OBJECTIVE: The purpose of this study was to use functional magnetic resonance imaging (fMRI) to probe the neural circuitry associated with reactivity to negative and positive affective stimuli in patients with major depressive disorder before treatment and after 2 and 8 weeks of treatment with venlafaxine. Relations between baseline neural activation and response to treatment were also evaluated.
METHOD: Patients with major depressive disorder (N=12) and healthy comparison subjects (N=5) were scanned on three occasions, during which trials of alternating blocks of affective and neutral pictorial visual stimuli were presented. Symptoms were evaluated at each testing occasion, and both groups completed self-report measures of mood. Statistical parametric mapping was used to examine the fMRI data with a focus on the group-by-time interactions.
RESULTS: Patients showed a significant reduction in depressive symptoms with treatment. Group-by-time interactions in response to the negative versus neutral stimuli were found in the left insular cortex and the left anterior cingulate. At baseline, both groups showed bilateral activation in the visual cortices, lateral prefrontal cortex, and amygdala in response to the negative versus neutral stimuli, with patients showing greater activation in the visual cortex and less activation in the left lateral prefrontal cortex. Patients with greater relative anterior cingulate activation at baseline in response to the negative versus neutral stimuli showed the most robust treatment response.
CONCLUSIONS: The findings underscore the importance of the neural circuitry activated by negative affect in depression and indicate that components of this circuitry can be changed within 2 weeks of treatment with antidepressant medication.
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BACKGROUND: Anxious temperament (AT) is identifiable early in life and predicts the later development of anxiety disorders and depression. Neuropeptide Y (NPY) is a putative endogenous anxiolytic neurotransmitter that adaptively regulates responses to stress and might confer resilience to stress-related psychopathology. With a well-validated nonhuman primate model of AT, we examined expression of the NPY system in the central nucleus (Ce) of the amygdala, a critical neural substrate for extreme anxiety.
METHODS: In 24 young rhesus monkeys, we measured Ce messenger RNA (mRNA) levels of all members of the NPY system that are detectable in the Ce with quantitative real time polymerase chain reaction. We then examined the relationship between these mRNA levels and both AT expression and brain metabolism.
RESULTS: Lower mRNA levels of neuropeptide Y receptor 1 (NPY1R) and NPY5R but not NPY or NPY2R in the Ce predicted elevated AT; mRNA levels for NPY1R and NPY5R in the motor cortex were not related to AT. In situ hybridization analysis provided for the first time a detailed description of NPY1R and NPY5R mRNA distribution in the rhesus amygdala and associated regions. Lastly, mRNA levels for these two receptors in the Ce predicted metabolic activity in several regions that have the capacity to regulate the Ce.
CONCLUSIONS: Decreased NPY signaling in the Ce might contribute to the altered metabolic activity that is a component of the neural substrate underlying AT. This suggests that enhancement of NPY signaling might reduce the risk to develop psychopathology.
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<p>Ironically, in spite of the label "affective disorders", research on affective disorders has little to say about just what is disordered about emotion in these illnesses. One major purpose of this Special Issue is to begin to raise this question as a legitimate domain of inquiry in studies of emotion and psychopathology. Historically, the literature on emotion in normal subjects has proceeded almost entirely independently of studies of emotion-related psychopathology. And, studies on psychopathology make virtually no reference to basic research on emotion in normals. Major advances have occurred in our understanding of the neural substrates of these affective processes. Their application to the study of disordered emotion in affective and anxiety disorders is comparatively recent. A goal of this Special Issue is to foster increased integration between research on the neural mechanisms underlying normal emotion and disordered emotion in depression and anxiety-related illnesses. It features exemplars of the best research at many levels, from animal studies of the detailed circuitry subserving fear and anxiety, to human studies of cognitive abnormalities in subjects with affective and anxiety disorders. It also highlights a myriad array of methods for making inferences about affective processes, ranging from the biological to the behavioral, and from the molecular to the molar. A central concept that figures prominently in this collection of articles is the importance of individual differences in different components of affective processes. The study of the brain circuitry that underlies such differences in affective style offers great promise in providing a biologically plausible way of parsing the affect domain and developing a theoretically compelling taxonomy of mechanisms that give rise to vulnerability to affective and anxiety disorders.</p>
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Emotions can color people’s attitudes toward unrelated objects in the environment. Existing evidence suggests that such emotional coloring is particularly strong when emotion-triggering information escapes conscious awareness. But is emotional reactivity stronger after nonconscious emotional provocation than after conscious emotional provocation, or does conscious processing specifically change the association between emotional reactivity and evaluations of unrelated objects? In this study, we independently indexed emotional reactivity and coloring as a function of emotional-stimulus awareness to disentangle these accounts. Specifically, we recorded skin-conductance responses to spiders and fearful faces, along with subsequent preferences for novel neutral faces during visually aware and unaware states. Fearful faces increased skin-conductance responses comparably in both stimulus-aware and stimulus-unaware conditions. Yet only when visual awareness was precluded did skin-conductance responses to fearful faces predict decreased likability of neutral faces. These findings suggest a regulatory role for conscious awareness in breaking otherwise automatic associations between physiological reactivity and evaluative emotional responses.
