BACKGROUND: Hypothalamic-pituitary-adrenal (HPA) system activation is adaptive in response to stress, and HPA dysregulation occurs in stress-related psychopathology. It is important to understand the mechanisms that modulate HPA output, yet few studies have addressed the neural circuitry associated with HPA regulation in primates and humans. Using high-resolution F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) in rhesus monkeys, we assessed the relation between individual differences in brain activity and HPA function across multiple contexts that varied in stressfulness.
METHODS: Using a logical AND conjunctions analysis, we assessed cortisol and brain metabolic activity with FDG-PET in 35 adolescent rhesus monkeys exposed to two threat and two home-cage conditions. To test the robustness of our findings, we used similar methods in an archival data set. In this data set, brain metabolic activity and cortisol were assessed in 17 adolescent male rhesus monkeys that were exposed to three stress-related contexts.
RESULTS: Results from the two studies revealed that subgenual prefrontal cortex (PFC) metabolism (Brodmann's area 25/24) consistently predicted individual differences in plasma cortisol concentrations regardless of the context in which brain activity and cortisol were assessed.
CONCLUSIONS: These findings suggest that activation in subgenual PFC may be related to HPA output across a variety of contexts (including familiar settings and novel or threatening situations). Individuals prone to elevated subgenual PFC activity across multiple contexts may be individuals who consistently show heightened cortisol and may be at risk for stress-related HPA dysregulation.
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Background Mindfulness Based Stress Reduction (MBSR) is a secular form of meditation training. The vast majority of the extant literature investigating the health effects of mindfulness interventions relies on wait-list control comparisons. Previous studies have found that meditation training over several months is associated with improvements in cognitive control and attention. Methodology/Principal Findings We used a visual continuous performance task (CPT) to test the effects of eight weeks of mindfulness training on sustained attention by comparing MBSR to the Health Enhancement Program (HEP), a structurally equivalent, active control condition in a randomized, longitudinal design (ClinicalTrials.gov, NCT01301105) focusing on a non-clinical population typical of MBSR participants. Researchers were blind to group assignment. 63 community participants were randomized to either MBSR (n = 31) or HEP (n = 32). CPT analyses were conducted on 29 MBSR participants and 25 HEP participants. We predicted that MBSR would improve visual discrimination ability and sustained attention over time on the CPT compared to HEP, with more home practice associated with greater improvements. Our hypotheses were not confirmed but we did find some evidence for improved visual discrimination similar to effects in partial replication of other research. Our study had sufficient power to demonstrate that intervention groups do not differ in their improvement over time in sustained attention performance. One of our primary predictions concerning the effects of intervention on attentional fatigue was significant but not interpretable. Conclusions Attentional sensitivity is not affected by mindfulness practice as taught in MBSR, but it is unclear whether mindfulness might positively affect another aspect of attention, vigilance. These results also highlight the relevant procedural modifications required by future research to correctly investigate the role of sustained attention in similar samples. Trial Registration ClinicalTrials.gov, NCT01301105
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Eudaimonic well-being—a sense of purpose, meaning, and engagement with life—is protective against psychopathology and predicts physical health, including lower levels of the stress hormone cortisol. Although it has been suggested that the ability to engage the neural circuitry of reward may promote well-being and mediate the relationship between well-being and health, this hypothesis has remained untested. To test this hypothesis, we had participants view positive, neutral, and negative images while fMRI data were collected. Individuals with sustained activity in the striatum and dorsolateral prefrontal cortex to positive stimuli over the course of the scan session reported greater well-being and had lower cortisol output. This suggests that sustained engagement of reward circuitry in response to positive events underlies well-being and adaptive regulation of the hypothalamic-pituitary-adrenal axis.
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Synaptic Self How Our Brains Become Who We Are. Joseph LeDoux. Viking, New York, 2002. 416 pp. $29.95, C$43.99. ISBN 0-670-03028-7.
LeDoux combines perspectives from neuroscience, philosophy, literature, and the history of science to explain how human personalities are created by our brains (and, in particular, by the synaptic connectivity within them).
