of infant cry perception
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-01-30
    J. Witteman, M.H. Van IJzendoorn, J.K. Rilling, P.A. Bos, N.O. Schiller, M.J Bakermans-Kranenburg

    Previous work suggests that infant cry perception is supported by an evolutionary old neural network consisting of the auditory system, the thalamocingulate circuit, the frontoinsular system, the reward pathway and the medial prefrontal cortex. Furthermore, gender and parenthood have been proposed to modulate processing of infant cries. The present meta-analysis (N = 350) confirmed involvement of the auditory system, the thalamocingulate circuit, the dorsal anterior insula, the pre-supplementary motor area and dorsomedial prefrontal cortex and the inferior frontal gyrus in infant cry perception, but not of the reward pathway. Structures related to motoric processing, possibly supporting the preparation of a parenting response, were also involved. Finally, females (more than males) and parents (more than non-parents) recruited a cortico-limbic sensorimotor integration network, offering a neural explanation for previously observed enhanced processing of infant cries in these sub-groups. Based on the results, an updated neural model of infant cry perception is presented.

  • Cerebral Plasticity as the Basis for Upper Limb Recovery following Brain Damage
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-01-30
    Martin Lotze, Aija Marie Ladda, Klaus Martin Stephan

    Neural plasticity is the basis for an adaptation process of functional and structural characteristics of the nervous system in response to a changing environment. However, changes during training in healthy volunteers are only partially comparable to that observed in patients with circumscribed lesions. Pathologies can even be associated with maladaptive plasticity. We first introduce basic processes underlying brain plasticity with respect to the sensorimotor system and outline their limitations. A number of methods showing potential in the evaluation of these processes are compared before literature on postlesional plasticity is reviewed. Approaches in monitoring plasticity processes of the healthy sensorimotor system are partially applicable after brain damage and for the documentation of recovery processes. Some of these techniques can further be used for outcome prediction or therapy selection and optimization. Extreme examples from athletes or professional musicians illustrate the amount of plastic changes the human brain can achieve. Profound understanding of neural plasticity in health and disease will help to modify and individually optimize therapy strategies in neurorehabilitation.

  • Cortical and subcortical contributions to context-control learning
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-01-24
    Yu-Chin Chiu, Tobias Egner

    “Cognitive control” describes our ability to strategically bias information processing in line with internal goals. Traditionally, research has focused on delineating the sources of top-down biasing, implicating the lateral prefrontal cortex. The past two decades, however, have seen increasing interest in the regulation of control, that is, how learning processes guide the context-sensitive application of top-down biasing. Here, we review and synthesize recent research into the cognitive and neural mechanisms of this type of “context-control learning”. We first discuss a fast-growing cognitive psychology literature documenting how specific cognitive control states can become associated with, and subsequently triggered by, contextual cues. We then review neuroimaging studies that speak to the neural substrates of contextual adjustments in control, with a particular focus on recent work that explicitly modeled context-control learning processes. We conclude that these studies suggest an important subcortical extension of the traditional frontal control network, as they indicate a key role for the caudate nucleus in forming associations between contextual cues and appropriate control settings.

  • Attention-Deficit/Hyperactivity Disorder and task-related heart rate variability: a systematic review and meta-analysis
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-01-24
    Andreea Robe, Anca Dobrean, Ioana A. Cristea, Costina-Ruxandra Păsărelu, Elena Predescu

    Background Research suggests that Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with autonomic nervous system dysregulation, but the findings were mixed. Method We conducted a literature review and meta-analysis to quantify the effect of ADHD on vagally-mediated heart rate variability (HRV). PsycINFO, PubMed, Web of Science and Scopus, were searched for case-control or cohort studies reporting measures of vagally-mediated HRV, after a task demand, among individuals with ADHD relative to healthy subjects. Results Thirteen articles comprising a total of 869 patients with ADHD and 909 healthy participants were included. As compared to controls, ADHD patients had reduced vagally-mediated HRV, corresponding to a small effect size (Hedge’sg = 0.209; CI 95% 0.01 to 0.40). Heterogeneity was high (Q (18) = 76.59, p < 0.001; I² = 77%). There was some evidence of small study effects. Task type, respiration rate assessment and associated comorbid disorders were statistically significant moderators. Conclusions These findings provide evidence for the associations between ADHD and autonomic dysregulation. Future studies addressing HRV reactivity are needed.

  • Peripersonal space (PPS) as a multisensory interface between the individual and the environment, defining the space of the self
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-01-24
    Andrea Serino

    Our brain has developed a specific system to represent the space closely surrounding the body, termed peripersonal space (PPS). This space has a key functional role as it is where all physical interactions with objects in the environment occur. Here I describe how multisensory neurons in a specific fronto-parietal network map the PPS by integrating tactile stimuli on the body with visual or auditory information related to external objects specifically when they are close to the body. I show how PPS representation is not only multisensory, but actually multisensory-motor, as the PPS system interacts with motor areas to trigger appropriate responses. The extent of PPS is not fixed, but it is shaped by experience, as PPS may encompass farther portions of space, once the individual has interacted with them, (e.g., with tools), or it contracts, if interactions are limited because of external constraints, body, or brain injury. Interactions between the individual and the environment are not only physical but may also be “abstract”. Recent data show that PPS adapts as a consequence of technology-mediated or social interactions. Finally, I propose that besides low-level sensory-motor representations of the space around the different parts of the body, mediating body-objects interactions, the multisensory PPS system also underlies a general representation of the self as distinct from the environment and the others. PPS thus supports self-location and contributes to bodily self-consciousness, and mediating higher-level cognitive functions.

  • The psychological scars of suicide: Accounting for how risk for suicidal behavior is heightened by its past occurrence
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-01-24
    Richard T. Liu

    Not only is suicidal behavior strongly predicted by its past occurrence, but the risk for recurrence appears to increase with each subsequent attempt. The current paper discusses a potential explanation for this phenomenon, that suicide attempts may leave a residual psychological scar that heightens risk for future attempts. This possibility is evaluated against two alternatives: (i) risk for first and subsequent suicide attempts is accounted for by a shared diathesis pre-existing the first lifetime attempt, and (ii) different rates of developmental decline in risk factors account for differences in prospective number of attempts. In this discussion, a formalized conceptual framework of psychological scarring is presented, along with considerations of particular relevance to its study. Finally, the clinical implications of determining the processes underlying the association between suicide attempts and heightened risk for recurrence are discussed.

  • Conflicting Emergences. Weak vs. strong emergence for the modelling of brain function
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-01-23
    Federico E. Turkheimer, Peter Hellyer, Angie A. Kehagia, Paul Expert, Louis-David Lord, Jakub Vohryzek, Jessica De Faria Dafflon, Mick Brammer, Robert Leech

    The concept of “emergence” has become commonplace in the modelling of complex systems, both natural and man-made; a functional property” emerges” from a system when it cannot be readily explained by the properties of the system’s sub-units. A bewildering array of adaptive and sophisticated behaviours can be observed from large ensembles of elementary agents such as ant colonies, bird flocks or by the interactions of elementary material units such as molecules or weather elements. Ultimately, emergence has been adopted as the ontological support of a number of attempts to model brain function. This manuscript aims to clarify the ontology of emergence and delve into its many facets, particularly into its “strong” and “weak” versions that underpin two different approaches to the modelling of behaviour. The first group of models is here represented by the “free energy” principle of brain function and the “integrated information theory” of consciousness. The second group is instead represented by computational models such as oscillatory networks that use mathematical scalable representations to generate emergent behaviours and are then able to bridge neurobiology with higher mental functions. Drawing on the epistemological literature, we observe that due to their loose mechanistic links with the underlying biology, models based on strong forms of emergence are at risk of metaphysical implausibility. This, in practical terms, translates into the overdetermination that occurs when the proposed model becomes only one of a large set of possible explanations for the observable phenomena. On the other hand, computational models that start from biologically plausible elementary units, hence are weakly emergent, are not limited by ontological faults and, if scalable and able to realistically simulate the hierarchies of brain output, represent a powerful vehicle for future neuroscientific research programmes.

