Cultivating a healthy neuro‐immune network: A health psychology approach

The field of psychoneuroimmunology (PNI) examines interactions among psychological and behavioral states, the brain, and the immune system. Research in PNI has elegantly documented effects of stress at multiple levels of the neuro‐immune network, with profound implications for both physical and mental health. In this review, we consider how the neuro‐immune network might be influenced by “positive” psychological and behavioral states, focusing on positive affect, eudaimonic well‐being, physical activity, and sleep. There is compelling evidence that these positive states and behaviors are associated with changes in immune activity in the body, including reductions in peripheral inflammatory processes relevant for physical health. Growing evidence from animal models also suggests effects of positive states on immune cells in the brain and the blood‐brain barrier, which then impact critical aspects of mood, cognition, and behavior. Tremendous advances are being made in our understanding of neuro‐immune dynamics; one of the central goals of this review is to highlight recent preclinical research in this area and consider how we can leverage these findings to investigate and cultivate a healthy neuro‐immune network in humans.     

前额叶皮质损伤患者的情绪异常

人类前额叶皮质与情绪之间有着密切的关系,文章在相关的临床和神经成像研究结果基础上,分析了前额叶皮质损伤对情绪行为造成的影响,分别概述了精神分裂症、重性抑郁和焦虑患者的情绪变化、前额叶切除对情绪的影响以及左右前额叶皮质与情绪的关系,重点阐述了前额叶功能异常的神经生理学特点,认为情绪的改变会随着前额叶皮质不同部位的结构缺损或功能变化而有所不同,此有利于对前额叶皮质损伤患者情绪异常的评价与防治。     

信任的认知神经网络模型

信任是指一方在基于对另一方行为期望的基础上愿意冒一定的风险, 以期在将来得到积极结果的心理过程。近年, 认知神经取向的研究对信任行为引起的特定脑区激活进行了考察, 却忽略了大规模脑网络在信任过程中的整体作用。在总结前人研究的基础上提出信任的认知神经网络模型, 并从认知神经网络视角对信任行为进行解释和整合。在模型中, 信任行为是动力系统、情感系统和认知系统相互作用的结果, 并分别与奖励网络、显著网络、中央执行网络和默认网络等神经网络激活有关。此外, 模型还强调信任行为的反馈机制, 以此构成完整的建构模型。模型阐明了心理系统与中枢神经网络之间的对应关系, 从认知神经角度解释了信任行为发生的心理机制和神经基础。     

Neural correlates of automatic mood regulation in girls at high risk for depression

Daughters of depressed mothers are at significantly elevated risk for developing a depressive disorder themselves. We have little understanding, however, of the specific factors that contribute to this risk. The ability to regulate negative affect effectively is critical to emotional and physical health and may play an important role in influencing risk for depression. We examined whether never-disordered daughters whose mothers have experienced recurrent episodes of depression during their daughters' lifetime differ from never-disordered daughters of never-disordered mothers in their patterns of neural activation during a negative mood induction and during automatic mood regulation. Sad mood was induced in daughters through the use of film clips; daughters then recalled positive autobiographical memories, a procedure shown previously to repair negative affect. During the mood induction, high-risk girls exhibited greater activation than did low-risk daughters in brain areas that have frequently been implicated in the experience of negative affect, including the amygdala and ventrolateral prefrontal cortex. In contrast, during automatic mood regulation, low-risk daughters exhibited greater activation than did their high-risk counterparts in brain areas that have frequently been associated with top-down regulation of emotion, including the dorsolateral prefrontal cortex and dorsal anterior cingulate cortex. These findings indicate that girls at high and low risk for depression differ in their patterns of neural activation both while experiencing, and while repairing negative affect, and suggest that anomalies in neural functioning precede the onset of a depressive episode.     

Stop that! Inhibition,sensitization, and their neurovisceral concomitants

There is increasing evidence that the behavior of living systems can be conceptualized as a self-organizing dynamical system. Moreover, evidence suggests that inhibitory processes give these systems the flexibility that is necessary for efficient functioning in the face of changing environmental demands. The process of sensitization can be conceived as a breakdown of inhibitory neural processes that can lead to maladaptive, perseverative behavior. In this paper we describe a model of inhibition and sensitization from a dynamical systems perspective. We show that inhibition is important for adaptive behavior across a number of levels of system functioning. Using our work on attention, emotion, and anxiety disorders we show the importance of both central - for example gamma-aminobutyric acid (GABA)-ergic - and peripheral - for example heart rate variability (HRV) - inhibitory processes and how they may be linked by a network of neural structures that guide the organism from one state of relative stability to another.     