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<p>It is important to identify effective non-pharmacological alternatives to stimulant medications that reduce symptoms of attention deficit hyperactivity disorder (ADHD). In this study of healthy young adults, we measured the effects of training in tai chi, which involves mindful attention to the body during movement. Using a non-randomized, controlled, parallel design, students in a 15-week introductory tai chi course (n = 28) and control participants (n = 44) were tested for ADHD indicators and cognitive function at three points over the course of the 15-weeks. The tai chi students' self-report of attention, but not hyperactivity-impulsivity, improved compared to controls. At baseline, inattention correlated positively with reaction time variability in an affective go/no-go task across all participants, and improvements in attention correlated with reductions in reaction time variability across the tai chi students. Affective bias changed in the tai chi students, as reaction times to positive- and negative-valenced words equalized over time. These results converge to suggest that tai chi training may help improve attention in healthy young adults. Further studies are needed to confirm these results and to evaluate tai chi as therapy for individuals with ADHD.</p>
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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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This article completes the analysis of parental narratives of tantrums had by 335 children aged 18 to 60 months. Modal tantrum durations were 0.5 to 1 minute; 75% of the tantrums lasted 5 minutes or less. If the child stamped or dropped to the floor in the first 30 seconds, the tantrum was likely to be shorter and the likelihood of parental intervention less. A novel analysis of behavior probabilities that permitted grouping of tantrums of different durations converged with our previous statistically independent results to yield a model of tantrums as the expression of two independent but partially overlapping emotional and behavioral processes: Anger and Distress. Anger rises quickly, has its peak at or near the beginning of the tantrum, and declines thereafter. Crying and comfort-seeking, components of Distress, slowly increase in probability across the tantrum. This model indicates that tantrums can provide a window on the intense emotional processes of childhood.
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An individual's affective style is influenced by many things, including the manner in which an individual responds to an emotional challenge. Emotional response is composed of a number of factors, two of which are the initial reactivity to an emotional stimulus and the subsequent recovery once the stimulus terminates or ceases to be relevant. However, most neuroimaging studies examining emotional processing in humans focus on the magnitude of initial reactivity to a stimulus rather than the prolonged response. In this study, we use functional magnetic resonance imaging to study the time course of amygdala activity in healthy adults in response to presentation of negative images. We split the amygdala time course into an initial reactivity period and a recovery period beginning after the offset of the stimulus. We find that initial reactivity in the amygdala does not predict trait measures of affective style. Conversely, amygdala recovery shows predictive power such that slower amygdala recovery from negative images predicts greater trait neuroticism, in addition to lower levels of likability of a set of social stimuli (neutral faces). These data underscore the importance of taking into account temporal dynamics when studying affective processing using neuroimaging.
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We present a new tensor-based morphometric framework that quantifies cortical shape variations using a local area element. The local area element is computed from the Riemannian metric tensors, which are obtained from the smooth functional parametrization of a cortical mesh. For the smooth parametrization, we have developed a novel weighted spherical harmonic (SPHARM) representation, which generalizes the traditional SPHARM as a special case. For a specific choice of weights, the weighted-SPHARM is shown to be the least squares approximation to the solution of an isotropic heat diffusion on a unit sphere. The main aims of this paper are to present the weighted-SPHARM and to show how it can be used in the tensor-based morphometry. As an illustration, the methodology has been applied in the problem of detecting abnormal cortical regions in the group of high functioning autistic subjects.
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Despite growing interest in emotion regulation, the degree to which psychophysiological measures of emotion regulation are stable over time remains unknown. We examined four-week test-retest reliability of corrugator electromyographic and eyeblink startle measures of negative emotion and its regulation. Both measures demonstrated similar sensitivity to the emotion manipulation, but only individual differences in corrugator modulation and regulation showed adequate reliability. Startle demonstrated diminished sensitivity to the regulation instructions across assessments and poor reliability. This suggests that corrugator represents a trait-like measure of voluntary emotion regulation, whereas startle should be used with caution for assessing individual differences. The data also suggest that corrugator and startle might index partially dissociable constructs and underscore the need to collect multiple measures of emotion.