  • Perceptual Phenomena in Destructured Sensory Fields: Probing The Brain’s Intrinsic Functional Architectures
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-01-19
    Vladimir Miskovic, Steven Jay Lynn, Jeffrey O. Bagg, Jourdan J. Pouliot, Matt Ríos, Jirí Wackermann

    Destructured sensory fields, involving homogenous stimulation with little or no time-varying structure, provide a fertile ground for testing hypotheses about predictive coding in the human brain. Extended exposure to sensory patterns that deviate substantially from the statistics of natural environments can elicit a bewildering range of perceptual phenomena, up to and including vivid oneiric imagery. We illustrate how this large variety of perceptual effects can be understood as the experiential counterpart of auto-generated neuronal dynamics, unconstrained by parameters that tune the waking sensorium. We synthesize the literature on autonomous neuronal activity across multiple spatiotemporal scales with generative models of brain function and evidence from artificial neural architectures. Perception, we argue, emerges from a process of non-random sampling from an intrinsic distribution of hypotheses rather than a direct transfer of information from the world. The imagery that occurs in altered sensory environments is explained as the outcome of an iterative search through internal world models in which the structural typology of percepts reflects the brain’s intrinsic functional architectures.

  • The auditory cortex and the emotional valence of sounds
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-01-18
    Giulia Concina, Annamaria Renna, Anna Grosso, Benedetto Sacchetti

    How and where sensory stimuli, such as tones or lights, are linked to valence is an important unresolved question in the field of neuroscience. The auditory cortex is essential to analyse the identity and the behavioural importance of tones paired with emotional events. On the contrary, whether the auditory cortex may also encode information on the emotional-motivational valence of sounds is much more controversial. Here, we reviewed recent studies showing that the activity of cortical neurons reflects information about the content of emotional stimuli paired with tones. Critically, the blockade of these neuronal processes prevents animals from recognising sounds as aversive or pleasant. Based on these findings, we proposed a conceptual model in which the auditory cortex may incorporate ascending information from subcortical nuclei about the valence of sounds in sound representations and may consequently drive the activity of subcortical structures towards emotionally laden tones. This hypothesis may also have important implications in the characterisation of neural circuits engaged by maladaptive affective disorders, such as phobias.

  • The reverse translation of a quantitative neuropsychiatric framework into preclinical studies: Focus on social interaction and behavior
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-01-16
    Tatiana Peleh, Kevin G.O. Ike, Emma J. Wams, Evan P. Lebois, Bastian Hengerer

    Following the Research Domain Criteria (RDoC) concept, major brain circuits are conserved in evolution and malfunctioning of a brain circuit will lead to specific behavioral symptoms. Reverse translation of patient-based findings from Alzheimer’s disease (AD), schizophrenia (SZ) and major depression (MD) patients to preclinical models accordingly can be a starting point for developing a deeper understanding of the functional circuit biology and contribute to the validation of new hypotheses for therapeutic intervention in patients. In the context of the EU funded PRISM project, a preclinical test battery of tasks has been selected and aligned with the clinical test battery. It allows for assessment of social functioning, sensory processing, attention and working memory and is designed for validation of biological substrates from human molecular landscaping of social withdrawal. This review will broadly summarize the available literature on tasks for studying social behavior in rodents and outline the development of a preclinical test battery for the PRISM project by reverse translation.

  • Spatial memory in Huntington’s disease: a comparative review of human and animal data
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-01-15
    Yifat Glikmann-Johnston, Kyle D. Fink, Peter Deng, Audrey Torrest, Julie C. Stout

    To improve the translational predictability of treatment strategies for Huntington’s disease (HD), sensitive and analogous cognitive outcomes are needed across HD animal models and humans. Spatial memory measures are promising candidates because they are based on ‘visual’ or ‘non-verbal’ cognition, and are commonly tested in both animals and humans. Here, we consider the suitability of spatial memory for strengthening translational links between animals and humans in HD research and clinical trials. We describe findings of spatial memory impairments in human HD and mouse models, including which aspects of spatial memory are most affected and at which time points in disease progression. We also describe the neural systems that underlie spatial memory and link spatial memory impairments to HD neuropathology, focussing on striatal and hippocampal systems. We provide a critical analysis of the literature in terms of the suitability of spatial memory for bridging the translational gap between species. Finally, we discuss possible neural mechanisms that might explain the spatial memory impairments seen in HD, and their relevance to potential treatments.

  • Roles of Aging in Sleep
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-01-12
    Hua-Hua Zhong, Bo Yu, Dan Luo, Liang-Yan Yang, Jin Zhang, Sha-Sha Jiang, Shao-Jie Hu, Yun-Yun Luo, Mei-wen Yang, Fen-fang Hong, Shu-Long Yang

    With aging, various factors deteriorate the normal sleep process that is essential for the restoration of functional and physical performance. Due to aging-related diseases, life changes, or aging itself, disturbances in normal sleep cycles can profoundly affect healthy aging. To understand the interconnections between aging and the factors influencing sleep, with emerging evidence accumulated in recent years, this study elaborates on the roles of aging in sleep from four perspectives: cortical thinning, white matter degeneration, neurotransmitter dysregulation, and circadian disorganization. In brief, with aging, cortical thinning can be induced by the deposition of neurotoxic substances, and white matter degeneration can be induced by vascular abnormalities. These alterations emerging in the brain jointly disrupt sleep spindles and slow waves, leading to sleep disturbances. Age-related dysregulation in neurotransmitters (including galanin, orexin, serotonin, and adenosine) directly impairs the sleep modulation system. Disorganization in the circadian system consisting of suprachiasmatic nucleus dysfunction, reduced light transmission, and local circadian clock disruption collectively interrupts circadian rhythms, also causing sleep disturbances in the older. Of note is the bidirectional relationship between aging and sleep, which required us to examine this issue from different perspectives.

  • Alcohol exposure during embryonic development: An opportunity to conduct systematic developmental time course analyses in zebrafish
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-01-11
    Amanda Facciol, Benjamin Tsang, Robert Gerlai

    Ethanol affects numerous neurobiological processes depending upon the developmental stage at which it reaches the vertebrate embryo. Exposure time dependency may explain the variable severity and manifestation of life-long symptoms observed in fetal alcohol spectrum disorder (FASD) patients. Characterization of behavioural deficits will help us understand developmental stage-dependency and its underlying biological mechanisms. Here we highlight pioneering studies that model FASD using zebrafish, including those that demonstrated developmental stage-dependency of alcohol effects on some behaviours. We also succinctly review the more expansive mammalian literature, briefly discuss potential developmental stage dependent biological mechanisms alcohol alters, and review some of the disadvantages of mammalian systems versus the zebrafish. We stress that the temporal control of alcohol administration in the externally developing zebrafish gives unprecedented precision and is a major advantage of this species over other model organisms employed so far. We also emphasize that the zebrafish is well suited for high throughput screening and will allow systematic exploration of embryonic-stage dependent alcohol effects via mutagenesis and drug screens.

