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Individuals who experience early adversity, such as child maltreatment, are at heightened risk for a broad array of social and health difficulties. However, little is known about how this behavioral risk is instantiated in the brain. Here we examine a neurobiological contribution to individual differences in human behavior using methodology appropriate for use with pediatric populations paired with an in-depth measure of social behavior. We show that alterations in the orbitofrontal cortex among individuals who experienced physical abuse are related to social difficulties. These data suggest a biological mechanism linking early social learning to later behavioral outcomes.
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An overview of the use of EEG to assess hemispheric differences in cognitive and affective processes is presented. Some of the advantages of using EEG to assess asymmetric hemispheric differences in the study of complex mental activity are described. Following this brief introduction, two conceptual issues which are central to studies of EEG asymmetries are introduced: (1) the distinction between hemispheric specialization and activation, and (2) the importance of rostral-caudal differences for the understanding of both specialization and activation. Three methodological issues in the use of EEG to assess hemispheric differences are then presented: (1) the use of asymmetry metrics, (2) muscle artifact, and (3) appropriate reference electrode location. Finally, some empirical examples of using EEG to assess affective and cognitive processes which illustrate these conceptual and methodological issues are described.
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OBJECTIVE: High-density EEG recording offers increased spatial resolution but requires careful consideration of how the density of electrodes affects the potentials being measured. Power differences as a function of electrode density and electrolyte spreading were examined and a method for correcting these differences was tested. METHODS: Separate EEG recordings from 8 participants were made using a high-density electrode net, first with 6 of 128 electrodes active followed by recordings with all electrodes active. For a subset of 4 participants measurements were counterbalanced with recordings made in the reversed order by drying the hair after the high-density recordings and using a fresh dry electrode net of the same size for the low-density recordings. Mean power values over 6 resting eyes open/closed EEG recordings at the 6 active electrodes common to both recording conditions were compared. Evidence for possible electrolyte spreading or bridging between electrodes was acquired by computing Hjorth electrical distances. Spherical spline interpolation was tested for correcting power values at electrodes affected by electrolyte spreading for these participants and for a subset of participants from a larger previous study. RESULTS: For both the complete set and the counterbalanced subset, significant decreases in power at the 6 common electrodes for the high-density recordings were observed across the range of the standard EEG bands (1-44 Hz). The number of bridges or amount of electrolyte spreading towards the reference electrode as evidenced by small Hjorth electrical distances served as a predictor of this power decrease. Spherical spline interpolation increased the power values at electrodes affected by electrolyte spreading and by a significant amount for the larger number of participants in the second group. CONCLUSIONS: Understanding signal effects caused by closely spaced electrodes, detecting electrolyte spreading and correcting its effects are important considerations for high-density EEG recordings. A combination of scalp maps of power density and plots of small Hjorth electrical distances can be used to identify electrodes affected by electrolyte spreading. Interpolation using spherical splines offers a method for correcting the potentials measured at these electrodes.
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<p>A school-based program of mindful awareness practices (MAPs) was evaluated in a randomized control study of 64 second- and third-grade children ages 7–9 years. The program was delivered for 30 minutes, twice per week, for 8 weeks. Teachers and parents completed questionnaires assessing children's executive function immediately before and following the 8-week period. Multivariate analysis of covariance on teacher and parent reports of executive function (EF) indicated an interaction effect between baseline EF score and group status on posttest EF. That is, children in the MAPs group who were less well regulated showed greater improvement in EF compared with controls. Specifically, those children starting out with poor EF who went through the MAPs training showed gains in behavioral regulation, metacognition, and overall global executive control. These results indicate a stronger effect of MAPs on children with executive function difficulties. The finding that both teachers and parents reported changes suggests that improvements in children's behavioral regulation generalized across settings. Future work is warranted using neurocognitive tasks of executive functions, behavioral observation, and multiple classroom samples to replicate and extend these preliminary findings.</p>

Muscle or electromyogenic (EMG) artifact poses a serious risk to inferential validity for any electroencephalography (EEG) investigation in the frequency-domain owing to its high amplitude, broad spectrum, and sensitivity to psychological processes of interest. Even weak EMG is detectable across the scalp in frequencies as low as the alpha band. Given these hazards, there is substantial interest in developing EMG correction tools. Unfortunately, most published techniques are subjected to only modest validation attempts, rendering their utility questionable. We review recent work by our laboratory quantitatively investigating the validity of two popular EMG correction techniques, one using the general linear model (GLM), the other using temporal independent component analysis (ICA). We show that intra-individual GLM-based methods represent a sensitive and specific tool for correcting on-going or induced, but not evoked (phase-locked) or source-localized, spectral changes. Preliminary work with ICA shows that it may not represent a panacea for EMG contamination, although further scrutiny is strongly warranted. We conclude by describing emerging methodological trends in this area that are likely to have substantial benefits for basic and applied EEG research.
