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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OBJECTIVES: To examine whether mindfulness meditation (MM) was associated with changes in objectively measured polysomnographic (PSG) sleep profiles and to relate changes in PSG sleep to subjectively reported changes in sleep and depression within the context of a randomized controlled trial. Previous studies have indicated that mindfulness and other forms of meditation training are associated with improvements in sleep quality. However, none of these studies used objective PSG sleep recordings within longitudinal randomized controlled trials of naïve subjects.
METHODS: Twenty-six individuals with partially remitted depression were randomized into an 8-week Mindfulness-Based Cognitive Therapy (MBCT) course or a waitlist control condition. Pre-post measurements included PSG sleep studies and subjectively reported sleep and depression symptoms.
RESULTS: According to PSG sleep, MM practice was associated with several indices of increased cortical arousal, including more awakenings and stage 1 sleep and less slow-wave sleep relative to controls, in proportion to amount of MM practice. According to sleep diaries, subjectively reported sleep improved post MBCT but not above and beyond controls. Beck Depression Inventory scores decreased more in the MBCT group than controls. Improvements in depression were associated with increased subjective sleep continuity and increased PSG arousal.
CONCLUSIONS: MM is associated with increases in objectively measured arousal during sleep with simultaneous improvements in subjectively reported sleep quality and mood disturbance. This pattern is similar to the profiles of positive responders to common antidepressant medications.
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<p>Measures of left-right asymmetry in resting brain activity were derived from spectral estimates of electroencephalogram (EEG) alpha-band power density in 13 homologous scalp electrode pairs from 81 right-handed individuals (43 F) on two occasions separated by 6 weeks. At a third, later session, these individuals completed a cognitive task, comparing word-pairs that systematically differed in affective tone. For an extended series of paired-comparisons, the subject chose the one word-pair that 'went together best'. Objectively, associative strength was comparable for both word-pairs. Individuals with relatively greater left-sided anterior frontal resting activity were more likely to select the more pleasant word-pair. Relations between word-pair selection and asymmetry in resting brain activity at central and posterior sites were not significant.</p>
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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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Temperamentally anxious individuals can be identified in childhood and are at risk to develop anxiety and depressive disorders. In addition, these individuals tend to have extreme asymmetric right prefrontal brain activity. Although common and clinically important, little is known about the pathophysiology of anxious temperament. Regardless, indirect evidence from rodent studies and difficult to interpret primate studies is used to support the hypothesis that the amygdala plays a central role. In previous studies using rhesus monkeys, we characterized an anxious temperament endophenotype that is associated with excessive anxiety and fear-related responses and increased electrical activity in right frontal brain regions. To examine the role of the amygdala in mediating this endophenotype and other fearful responses, we prepared monkeys with selective fiber sparing ibotenic acid lesions of the amygdala. Unconditioned trait-like anxiety-fear responses remained intact in monkeys with >95% bilateral amygdala destruction. In addition, the lesions did not affect EEG frontal asymmetry. However, acute unconditioned fear responses, such as those elicited by exposure to a snake and to an unfamiliar threatening conspecific were blunted in monkeys with >70% lesions. These findings demonstrate that the primate amygdala is involved in mediating some acute unconditioned fear responses but challenge the notion that the amygdala is the key structure underlying the dispositional behavioral and physiological characteristics of anxious temperament.
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<p>Virtually all developmental neuropsychiatric disorders involve some dysfunction or dysregulation of emotion. Moreover, many psychiatric disorders with adult onset have early subclinical manifestations in children. This essay selectively reviews the literature on the neuroimaging of affect and disorders of affect in children. Some critical definitional and conceptual issues are first addressed, including the distinctions between the perception and production of emotion and between emotional states and traits. Developmental changes in morphometric measures of brain structure are then discussed and the implications of such findings for studies of functional brain activity are considered. Data on functional neuroimaging and childhood depression are then reviewed. While the extant data in this area are meager, they are consistent with studies in adults that have observed decreased left-sided anterolateral prefrontal cortex activation in depression. Studies in children on the recognition of emotion and affective intent in faces using functional magnetic resonance imaging are then reviewed. These findings indicate that the amygdala plays an important role in such affective face processing in children, similar to the patterns of activation observed in adults. Moreover, one study has reported abnormalities in amygdala activation during a task requiring the judgment of affective intent from the eye region of the face in subjects with autism. Some of the methodological complexities of developmental research in this area are discussed, and directions for future research are suggested.</p>
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BACKGROUND: Anhedonia, a reduced ability to experience pleasure, is a chief symptom of major depressive disorder and is related to reduced frontostriatal connectivity when attempting to upregulate positive emotion. The present study examined another facet of positive emotion regulation associated with anhedonia-namely, the downregulation of positive affect-and its relation to prefrontal cortex (PFC) activity.