  • The course and prognostic factors of cognitive outcomes after traumatic brain injury: a systematic review
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-01-11
    Tatyana Mollayeva, Shirin Mollayeva, Nicole Pacheco, Andrea D’Souza, Angela Colantonio

    Despite indications that TBI may be a precursor of cognitive decline and subsequent development of Alzheimer’s disease, little is known about the time course of this relationship and the factors involved. This systematic review summarizes the evidence pertinent to this subject matter. All English language studies of longitudinal design, and works cited within them, found in six literature databases, were considered, and their quality assessed. Of 65 articles appraised, 44 studies were selected. Results were organized by timing of assessments, injury severity, and cognitive domains assessed. Differences in the course of cognitive performance were observed across injury severity groups and cognitive domains, with differential proportions of reports of improvement, decline, or no change over time. The evidence for genetic, sex-, age-, and injury-related factors as determinants of cognitive outcome was inconsistent. The non-uniform trajectory of cognitive performance post-TBI supports the notion that this construct is non-homogeneous, and that different factors influence its course. Agreement on a core set of predictors and consideration of psychometric properties of outcome measures is needed.

  • Disturbed redox homeostasis and oxidative stress: Potential players in the developmental regression in Rett syndrome
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-01-09
    Michael Müller

    Rett syndrome (RTT) is a neurodevelopmental disorder affecting mostly girls. A seemingly normal initial development is followed by developmental stagnation and regression, leading to severe mental impairment with autistic features, motor dysfunction, irregular breathing and epilepsy. Currently, a cure does not exist. Due to the close association of RTT with mitochondrial alterations, cellular redox-impairment and oxidative stress, compounds stabilizing mitochondrial function, cellular redox-homeostasis, and oxidant detoxification are increasingly considered as treatment concepts. Indeed, antioxidants and free-radical scavengers ameliorate certain aspects of the complex and severe clinical presentation of RTT. To further evaluate these strategies, reliable biosensors are needed to quantify redox-conditions in brain and peripheral organs of mouse models or in patient-derived cells. Genetically-encoded redox-sensors meet these requirements. Expressed in transgenic mouse-models such as our unique Rett-redox indicator mice, they will report for any cell type desired the severity of oxidant stress throughout the various disease stages of RTT. Furthermore, these sensors will be crucial to evaluate in vitro and in vivo the outcome of mitochondria- and redox-balance targeted treatments.

  • Sensory Processing Sensitivity in the context of Environmental Sensitivity: a critical review and development of research agenda
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-01-09
    Corina U. Greven, Francesca Lionetti, Charlotte Booth, Elaine Aron, Elaine Fox, Haline E. Schendan, Michael Pluess, Hilgo Bruining, Bianca Acevedo, Patricia Bijttebier, Judith Homberg

    Sensory Processing Sensitivity (SPS) is a common, heritable and evolutionarily conserved trait describing inter-individual differences in sensitivity to both negative and positive environments. Despite societal interest in SPS, scientific knowledge is lagging behind. Here we critically discuss how SPS relates to other theories, how to measure SPS, whether SPS is a continuous vs categorical trait, its relation to other temperament and personality traits, the underlying aetiology and neurobiological mechanisms, and relations to both typical and atypical development, including mental and sensory disorders. Drawing on the diverse expertise of the authors, we set an agenda for future research to stimulate the field. We conclude that SPS increases risk for stress-related problems in response to negative environments, but also provides greater benefit from positive and supportive experiences. The field requires more reliable and objective assessment of SPS, deeper understanding of its mechanisms to differentiate it from other traits. Future research needs to target prevention of adverse effects associated with SPS, and exploitation of its positive potential to improve well-being and mental health.

  • Pair-bonding, Fatherhood, and the Role of Testosterone: A Meta-Analytic Review
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-01-09
    Nicholas M. Grebe, Ruth E. Sarafin, Chance R. Strenth, Samuele Zilioli

    Males of many species must allocate limited energy budgets between mating and parenting effort. The Challenge Hypothesis provides a framework for understanding these life-history trade-offs via the disparate roles of testosterone (T) in aggression, sexual behavior, and parenting. It predicts that males pursuing mating opportunities have higher T than males pursuing paternal strategies, and in humans, many studies indeed report that men who are fathers and/or pair-bonded have lower T than childless and/or unpaired men. However, the magnitude of these effects, and the influence of methodological variation on effect sizes, have not been quantitatively assessed. We meta-analyzed 114 effects from 66 published and unpublished studies covering four predictions inspired by the Challenge Hypothesis. We confirm that pair-bonded men have lower T than single men, and fathers have lower T than childless men. Furthermore, men more oriented toward pair-bonding or offspring investment had lower T. We discuss the practical meaningfulness of the effect sizes we estimate in relation to known factors (e.g., aging, geographic population) that influence men’s T concentrations.

  • Functional imaging studies of Impulse Control Disorders in Parkinson’s disease need a stronger neurocognitive footing
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-01-09
    Garance M Meyer, Charlotte Spay, Chloé Laurencin, Bénédicte Ballanger, Guillaume Sescousse, Philippe Boulinguez

    Impulse control disorders (ICDs) in Parkinson’s disease (PD) are associated with dopaminergic dysfunction and treatment, but have no satisfactory therapeutic solution. While studies assessing the neurofunctional bases of ICDs are important for advancing our understanding and management of ICDs, they remain sparse and inconsistent. Based on a systematic analysis of the neuroimaging literature, the present review pinpoints various abnormalities beyond the mesocorticolimbic circuit that supports reward processing, suggesting possible dysfunction at the sensorimotor, executive and affective levels. We advocate that: 1) Future studies should use more sophisticated psychological models and behavioral designs that take into account the potentially multifaceted aspect of ICDs; this would allow a more accurate assessment of the underlying neurocognitive processes, which are not all dependent on the dopaminergic system. 2) Future neuroimaging studies should rely more strongly on task-based, event-related analyses to disentangle the various mechanisms that can be dysfunctional in ICDs. We believe these guidelines constitute a prerequisite towards distinguishing causes, correlates and individual susceptibility factors of PD patients with ICDs.

  • Why would Parkinson’s disease lead to sudden changes in creativity, motivation, or style with visual art?: A review of case evidence and new, contextual, and genetic hypotheses
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-01-08
    Jon O. Lauring, Tomohiro Ishizu, Hana H. Kutlikova, Felix Dörflinger, Steven Haugbøl, Helmut Leder, Ron Kupers, Matthew Pelowski

    Parkinson’s disease (PD) is a devastating diagnosis with, however, potential for an extremely intriguing aesthetic component. Despite motor and cognitive deficits, an emerging collection of studies report a burst of visual artistic output and alterations in produced art in a subgroup of patients. This provides a unique window into the neurophysiological bases for why and how we might create and enjoy visual art, as well as into general brain function and the nature of PD or other neurodegenerative diseases. However, there has not been a comprehensive organization of literature on this topic. Nor has there been an attempt to connect case evidence and knowledge on PD with present understanding of visual art making in psychology and neuroaesthetics in order to propose hypotheses for documented artistic changes. Here, we collect the current research on this topic, tie this to PD symptoms and neurobiology, and provide new theories focusing on dopaminergic neuron damage, over-stimulation from dopamine agonist therapy, and context or genetic factors revealing the neurobiological basis of the visual artistic brain.