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The information processing capacity of the human mind is limited, as is evidenced by the attentional blink—a deficit in identifying the second of two targets (T1 and T2) presented in close succession. This deficit is thought to result from an overinvestment of limited resources in T1 processing. We previously reported that intensive mental training in a style of meditation aimed at reducing elaborate object processing, reduced brain resource allocation to T1, and improved T2 accuracy [Slagter, H. A., Lutz, A., Greischar, L. L., Francis, A. D., Nieuwenhuis, S., Davis, J., et al. Mental training affects distribution of limited brain resources. PloS Biology, 5, e138, 2007]. Here we report EEG spectral analyses to examine the possibility that this reduction in elaborate T1 processing rendered the system more available to process new target information, as indexed by T2-locked phase variability. Intensive mental training was associated with decreased cross-trial variability in the phase of oscillatory theta activity after successfully detected T2s, in particular, for those individuals who showed the greatest reduction in brain resource allocation to T1. These data implicate theta phase locking in conscious target perception, and suggest that after mental training the cognitive system is more rapidly available to process new target information. Mental training was not associated with changes in the amplitude of T2-induced responses or oscillatory activity before task onset. In combination, these findings illustrate the usefulness of systematic mental training in the study of the human mind by revealing the neural mechanisms that enable the brain to successfully represent target information.
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The information processing capacity of the human mind is limited, as is evidenced by the attentional blink-a deficit in identifying the second of two targets (T1 and T2) presented in close succession. This deficit is thought to result from an overinvestment of limited resources in T1 processing. We previously reported that intensive mental training in a style of meditation aimed at reducing elaborate object processing, reduced brain resource allocation to T1, and improved T2 accuracy [Slagter, H. A., Lutz, A., Greischar, L. L., Francis, A. D., Nieuwenhuis, S., Davis, J., et al. Mental training affects distribution of limited brain resources. PloS Biology, 5, e138, 2007]. Here we report EEG spectral analyses to examine the possibility that this reduction in elaborate T1 processing rendered the system more available to process new target information, as indexed by T2-locked phase variability. Intensive mental training was associated with decreased cross-trial variability in the phase of oscillatory theta activity after successfully detected T2s, in particular, for those individuals who showed the greatest reduction in brain resource allocation to T1. These data implicate theta phase locking in conscious target perception, and suggest that after mental training the cognitive system is more rapidly available to process new target information. Mental training was not associated with changes in the amplitude of T2-induced responses or oscillatory activity before task onset. In combination, these findings illustrate the usefulness of systematic mental training in the study of the human mind by revealing the neural mechanisms that enable the brain to successfully represent target information.
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<p>ABSTRACT: For most of this past century, scholarship on the topics of personality and emotion has emerged from the humanities and social sciences. In the past decade, a remarkable change has occurred in the influence of neuroscience on the conceptualization and study of these phenomena. This article argues that the categories that have emerged from psychiatric nosology and descriptive personality theory may be inadequate, and that new categories and dimensions derived from neuroscience research may produce a more tractable parsing of this complex domain. The article concludes by noting that the discovery of these biological differences among individuals does not imply that the origins of these differences lie in heritable influences. Experiential shaping of the brain circuitry underlying emotion is powerful. The neural architecture provides the final common pathway through which culture, social factors, and genetics all operate together.</p>
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Early theorists (Freud and Darwin) speculated that extremely shy children, or those with anxious temperament, were likely to have anxiety problems as adults. More recent studies demonstrate that these children have heightened responses to potentially threatening situations reacting with intense defensive responses that are characterized by behavioral inhibition (BI) (inhibited motor behavior and decreased vocalizations) and physiological arousal. Confirming the earlier impressions, data now demonstrate that children with this disposition are at increased risk to develop anxiety, depression, and comorbid substance abuse. Additional key features of anxious temperament are that it appears at a young age, it is a stable characteristic of individuals, and even in non-threatening environments it is associated with increased psychic anxiety and somatic tension. To understand the neural underpinnings of anxious temperament, we performed imaging studies with 18-fluoro-deoxyglucose (FDG) high-resolution Positron Emission Tomography (PET) in young rhesus monkeys. Rhesus monkeys were used because they provide a well validated model of anxious temperament for studies that cannot be performed in human children. Imaging the same animal in stressful and secure contexts, we examined the relation between regional metabolic brain activity and a trait-like measure of anxious temperament that encompasses measures of BI and pituitary-adrenal reactivity. Regardless of context, results demonstrated a trait-like pattern of brain activity (amygdala, bed nucleus of stria terminalis, hippocampus, and periaqueductal gray) that is predictive of individual phenotypic differences. Importantly, individuals with extreme anxious temperament also displayed increased activity of this circuit when assessed in the security of their home environment. These findings suggest that increased activity of this circuit early in life mediates the childhood temperamental risk to develop anxiety and depression. In addition, the findings provide an explanation for why individuals with anxious temperament have difficulty relaxing in environments that others perceive as non-stressful.