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The nature of the affective deficit that characterizes social anhedonia is not well understood. Emotionally evocative visual stimuli were presented to undergraduates identified as anhedonic or normal, based on their scores on the revised Social Anhedonia Scale. The affective stimuli were chosen to elicit positive and negative emotion; a subset of slides were specifically chosen to include social-interpersonal content. In the acoustic startle paradigm, participants were administered startle probes (50-ms 95 dB white noise bursts) while viewing images from the International Affective Picture System. Socially anhedonic individuals did not differ from normally hedonic individuals in terms of their physiological response to the stimuli, regardless of the nature of the content of the stimuli. However, on the self-report measures of trait affectivity, the socially anhedonic individuals reported significantly lower levels of positive affect and higher levels of negative affect. These findings suggest that the affective deficits reported by socially anhedonic individuals are not global in nature.
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In children, behavioral inhibition (BI) in response to potential threat predicts the development of anxiety and affective disorders, and primate lesion studies suggest involvement of the orbitofrontal cortex (OFC) in mediating BI. Lesion studies are essential for establishing causality in brain-behavior relationships, but should be interpreted cautiously because the impact of a discrete lesion on a complex neural circuit extends beyond the lesion location. Complementary functional imaging methods assessing how lesions influence other parts of the circuit can aid in precisely understanding how lesions affect behavior. Using this combination of approaches in monkeys, we found that OFC lesions concomitantly alter BI and metabolism in the bed nucleus of stria terminalis (BNST) region and that individual differences in BNST activity predict BI. Thus it appears that an important function of the OFC in response to threat is to modulate the BNST, which may more directly influence the expression of BI.
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Positive affect elicited in a mother toward her newborn infant may be one of the most powerful and evolutionarily preserved forms of positive affect in the emotional landscape of human behavior. This study examined the neurobiology of this form of positive emotion and in so doing, sought to overcome the difficulty of eliciting robust positive affect in response to visual stimuli in the physiological laboratory. Six primiparous human mothers with no indications of postpartum depression brought their infants into the laboratory for a photo shoot. Approximately 6 weeks later, they viewed photographs of their infant, another infant, and adult faces during acquisition of functional magnetic resonance images (fMRI). Mothers exhibited bilateral activation of the orbitofrontal cortex (OFC) while viewing pictures of their own versus unfamiliar infants. While in the scanner, mothers rated their mood more positively for pictures of their own infants than for unfamiliar infants, adults, or at baseline. The orbitofrontal activation correlated positively with pleasant mood ratings. In contrast, areas of visual cortex that also discriminated between own and unfamiliar infants were unrelated to mood ratings. These data implicate the orbitofrontal cortex in a mother's affective responses to her infant, a form of positive emotion that has received scant attention in prior human neurobiological studies. Furthermore, individual variations in orbitofrontal activation to infant stimuli may reflect an important dimension of maternal attachment.