  • Chronobiology of Limbic Seizures: Potential Mechanisms and Prospects of Chronotherapy for Mesial Temporal Lobe Epilepsy
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-01-07
    Daniel Leite Góes Gitai, Tiago Gomes de Andrade, Ygor Daniel Ramos dos Santos, Sahithi Attaluri, Ashok K. Shetty

    Mesial Temporal Lobe Epilepsy (mTLE) characterized by progressive development of complex partial seizures originating from the hippocampus is the most prevalent and refractory type of epilepsy. One of the remarkable features of mTLE is the rhythmic pattern of occurrence of spontaneous seizures, implying a dependence on the endogenous clock system for seizure threshold. Conversely, circadian rhythms are affected by epilepsy too. Comprehending how the circadian system and seizures interact with each other is essential for understanding the pathophysiology of epilepsy as well as for developing innovative therapies that are efficacious for better seizure control. In this review, we confer how the temporal dysregulation of the circadian clock in the hippocampus combined with multiple uncoupled oscillators could lead to periodic seizure occurrences and comorbidities. Unraveling these associations with additional research would help in developing chronotherapy for mTLE, based on the chronobiology of spontaneous seizures. Notably, differential dosing of antiepileptic drugs over the circadian period and/or strategies that resynchronize biological rhythms may substantially improve the management of seizures in mTLE patients.

  • From the Microscope to the Magnet: Disconnection in Schizophrenia and Bipolar Disorder
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-01-07
    Ellen Ji, Florian Lejuste, Samuel Sarrazin, Josselin Houenou

    White matter (WM) abnormalities have implicated schizophrenia (SZ) and bipolar disorder (BD) as disconnection syndromes, yet the extent to which these abnormalities are shared versus distinct remains unclear. Diffusion tensor imaging (DTI) studies yield a putative measure of WM integrity while neuropathological studies provide more specific microstructural information. We therefore systematically reviewed all neuropathological (n = 12) and DTI (n = 11) studies directly comparing patients with SZ and BD. Most studies (18/23) reported no difference between patient groups. Changes in oligodendrocyte density, myelin staining and gene, protein and mRNA expression were found in SZ and/or BD patients as compared to healthy individuals, while DTI studies showed common alterations in thalamic radiations, uncinate fasciculus, corpus callosum, longitudinal fasciculus and corona radiata. Altogether, findings suggest shared disconnectivity in SZ and BD, which are likely related to their considerable overlap. Above all, neuroimaging findings corroborated neuropathological findings in the prefrontal cortex, demonstrating the utility of integrating multiple methodologies. Focusing on clinical dimensions over disease entities will advance our understanding of disconnectivity and help inform preventive medicine.

  • Is there room for attentional impairments in binge drinking? A commentary on Carbia et al. (2018)
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-01-07
    Séverine Lannoy, Alexandre Heeren, Valérie Dormal, Joël Billieux, Pierre Maurage

    Binge drinking is an excessive pattern of alcohol use, highly prevalent in adolescents and young adults. Several studies have explored the cognitive impairments associated with binge drinking, and Carbia et al. (2018) recently proposed a systematic review of these impairments. Although this review offers an insightful and up-to-date synthesis of this research field, the authors concluded that binge drinking is not associated with attentional impairments. We argue that such conclusion is premature. We identified published studies not mentioned by Carbia et al. (2018), which documented attentional impairments in binge drinking. In particular, a differential exploration of attentional networks has suggested that binge drinkers not only exhibit impairments for the executive control of attention, but also for its alerting network. We thus recommend a better consideration of attention in future experimental and translational research agendas.

  • Overcoming Avoidance in Anxiety Disorders: The Contributions of Pavlovian and Operant Avoidance Extinction Methods
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-01-07
    Simon Dymond

    Avoidance is generally adaptive, yet excessive threat-avoidance may soon become maladaptive and lead to functional impairment and psychopathology. Laboratory-based treatment research has provided important insights about the acquisition, maintenance, and extinction of maladaptive avoidance. Despite this, laboratory research on avoidance learning and extinction in humans is relatively underdeveloped. A better understanding of avoidance extinction methods has implications for basic research with humans and the development of treatment interventions aimed at replacing maladaptive behavior with an adaptive, functional repertoire. The present article reviews, for the first time, the use of the term extinction in human research on avoidance, contrasts existing Pavlovian and operant approaches to the extinction of avoidance, considers the validity of approaches to avoidance extinction, and suggests a consistent terminology and research gaps for future translational research on anxiety and related disorders.

  • Variation in Fourteen Brain Structure Volumes in Schizophrenia: A Comprehensive Meta-Analysis of 246 Studies
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-01-04
    Susan S. Kuo, Michael F. Pogue-Geile

    Despite hundreds of structural MRI studies documenting smaller brain volumes on average in schizophrenia compared to controls, little attention has been paid to group differences in the variability of brain volumes. Examination of variability may help interpret mean group differences in brain volumes and aid in better understanding the heterogeneity of schizophrenia. Variability in 246 MRI studies was meta-analyzed for 13 structures that have shown medium to large mean effect sizes (Cohen’s d≥0.4): intracranial volume, total brain volume, lateral ventricles, third ventricle, total gray matter, frontal gray matter, prefrontal gray matter, temporal gray matter, superior temporal gyrus gray matter, planum temporale, hippocampus, fusiform gyrus, insula; and a control structure, caudate nucleus. No significant differences in variability in cortical/subcortical volumes were detected in schizophrenia relative to controls. In contrast, increased variability was found in schizophrenia compared to controls for intracranial and especially lateral and third ventricle volumes. These findings highlight the need for more attention to ventricles and detailed analyses of brain volume distributions to better elucidate the pathophysiology of schizophrenia.

  • Down syndrome: neurobiological alterations and therapeutic targets
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-01-04
    Rosa Anna Vacca, Sweta Bawari, Daniela Valenti, Devesh Tewari, Seyed Fazel Nabavi, Samira Shirooie, Archana N. Sah, Mariateresa Volpicella, Nady Braidy, Seyed Mohammad Nabavi

    Down syndrome (DS) is a genetic disease that occurs due to an aneuploidy of human chromosome 21. Trisomy of chromosome 21 is a primary genetic cause of developmental abnormalities leading to cognitive and learning deficits. Impairments in GABAergic transmission, noradrenergic neuronal loss, anomalous glutamatergic transmission and N-methyl-d-aspartate receptor signalling, mitochondrial dysfunction, increased oxidative stress and inflammation, differentially expressed microRNAs, increased expression of crucial chromosome 21 genes, and DNA hyper-methylation and hyperactive homocysteine trans-sulfuration pathway, are common incongruities that have been reported in DS and might contribute to cognitive impairment and intellectual disability. This review provides an update on metabolic and neurobiological alterations in DS. It also provides an overview of the currently available pharmacological therapies that may influence and/or reverse these alterations in DS.

  • The structural connectome in traumatic brain injury: A meta-analysis of graph metrics
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-01-04
    Phoebe Imms, Adam Clemente, Mark Cook, Wendyl D’Souza, Peter H. Wilson, Derek K. Jones, Karen Caeyenberghs

    IMMS, P., A. Clemente, M. Cook, W. D’Souza, P. H. Wilson, D. K., Jones & K. Caeyenberghs. Insights into traumatic brain injury from graph theory: A meta-analysis. Neurosci. Biobehav. Rev. 95(1) XXX-XXX, 2018. - Although recent structural connectivity studies of traumatic brain injury (TBI) have used graph theory to evaluate alterations in global integration and functional segregation, pooled analysis is needed to examine the robust patterns of change in graph metrics across studies. Following a systematic search, 15 studies met the inclusion criteria for review. Of these, ten studies were included in a random-effects meta-analysis of global graph metrics, and subgroup analyses examined the confounding effects of severity and time since injury. The meta-analysis revealed significantly higher values of normalised clustering coefficient (g = 1.445, CI=[0.512, 2.378], p = 0.002) and longer characteristic path length (g = 0.514, CI=[0.190, 0.838], p = 0.002) in TBI patients compared with healthy controls. Our findings suggest that the TBI structural network has shifted away from the balanced small-world network towards a regular lattice. Therefore, these graph metrics may be useful markers of neurocognitive dysfunction in TBI. We conclude that the pattern of change revealed by our analysis should be used to guide hypothesis-driven research into the role of graph metrics as diagnostic and prognostic biomarkers.