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The experience of pain occurs when the level of a stimulus is sufficient to elicit a marked affective response, putatively to warn the organism of potential danger and motivate appropriate behavioral responses. Understanding the biological mechanisms of the transition from innocuous to painful levels of sensation is essential to understanding pain perception as well as clinical conditions characterized by abnormal relationships between stimulation and pain response. Thus, the primary objective of this study was to characterize the neural response associated with this transition and the correspondence between that response and subjective reports of pain. Towards this goal, this study examined BOLD response profiles across a range of temperatures spanning the pain threshold. 14 healthy adults underwent functional magnetic resonance imaging (fMRI) while a range of thermal stimuli (44-49°C) were applied. BOLD responses showed a sigmoidal profile along the range of temperatures in a network of brain regions including insula and mid-cingulate, as well as a number of regions associated with motor responses including ventral lateral nuclei of the thalamus, globus pallidus and premotor cortex. A sigmoid function fit to the BOLD responses in these regions explained up to 85% of the variance in individual pain ratings, and yielded an estimate of the temperature of steepest transition from non-painful to painful heat that was nearly identical to that generated by subjective ratings. These results demonstrate a precise characterization of the relationship between objective levels of stimulation, resulting neural activation, and subjective experience of pain and provide direct evidence for a neural mechanism supporting the nonlinear transition from innocuous to painful levels along the sensory continuum.
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Planned and reflexive behaviors often occur in the presence of emotional stimuli and within the context of an individual's acute emotional state. Therefore, determining the manner in which emotion and attention interact is an important step toward understanding how we function in the real world. Participants in the current investigation viewed centrally displayed, task-irrelevant, face distractors (angry, neutral, happy) while performing a lateralized go/no-go continuous performance task. Lateralized go targets and no-go lures that did not spatially overlap with the faces were employed to differentially probe processing in the left (LH) and right (RH) cerebral hemispheres. There was a significant interaction between expression and hemisphere, with an overall pattern such that angry distractors were associated with relatively more RH inhibitory errors than neutral or happy distractors and happy distractors with relatively more LH inhibitory errors than angry or neutral distractors. Simple effects analyses confirmed that angry faces differentially interfered with RH relative to LH inhibition and with inhibition in the RH relative to happy faces. A significant three-way interaction further revealed that state anxiety moderated relations between emotional expression and hemisphere. Under conditions of low cognitive load, more intense anxiety was associated with relatively greater RH than LH impairment in the presence of both happy and threatening distractors. By contrast, under high load, only angry distractors produced greater RH than LH interference as a function of anxiety.
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OBJECTIVES: Affective neuroscience research that investigates core symptoms of pediatric bipolar disorder (PBD) may be effective in differentiating PBD phenotypes. The current study used affect-modulated startle to examine potential differences in reactivity to emotional stimuli (reward and punishment) in narrow and broad phenotype PBD and controls.
METHODS: Thirty children meeting DSM-IV bipolar disorder criteria (i.e. narrow phenotype PBD with defined manic episodes with elevated/expansive mood), 19 children meeting criteria for severe mood dysregulation (i.e. broad phenotype with chronic irritability, hyper-reactivity, and hyperarousal), and 19 controls completed a lottery startle paradigm involving reward (money) and punishment (loud noise). Startle probes were presented during anticipation of the emotional stimulus, immediately following the presentation of the stimulus, or during return to baseline following the stimulus.