Psychopharmacology in fragile X syndrome--present and future

In addition to cognitive disability, fragile X syndrome (FXS) is associated with behavioral problems that are often functionally limiting. There are few controlled trials to guide treatment; however, available information does suggest that medications can be quite helpful for a number of categories of behavioral disturbance in FXS. Specifically, stimulants appear to be quite useful for management of distractibility, hyperactivity, and impulsive behavior; antidepressants help with anxiety, obsessive-compulsive behaviors and mood dysregulation; and antipsychotics can reduce aggression. These medications are supportive and help minimize dysfunctional behaviors and maximize functioning. As more is learned about the neural functions of FMRP, medications in the future will be expected to target specific synaptic mechanisms dysregulated in FXS brain and thus ameliorate the cognitive deficit with resultant behavioral improvements. This article summarizes knowledge about effectiveness and approaches to management of currently available psychopharmacology for behavior in FXS and discusses early leads to future treatments for cognition.     

The subgenual anterior cingulate cortex in mood disorders

The anterior cingulate cortex (ACC) ventral to the genu of the corpus callosum has been implicated in the modulation of emotional behavior on the basis of neuroimaging studies in humans and lesion analyses in experimental animals. In a combined positron emission tomography/magnetic resonance imaging study of mood disorders, we demonstrated that the mean gray matter volume of this "subgenual" ACC (sgACC) cortex is abnormally reduced in subjects with major depressive disorder (MDD) and bipolar disorder, irrespective of mood state. Neuropathological assessments of sgACC tissue acquired postmortem from subjects with MDD or bipolar disorder confirmed the decrement in gray matter volume, and revealed that this abnormality was associated with a reduction in glia, with no equivalent loss of neurons. In positron emission tomography studies, the metabolic activity was elevated in this region in the depressed relative to the remitted phases of the same MDD subjects, and effective antidepressant treatment was associated with a reduction in sgACC activity. Other laboratories replicated and extended these findings, and the clinical importance of this treatment effect was underscored by a study showing that deep brain stimulation of the sgACC ameliorates depressive symptoms in treatment-resistant MDD. This article discusses the functional significance of these findings within the context of the preclinical literature that implicates the putative homologue of this region in the regulation of emotional behavior and stress response. In experimental animals, this region participates in an extended "visceromotor network" of structures that modulates autonomic/neuroendocrine responses and neurotransmitter transmission during the neural processing of reward, fear, and stress. These data thus hold important implications for the development of neural models of depression that can account for the abnormal motivational, neuroendocrine, autonomic, and emotional manifestations evident in human mood disorders.     

Hippocampus, cortex, and basal ganglia: insights from computational models of complementary learning systems

We present a framework for understanding how the hippocampus, neocortex, and basal ganglia work together to support cognitive and behavioral function in the mammalian brain. This framework is based on computational tradeoffs that arise in neural network models, where achieving one type of learning function requires very different parameters from those necessary to achieve another form of learning. For example, we dissociate the hippocampus from cortex with respect to general levels of activity, learning rate, and level of overlap between activation patterns. Similarly, the frontal cortex and associated basal ganglia system have important neural specializations not required of the posterior cortex system. Taken together, this overall cognitive architecture, which has been implemented in functioning computational models, provides a rich and often subtle means of explaining a wide range of behavioral and cognitive neuroscience data. Here, we summarize recent results in the domains of recognition memory, contextual fear conditioning, effects of basal ganglia lesions on stimulus-response and place learning, and flexible responding.     