  • Neurochemical Changes in the Aging Brain: A Systematic Review
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-01-06
    Carlee Cleeland, Andrew Pipingas, Andrew Scholey, David White

    Magnetic resonance spectroscopy (MRS) holds promise for understanding neurochemical mechanisms associated with human cognitive aging in vivo. Recent advances in magnetic field strength and methods provide the opportunity to examine neurometabolites with greater accuracy and detail. The current review summarizes recent literature on age-associated neurometabolite changes as measured by proton MRS, and the associations with cognition in non-clinical populations. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 179 studies were screened for review, of these, 42 were eligible. When a subset of studies were assessed based on voxel placement, magnetic field strength and sample size, N acetyl aspartate (NAA) concentration was consistently reduced with age predominantely in the frontal lobe and Myo- inositol (mI) concentration increased with age consistently in the posterior cingulate cortex (PCC). These findings are of particular interest as these NAA and mI changes mirror neurometabolite changes often seen in Alzheimer disease. The findings of this review provide further evidence of the potential for 1H-MRS to track age-related neurometabolite changes.

  • The link between maternal obesity and offspring neurobehavior: a systematic review of animal experiments
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-01-03
    Malou D. Menting, Cornelieke van de Beek, Stijn Mintjens, Kimberley E. Wever, Aniko Korosi, Susan E. Ozanne, Jacqueline Limpens, Tessa J. Roseboom, Carlijn Hooijmans, Rebecca C. Painter

    Maternal obesity in pregnancy is associated with neurobehavioral problems in the offspring. Establishing causality has been challenging in existing human studies, due to confounding by genetic and postnatal environment. Animal experiments can improve our understanding of this association. This systematic review examined the effects of maternal obesity in pregnancy on offspring neurobehavior in animal models. We included 26 studies (1047 offspring animals). Meta-analyses showed that offspring of obese mothers displayed higher levels of locomotor activity (standardized mean difference (SMD) .34 [.10;.58]) and anxiety behavior (SMD .47 [.16;.79]) than offspring of lean mothers, but similar memory abilities (SMD -.06 [-.52;.39]). Meta-analysis of learning abilities was not sensible due to heterogeneity. Although the evidence was heterogeneous and the quality of the included studies generally unclear, this systematic review of animal studies indicates an effect of maternal obesity on increased offspring locomotor activity and anxiety, but not on offspring memory performance. These findings may be important from a public health perspective since obesity is rapidly increasing worldwide, and warrant further research.

  • Brain activation during human defensive behaviour: a systematic review and preliminary meta-analysis
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-01-03
    Fiona Patrick, Matthew J Kempton, Lindsey Marwood, Steven C R Williams, Allan H Young, Adam Perkins

    The neural underpinnings of defensive behaviour have implications for both basic research and clinical translation. This review systematically collates published research on neural response during simple avoidance of threat and approach-avoidance behaviour during goal-conflicting situations and presents an exploratory meta-analysis of available whole-brain data. Scopus, PsychInfo and Web of Science databases were searched for the period up to March 2018. 1,348 simple avoidance and 1,910 goal-conflict publications were initially identified; following review, 8 simple avoidance and 11 goal-conflict studies were included, with 5 datasets used in a preliminary meta-analysis. A move from forebrain-to-midbrain activation as threat becomes more pertinent was noted, indicating support for the Reinforcement Sensitivity Theory of behaviour and general compatibility with animal work. However, these findings were not reflected in the subsequent preliminary meta-analysis. This review highlights the considerable heterogeneity in currently available defensive behaviour paradigms and the lack of research in clinically relevant populations.

  • Neuroimaging of Individual Differences: A Latent Variable Modeling Perspective
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-01-03
    Shelly R. Cooper, Joshua J. Jackson, Deanna M. Barch, Todd S. Braver

    Neuroimaging data is being increasingly utilized to address questions of individual difference. When examined with task-related fMRI (t-fMRI), individual differences are typically investigated via correlations between the BOLD activation signal at every voxel and a particular behavioral measure. This can be problematic because: 1) correlational designs require evaluation of t-fMRI psychometric properties, yet these are not well understood; and 2) bivariate correlations are severely limited in modeling the complexities of brain-behavior relationships. Analytic tools from psychometric theory such as latent variable modeling (e.g., structural equation modeling) can help simultaneously address both concerns. This review explores the advantages gained from integrating psychometric theory and methods with cognitive neuroscience for the assessment and interpretation of individual differences. The first section provides background on classic and modern psychometric theories and analytics. The second section details current approaches to t-fMRI individual difference analyses and their psychometric limitations. The last section uses data from the Human Connectome Project to provide illustrative examples of how t-fMRI individual differences research can benefit by utilizing latent variable models.

  • The evolutionarily conserved role of melatonin in CNS disorders and behavioral regulation: translational lessons from zebrafish
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-01-03
    Rafael Genario, Ana C.V.V. Giacomini, Konstantin A. Demin, Bruna E. dos Santos, Natalia I. Marchiori, Angrey D. Volgin, Alim Bashirzade, Tamara G. Amstislavskaya, Murilo S. de Abreu, Allan V. Kalueff

    Melatonin is an important hormone regulating circadian rhythm, neuroprotection and neuroimmune processes. However, its exact physiological roles in brain mechanisms remain poorly understood. Here, we summarize the mounting evidence implicating melatonin in brain disorders and behavior, based on clinical and experimental studies in-vivo. In addition to rodent models, the zebrafish (Danio rerio) is becoming increasingly utilized in biomedical and neuroscience research. Here, we discuss melatonin neurobiology of zebrafish, and parallel these findings with clinical and rodent data. We also discuss the genomic effects of melatonin in zebrafish, and emphasize the growing utility of zebrafish models to study melatonin neurobiology and drug discovery.

  • The midbrain periaqueductal gray as an integrative and interoceptive neural structure for breathing
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-01-03
    Olivia K. Faull, Hari H. Subramanian, Martyn Ezra, Kyle T.S. Pattinson

    The periaqueductal gray (PAG) plays a critical role in autonomic function and behavioural responses to threatening stimuli. Recent evidence has revealed the PAG’s potential functions in the perception of breathlessness, a highly threatening respiratory symptom. In this review, we outline the current evidence in animals and humans on the role of the PAG in respiratory control, and in the perception of breathlessness. While recent work has unveiled dissociable brain activity within the lateral PAG during perception of breathlessness, and ventrolateral PAG during conditioned anticipation in healthy humans, this is yet to be translated into diseases dominated by breathlessness symptomology, such as chronic obstructive pulmonary disease. Understanding how the sub-structures of the PAG differentially interact with interoceptive brain networks involved in the perception of breathlessness will help us towards understanding discordant symptomology, and may reveal treatment targets for those debilitated by chronic and pervasive breathlessness

  • Kinematic and kinetic gait analysis to evaluate functional recovery in thoracic spinal cord injured rats
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-01-03
    Camila Cardoso Diogo, Luís Maltez da Costa, José Eduardo Pereira, Vítor Filipe, Pedro Alexandre Couto, Stefano Geuna, Paulo A. Armada-da-Silva, Ana Colette Maurício, Artur S.P. Varejão

    The recovery of walking function following spinal cord injury (SCI) is of major importance to patients and clinicians. In experimental SCI studies, a rat model is widely used to assess walking function, following thoracic spinal cord lesion. In an effort to provide a resource which investigators can refer to when seeking the most appropriate functional assay, the authors have compiled and categorized the behavioral assessments used to measure the deficits and recovery of the gait in thoracic SCI rats. These categories include kinematic and kinetic measurements. Within this categorization, we discuss the advantages and disadvantages of each type of measurement. The present review includes the type of outcome data that they produce, the technical difficulty and the time required to potentially train the animals to perform them, and the need for expensive or highly specialized equipment. The use of multiple kinematic and kinetic parameters is recommended to identify subtle deficits and processes involved in the compensatory mechanisms of walking function after experimental thoracic SCI in rats.