METHODS: Neuroimaging data were collected from 27 individuals meeting criteria for major depressive disorder as they attempted to suppress positive emotion during a positive emotion regulation task. Their PFC activation pattern was compared with the PFC activation pattern exhibited by 19 healthy control subjects during the same task. Anhedonia scores were collected at three time points: at baseline (time 1), 8 weeks after time 1 (i.e., time 2), and 6 months after time 1 (i.e., time 3). Prefrontal cortex activity at time 1 was used to predict change in anhedonia over time. Analyses were conducted utilizing hierarchical linear modeling software.
RESULTS: Depressed individuals who could not inhibit positive emotion-evinced by reduced right ventrolateral prefrontal cortex activity during attempts to dampen their experience of positive emotion in response to positive visual stimuli-exhibited a steeper anhedonia reduction slope between baseline and 8 weeks of treatment with antidepressant medication (p < .05). Control subjects showed a similar trend between baseline and time 3.
CONCLUSIONS: To reduce anhedonia, it may be necessary to teach individuals how to counteract the functioning of an overactive pleasure-dampening prefrontal inhibitory system.
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Baseline resting electroencephalogram (EEG) activity was recorded from 6 normothymic depressives and 8 controls using three different reference montages. Power in all frequency bands was extracted by Fourier transformation. Significant Group X Region X Hemisphere interactions were found consistently for alpha band power only. Previously depressed subjects had less left-sided anterior and less right-sided posterior activation (i.e., more alpha activity) than did never depressed subjects. Previously depressed subjects had no history of pharmacological treatment and did not differ from controls in emotional state at the time of testing. The pattern of anterior and posterior asymmetry in the previously depressed subjects is similar to that found in acutely depressed subjects and suggests that this may be a state-independent marker for depression.
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Significant progress has been made in our understanding of the neural substrates of emotion and its disorders. Neuroimaging methods have been used to characterize the circuitry underlying disorders of emotion. Particular emphasis has been placed on the prefrontal cortex, anterior cingulate, parietal cortex, and the amygdala as critical components of the circuitry that may be dysfunctional in both depression and anxiety.
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Although once considered disruptive, self-conscious emotions are now theorized to be fundamentally involved in the regulation of social behavior. The present study examined the social regulation function of self-conscious emotions by comparing healthy participants with a neuropsychological population--patients with orbitofrontal lesions--characterized by selective regulatory deficits. Orbitofrontal patients and healthy controls participated in a series of tasks designed to assess their social regulation and self-conscious emotions. Another task assessed the ability to infer others' emotional states, an appraisal process involved in self-conscious emotion. Consistent with the theory that self-conscious emotions are important for regulating social behavior, the findings show that deficient behavioral regulation is associated with inappropriate self-conscious emotions that reinforce maladaptive behavior. Additionally, deficient behavioral regulation is associated with impairments in interpreting the self-conscious emotions of others.
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Electroencephalogram (EEG) alpha power has been demonstrated to be inversely related to mental activity and has subsequently been used as an indirect measure of brain activation. The thalamus has been proposed as an important site for modulation of rhythmic alpha activity. Studies in animals have suggested that cortical alpha rhythms are correlated with alpha rhythms in the thalamus. However, little empirical evidence exists for this relation in humans. In the current study, resting EEG and a fluorodeoxyglucose positron emission tomography scan were measured during the same experimental session. Over a 30-min period, average EEG alpha power across 28 electrodes from 27 participants was robustly inversely correlated with glucose metabolic activity in the thalamus. These data provide the first evidence for a relation between alpha EEG power and thalamic activity in humans.