The influence of sad mood on cognition

Neuroimaging has identified an overlapping network of brain regions whose activity is modulated by mood and cognition. Studies of depressed individuals have shown changes in perception, attention, memory, and executive functions. This suggests that mood has a pervasive effect on cognition. Direct evidence of the effect of sad mood on cognition is surprisingly limited, however. Published studies have generally addressed a single cognitive ability per study because the fleeting nature of laboratory-induced mood precludes extended testing, and robust findings are limited to mood effects on memory for emotional stimuli. In this study, sad mood was induced and prolonged, enabling the effects of mood to be assessed for an array of abilities, including those that share neural substrates with sad mood and those affected by depression. Sad mood affected memory for emotional words and facial emotion recognition, but not the other processes measured, with a significant nonuniformity of effect over tasks. These results are consistent with circumscribed effects of sad mood on certain emotion-related cognitive processes, but not on cognition more generally.     

The psychobiology of stress

Stressful life experience can have significant effects on a variety of physiological systems, including the autonomic nervous system, the hypothalamic-pituitary-adrenal axis, and the immune system. These relationships can be bidirectional; for example, immune cell products can act on the brain, altering mood and cognition, potentially contributing to depression. Although acute physiological alterations may be adaptive in the short term, chronic or repeated provocation can result in damage to health. The central dogma in the field of stress research assumes a stereotyped physiological response to all stressors (the generality model). However, increasing evidence suggests that specific stressful conditions and the specific way an organism appraises these conditions can elicit qualitatively distinct emotional and physiological responses (the integrated specificity model). For example, appraisals of threat (vs. challenge), uncontrollability, and negative social evaluation have been shown to provoke specific psychobiological responses. Emotional responses appear to have specific neural substrates, which can result in differentiated alterations in peripheral physiological systems, so that it is incorrect to presume a uniform stress response.     

Does bingeing restore bulimics' alleged 5-HT-deficiency?

The co-occurrence of bingeing and depressed mood in bulimics may be explained by one pathogenic process: hyposerotonergic functioning. A relatively high carbohydrate intake improves mood and raises 5-HT level. Therefore, several authors suggested that the carbohydrate intake during binges may be a form of self-medication to compensate for bulimics' alleged hyposerotonergic functioning, thereby improving mood. This view, in which bingeing compensates for central 5-HT deficiencies, assumes that bulimics' binges contain relatively more carbohydrates than bulimics' non-binge-eating episodes. In the present study, bulimics' binge-eating and non-binge-eating episodes were compared as to macronutrient and calorie intake. However, no support was found for the hypothesis that binge-eating enhances brain serotonin.     

拖延行为的认知神经模型及干预

拖延是一种普遍存在, 具有跨时间和跨情景稳定性的问题行为, 它会危害到人们的学习、工作和身心健康。然而目前拖延行为的认知神经机制仍不清晰, 且缺乏因果证据, 本项目拟从拖延的时间决策模型和三重神经结构网络模型出发, 构建拖延的认知神经模型, 并利用认知干预和神经调控技术, 检验和完善拖延行为的认知神经模型, 进而试图制定拖延的精准化干预方案。本项目分为3部分：(1)从记录与关联研究的视角出发, 利用多模态神经影像方法系统考察拖延行为的认知神经机制; (2)从因果/近因果研究视角出发, 利用认知干预和神经调控技术, 验证并完善拖延的认知神经模型; (3)从临床应用的视角出发, 建立拖延行为障碍的临床筛查-诊断体系, 并制定精准化治疗方案。本项目的开展对于探明拖延产生的核心认知神经机制具有十分重要的理论贡献, 同时对于拖延行为的有效预防和精准治疗具有重要的现实意义。     

Endocrinology of menopausal transition and its brain implications

The central nervous system is one of the main target tissues for sex steroid hormones, which act on both through genomic mechanisms, modulating synthesis, release, and metabolism of many neuropeptides and neurotransmitters, and through non-genomic mechanisms, influencing electrical excitability, synaptic function, morphological features, and neuron-glia interactions. During the climacteric period, sex steroid deficiency causes many neuroendocrine changes. At the hypothalamic level, estrogen withdrawal gives rise to vasomotor symptoms, to eating behavior disorders, and altered blood pressure control. On the other hand, at the limbic level, the changes in serotoninergic, noradrenergic, and opioidergic tones contribute to the modifications in mood, behavior, and nociception. Hormone replacement therapy (HRT) positively affects climateric depression throughout a direct effect on neural activity and on the modulation of adrenergic and serotoninergic tones and may modulate the decrease in cognitive efficiency observed in climaterium. The identification of the brain as a de novo source of neurosteroids, suggests that the modifications in mood and cognitive performances occurring in postmenopausal women may also be related to a change in the levels of neurosteroids. These findings open new perspectives in the study of the effects of sex steroids on the central nervous system and on the possible use of alternative and/or auxiliary HRT.     