  • Progress in Brain Cannabinoid CB2 Receptor Research: From Genes to Behavior
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-01-03
    Chloe J. Jordan, Zheng-Xiong Xi

    The type 2 cannabinoid receptor (CB2R) was initially regarded as a peripheral cannabinoid receptor. However, recent technological advances in gene detection, alongside the availability of transgenic mouse lines, indicate that CB2Rs are expressed in both neurons and glial cells in the brain under physiological and pathological conditions, and are involved in multiple functions at cellular and behavioral levels. Brain CB2Rs are inducible and neuroprotective via up-regulation in response to various insults, but display species differences in gene and receptor structures, CB2R expression, and receptor responses to various CB2R ligands. CB2R transcripts also differ between the brain and spleen. In the brain, CB2A is the major transcript isoform, while CB2A and CB2B transcripts are present at higher levels in the spleen. These new findings regarding brain versus spleen CB2R isoforms may in part explain why early studies failed to detect brain CB2R gene expression. Here, we review evidence supporting the expression and function of brain CB2R from gene and receptor levels to cellular functioning, neural circuitry, and animal behavior.

  • Social, Self, (Situational), and Affective Processes in Medial Prefrontal Cortex (MPFC): Causal, Multivariate, and Reverse Inference Evidence
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-01-02
    Matthew D. Lieberman, Mark A. Straccia, Meghan L. Meyer, Meng Du, Kevin M. Tan

    The medial prefrontal cortex (MPFC) has been posited to serve a variety of social, affective, and cognitive functions. These conclusions have largely been driven by forward inference analyses (e.g. GLM fMRI studies and meta-analyses) that indicate where domain-specific tasks tend to produce activity but tell us little about what those regions do. Here, we take a multi-method, multi-domain approach to the functionality of MPFC subdivisions within Brodmann areas 9-11. We consider four methods that each have reverse inference or causal inference value: lesion work, transcranial magnetic stimulation, multivariate pattern analysis, and Neurosynth analyses. The Neurosynth analyses include multi-term reverse inference analyses that compare several domains of interest to one another at once. We examine the evidence supporting structure-function links in five domains: social cognition, self, value, emotional experience, and mental time travel. The evidence is considered for each of three MPFC subdivisions: dorsomedial prefrontal cortex (DMPFC), anteromedial prefrontal cortex (AMPFC), and ventromedial prefrontal cortex (VMPFC). Although there is evidentiary variability across methods, the results suggest that social processes are functionally linked to DMPFC (and somewhat surprisingly in VMPFC), self processes are linked to AMPFC, and affective processes are linked to AMPFC and VMPFC. There is also a relatively non-selective region of VMPFC that may support situational processing, a process key to each domain, but also independent of each.

  • The biological origins of rituals: An interdisciplinary perspective
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2019-01-02
    Matteo Tonna, Carlo Marchesi, Stefano Parmigiani

    Ritual behavior is ubiquitous, marking animal motor patterns, normal and psychopathological behavior in human individuals as well as every human culture. Moreover, formal features of rituals appears to be highly conserved along phylogeny and characterized by a circular and spatio-temporal structure typical of habitual behavior with internal repetition of non-functional acts and redirection of attention to the “script” of the performance. A continuity, based on highly conserved cortico-striatal loops, can be traced from animal rituals to human individual and collective rituals with psychopathological compulsions at the crossing point. The transition from “routinization” to “ritualization” may have been promoted to deal with environmental unpredictability in non-social contexts and, through motor synchronization, to enhance intra-group cohesion and communication in social contexts. Ultimately, ritual, following its biological constraints exerts a “homeostatic” function on the environment (social and non-social) under conditions of unpredictability.

  • How stress and glucocorticoids timing-dependently affect extinction and relapse
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2018-12-27
    Shira Meir Drexler, Christian J. Merz, Valerie L. Jentsch, Oliver T. Wolf

    In recent years, various research groups aimed to augment extinction learning (the most important underlying mechanism of exposure therapy) using glucocorticoids (GCs), in particular the stress hormone cortisol. In this review, we introduce the STaR (Stress Timing affects Relapse) model, a theoretical model of the timing-dependent effects of stress/GCs treatment on extinction and relapse. In particular, we show that (1) pre-extinction stress/GCs promote memory consolidation in a context-independent manner, making extinction memory more resistant to relapse following context change. )2) Post-extinction stress also enhances extinction consolidation, but in a context-bound manner. These differences may result from the timing-dependent effects of cortisol on emotional memory contextualization. At the neural level, extinction facilitation is reflected in alterations in the amygdala-hippocampal-prefrontal cortex network. )3) Stress/GCs before a retrieval test impair extinction retrieval and promote relapse. This may result from strengthening amygdala signaling or disruption of the inhibitory functioning of the prefrontal cortex. The STaR model can contribute to the understanding and prevention of relapse processes.

  • The neural correlates of discrete gait characteristics in ageing: A Structured Review
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2018-12-13
    Joanna Wilson, Liesl Allcock, Ríona Mc Ardle, John-Paul Taylor, Lynn Rochester

    Gait is complex, described by diverse characteristics underpinned by widespread central nervous system networks including motor and cognitive functions. Despite this, neural substrates of discrete gait characteristics are poorly understood, limiting understanding of gait impairment in ageing and disease. This structured review aims to map gait characteristics, defined from a pre-specified model reflecting independent gait domains, to brain imaging parameters in older adults. Fifty-two studies of 38,029 yielded were reviewed. Studies showed inconsistent approaches when mapping gait assessment to neural substrates, limiting conclusions. Gait impairments typically associated with brain deterioration, specifically grey matter atrophy and white matter integrity loss. Gait velocity, a global measure of gait control, was most frequently associated with these imaging markers within frontal and basal ganglia regions, and its decline predicted from white matter volume and integrity measurements. Fewer studies assessed additional gait measures or functional imaging parameters. Future studies mapping regional neuroanatomical and functional correlates of gait are needed, including those which take a multi-process network perspective to better understand mobility in health and disease.

  • Upregulated levels and pathological aggregation of abnormally phosphorylated Tau-Protein in children with neurodevelopmental disorders
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2018-12-11
    Marija Rankovic, Markus Zweckstetter

    The tubulin-associated unit (Tau) protein is an intrinsically disordered protein that plays a well-established role in promoting microtubule assembly and stabilization in neuronal axons at all stages of development. Identification of new interacting partners and different sub-cellular localizations of Tau in recent years led to the discovery of novel physiological functions in regulation of neuronal activity, neurogenesis, long-term depression, iron export and genomic integrity. In addition, Tau gene mutations, aberrant mRNA splicing and abnormal post-translational modifications, such as hyperphosphorylation, lead to formation of pathological, insoluble Tau aggregates that are a hallmark of neurodegenerative diseases, collectively known as tauopathies. Characterized by synaptic dysfunction, neuroinflammation/neuronal cell death and dementia, tauopathies are designated as a group of adult-onset neurodegenerative diseases. Recent studies summarized in this review now document several neurological conditions and diseases in an early life stage with upregulated levels or even pathological aggregation of abnormally phosphorylated Tau protein. These findings suggest that Tau might play a previously underestimated role in neurodevelopmental disorders and regression in children.