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<p>Reviews selective behavioral, psychophysiological, and neuropsychological research bearing on how affective space should be parsed. Neither facial expression nor autonomic nervous system activity is found to provide unique markers for particular discrete emotions. The dimensions of approach and withdrawal are introduced as fundamental systems relevant to differentiating affective space. The role of frontal and anterior temporal asymmetries in mediating approach- and withdrawal-related emotion is considered. Individual differences in tonic anterior activation asymmetry are present and are relatively stable over time. Such differences are associated with an individual's propensity to display different types of emotion, mood, and psychopathology. The conceptual and methodological implications of this perspective are considered.</p>
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Examined were electroencephalogram (EEG) asymmetries during the presence of discrete facial signs of emotion among 10-month-old infants who were tested in a standard stranger- and mother-approach paradigm that included a brief separation from mother. Data underscore the usefulness of EEG measures of hemispheric activation in differentiating among certain emotional states. (RH)
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The purpose of the present study was twofold: (1) to obtain information on central mechanisms underlying cardiac self-regulation by comparing changes in cerebral asymmetry during self-control of heart rate with changes observed during the production of affective imagery; and (2) to explore sex differences in hemispheric function during performance of these two tasks. Heart rate (HR) and bilateral parietal EEG filtered for alpha were recorded from 20 right-handed males and females during two discrete experimental phases: cardiac control and image self-generation. HR showed significant effects between up versus down in prefeedback and feedback, and between anger versus relaxing imagery in the image phase. The EEG data indicated similar patterns of hemispheric asymmetry in both sexes during prefeedback. However, with the introduction of feedback, females shifted to greater relative right hemisphere activation comparable to what they show when specifically instructed to think emotional thoughts; males showed little differentiation between conditions. These data indicate that the Self-regulation of HR with biofeedback in males and females may be accomplished by the utilization of strategies involving different underlying patterns of neuropsychological processes.
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Neuroimage phenotyping for psychiatric and neurological disorders is performed using voxelwise analyses also known as voxel based analyses or morphometry (VBM). A typical voxelwise analysis treats measurements at each voxel (e.g., fractional anisotropy, gray matter probability) as outcome measures to study the effects of possible explanatory variables (e.g., age, group) in a linear regression setting. Furthermore, each voxel is treated independently until the stage of correction for multiple comparisons. Recently, multi-voxel pattern analyses (MVPA), such as classification, have arisen as an alternative to VBM. The main advantage of MVPA over VBM is that the former employ multivariate methods which can account for interactions among voxels in identifying significant patterns. They also provide ways for computer-aided diagnosis and prognosis at individual subject level. However, compared to VBM, the results of MVPA are often more difficult to interpret and prone to arbitrary conclusions. In this paper, first we use penalized likelihood modeling to provide a unified framework for understanding both VBM and MVPA. We then utilize statistical learning theory to provide practical methods for interpreting the results of MVPA beyond commonly used performance metrics, such as leave-one-out-cross validation accuracy and area under the receiver operating characteristic (ROC) curve. Additionally, we demonstrate that there are challenges in MVPA when trying to obtain image phenotyping information in the form of statistical parametric maps (SPMs), which are commonly obtained from VBM, and provide a bootstrap strategy as a potential solution for generating SPMs using MVPA. This technique also allows us to maximize the use of available training data. We illustrate the empirical performance of the proposed framework using two different neuroimaging studies that pose different levels of challenge for classification using MVPA.
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The response to painful stimulation depends not only on peripheral nociceptive input but also on the cognitive and affective context in which pain occurs. One contextual variable that affects the neural and behavioral response to nociceptive stimulation is the degree to which pain is perceived to be controllable. Previous studies indicate that perceived controllability affects pain tolerance, learning and motivation, and the ability to cope with intractable pain, suggesting that it has profound effects on neural pain processing. To date, however, no neuroimaging studies have assessed these effects. We manipulated the subjects' belief that they had control over a nociceptive stimulus, while the stimulus itself was held constant. Using functional magnetic resonance imaging, we found that pain that was perceived to be controllable resulted in attenuated activation in the three neural areas most consistently linked with pain processing: the anterior cingulate, insular, and secondary somatosensory cortices. This suggests that activation at these sites is modulated by cognitive variables, such as perceived controllability, and that pain imaging studies may therefore overestimate the degree to which these responses are stimulus driven and generalizable across cognitive contexts.