Stress management effects on psychological, endocrinological, and immune functioning in men with HIV infection: empirical support for a psychoneuroimmunological model

We present a psychoneuroimmunologic (PNI) model for Human Immunodeficiency Virus (HIV) infection, describe a 10-week group-based cognitive behavioral stress management (CBSM) intervention and summarize research demonstrating the effects of this intervention on mood, neuroendocrine (Hypothalamic Pituitary Adrenal [HPA], Hypothalamic Pituitary Gonadal [HPG] and Sympathetic Nervous System [SNS] hormones) and immune system status (lymphocyte subsets, anti-viral immune function) in HIV-infected persons. This work demonstrates that changes in relaxation skills, cognitive coping strategies and social support may mediate the mood effects of CBSM, and that these mood changes may mediate adrenal hormone regulation indicated by reductions in 24-h urinary cortisol (with reduced depressed mood) and norepinephrine (with reduced anxiety) and increases in serum DHEA-S and testosterone levels (with reduced depressed mood). Results also suggest that CBSM-related changes in production of these hormones may explain, in part, the effects of this intervention on short-term changes in IgG antibody titers to herpesviruses (with increased DHEA-S-to-cortisol ratio), and longer-term changes in lymphocyte subpopulations such as CD8 suppressor/cytotoxic cells (with reductions in urinary noradrenaline output) and transitional na?ve CD4 cells (with reductions in urinary cortisol output). Thus a multi-modal CBSM intervention is associated with alterations in mood, neuroendocrine functioning and immunologic status that may have health implications for HIV infection.     

Centrally elicited aggressive behavior: A model system for the study of episodic neurobehavioral pathologies?

Studies in which the predatory-like attack of a cat upon a rat has been elicited by electrical brain stimulation have been briefly reviewed with an emphasis on the question of where within the central nervous system such brain stimulation is producing its behaviorally meaningful effects. Two opposing but by no means mutually exclusive views are considered. The first is that brain stimulation elicits this behavior pattern primarily because it affects a specific motivated behavior system that is organized discretely in the midbrain and pons. The second is that forebrain neural activity is modulated in behaviorally significant ways by brainstem stimulation, which elicits predatory-like aggressive behavior in the cat. The possibility that further research on the altered state of central nervous system activity, induced by brain stimulation which elicits aggressive behavior in the cat, may lead to a further understanding of the altered states of central nervous system activity that underlie the aggressive dyscontrol syndrome and other episodic state disorders is discussed.     

New lessons from knockout mice: The role of serotonin during development and its possible contribution to the origins of neuropsychiatric disorders

Serotonin (5-HT) modulates numerous processes in the central nervous system that are relevant to neuropsychiatric function and dysfunction. It exerts significant effects on anxiety, mood, impulsivity, sleep, ingestive behavior, reward systems, and psychosis. Serotonergic dysfunction has been implicated in several psychiatric conditions but efforts to more clearly understand the mechanisms of this influence have been hampered by the complexity of this system at the receptor level. There are at least 14 distinct receptors that mediate the effects of 5-HT as well as several enzymes that control its synthesis and metabolism. Pharmacologic agents that target specific receptors have provided clues regarding the function of these receptors in the human brain. 5-HT is also an important modulator of neural development and several groups have employed a genetic strategy relevant to behavior. Several inactivation mutations of specific 5-HT receptors have been generated producing interesting behavioral phenotypes related to anxiety, depression, drug abuse, psychosis, and cognition. In many cases, knockout mice have been used to confirm what has already been suspected based on pharmacologic studies. In other instances, mutations have demonstrated new functions of serotonergic genes in development and behavior.     