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The authors present an overview of the neural bases of emotion. They underscore the role of the prefrontal cortex (PFC) and amygdala in 2 broad approach- and withdrawal-related emotion systems. Components and measures of affective style are identified. Emphasis is given to affective chronometry and a role for the PFC in this process is proposed. Plasticity in the central circuitry of emotion is considered, and implications of data showing experience-induced changes in the hippocampus for understanding psychopathology and stress-related symptoms are discussed. Two key forms of affective plasticity are described--context and regulation. A role for the hippocampus in context-dependent normal and dysfunctional emotional responding is proposed. Finally, implications of these data for understanding the impact on neural circuitry of interventions to promote positive affect and on mechanisms that govern health and disease are considered.
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BACKGROUND: Relationships between aberrant social functioning and depression have been explored via behavioral, clinical, and survey methodologies, highlighting their importance in the etiology of depression. The neural underpinnings of these relationships, however, have not been explored. METHODS: Nine depressed participants and 14 never-depressed control subjects viewed emotional and neutral pictures at two functional magnetic resonance imaging (fMRI) scanning sessions approximately 22 weeks apart. In the interim, depressed patients received the antidepressant Venlafaxine. Positively rated images were parsed into three separate comparisons: social interaction, human faces, and sexual images; across scanning session, activation to these images was compared with other positively rated images. RESULTS: For each of the three social stimulus types (social interaction, faces, sexual images), a distinguishable circuitry was activated equally in non-depressed control subjects and post-treatment depressed subjects but showed a hypo-response in the depressed group pre-treatment. These structures include regions of prefrontal, temporal, and parietal cortices, insula, basal ganglia, and the hippocampus. CONCLUSIONS: The neural hypo-response to positively valenced social stimuli that is observed in depression remits as response to antidepressant medication occurs, suggesting a state-dependent deficiency in response to positive social incentives. These findings underscore the importance of addressing social dysfunction in research and treatment of depression.
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Metacognition refers to any knowledge or cognitive process that monitors or controls cognition. We highlight similarities between metacognitive and executive control functions, and ask how these processes might be implemented in the human brain. A review of brain imaging studies reveals a circuitry of attentional networks involved in these control processes, with its source located in midfrontal areas. These areas are active during conflict resolution, error correction, and emotional regulation. A developmental approach to the organization of the anatomy involved in executive control provides an added perspective on how these mechanisms are influenced by maturation and learning, and how they relate to metacognitive activity.

BACKGROUND: Two core characteristics of pathologic fear are its rapid onset and resistance to cognitive regulation. We hypothesized that activation of the amygdala early in the presentation of fear-relevant visual stimuli would distinguish phobics from nonphobics. METHODS: Chronometry of amygdala activation to phobia-relevant pictures was assessed in 13 spider phobics and 14 nonphobics using functional magnetic resonance imaging (fMRI). RESULTS: Blood oxygen level-dependent (BOLD) responses in the amygdala early in picture processing consistently differentiated between phobic and nonphobic subjects, as well as between phobogenic and nonphobogenic stimuli among phobics. Furthermore, amygdalar BOLD responses associated with timing but not magnitude of activation predicted affective responses to phobogenic stimuli. Computational modeling procedures were used to identify patterns of neural activation in the amygdala that could yield the observed BOLD data. These data suggest that phobic responses were characterized by strong but brief amygdala responses, whereas nonphobic responses were weaker and more sustained. CONCLUSIONS: Results are discussed in the context of the amygdala's role in rapid threat detection and the vigilance-avoidance hypothesis of anxiety. These data highlight the importance of examining the neural substrates of the immediate impact of phobogenic stimuli for understanding pathological fear.
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The LASS theory proposes that Language and Situated Simulation both play central roles in conceptual processing. Depending on stimuli and task conditions, different mixtures of language and simulation occur. When a word is processed in a conceptual task, it first activates other linguistic forms, such as word associates. More slowly, the word activates a situated simulation to represent its meaning in neural systems for perception, action, and mental states. An fMRI experiment tested the LASS account. In a first scanning session, participants performed the property generation task to provide a measure of conceptual processing. In a second scanning session a week later, participants performed two localizer tasks measuring word association and situated simulation. Conjunction analyses supported predictions of the LASS theory. Activations early in conceptual processing overlapped with activations for word association. Activations late in conceptual processing overlapped with activations for situation generation. These results, along with others in the literature, indicate that conceptual processing uses multiple representations, not one. Furthermore, researchers must be careful drawing conclusions about conceptual processing, given that different paradigms are likely to produce different mixtures of language and simulation. Whereas some paradigms produce high levels of linguistic processing and low levels of simulation, other paradigms produce the opposite pattern.
