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This past year has seen significant advances in our understanding of the physiology of emotion. Attention continues to focus on the amygdala and its interconnections with prefrontal cortical regions. New evidence underscores the importance of lateralization for emotion. There are also new findings on the physiological predictors of individual differences in emotional behavior and experience, and on the role of autonomic arousal in emotional memory.
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OBJECTIVE: The underlying changes in biological processes that are associated with reported changes in mental and physical health in response to meditation have not been systematically explored. We performed a randomized, controlled study on the effects on brain and immune function of a well-known and widely used 8-week clinical training program in mindfulness meditation applied in a work environment with healthy employees. METHODS: We measured brain electrical activity before and immediately after, and then 4 months after an 8-week training program in mindfulness meditation. Twenty-five subjects were tested in the meditation group. A wait-list control group (N = 16) was tested at the same points in time as the meditators. At the end of the 8-week period, subjects in both groups were vaccinated with influenza vaccine. RESULTS: We report for the first time significant increases in left-sided anterior activation, a pattern previously associated with positive affect, in the meditators compared with the nonmeditators. We also found significant increases in antibody titers to influenza vaccine among subjects in the meditation compared with those in the wait-list control group. Finally, the magnitude of increase in left-sided activation predicted the magnitude of antibody titer rise to the vaccine. CONCLUSIONS: These findings demonstrate that a short program in mindfulness meditation produces demonstrable effects on brain and immune function. These findings suggest that meditation may change brain and immune function in positive ways and underscore the need for additional research.

Anxious temperament (AT) in human and non-human primates is a trait-like phenotype evident early in life that is characterized by increased behavioural and physiological reactivity to mildly threatening stimuli. Studies in children demonstrate that AT is an important risk factor for the later development of anxiety disorders, depression and comorbid substance abuse. Despite its importance as an early predictor of psychopathology, little is known about the factors that predispose vulnerable children to develop AT and the brain systems that underlie its expression. To characterize the neural circuitry associated with AT and the extent to which the function of this circuit is heritable, we studied a large sample of rhesus monkeys phenotyped for AT. Using 238 young monkeys from a multigenerational single-family pedigree, we simultaneously assessed brain metabolic activity and AT while monkeys were exposed to the relevant ethological condition that elicits the phenotype. High-resolution (18)F-labelled deoxyglucose positron-emission tomography (FDG-PET) was selected as the imaging modality because it provides semi-quantitative indices of absolute glucose metabolic rate, allows for simultaneous measurement of behaviour and brain activity, and has a time course suited for assessing temperament-associated sustained brain responses. Here we demonstrate that the central nucleus region of the amygdala and the anterior hippocampus are key components of the neural circuit predictive of AT. We also show significant heritability of the AT phenotype by using quantitative genetic analysis. Additionally, using voxelwise analyses, we reveal significant heritability of metabolic activity in AT-associated hippocampal regions. However, activity in the amygdala region predictive of AT is not significantly heritable. Furthermore, the heritabilities of the hippocampal and amygdala regions significantly differ from each other. Even though these structures are closely linked, the results suggest differential influences of genes and environment on how these brain regions mediate AT and the ongoing risk of developing anxiety and depression.
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The authors examined the hypothesis that rhesus monkeys with extreme right frontal electroencephalographic activity would have higher cortisol levels and would be more fearful compared with monkeys with extreme left frontal activity. The authors first showed that individual differences in asymmetric frontal electrical activity are a stable characteristic. Next, the authors demonstrated that relative right asymmetric frontal activity and cortisol levels are correlated in animals 1 year of age. Additionally, extreme right frontal animals had elevated cortisol concentrations and more intense defensive responses. At 3 years of age, extreme right frontal animals continued to have elevated cortisol concentrations. These findings demonstrate important relations among extreme asymmetric frontal electrical activity, cortisol levels, and trait-like fear-related behaviors in young rhesus monkeys.
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Biological systems are particularly prone to variation, and the authors argue that such variation must be regarded as important data in its own right. The authors describe a method in which individual differences are studied within the framework of a general theory of the population as a whole and illustrate how this method can be used to address three types of issues: the nature of the mechanisms that give rise to a specific ability, such as mental imagery; the role of psychological or biological mediators of environmental challenges, such as the biological bases for differences in dispositional mood; and the existence of processes that have nonadditive effects with behavioral and physiological variables, such as factors that modulate the response to stress and its effects on the immune response.