  • The uncertain brain: A co-ordinate based meta-analysis of the neural signatures supporting uncertainty during different contexts
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2018-12-11
    Jayne Morriss, Martin Gell, Carien M. van Reekum

    Uncertainty is often inevitable in everyday life and can be both stressful and exciting. Given its relevance to psychopathology and wellbeing, recent research has begun to address the brain basis of uncertainty. In the current review we examined whether there are discrete and shared neural signatures for different uncertain contexts. From the literature we identified three broad categories of uncertainty currently empirically studied using functional MRI (fMRI): basic threat and reward uncertainty, decision-making under uncertainty, and associative learning under uncertainty. We examined the neural basis of each category by using a coordinate based meta-analysis, where brain activation foci from previously published fMRI experiments were drawn together (1998-2017; 87 studies). The analyses revealed shared and discrete patterns of neural activation for uncertainty, such as the insula and amygdala, depending on the category. Such findings will have relevance for researchers attempting to conceptualise uncertainty, as well as clinical researchers examining the neural basis of uncertainty in relation to psychopathology.

  • Challenges and Demand for Modeling Disorders of Consciousness following Traumatic Brain Injury
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2018-12-11
    John C. O’Donnell, Kevin D. Browne, Todd J. Kilbaugh, H. Isaac Chen, John Whyte, D. Kacy Cullen

    Following severe traumatic brain injury (TBI), many patients experience coma — an unresponsive state lacking wakefulness or awareness. Coma rarely lasts more than two weeks, and emergence involves passing through a state of wakefulness without awareness of self or environment. Patients that linger in these Disorders of Consciousness (DoC) undergo clinical assessments of awareness for diagnosis into Unresponsive Wakefulness Syndrome (no awareness, also called vegetative state) or Minimally Conscious State (periodic increases in awareness). These diagnoses are notoriously inaccurate, offering little prognostic value. Recovery of awareness is unpredictable, returning within weeks, years, or never. This leaves patients’ families with difficult decisions and little information on which to base them. Clinical studies have made significant advancements, but remain encumbered by high variability, limited data output, and a lack of necessary controls. Herein we discuss the clear and present need to establish a preclinical model of TBI-induced DoC, the significant challenges involved, and how such a model can be applied to support DoC research.

  • Dance for neuroplasticity: a descriptive systematic review
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2018-12-10
    Lavinia Teixeira-Machado, Ricardo Mario Arida, Jair de Jesus Mari

    We conducted a systematic review of randomized clinical trials to investigate whether dance practice promotes neuroplasticity. We also determined how dancing is able to alter (1) brain volumes and structures (2) brain function, (3) psychomotor adjustment and (4) levels of neurotrophic factors. This systematic review formulated a research question based on PICO, according to the guidelines for systematic reviews and meta-analyzes (PRISMA), “What is the influence of dance practice on neuroplasticity in already mature brains?” We screened 1071 studies and from these eight studies were included in the review. Of the selected studies, all demonstrated positive structural and/or functional changes. Structural changes included increased hippocampal volume, gray matter volume in the left precentral and parahippocampal gyrus, and white matter integrity. Functional changes included alterations in cognitive function such as significant improvement in memory, attention, body balance, psychosocial parameters and altered peripheral neurotrophic factor. Based on the evidence, dance practice integrates brain areas to improve neuroplasticity.

  • A systematic review on the therapeutic effectiveness of non-invasive brain stimulation for the treatment of anxiety disorders
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2018-12-10
    C.M Vicario, M.A Salehinejad, K. Felmingham, G. Martino, M A Nitsche

    The interest in the use of non-invasive brain stimulation for enhancing neural functions and reducing symptoms in anxiety disorders is growing. Based on the DSM-V classification for anxiety disorders, we examined all available research using repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) for the treatment of specific phobias, social anxiety disorder, panic disorder, agoraphobia, and generalized anxiety disorder. A systematic literature search conducted in PubMed and Google Scholar databases provided 26 results: 12 sham-controlled studies and 15 not sham-controlled studies. With regard to the latter sub-group of studies, 9 were case reports, and 6 open label studies. Overall, our work provides preliminary evidence that both, excitatory stimulation of the left prefrontal cortex and inhibitory stimulation of the right prefrontal cortex can reduce symptom severity in anxiety disorders. The current results are discussed in the light of a model for the treatment for anxiety disorders via non-invasive brain stimulation, which is based on up-/downregulation mechanisms and might serve as guide for future systematic investigations in the field.

  • Exploring the potential role of mesocorticolimbic circuitry in motivation for and adherence to chronic pain self-management interventions
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2018-12-10
    Janelle E. Letzen, David A. Seminowicz, Claudia M. Campbell, Patrick H. Finan

    Adherence to pain self-management strategies is associated with favorable psychobehavioral outcomes among individuals with chronic pain. Substantive adherence to treatments teaching these adaptive skills proves challenging, resulting in poor individual and societal outcomes. Evidence demonstrates motivation for behavior change as a key predictor of treatment adherence. Despite behavioral techniques that target motivation, however, nonadherence persists as a barrier to positive clinical outcomes in chronic pain. Understanding the neurobiological mechanisms underlying treatment motivation might highlight novel avenues for augmentative therapies. The purpose of this review is to present theory and evidence that the mesocorticolimbic system (i.e., brain circuitry associated with reward processing and motivation) contributes to treatment motivation among chronic pain patients, ultimately influencing adherence. We review evidence for motivation as a key adherence determinant, detail neuroimaging findings relating mesocorticolimbic circuitry and motivation, and discuss data supporting mesocorticolimbic dysfunction among chronic pain patients. We propose a neurobehavioral model for adherence to pain self-management interventions, listing testable hypotheses. Finally, we discuss potential research and intervention implications from the proposed model.

  • A meta-analytical evaluation of the dual-hormone hypothesis: Does cortisol moderate the relationship between testosterone and status, dominance, risk taking, aggression, and psychopathy?
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2018-12-07
    Mr Tycho Dekkers

    According to the dual-hormone hypothesis, the relationship between testosterone and status-relevant behavior is moderated by cortisol, suggesting this relationship only exists when cortisol is low. In the current study, a meta-analysis (including 30 papers with 33 studies, 49 effect sizes, n = 8538) on the interaction effect of testosterone and cortisol on status-relevant behavior (i.e. status, dominance, risk taking, aggression, and psychopathy) was performed. There was only marginal support for the dual-hormone hypothesis: The effect size of the interaction between testosterone and cortisol on status-relevant behavior was significant but very small (r = -.061, p = .026), which was corroborated by follow-up meta-analyses on simple slopes on low and high cortisol. Effect sizes were largest for direct status measures, although not significantly different from other outcome measures. Similarly, effect sizes seemed larger for men than for women. However, robustness analyses indicated signs of publication bias, enhanced significance due to potential flexibility in data-analysis, and a lack of power of individual studies, emphasizing the need for a large, pre-registered study.