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Previous research indicates that drug motivational systems are instantiated in structures that process information related to incentive, motivational drive, memorial, motor/habit, craving, and cognitive control processing. The present research tests the hypothesis that activity in such systems will be powerfully affected by the combination of drug anticipation and drug withdrawal. Event-related fMRI was used to examine activation in response to a preinfusion warning cue in two experimental sessions that manipulated withdrawal status. Significant cue-induced effects were seen in the caudate, ventral anterior nucleus of the thalamus, the insula, subcallosal gyrus, nucleus accumbens, and anterior cingulate. These results suggest that withdrawal and nicotine anticipation produce (1) different motor preparatory and inhibitory response processing and (2) different craving related processing.
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The influence of approach and avoidance tendencies on affect, reasoning, and behavior has attracted substantial interest from researchers across various areas of psychology. Currently, frontal electroencephalographic (EEG) asymmetry in favor of left prefrontal regions is assumed to reflect the propensity to respond with approach-related tendencies. To test this hypothesis, we recorded resting EEG in 18 subjects, who separately performed a verbal memory task under three incentive conditions (neutral, reward, and punishment). Using a source-localization technique, we found that higher task-independent alpha2 (10.5-12 Hz) activity within left dorsolateral prefrontal and medial orbitofrontal regions was associated with stronger bias to respond to reward-related cues. Left prefrontal resting activity accounted for 54.8% of the variance in reward bias. These findings not only confirm that frontal EEG asymmetry modulates the propensity to engage in appetitively motivated behavior, but also provide anatomical details about the underlying brain systems.
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Examined whether certain features of infant temperament might be related to individual differences in the asymmetry of resting frontal activation. EEG was recorded from the left and right frontal and parietal scalp regions of 13 normal 10-month-old infants. Infant behavior was then observed during a brief period of maternal separation. Those infants who cried in response to maternal separation showed greater right frontal activation during the preceding baseline period compared with infants who did not cry. Frontal activation asymmetry may be a state-independent marker for individual differences in threshold of reactivity to stressful events and vulnerability to particular emotions.
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Major depression is a heterogeneous condition, and the search for neural correlates specific to clinically defined subtypes has been inconclusive. Theoretical considerations implicate frontostriatal, particularly subgenual prefrontal cortex (PFC), dysfunction in the pathophysiology of melancholia--a subtype of depression characterized by anhedonia--but no empirical evidence has been found yet for such a link. To test the hypothesis that melancholic, but not nonmelancholic depression, is associated with the subgenual PFC impairment, concurrent measurement of brain electrical (electroencephalogram, EEG) and metabolic (positron emission tomography, PET) activity were obtained in 38 unmedicated subjects with DSM-IV major depressive disorder (20 melancholic, 18 nonmelancholic subjects), and 18 comparison subjects. EEG data were analyzed with a tomographic source localization method that computed the cortical three-dimensional distribution of current density for standard frequency bands, allowing voxelwise correlations between the EEG and PET data. Voxel-based morphometry analyses of structural magnetic resonance imaging (MRI) data were performed to assess potential structural abnormalities in melancholia. Melancholia was associated with reduced activity in the subgenual PFC (Brodmann area 25), manifested by increased inhibitory delta activity (1.5-6.0 Hz) and decreased glucose metabolism, which themselves were inversely correlated. Following antidepressant treatment, depressed subjects with the largest reductions in depression severity showed the lowest post-treatment subgenual PFC delta activity. Analyses of structural MRI revealed no group differences in the subgenual PFC, but in melancholic subjects, a negative correlation between gray matter density and age emerged. Based on preclinical evidence, we suggest that subgenual PFC dysfunction in melancholia may be associated with blunted hedonic response and exaggerated stress responsiveness.