RESULTS: By self-report, patients and controls found the putative punishment to be preferable to the neutral condition. In the reward condition, patient samples reported greater arousal than did controls, but no between-group differences were found on the magnitude of startle response during the reward, punishment, or neutral conditions.
CONCLUSIONS: The failure to find differences in affect-modulated startle between control children and those with narrow or broad PBD phenotypes speaks to the methodological challenges associated with studying reward mechanisms in PBD. Alternative paradigms that focus on different aspects of reward mechanisms are discussed.
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Most of the extant literature investigating the health effects of mindfulness interventions relies on wait-list control comparisons. The current article specifies and validates an active control condition, the Health Enhancement Program (HEP), thus providing the foundation necessary for rigorous investigations of the relative efficacy of Mindfulness Based Stress Reduction (MBSR) and for testing mindfulness as an active ingredient. 63 participants were randomized to either MBSR (n = 31) or HEP (n = 32). Compared to HEP, MBSR led to reductions in thermal pain ratings in the mindfulness- but not the HEP-related instruction condition (η(2) = .18). There were significant improvements over time for general distress (η(2) = .09), anxiety (η(2) = .08), hostility (η(2) = .07), and medical symptoms (η(2) = .14), but no effects of intervention. Practice was not related to change. HEP is an active control condition for MBSR while remaining inert to mindfulness. These claims are supported by results from a pain task. Participant-reported outcomes (PROs) replicate previous improvements to well-being in MBSR, but indicate that MBSR is no more effective than a rigorous active control in improving these indices. These results emphasize the importance of using an active control condition like HEP in studies evaluating the effectiveness of MBSR.
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Muscle electrical activity, or "electromyogenic" (EMG) artifact, poses a serious threat to the validity of electroencephalography (EEG) investigations in the frequency domain. EMG is sensitive to a variety of psychological processes and can mask genuine effects or masquerade as legitimate neurogenic effects across the scalp in frequencies at least as low as the alpha band (8-13 Hz). Although several techniques for correcting myogenic activity have been described, most are subjected to only limited validation attempts. Attempts to gauge the impact of EMG correction on intracerebral source models (source "localization" analyses) are rarer still. Accordingly, we assessed the sensitivity and specificity of one prominent correction tool, independent component analysis (ICA), on the scalp and in the source-space using high-resolution EEG. Data were collected from 17 participants while neurogenic and myogenic activity was independently varied. Several protocols for classifying and discarding components classified as myogenic and non-myogenic artifact (e.g., ocular) were systematically assessed, leading to the exclusion of one-third to as much as three-quarters of the variance in the EEG. Some, but not all, of these protocols showed adequate performance on the scalp. Indeed, performance was superior to previously validated regression-based techniques. Nevertheless, ICA-based EMG correction exhibited low validity in the intracerebral source-space, likely owing to incomplete separation of neurogenic from myogenic sources. Taken with prior work, this indicates that EMG artifact can substantially distort estimates of intracerebral spectral activity. Neither regression- nor ICA-based EMG correction techniques provide complete safeguards against such distortions. In light of these results, several practical suggestions and recommendations are made for intelligently using ICA to minimize EMG and other common artifacts.
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EEG and EEG source-estimation are susceptible to electromyographic artifacts (EMG) generated by the cranial muscles. EMG can mask genuine effects or masquerade as a legitimate effect-even in low frequencies, such as alpha (8-13 Hz). Although regression-based correction has been used previously, only cursory attempts at validation exist, and the utility for source-localized data is unknown. To address this, EEG was recorded from 17 participants while neurogenic and myogenic activity were factorially varied. We assessed the sensitivity and specificity of four regression-based techniques: between-subjects, between-subjects using difference-scores, within-subjects condition-wise, and within-subject epoch-wise on the scalp and in data modeled using the LORETA algorithm. Although within-subject epoch-wise showed superior performance on the scalp, no technique succeeded in the source-space. Aside from validating the novel epoch-wise methods on the scalp, we highlight methods requiring further development.