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Tasks that tax working memory (WM) have consistently been found to decrease mind wandering. These findings may indicate that maintenance of mind wandering requires WM resources, such that mind wandering cannot persist when WM resources are being consumed by a task. An alternative explanation for these findings, however, is that mind wandering persists without the support of WM but is nonetheless decreased during any demanding task because good task performance requires that attention be restricted from task-unrelated thought (TUT). The present study tested these two competing theories by investigating whether individuals with greater WM resources mind-wander more during an undemanding task, as would be predicted only by the theory that WM supports TUT. We found that individuals with higher WM capacity reported more TUT in undemanding tasks, which suggests that WM enables the maintenance of mind wandering.
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<p>Parents of 53 children categorized as behaviorally inhibited or uninhibited at age 30 mo were assessed on measures of affectivity, personality, and behavior. Parents of inhibited children showed lower extraversion, higher avoidance and shyness and faster drawing times on a task involving uncertainty than did parents of uninhibited children. Faster speed on the uncertainty task was interpreted as evidence of increased anxious responding. The Extroversion, Avoidance, Shyness, and Sociability scales loaded heavily on a single factor, the scores of which differed significantly by group. Child behavioral inhibition (BI) negatively correlated with maternal scores on the Extroversion scale and the extracted factor, and positively correlated with maternal scores on the Avoidance scale. BI correlated with both maternal and paternal scores on the uncertainty task in the predicted direction. Low parental extraversion, high paternal avoidance and shyness, and parental tendency toward anxious responding were associated with BI in children.</p>
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Our outside world changes continuously, for example, when driving through traffic. An important question is how our brain deals with this constant barrage of rapidly changing sensory input and flexibly selects only newly goal-relevant information for further capacity-limited processing in working memory. The challenge our brain faces is experimentally captured by the attentional blink (AB): an impairment in detecting the second of two target stimuli presented in close temporal proximity among distracters. Many theories have been proposed to explain this deficit in processing goal-relevant information, with some attributing the AB to capacity limitations related to encoding of the first target and others assigning a critical role to on-line selection mechanisms that control access to working memory. The current study examined the role of striatal dopamine in the AB, given its known role in regulating the contents of working memory. Specifically, participants performed an AB task and their basal level of dopamine D2-like receptor binding was measured using PET and [F-18]fallypride. As predicted, individual differences analyses showed that greater D2-like receptor binding in the striatum was associated with a larger AB, implicating striatal dopamine and mechanisms that control access to working memory in the AB. Specifically, we propose that striatal dopamine may determine the AB by regulating the threshold for working memory updating, providing a testable physiological basis for this deficit in gating rapidly changing visual information. A challenge for current models of the AB lies in connecting more directly to these neurobiological data.
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The experience of pain arises from both physiological and psychological factors, including one's beliefs and expectations. Thus, placebo treatments that have no intrinsic pharmacological effects may produce analgesia by altering expectations. However, controversy exists regarding whether placebos alter sensory pain transmission, pain affect, or simply produce compliance with the suggestions of investigators. In two functional magnetic resonance imaging (fMRI) experiments, we found that placebo analgesia was related to decreased brain activity in pain-sensitive brain regions, including the thalamus, insula, and anterior cingulate cortex, and was associated with increased activity during anticipation of pain in the prefrontal cortex, providing evidence that placebos alter the experience of pain.
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Individuals with fragile X syndrome (FXS) commonly display characteristics of social anxiety, including gaze aversion, increased time to initiate social interaction, and difficulty forming meaningful peer relationships. While neural correlates of face processing, an important component of social interaction, are altered in FXS, studies have not examined whether social anxiety in this population is related to higher cognitive processes, such as memory. This study aimed to determine whether the neural circuitry involved in face encoding was disrupted in individuals with FXS, and whether brain activity during face encoding was related to levels of social anxiety. A group of 11 individuals with FXS (5 M) and 11 age- and gender-matched control participants underwent fMRI scanning while performing a face encoding task with online eye-tracking. Results indicate that compared to the control group, individuals with FXS exhibited decreased activation of prefrontal regions associated with complex social cognition, including the medial and superior frontal cortex, during successful face encoding. Further, the FXS and control groups showed significantly different relationships between measures of social anxiety (including gaze-fixation) and brain activity during face encoding. These data indicate that social anxiety in FXS may be related to the inability to successfully recruit higher level social cognition regions during the initial phases of memory formation.