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The relationships between brain electrical and metabolic activity are being uncovered currently in animal models using invasive methods; however, in the human brain this relationship remains not well understood. In particular, the relationship between noninvasive measurements of electrical activity and metabolism remains largely undefined. To understand better these relations, cerebral activity was measured simultaneously with electroencephalography (EEG) and positron emission tomography using [(18)f]-fluoro-2-deoxy-D-glucose (PET-FDG) in 12 normal human subjects during rest. Intracerebral distributions of current density were estimated, yielding tomographic maps for seven standard EEG frequency bands. The PET and EEG data were registered to the same space and voxel dimensions, and correlational maps were created on a voxel-by-voxel basis across all subjects. For each band, significant positive and negative correlations were found that are generally consistent with extant understanding of EEG band power function. With increasing EEG frequency, there was an increase in the number of positively correlated voxels, whereas the lower alpha band (8.5-10.0 Hz) was associated with the highest number of negative correlations. This work presents a method for comparing EEG signals with other more traditionally tomographic functional imaging data on a 3-D basis. This method will be useful in the future when it is applied to functional imaging methods with faster time resolution, such as short half-life PET blood flow tracers and functional magnetic resonance imaging.
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<p>BACKGROUND: Functional magnetic resonance imaging (fMRI) techniques were used to identify the neural circuitry underlying emotional processing in control and depressed subjects. Depressed subjects were studied before and after treatment with venlafaxine. This new technique provides a method to noninvasively image regional brain function with unprecedented spatial and temporal resolution. METHOD: Echo-planar imaging was used to acquire whole brain images while subjects viewed positively and negatively valenced visual stimuli. Two control subjects and two depressed subjects who met DSM-IV criteria for major depression were scanned at baseline and 2 weeks later. Depressed subjects were treated with venlafaxine after the baseline scan. RESULTS: Preliminary results from this ongoing study revealed three interesting trends in the data. Both depressed patients demonstrated considerable symptomatic improvement at the time of the second scan. Across control and depressed subjects, the negative compared with the positive pictures elicited greater global activation. In both groups, activation induced by the negative pictures decreased from the baseline scan to the 2-week scan. This decrease in activation was also present in the control subjects when they were exposed to the positive pictures. In contrast, when the depressed subjects were presented with the positive pictures they showed no activation at baseline, whereas after 2 weeks of treatment an area of activation emerged in right secondary visual cortex. CONCLUSION: While preliminary, these results demonstrate the power of using fMRI to study emotional processes in normal and depressed subjects and to examine mechanisms of action of antidepressant drugs.</p>
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The development of social emotions such as compassion is crucial for successful social interactions as well as for the maintenance of mental and physical health, especially when confronted with distressing life events. Yet, the neural mechanisms supporting the training of these emotions are poorly understood. To study affective plasticity in healthy adults, we measured functional neural and subjective responses to witnessing the distress of others in a newly developed task (Socio-affective Video Task). Participants’ initial empathic responses to the task were accompanied by negative affect and activations in the anterior insula and anterior medial cingulate cortex—a core neural network underlying empathy for pain. Whereas participants reacted with negative affect before training, compassion training increased positive affective experiences, even in response to witnessing others in distress. On the neural level, we observed that, compared with a memory control group, compassion training elicited activity in a neural network including the medial orbitofrontal cortex, putamen, pallidum, and ventral tegmental area—brain regions previously associated with positive affect and affiliation. Taken together, these findings suggest that the deliberate cultivation of compassion offers a new coping strategy that fosters positive affect even when confronted with the distress of others.
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The capacity to anticipate aversive circumstances is central not only to successful adaptation but also to understanding the abnormalities that contribute to excessive worry and anxiety disorders. Forecasting and reacting to aversive events mobilize a host of affective and cognitive capacities and corresponding brain processes. Rapid event-related functional magnetic resonance imaging (fMRI) in 21 healthy volunteers assessed the overlap and divergence in the neural instantiation of anticipating and being exposed to aversive pictures. Brain areas jointly activated by the anticipation of and exposure to aversive pictures included the dorsal amygdala, anterior insula, dorsal anterior cingulate cortex (ACC), right dorsolateral prefrontal cortex (DLPFC), and right posterior orbitofrontal cortex (OFC). Anticipatory processes were uniquely associated with activations in rostral ACC, a more superior sector of the right DLPFC, and more medial sectors of the bilateral OFC. Activation of the right DLPFC in anticipation of aversion was associated with self-reports of increased negative affect, whereas OFC activation was associated with increases in both positive and negative affect. These results show that anticipation of aversion recruits key brain regions that respond to aversion, thereby potentially enhancing adaptive responses to aversive events.