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<p>The human voice is one of the principal conveyers of social and affective communication. Yet relatively little is known about the neural circuitry that supports the recognition of different vocally expressed emotions. We conducted an FMRI study to examine the brain responses to vocal expressions of anger and happiness, and to test whether specific brain regions showed preferential engagement in the processing of one emotion over the other. We also tested the extent to which simultaneously presented facial expressions of the same or different emotions would enhance brain responses, and to what degree such responses depend on attention towards the vocal expression. Forty healthy individuals were scanned while listening to vocal expressions of anger or happiness, while at the same time watching congruent or discrepant facial expressions. Happy voices elicited significantly more activation than angry voices in right anterior and posterior middle temporal gyrus (MTG), left posterior MTG and right inferior frontal gyrus. Furthermore, for the left MTG region, happy voices were related to higher activation only when paired with happy faces. Activation in the left insula, left amygdala and hippocampus, and rostral anterior cingulate cortex showed an effect of selectively attending to the vocal stimuli. Our results identify a network of regions implicated in the processing of vocal emotion, and suggest a particularly salient role for vocal expressions of happiness.</p>
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Facial expressions of pain are an important part of the pain response, signaling distress to others and eliciting social support. To evaluate how voluntary modulation of this response contributes to the pain experience, 29 subjects were exposed to thermal stimulation while making standardized pain, control, or relaxed faces. Dependent measures were self-reported negative effect (valence and arousal) as well as the intensity of nociceptive stimulation required to reach a given subjective level of pain. No direct social feedback was given by the experimenter. Although the amount of nociceptive stimulation did not differ across face conditions, subjects reported more negative effects in response to painful stimulation while holding the pain face. Subsequent analyses suggested the effects were not due to preexisting differences in the difficulty or unpleasantness of making the pain face. These results suggest that voluntary pain expressions have no positively reinforcing (pain attenuating) qualities, at least in the absence of external contingencies such as social reinforcement, and that such expressions may indeed be associated with higher levels of negative affect in response to similar nociceptive input.
PERSPECTIVE: This study demonstrates that making a standardized pain face increases negative affect in response to nociceptive stimulation, even in the absence of social feedback. This suggests that exaggerated facial displays of pain, although often socially reinforced, may also have unintended aversive consequences.
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We used measures of regional brain electrical activity to show that not all smiles are the same. Only one form of smiling produced the physiological pattern associated with enjoyment. Our finding helps to explain why investigators who treated all smiles as the same found smiles to be ubiquitous, occurring when people are unhappy as well as happy. Also, our finding that voluntarily making two different kinds of smiles generated the same two patterns of regional brain activity as was found when these smiles occur involuntarily suggests that it is possible to generate deliberately some of the physiological change which occurs during spontaneous positive affect.
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We present a novel weighted Fourier series (WFS) representation for cortical surfaces. The WFS representation is a data smoothing technique that provides the explicit smooth functional estimation of unknown cortical boundary as a linear combination of basis functions. The basic properties of the representation are investigated in connection with a self-adjoint partial differential equation and the traditional spherical harmonic (SPHARM) representation. To reduce steep computational requirements, a new iterative residual fitting (IRF) algorithm is developed. Its computational and numerical implementation issues are discussed in detail. The computer codes are also available at http://www.stat.wisc.edu/-mchung/softwares/weighted.SPHARM/weighted-SPHARM.html. As an illustration, the WFS is applied i n quantifying the amount ofgray matter in a group of high functioning autistic subjects. Within the WFS framework, cortical thickness and gray matter density are computed and compared.
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This commentary provides reflections on the current state of affairs in research on EEG frontal asymmetries associated with affect. Although considerable progress has occurred since the first report on this topic 25 years ago, research on frontal EEG asymmetries associated with affect has largely evolved in the absence of any serious connection with neuroscience research on the structure and function of the primate prefrontal cortex (PFC). Such integration is important as this work progresses since the neuroscience literature can help to understand what the prefrontal cortex is "doing" in affective processing. Data from the neuroscience literature on the heterogeneity of different sectors of the PFC are introduced and more specific hypotheses are offered about what different sectors of the PFC might be doing in affect. A number of methodological issues associated with EEG measures of functional prefrontal asymmetries are also considered.
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