  • Regression in Children with Epilepsy
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2018-12-08
    Peter Camfield, Carol Camfield

    Regression in children with epilepsy may involve loss of cognitive abilities, failure to progress or a slowing of developmental trajectory. A few seizures do not lead to regression. Large numbers of seizures may be associated with regression but the cause is an important cofounder. Individual spike discharges on EEG are associated with transient cognitive impairment and continuous spike discharges with regression. Regression may be global in continuous spike wave in slow sleep (CSWS) or specific (auditory agnosia) in Landau Kleffner syndrome. Regression is mild and transient in Rolandic Epilepsy or profound and permanent in West Syndrome. Epilepsy syndromes grouped under “epileptic encephalopathies” may lead to regression, although proof of this concept is not strong for many syndromes. The absence of cognitive assessment before epilepsy onset, the contribution of the cause and complications of treatment make for difficult methodological problems. The large majority of children with epilepsy do not have regression. There is need for more longitudinal studies of children with epileptic encephalopathies and other epilepsies associated with regression.

  • Chronic Unpredictable Mild Stress for Modeling Depression in Rodents:Meta-analysis of Model Reliability
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2018-12-06
    Svitlana Antoniuk, Monika Bijata, Evgeni Ponimaskin, Jakub Wlodarczyk

    Depression is currently among the top five leading causes of the global burden of disease. Chronic unpredictable mild stress (CUMS) is currently the most commonly used, reliable, and effective rodent model of depression. However, for unclear reasons, this protocol is often difficult to reproduce in different laboratories. We performed a meta-analysis of studies that used the CUMS paradigm to evaluate depressive-like behavior in rodents. We sought to identify strain-dependent susceptibility to stress based on the development of one of the main end points of the model, “anhedonia.” The meta-analysis indicated that the CUMS protocol is a robust animal model of depression and is strongly associated with anhedonic behavior in rodents. However, high heterogeneity was found in the single subgroup analysis, which was attributable to modification of the CUMS and sucrose preference protocols. This may explain difficulties in reproducing stress protocols by different research groups.

  • Time perception and impulsivity: A proposed relationship in addictive disorders
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2018-12-06
    Cecilia Paasche, Sébastien Weibel, Marc Wittmann, Laurence Lalanne

    Addictive disorders are characterized by impulsive behavior that leads to difficulties in preventing certain behaviors despite negative consequences. This symptom predisposes to a vulnerability in developing addictive disorders and is also aggravated by the addiction process itself. As such, understanding the underlying mechanisms of impulsivity is a challenge for understanding the pathophysiology of addiction. One common link between impulsivity and addiction is that both involve actions and decisions that are realized faster than they should be in time. Impulsive traits increase the tendency to choose immediate gratification instead of delayed gratification even when preferred. This observation suggests a relationship between impulsivity and time processing. To better understand this relationship, we reviewed the literature that describes the relationship between time processing and impulsivity in addictive disorders in humans. Despite a lack of literature concerning this question in alcohol, cannabis and gambling disorders, we highlight that addictive behaviors are a good model for understanding the pathophysiology of impulsivity, and could help us to better understand the relationship between time perception and impulsivity.

  • Fentanyl: Receptor Pharmacology, Abuse Potential, and Implications for Treatment
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2018-12-05
    Sandra D. Comer, Catherine M. Cahill

    Opioid overdoses, many of which are attributed to use of illicit fentanyl, are currently one of the leading causes of death in the U.S. Although fentanyl has been used safely for decades in clinical settings, the widespread use of illicit fentanyl is a recent phenomenon. Starting in 2013, illicitly manufactured fentanyl and its analogs began to appear on the streets. These substances were added to or sold as heroin, often unbeknownst to the user. Because fentanyl is so potent, only small amounts are needed to produce pharmacological effects, but the margin between safe and toxic doses is narrow. Surprisingly little is known about the exact signaling mechanisms underlying fentanyl-related respiratory depression or the effectiveness of naloxone in reversing this effect. Similarly, little is known about the ability of treatment medications such as buprenorphine, methadone, or naltrexone to reduce illicit fentanyl use. The present article reviews the receptor, preclinical and clinical pharmacology of fentanyl, and how its pharmacology may predict the effectiveness of currently approved medications for treating illicit fentanyl use.

  • From “bedside” to “bench” and back: a translational approach to studying dopamine dysfunction in schizophrenia
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2018-12-05
    Anissa Abi-Dargham

    Despite multiple lines of research, a mechanistic understanding of schizophrenia remains elusive. Neuroimaging studies have yielded observations that can be used in translational studies in animals to attempt to uncover their cellular and circuit basis and their significance for the diseased human brain. Enhanced D2 stimulation in the striatum is a well replicated and established observation in patients with schizophrenia. This “bedside” observation was reproduced “at the bench” level by creating a transgenic mouse overexpressing D2 receptors in dorsal striatum (D2R-OE mouse). The D2R-OE mouse showed multiple behavioral, molecular, electrophysiological and anatomical alterations. Some of these are consistent with findings in patients with schizophrenia, providing construct validity to the model and mechanistic insights for the observations made in humans. Other findings were novel, and provide an opportunity for a reverse translational effort back into the clinic. In this review we will summarize the process of translation and back translation from the D2R-OE mouse and describe the insights into the pathophysiology of the disease gained through this type of translational work.

  • Apolipoprotein E and affective symptoms in mild cognitive impairment and Alzheimer’s disease dementia: a systematic review and meta-analysis
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2018-12-01
    Leonie C.P. Banning, Inez H.G.B. Ramakers, Kay Deckers, Frans R.J. Verhey, Pauline Aalten

    Objective APOE status has been associated to affective symptoms in cognitively impaired subjects, with conflicting results. Methods Databases CINAHL, Embase, PsychINFO and PubMed were searched for studies evaluating APOE genotype with affective symptoms in MCI and AD dementia. Symptoms were meta-analyzed separately and possible sources of heterogeneity were examined. Results Fifty-three abstracts fulfilled the eligibility criteria. No association was found between the individual symptoms and APOE ε4 carriership or zygosity. For depression and anxiety, only pooled unadjusted estimates showed positive associations with between-study heterogeneity, which could be explained by variation in study design, setting and way of symptom assessment Conclusions There is no evidence that APOE ε4 carriership or zygosity is associated with the presence of depression, anxiety, apathy, agitation, irritability or sleep disturbances in cognitively impaired subjects. Future research should shift its focus from this single polymorphism to a more integrated view of other biological factors.

  • Transfer of maternal psychosocial stress to the fetus
    Neurosci. Biobehav. Rev. (IF 8.037) Pub Date : 2017-02-22
    Florian Rakers, Sven Rupprecht, Michelle Dreiling, Christoph Bergmeier, Otto W. Witte, Matthias Schwab

    Psychosocial maternal stress experienced during different vulnerable periods throughout gestation is thought to increase the individual’s risk to develop neuropsychiatric, cardiovascular and metabolic disease in later life. Cortisol has generally been identified as the major mediator of maternal stress transfer to the fetus. Its lipophilic nature allows a trans-placental passage and thus excessive maternal cortisol could persistently impair the development of the fetal hypothalamic-pituitary-adrenal axis (HPAA). However, cortisol alone cannot fully explain all effects of maternal stress especially during early to mid pregnancy before maturation of the fetal HPAA has even begun and expression of fetal glucocorticoid receptors is limited. This review focuses on mediators of maternal fetal stress transfer that in addition to cortisol have been proposed as transmitters of maternal stress: catecholamines, cytokines, serotonin/tryptophan, reactive-oxygen-species and the maternal microbiota. We propose that the effects of psychosocial maternal stress on fetal development and health and disease in later life are not a consequence of a single pathway but are mediated by multiple stress-transfer mechanisms acting together in a synergistic manner.

  • Prenatal stress and epigenetics
    Neurosci. Biobehav. Rev. (IF 8.037) 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.

  • Experience-induced transgenerational (re-)programming of neuronal structure and functions: Impact of stress prior and during pregnancy
    Neurosci. Biobehav. Rev. (IF 8.037) 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.

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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