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BACKGROUND: The broad autism phenotype includes subclinical autistic characteristics found to have a higher prevalence in unaffected family members of individuals with autism. These characteristics primarily affect the social aspects of language, communication, and human interaction. The current research focuses on possible neurobehavioral characteristics associated with the broad autism phenotype. METHODS: We used a face-processing task associated with atypical patterns of gaze fixation and brain function in autism while collecting brain functional magnetic resonance imaging (fMRI) and eye tracking in unaffected siblings of individuals with autism. RESULTS: We found robust differences in gaze fixation and brain function in response to images of human faces in unaffected siblings compared with typically developing control individuals. The siblings' gaze fixations and brain activation patterns during the face processing task were similar to that of the autism group and showed decreased gaze fixation along with diminished fusiform activation compared with the control group. Furthermore, amygdala volume in the siblings was similar to the autism group and was significantly reduced compared with the control group. CONCLUSIONS: Together, these findings provide compelling evidence for differences in social/emotional processing and underlying neural circuitry in siblings of individuals with autism, supporting the notion of unique endophenotypes associated with the broad autism phenotype.
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Recent studies have identified a distributed network of brain regions thought to support cognitive reappraisal processes underlying emotion regulation in response to affective images, including parieto-temporal regions and lateral/medial regions of prefrontal cortex (PFC). A number of these commonly activated regions are also known to underlie visuospatial attention and oculomotor control, which raises the possibility that people use attentional redeployment rather than, or in addition to, reappraisal as a strategy to regulate emotion. We predicted that a significant portion of the observed variance in brain activation during emotion regulation tasks would be associated with differences in how participants visually scan the images while regulating their emotions. We recorded brain activation using fMRI and quantified patterns of gaze fixation while participants increased or decreased their affective response to a set of affective images. fMRI results replicated previous findings on emotion regulation with regulation differences reflected in regions of PFC and the amygdala. In addition, our gaze fixation data revealed that when regulating, individuals changed their gaze patterns relative to a control condition. Furthermore, this variation in gaze fixation accounted for substantial amounts of variance in brain activation. These data point to the importance of controlling for gaze fixation in studies of emotion regulation that use visual stimuli.
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Although there are many imaging studies on traditional ROI-based amygdala volumetry, there are very few studies on modeling amygdala shape variations. This paper presents a unified computational and statistical framework for modeling amygdala shape variations in a clinical population. The weighted spherical harmonic representation is used to parameterize, smooth out, and normalize amygdala surfaces. The representation is subsequently used as an input for multivariate linear models accounting for nuisance covariates such as age and brain size difference using the SurfStat package that completely avoids the complexity of specifying design matrices. The methodology has been applied for quantifying abnormal local amygdala shape variations in 22 high functioning autistic subjects.
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The prefrontal cortex (PFC) has been well known for its role in higher order cognition, affect regulation and social reasoning. Although the precise underpinnings have not been sufficiently described, increasing evidence also supports a prefrontal involvement in the regulation of the hypothalamus-pituitary-adrenal (HPA) axis. Here we investigate the PFC's role in HPA axis regulation during a psychosocial stress exposure in 14 healthy humans. Regional brain metabolism was assessed using positron emission tomography (PET) and injection of fluoro-18-deoxyglucose (FDG). Depending on the exact location within the PFC, increased glucose metabolic rate was associated with lower or higher salivary cortisol concentration in response to a psychosocial stress condition. Metabolic glucose rate in the rostral medial PFC (mPFC) (Brodman area (BA) 9 and BA 10) was negatively associated with stress-induced salivary cortisol increases. Furthermore, metabolic glucose rate in these regions was inversely coupled with changes in glucose metabolic rate in other areas, known to be involved in HPA axis regulation such as the amygdala/hippocampal region. In contrast, metabolic glucose rate in areas more lateral to the mPFC was positively associated with saliva cortisol. Subjective ratings on task stressfulness, task controllability and self-reported dispositional mood states also showed positive and negative associations with the glucose metabolic rate in prefrontal regions. These findings suggest that in humans, the PFC is activated in response to psychosocial stress and distinct prefrontal metabolic glucose patterns are linked to endocrine stress measures as well as subjective ratings on task stressfulness, controllability as well as dispositional mood states.
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According to the Conceptual Act Theory of Emotion, the situated conceptualization used to construe a situation determines the emotion experienced. A neuroimaging experiment tested two core hypotheses of this theory: (1) different situated conceptualizations produce different forms of the same emotion in different situations, (2) the composition of a situated conceptualization emerges from shared multimodal circuitry distributed across the brain that produces emotional states generally. To test these hypotheses, the situation in which participants experienced an emotion was manipulated. On each trial, participants immersed themselves in a physical danger or social evaluation situation and then experienced fear or anger. According to Hypothesis 1, the brain activations for the same emotion should differ as a function of the preceding situation (after removing activations that arose while constructing the situation). According to Hypothesis 2, the critical activations should reflect conceptual processing relevant to the emotion in the current situation, drawn from shared multimodal circuitry underlying emotion. The results supported these predictions and demonstrated the compositional process that produces situated conceptualizations dynamically.
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