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OBJECTIVE Deficits in positive affect and their neural bases have been associated with major depression. However, whether reductions in positive affect result solely from an overall reduction in nucleus accumbens activity and fronto-striatal connectivity or the additional inability to sustain engagement of this network over time is unknown. The authors sought to determine whether treatment-induced changes in the ability to sustain nucleus accumbens activity and fronto-striatal connectivity during the regulation of positive affect are associated with gains in positive affect. METHOD Using fMRI, the authors assessed the ability to sustain activity in reward-related networks when attempting to increase positive emotion during performance of an emotion regulation paradigm in 21 depressed patients before and after 2 months of antidepressant treatment. Over the same interval, 14 healthy comparison subjects underwent scanning as well. RESULTS After 2 months of treatment, self-reported positive affect increased. The patients who demonstrated the largest increases in sustained nucleus accumbens activity over the 2 months were those who demonstrated the largest increases in positive affect. In addition, the patients who demonstrated the largest increases in sustained fronto-striatal connectivity were also those who demonstrated the largest increases in positive affect when controlling for negative affect. None of these associations were observed in healthy comparison subjects. CONCLUSIONS Treatment-induced change in the sustained engagement of fronto-striatal circuitry tracks the experience of positive emotion in daily life. Studies examining reduced positive affect in a variety of psychiatric disorders might benefit from examining the temporal dynamics of brain activity when attempting to understand changes in daily positive affect.
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<p>OBJECTIVES: The study objectives were to develop and objectively assess the therapeutic effect of a novel movement-based complementary and alternative medicine approach for children with an autism-spectrum disorder (ASD). DESIGN: A within-subject analysis comparing pre- to post-treatment scores on two standard measures of childhood behavioral problems was used. SETTINGS AND LOCATION: The intervention and data analysis occurred at a tertiary care, medical school teaching hospital. SUBJECTS: Twenty-four (24) children aged 3-16 years with a diagnosis of an ASD comprised the study group. INTERVENTION: The efficacy of an 8-week multimodal yoga, dance, and music therapy program based on the relaxation response (RR) was developed and examined. OUTCOME MEASURES: The study outcome was measured using The Behavioral Assessment System for Children, Second Edition (BASC-2) and the Aberrant Behavioral Checklist (ABC). RESULTS: Robust changes were found on the BASC-2, primarily for 5-12-year-old children. Unexpectedly, the post-treatment scores on the Atypicality scale of the BASC-2, which measures some of the core features of autism, changed significantly (p=0.003). CONCLUSIONS: A movement-based, modified RR program, involving yoga and dance, showed efficacy in treating behavioral and some core features of autism, particularly for latency-age children.</p>
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Depression has been associated with dysfunctional executive functions and abnormal activity within the anterior cingulate cortex (ACC), a region critically involved in action regulation. Prior research invites the possibility that executive deficits in depression may arise from abnormal responses to negative feedback or errors, but the underlying neural substrates remain unknown. We hypothesized that abnormal reactions to error would be associated with dysfunctional rostral ACC activity, a region previously implicated in error detection and evaluation of the emotional significance of events. To test this hypothesis, subjects with low and high Beck Depression Inventory (BDI) scores performed an Eriksen Flanker task. To assess whether tonic activity within the rostral ACC predicted post-error adjustments, 128-channel resting EEG data were collected before the task and analyzed with low-resolution electromagnetic tomography (LORETA) using a region-of-interest approach. High BDI subjects were uniquely characterized by significantly lower accuracy after incorrect than correct trials. Mirroring the behavioral findings, high BDI subjects had significantly reduced pretask gamma (36.5-44 Hz) current density within the affective (rostral; BA24, BA25, BA32) but not cognitive (dorsal; BA24', BA32') ACC subdivision. For low, but not high, BDI subjects pretask gamma within the affective ACC subdivision predicted post-error adjustments even after controlling for activity within the cognitive ACC subdivision. Abnormal responses to errors may thus arise due to lower activity within regions subserving affective and/or motivational responses to salient cues. Because rostral ACC regions have been implicated in treatment response in depression, our findings provide initial insight into putative mechanisms fostering treatment response.