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Children with anxious temperament (AT) are particularly sensitive to new social experiences and have increased risk for developing anxiety and depression. The young rhesus monkey is optimal for studying the origin of human AT because it shares with humans the genetic, neural, and phenotypic underpinnings of complex social and emotional functioning. In vivo imaging in young monkeys demonstrated that central nucleus of the amygdala (Ce) metabolism is relatively stable across development and predicts AT. Transcriptome-wide gene expression, which reflects combined genetic and environmental influences, was assessed within the Ce. Results support a maladaptive neurodevelopmental hypothesis linking decreased amygdala neuroplasticity to early-life dispositional anxiety. For example, high AT individuals had decreased mRNA expression of neurotrophic tyrosine kinase, receptor, type 3 (NTRK3). Moreover, variation in Ce NTRK3 expression was inversely correlated with Ce metabolism and other AT-substrates. These data suggest that altered amygdala neuroplasticity may play a role the early dispositional risk to develop anxiety and depression.
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BACKGROUND: Asymmetric patterns of frontal brain activity and brain corticotropin-releasing hormone (CRH) systems have both been separately implicated in the processing of normal and abnormal emotional responses. Previous studies in rhesus monkeys demonstrated that individuals with extreme right frontal asymmetric brain electrical activity have high levels of trait-like fearful behavior and increased plasma cortisol concentrations. METHODS: In this study we assessed cerebrospinal fluid (CSF) CRH concentrations in monkeys with extreme left and extreme right frontal brain electrical activity. CSF was repeatedly collected at 4, 8, 14, 40, and 52 months of age. RESULTS: Monkeys with extreme right frontal brain activity had increased CSF CRH concentrations at all ages measured. In addition, individual differences in CSF CRH concentrations were stable from 4 to 52 months of age. CONCLUSIONS: These findings suggest that, in primates, the fearful endophenotype is characterized by increased fearful behavior, a specific pattern of frontal electrical activity, increased pituitary-adrenal activity, and increased activity of brain CRH systems. Data from other preclinical studies suggests that the increased brain CRH activity may underlie the behavioral and physiological characteristics of fearful endophenotype.
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The cholinergic system has consistently been implicated in Pavlovian fear conditioning. Considerable work has been done to localize specific nicotinic receptor subtypes in the hippocampus and determine their functional importance; however, the specific function of many of these subtypes has yet to be determined. An alpha7 nicotinic antagonist methyllycaconitine (MLA) (35 microg), and a broad spectrum non-alpha7 nicotinic antagonist mecamylamine (35 microg) was injected directly into the dorsal hippocampus or overlying cortex either 15 min pre-, 1 min post-, or 6h post-fear conditioning. One week after conditioning, retention of contextual and cue (tone) conditioning were assessed. A significant impairment in retention of contextual fear was observed when mecamylamine was injected 15 min pre- and 1 min post-conditioning. No significant impairment was observed when mecamylamine was injected 6h post-conditioning. Likewise, a significant impairment in retention of contextual fear was observed when MLA was injected 1 min post-conditioning; however, in contrast, MLA did not show any significant impairments when injected 15 min pre-conditioning, but did show a significant impairment when injected 6h post-conditioning. There were no significant impairments observed when either drug was injected into overlying cortex. No significant impairments were observed in cue conditioning for either drug. In general, specific temporal dynamics involved in nicotinic receptor function were found relative to time of receptor dysfunction. The results indicate that the greatest deficits in long-term retention (1 week) of contextual fear are produced by central infusion of MLA minutes to hours post-conditioning or mecamylamine within minutes of conditioning.
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First described for use in mapping the human visual cortex in 1991, functional magnetic resonance imaging (fMRI) is based on blood-oxygen level dependent (BOLD) changes in cortical regions that occur during specific tasks. Typically, an overabundance of oxygenated (arterial) blood is supplied during activation of brain areas. Consequently, the venous outflow from the activated areas contains a higher concentration of oxyhemoglobin, which changes the paramagnetic properties of the tissue that can be detected during a T2-star acquisition. fMRI data can be acquired in response to specific tasks or in the resting state. fMRI has been widely applied to studying physiologic and pathophysiologic diseases of the brain. This review will discuss the most common current clinical applications of fMRI as well as emerging directions.
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What is compassion? And how did it evolve? In this review, we integrate 3 evolutionary arguments that converge on the hypothesis that compassion evolved as a distinct affective experience whose primary function is to facilitate cooperation and protection of the weak and those who suffer. Our empirical review reveals compassion to have distinct appraisal processes attuned to undeserved suffering; distinct signaling behavior related to caregiving patterns of touch, posture, and vocalization; and a phenomenological experience and physiological response that orients the individual to social approach. This response profile of compassion differs from those of distress, sadness, and love, suggesting that compassion is indeed a distinct emotion. We conclude by considering how compassion shapes moral judgment and action, how it varies across different cultures, and how it may engage specific patterns of neural activation, as well as emerging directions of research.