Stress and cytokine-elicited neuroendocrine and neurotransmitter sensitization: implications for depressive illness

Stressful events, by their effects on neurotransmitter and neuroendocrine processes, are thought to favor the development or exacerbation of depressive illness. In as much as immunological challenge, may provoke stressor-like neuroendocrine and central neurochemical changes, the view was offered that immune activation essentially acts like a stressor and may contribute to the evolution of affective illness. In this respect, viral and bacterial infections appear to influence behavioral/metabolic (e.g. fever, anorexia, somnolence) and neurotransmitter functioning through the release of cytokines, which act as messengers between the immune system and brain. The present report provides a brief overview of the neurochemical consequences of proinflammatory cytokine treatments, particularly the actions of interleukin (IL)-1beta and tumor necrosis factor-alpha. As well, synergy with psychogenic and neurogenic stressors are described, as are data showing that cytokines, like stressors, may have time-dependent proactive (sensitization) effects, so that reexposure to the treatments greatly augments hypothalamic-pituitary-adrenal activity, as well as central neurochemical changes. Indeed, the neurotransmitter alterations are not restricted to hypothalamic nuclei, but occur in several extrahypothalamic sites, including various limbic regions. It is suggested that by virtue of these neurochemical changes, cytokines may have both immediate and proactive effects on mood states.     

中枢肥大细胞在脑功能和行为调节中的作用

已知肥大细胞作为免疫细胞在过敏反应和炎性疾病中发挥重要作用。肥大细胞在中枢亦有表达, 但对其作用了解不足。新近的研究发现中枢肥大细胞在脑功能和行为调节中发挥重要的内源性平衡作用。一方面, 中枢肥大细胞在维持相关脑区发育, 正常神经活动, 以及动机, 情绪和认知等多种行为中发挥保护性作用, 各种应激条件诱导的中枢肥大细胞表达和活动改变参与脑和行为的适应性反应过程。另一方面, 中枢肥大细胞过度激活或者过度抑制都可导致脑功能和行为异常, 并参与某些免疫相关心身疾病的病理过程。体外神经解剖学和功能学研究证据提示中枢肥大细胞与神经系统间存在结构性和功能性相互作用网络。肥大细胞和神经组织间通过形成类似突触的结构性联系直接影响相邻细胞的活动。肥大细胞还可以通过脱颗粒释放多种生物活性介质调节神经活动, 同时表达多种受体接受脑内免疫性和神经性分子调节。但是目前对于中枢肥大细胞-神经系统相互作用的认识主要基于体外研究, 其在脑内相互作用方式及其与特定脑区功能和行为表型的关系所知甚少, 开展相关研究可以为认识脑与行为的神经免疫调节机制提供新的视角。     

急性疼痛与慢性疼痛对奖赏加工的影响及神经机制

疼痛和奖赏能够为个体提供不同的行为动机和主观价值体验,寻求奖赏和避免疼痛对于生存都很重要。疼痛可划分为急性疼痛和慢性疼痛,奖赏可区分为预期阶段的动机成分和体验阶段的享乐成分。奖赏对疼痛的抑制作用已经被广泛证实,但关于疼痛对奖赏的影响,目前的研究结果并不一致。因此需要进一步区分并探究急性疼痛与慢性疼痛对奖赏加工不同阶段的影响,分析两种疼痛对奖赏加工产生不一致影响的现象。这种现象出现的原因可能与急性疼痛向慢性疼痛转变过程中出现的奖赏加工能力缺陷有关。未来可以考虑从改善奖赏加工能力缺陷的角度进行检测和治疗,提前预防急性疼痛向慢性疼痛转变。     

Animal,but not human,faces engage the distributed face network in adolescents with autism

Multiple hypotheses have been offered to explain the impaired face‐processing behavior and the accompanying underlying disruptions in neural circuitry among individuals with autism. We explored the specificity of atypical face‐processing activation and potential alterations to fusiform gyrus (FG) morphology as potential underlying mechanisms. Adolescents with high functioning autism (HFA) and age‐matched typically developing (TD) adolescents were scanned with sMRI and fMRI as they observed human and animal faces. In spite of exhibiting comparable face recognition behavior, the HFA adolescents evinced hypo‐activation throughout the face‐processing system in response to unfamiliar human, but not animal, faces. They also exhibited greater activation in affective regions of the face‐processing network in response to animal, but not human, faces. Importantly, this atypical pattern of activation in response to human faces was not related to atypical structural properties of the FG. This atypical neural response to human faces in autism may stem from abnormalities in the ability to represent the reward value of social (i.e. conspecific) stimuli.