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<p>Abstract This article presents a model of the structure of emotion developed primarily from a consideration of neuropsychological evidence and behavioural data which have bearing on neuropsychological theories. Valence is first considered and highlighted as a defining characteristic of emotion. Next, the use of facial behaviour and autonomic nervous system patterns as defining characteristics of discrete emotions is questioned on empirical and conceptual grounds. The regulation of emotion is considered and proposed to affect the very structure of emotion itself. If there is an invariant pattern of biological activity across different instantiations of the same emotion, it is likely to be found in higher-order associative networks of central nervous system activity, the very same networks that subserve goal-directed behaviour and other cognitive functions. Drawing upon evolutionary considerations, it is argued that what is basic about emotion are the dimensions of approach and withdrawal. The nature of the linkage between such action tendencies and emotion is discussed.</p>
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Marital stress is associated with a higher incidence of psychiatric disorders, in particular major depression. One pathway through which marital stress may impact emotional health is by compromising emotion-responding processes. We examined a longitudinal sample of adults (N = 116; 59 males; 39-84 years) to verify how marital stress predicts reactivity to, and recovery from, emotional provocation. Individuals watched positive, neutral, and negative pictures while an objective measure of affective state, corrugator supercilii muscle activity, was recorded continuously. Our results indicate that marital stress is associated with short-lived responses to positive pictures, indexed by a less persistent decrease in corrugator activity after picture offset. Extending beyond the prior focus on negative emotional processes, these results suggest that social stress may impact health by influencing the time course of responding to positive events.
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<p>BACKGROUND: Increasingly, researchers attend to both positive and negative aspects of mental health. Such distinctions call for clarification of whether psychological well-being and ill-being comprise opposite ends of a bipolar continuum, or are best construed as separate, independent dimensions of mental health. Biology can help resolve this query--bipolarity predicts 'mirrored' biological correlates (i.e. well-being and ill-being correlate similarly with biomarkers, but show opposite directional signs), whereas independence predicts 'distinct' biological correlates (i.e. well-being and ill-being have different biological signatures). METHODS: Multiple aspects of psychological well-being (eudaimonic, hedonic) and ill-being (depression, anxiety, anger) were assessed in a sample of aging women (n = 135, mean age = 74) on whom diverse neuroendocrine (salivary cortisol, epinephrine, norepinephrine, DHEA-S) and cardiovascular factors (weight, waist-hip ratio, systolic and diastolic blood pressure, HDL cholesterol, total/HDL cholesterol, glycosylated hemoglobin) were also measured. RESULTS: Measures of psychological well-being and ill-being were significantly linked with numerous biomarkers, with some associations being more strongly evident for respondents aged 75+. Outcomes for seven biomarkers supported the distinct hypothesis, while findings for only two biomarkers supported the mirrored hypothesis. CONCLUSION: This research adds to the growing literature on how psychological well-being and mental maladjustment are instantiated in biology. Population-based inquiries and challenge studies constitute important future directions.</p>
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Purpose in life predicts both health and longevity suggesting that the ability to find meaning from life’s experiences, especially when confronting life’s challenges, may be a mechanism underlying resilience. Having purpose in life may motivate reframing stressful situations to deal with them more productively, thereby facilitating recovery from stress and trauma. In turn, enhanced ability to recover from negative events may allow a person to achieve or maintain a feeling of greater purpose in life over time. In a large sample of adults (aged 36-84 years) from the MIDUS study (Midlife in the U.S., http://www.midus.wisc.edu/), we tested whether purpose in life was associated with better emotional recovery following exposure to negative picture stimuli indexed by the magnitude of the eyeblink startle reflex (EBR), a measure sensitive to emotional state. We differentiated between initial emotional reactivity (during stimulus presentation) and emotional recovery (occurring after stimulus offset). Greater purpose in life, assessed over two years prior, predicted better recovery from negative stimuli indexed by a smaller eyeblink after negative pictures offset, even after controlling for initial reactivity to the stimuli during the picture presentation, gender, age, trait affect, and other well-being dimensions. These data suggest a proximal mechanism by which purpose in life may afford protection from negative events and confer resilience is through enhanced automatic emotion regulation after negative emotional provocation.
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