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This project involves developing syllabi for two courses, an introduction to American Studies and an English Department senior seminar. It focuses on nature writers-not only literary authors, but natural and social scientists-who are also contemplatives: Henry David Thoreau, John Muir, Barry Lopez, Gary Snyder, Richard Nelson, Terry Tempest Williams, Linda Hogan and others. Themes explored in these texts include dwelling, home and universe, comparative traditions, science, travel, the lessons of history, embodiment, ecofeminism, green movements and environmental justice, and imaginative versions of landscape by the privileged juxtaposed to the lived experience of the disempowered. Since contemplation of nature is what most nature writers in fact do, students involve themselves as well in contemplative practice. They begin each class period with meditation as a centering exercise; write contemplative journal entries on their readings; and reflect deeply on these entries and turn them into papers. Further, the act of contemplation for nature writers does not end in solitude, but in emergence in a connection to the world. To this end, there is a community service component in these courses, compulsory in the introductory course and voluntary in the senior seminar.

In a recent neuroimaging study of macaque monkeys, Gil-da-Costa and colleagues reported that a distributed circuit of modality-specific properties represents macaques' conceptual knowledge of social situations. The circuit identified shows striking similarities to analogous circuits in humans that represent conceptual knowledge. This parallel suggests that a common architecture underlies the conceptual systems of different species, although with additional systems extending human conceptual abilities significantly.
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The corticotrophin-releasing hormone (CRH) system integrates the stress response and is associated with stress-related psychopathology. Previous reports have identified interactions between childhood trauma and sequence variation in the CRH receptor 1 gene (CRHR1) that increase risk for affective disorders. However, the underlying mechanisms that connect variation in CRHR1 to psychopathology are unknown. To explore potential mechanisms, we used a validated rhesus macaque model to investigate association between genetic variation in CRHR1, anxious temperament (AT) and brain metabolic activity. In young rhesus monkeys, AT is analogous to the childhood risk phenotype that predicts the development of human anxiety and depressive disorders. Regional brain metabolism was assessed with (18)F-labeled fluoro-2-deoxyglucose (FDG) positron emission tomography in 236 young, normally reared macaques that were also characterized for AT. We show that single nucleotide polymorphisms (SNPs) affecting exon 6 of CRHR1 influence both AT and metabolic activity in the anterior hippocampus and amygdala, components of the neural circuit underlying AT. We also find evidence for association between SNPs in CRHR1 and metabolism in the intraparietal sulcus and precuneus. These translational data suggest that genetic variation in CRHR1 affects the risk for affective disorders by influencing the function of the neural circuit underlying AT and that differences in gene expression or the protein sequence involving exon 6 may be important. These results suggest that variation in CRHR1 may influence brain function before any childhood adversity and may be a diathesis for the interaction between CRHR1 genotypes and childhood trauma reported to affect human psychopathology.
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Cyclic AMP (cAMP) is a second messenger involved in many processes including mnemonic processing and anxiety. Memory deficits and anxiety are noted in the phenotype of fragile X (FX), the most common heritable cause of mental retardation and autism. Here we review reported observations of altered cAMP cascade function in FX and autism. Cyclic AMP is a potentially useful biochemical marker to distinguish autism comorbid with FX from autism per se and the cAMP cascade may be a viable therapeutic target for both FX and autism.
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PET imaging of the neuroreceptor systems in the brain has earned a prominent role in studying normal development, neuropsychiatric illness and developing targeted drugs. The dopaminergic system is of particular interest due to its role in the development of cognitive function and mood as well as its suspected involvement in neuropsychiatric illness. Nonhuman primate animal models provide a valuable resource for relating neurochemical changes to behavior. To facilitate comparison within and between primate models, we report in vivo D2/D3 binding in a large cohort of adolescent rhesus monkeys. METHODS: In this work, the in vivo D2/D3 dopamine receptor availability was measured in a cohort of 33 rhesus monkeys in the adolescent stage of development (3.2-5.3 years). Both striatal and extrastriatal D2/D3 binding were measured using [F-18]fallypride with a high resolution small animal PET scanner. The distribution volume ratio (DVR) was measured for all subjects and group comparisons of D2/D3 binding among the cohort were made based on age and sex. Because two sequential studies were acquired from a single [F-18]fallypride batch, the effect of competing (unlabeled) ligand mass was also investigated. RESULTS: Among this cohort, the rank order of regional D2/D3 receptor binding did not vary from previous studies with adult rhesus monkeys, with: putamen>caudate>ventral striatum>amygdala approximately substantia nigra>medial dorsal thalamus>lateral temporal cortex approximately frontal cortex. The DVR coefficient of variation ranged from 14%-26%, with the greatest variance seen in the head of the caudate. There were significant sex differences in [F-18]fallypride kinetics in the pituitary gland, but this was not observed for regions within the blood-brain barrier. Furthermore, no regions in the brain showed significant sex or age related differences in DVR within this small age range. Based on a wide range of injected fallypride mass across the cohort, significant competition effects could only be detected in the substantia nigra, thalamus, and frontal cortex, and were not evident above intersubject variability in all other regions. CONCLUSION: These data represent the first report of large cohort in vivo D2/D3 dopamine whole brain binding in the adolescent brain and will serve as a valuable comparison for understanding dopamine changes during this critical time of development and provide a framework for creating a dopaminergic biochemical atlas for the rhesus monkey.