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This article assessed whether resting electroencephalographic (EEG) asymmetry in anterior regions of the brain can predict affective responses to emotion elicitors. Baseline EEG was recorded from 32 female adults, after which Ss viewed film clips preselected to elicit positive or negative affect. Resting alpha power asymmetry in the frontal region significantly predicted self-reported global negative affect in response to clips and predicted the difference between global positive and negative affect. Analyses of discrete emotions revealed a strong relation between frontal asymmetry and fear responses to films. Effects were independent of Ss mood ratings at the time at which baseline EEG was measured. Resting anterior asymmetry may be a state-independent index of the individual's predisposition to respond affectively.
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Resting respiratory sinus arrhythmia (RSAREST) indexes important aspects of individual differences in emotionality. In the present investigation, the authors address whether RSAREST is associated with tonic positive or negative emotionality, and whether RSAREST relates to phasic emotional responding to discrete positive emotion-eliciting stimuli. Across an 8-month, multiassessment study of first-year university students (n = 80), individual differences in RSAREST were associated with positive but not negative tonic emotionality, assessed at the level of personality traits, long-term moods, the disposition toward optimism, and baseline reports of current emotional states. RSAREST was not related to increased positive emotion, or stimulus-specific emotion, in response to compassion-, awe-, or pride-inducing stimuli. These findings suggest that resting RSA indexes aspects of a person's tonic positive emotionality.
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Several different models postulate that depression is associated with decreased approach-related behavior. Relatively little has been done to date to specifically investigate this issue. In the present study, a signal-detection analysis was used to examine the response biases of dysphoric and nondysphoric female undergraduates during 3 payoff conditions: neutral, reward, and punishment. As predicted, the dysphoric subjects had a smaller change in bias from the neutral to the reward condition compared with the nondysphoric group. The 2 groups did not differ during the neutral and punishment conditions. These findings are consistent with the hypothesis that the left frontal hypoactivation observed in depression reflects a deficit in approach-related behavior.
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Although several studies have examined anterior asymmetric brain electrical activity and cortisol in infants, children, and adults, the direct association between asymmetry and cortisol has not systematically been reported. In nonhuman primates, greater relative right anterior activation has been associated with higher cortisol levels. The current study examines the relation between frontal electroencephalographic (EEG) asymmetry and cortisol (basal and reactive) and withdrawal-related behaviors (fear and sadness) in 6-month-old infants. As predicted, the authors found that higher basal and reactive cortisol levels were associated with extreme right EEG asymmetry. EEG during the withdrawal-negative affect task was associated with fear and sadness behaviors. Results are interpreted in the context of the previous primate work, and some putative mechanisms are discussed.
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Drawing on recent claims in the study of relationships, attachment, and emotion, the authors hypothesized that romantic love serves a commitment-related function and sexual desire a reproduction-related function. Consistent with these claims, in Study 1, brief experiences of romantic love and sexual desire observed in a 3-min interaction between romantic partners were related to distinct feeling states, distinct nonverbal displays, and commitment- and reproductive-related relationship outcomes, respectively. In Study 2, the nonverbal display of romantic love was related to the release of oxytocin. Discussion focuses on the place of romantic love and sexual desire in the literature on emotion.
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This brief commentary highlights seven sins in the study of emotion that are explicitly treated in contemporary affective neuroscience. These sins are (1) Affect and cognition are subserved by separate and independent neural circuits; (2) Affect is subcortical; (3) Emotions are in the head; (4) Emotions can be studied from a purely psychological perspective; (5) Emotions are similar in structure across age and species; (6) Specific emotions are instantiated in discrete locations in the brain; and (7) Emotions are conscious feeling states. Each of these is briefly discussed and evidence from affective neuroscience that bears on these sins is noted. The articles in this Special Issue underscore the vitality of research in affective neuroscience and illustrate how some of these sins can be addressed and rectified using concepts and methods from affective neuroscience.
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This paper reports three studies showing sex differences in EEG asymmetry during self-generated cognitive and affective tasks. In the first experiment, bilateral EEG, quantified for alpha on-line, was recorded from right-handed subjects while they either whistled, sang or recited lyrics of familiar songs. The results revealed significant asymmetry between the whistle and talk conditions only for subjects with no familial left-handedness and, within this group, only for females and not for males. In the second experiment, bilateral EEG was recorded while right-handed subjects (with no familial left-handedness) self-induced covert affective and non-affective states. Results revealed significantly greater relative right-hemisphere activation during emotion versus non-emotion trials only in females; males showed no significant task-dependent shifts in asymmetry between conditions. The third experiment was designed to test the hypothesis that females show greater percent time asymmetry than males during biofeedback training for symmetrical and asymmetrical EEG patterns. Results confirmed this prediction as well as indicating that females show better control of such asymmetrical cortical patterning. These findings provide new neuropsychological support for the hypothesis of greater bilateral flexibility in females during self-generation tasks.
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The development of functional neuroimaging of emotion holds the promise to enhance our understanding of the biological bases of affect and improve our knowledge of psychiatric diseases. However, up to this point, researchers have been unable to objectively, continuously and unobtrusively measure the intensity and dynamics of affect concurrently with functional magnetic resonance imaging (fMRI). This has hindered the development and generalizability of our field. Facial electromyography (EMG) is an objective, reliable, valid, sensitive, and unobtrusive measure of emotion. Here, we report the successful development of a method for simultaneously acquiring fMRI and facial EMG. The ability to simultaneously acquire brain activity and facial physiology will allow affective neuroscientists to address theoretical, psychiatric, and individual difference questions in a more rigorous and generalizable way.
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OBJECTIVE: To test the hypothesis that socioeconomic status (SES) would be associated with sleep quality measured objectively, even after controlling for related covariates (health status, psychosocial characteristics). Epidemiological studies linking SES and sleep quality have traditionally relied on self-reported assessments of sleep.
METHODS: Ninety-four women, 61 to 90 years of age, participated in this study. SES was determined by pretax household income and years of education. Objective and subjective assessments of sleep quality were obtained using the NightCap sleep system and the Pittsburgh Sleep Quality Index (PSQI), respectively. Health status was determined by subjective health ratings and objective measures of recent and chronic illnesses. Depressive symptoms and neuroticism were quantified using the Center for Epidemiological Studies Depression Scale and the Neuroticism subscale of the NEO Personality Inventory, respectively.
RESULTS: Household income significantly predicted sleep latency and sleep efficiency even after adjusting for demographic factors, health status, and psychosocial characteristics. Income also predicted PSQI scores, although this association was significantly attenuated by inclusion of neuroticism in multivariate analyses. Education predicted both sleep latency and sleep efficiency, but the latter association was partially reduced after health status and psychosocial measures were included in analyses. Education predicted PSQI sleep efficiency component scores, but not global scores.
CONCLUSIONS: These results suggest that SES is robustly linked to both subjective and objective sleep quality, and that health status and psychosocial characteristics partially explain these associations.
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Although tantrums are among the most common behavioral problems of young children and may predict future antisocial behavior, little is known about them. To develop a model of this important phenomenon of early childhood, behaviors reported in parental narratives of the tantrums of 335 children aged 18 to 60 months were encoded as present or absent in consecutive 30-second periods. Principal Component (PC) analysis identified Anger and Distress as major, independent emotional and behavioral tantrum constituents. Anger-related behaviors formed PCs at three levels of intensity. High-intensity anger decreased with age, and low-intensity anger increased. Distress, the fourth PC, consisted of whining, crying, and comfort-seeking. Coping Style, the fifth PC, had high but opposite loadings on dropping down and running away, possibly reflecting the tendency to either "submit" or "escape." Model validity was indicated by significant correlations of the PCs with tantrum variables that were, by design, not included in the PC analysis.
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