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The authors present an overview of the neural bases of emotion. They underscore the role of the prefrontal cortex (PFC) and amygdala in 2 broad approach- and withdrawal-related emotion systems. Components and measures of affective style are identified. Emphasis is given to affective chronometry and a role for the PFC in this process is proposed. Plasticity in the central circuitry of emotion is considered, and implications of data showing experience-induced changes in the hippocampus for understanding psychopathology and stress-related symptoms are discussed. Two key forms of affective plasticity are described--context and regulation. A role for the hippocampus in context-dependent normal and dysfunctional emotional responding is proposed. Finally, implications of these data for understanding the impact on neural circuitry of interventions to promote positive affect and on mechanisms that govern health and disease are considered.
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Prior research has demonstrated that people who are more connected with nature report more subjective well-being. However, guided by the sensitization model of well-being, we expected that the positive relation between connectedness with nature and psychological well-being would only be significant for those who tend to engage in nature's beauty (i.e., experience positive emotional responses when witnessing nature's beauty). In Study 1, we found the positive relation between connectedness with nature and life satisfaction was only significant for individuals higher, and not those lower, on engagement with natural beauty. Study 2 conceptually replicated this finding using self-esteem as an outcome. Moreover, the results were not affected by age, gender, Big Five personality traitsĀ (Study 1) or social desirability (Study 2). Thus, the current research extends past literature and demonstrates that connectedness with nature only predicts well-being when individuals are also emotionally attuned to nature's beauty.
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A translation of the Kabbalah for the layperson includes a compact presentation of each primary text and features a practical analysis and vital historical information that offers insight into the various aspects of Jewish mysticism.

Neuroanatomists posit that the central nucleus of the amygdala (Ce) and bed nucleus of the stria terminalis (BST) comprise two major nodes of a macrostructural forebrain entity termed the extended amygdala. The extended amygdala is thought to play a critical role in adaptive motivational behavior and is implicated in the pathophysiology of maladaptive fear and anxiety. Resting functional connectivity of the Ce was examined in 107 young anesthetized rhesus monkeys and 105 young humans using standard resting-state functional magnetic resonance imaging (fMRI) methods to assess temporal correlations across the brain. The data expand the neuroanatomical concept of the extended amygdala by finding, in both species, highly significant functional coupling between the Ce and the BST. These results support the use of in vivo functional imaging methods in nonhuman and human primates to probe the functional anatomy of major brain networks such as the extended amygdala.
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The relation between brain activity and the immune system was evaluated by assessing immune responses in 20 healthy women who manifested extreme differences in the asymmetry of frontal cortex activation. One group showed extreme and stable left frontal activation; the other group showed extreme and stable right frontal activation. As predicted, women with extreme right frontal activation had significantly lower levels of natural killer cell activity (at effector:target cell ratios of 33:1 and 11:1) than did left frontally activated individuals. This difference did not extend to two other immune measures, lymphocyte proliferation and T-cell subsets. However, higher immunoglobulin levels of the M class were observed in the right frontal group. In this study, the immune patterns could not be accounted for by plasma cortisol levels, anxiety- and depression-related symptomatology, or recent health histories. These findings support the hypothesis that there is a specific association between frontal brain asymmetry and certain immune responses.
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Research on the anatomical bases of interhemispheric interaction, including individual differences in corpus callosum (CC) anatomy, is reviewed. These anatomical findings form the basis for the discussion of two major themes. The first considers interhemispheric transfer time (IHTT) and related issues. These include varieties of IHTT and possible directional asymmetries of IHTT. Evidence suggests that pathological variations in IHTT may have cognitive consequences. The second involves conditions under which interhemispheric interaction is necessary and beneficial. The data suggest that when both hemispheres have some competence at a difficult task, there is a benefit to interhemispheric interaction. The role of the CC in the dynamic distribution of attention may be particularly relevant to this advantage. Throughout the article reference is made to individual differences and developmental changes associated with interhemispheric interaction.
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