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Although the co-occurrence of negative affect and pain is well recognized, the mechanism underlying their association is unclear. To examine whether a common self-regulatory ability impacts the experience of both emotion and pain, we integrated neuroimaging, behavioral, and physiological measures obtained from three assessments separated by substantial temporal intervals. Our results demonstrated that individual differences in emotion regulation ability, as indexed by an objective measure of emotional state, corrugator electromyography, predicted self-reported success while regulating pain. In both emotion and pain paradigms, the amygdala reflected regulatory success. Notably, we found that greater emotion regulation success was associated with greater change of amygdalar activity following pain regulation. Furthermore, individual differences in degree of amygdalar change following emotion regulation were a strong predictor of pain regulation success, as well as of the degree of amygdalar engagement following pain regulation. These findings suggest that common individual differences in emotion and pain regulatory success are reflected in a neural structure known to contribute to appraisal processes.
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The amygdalae are important, if not critical, brain regions for many affective, attentional and memorial processes, and dysfunction of the amygdalae has been a consistent finding in the study of clinical depression. Theoretical models of the functional neuroanatomy of both normal and psychopathological affective processes which posit cortical hemispheric specialization of functions have been supported by both lesion and functional neuroimaging studies in humans. Results from human neuroimaging studies in support of amygdalar hemispheric specialization are inconsistent. However, recent results from human lesion studies are consistent with hemispheric specialization. An important, yet largely ignored, feature of the amygdalae in the primate brain--derived from both neuroanatomical and electrophysiological data--is that there are virtually no direct interhemispheric connections via the anterior commissure (AC). This feature stands in stark contrast to that of the rodent brain wherein virtually all amygdalar nuclei have direct interhemispheric connections. We propose this feature of the primate brain, in particular the human brain, is a result of influences from frontocortical hemispheric specialization which have developed over the course of primate brain evolution. Results consistent with this notion were obtained by examining the nature of human amygdalar interhemispheric connectivity using both functional magnetic resonance imaging (FMRI) and positron emission tomography (PET). We found modest evidence of amygdalar interhemispheric functional connectivity in the non-depressed brain, whereas there was strong evidence of functional connectivity in the depressed brain. We interpret and discuss the nature of this connectivity in the depressed brain in the context of dysfunctional frontocortical-amygdalar interactions which accompany clinical depression.
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OBJECTIVE: The anticipation of adverse outcomes, or worry, is a cardinal symptom of generalized anxiety disorder. Prior work with healthy subjects has shown that anticipating aversive events recruits a network of brain regions, including the amygdala and anterior cingulate cortex. This study tested whether patients with generalized anxiety disorder have alterations in anticipatory amygdala function and whether anticipatory activity in the anterior cingulate cortex predicts treatment response. METHOD: Functional magnetic resonance imaging (fMRI) was employed with 14 generalized anxiety disorder patients and 12 healthy comparison subjects matched for age, sex, and education. The event-related fMRI paradigm was composed of one warning cue that preceded aversive pictures and a second cue that preceded neutral pictures. Following the fMRI session, patients received 8 weeks of treatment with extended-release venlafaxine. RESULTS: Patients with generalized anxiety disorder showed greater anticipatory activity than healthy comparison subjects in the bilateral dorsal amygdala preceding both aversive and neutral pictures. Building on prior reports of pretreatment anterior cingulate cortex activity predicting treatment response, anticipatory activity in that area was associated with clinical outcome 8 weeks later following treatment with venlafaxine. Higher levels of pretreatment anterior cingulate cortex activity in anticipation of both aversive and neutral pictures were associated with greater reductions in anxiety and worry symptoms. CONCLUSIONS: These findings of heightened and indiscriminate amygdala responses to anticipatory signals in generalized anxiety disorder and of anterior cingulate cortex associations with treatment response provide neurobiological support for the role of anticipatory processes in the pathophysiology of generalized anxiety disorder.
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This study compared the asymmetry of different features of brain electrical activity during the performance of a verbal task (word finding) and a spatial task (dot localization) that had been carefully matched on psychometric properties and accompanying motor activity. Nineteen right-handed subjects were tested. EEG was recorded from F3, F4, C3, C4, P3, and P4, referred to both CZ and computer-derived averaged-ears references, and Fourier transformed. Power in the delta, theta, alpha, and beta bands was computed. There were significant Task X Hemisphere effects in all bands for CZ-referenced data and for the alpha and beta bands for ears-referenced data. The effects were always either greater power suppression in the hemisphere putatively most engaged in task processing or greater power in the opposite hemisphere. Correlations between EEG and task performance indicated that CZ-referenced parietal alpha asymmetry accounted for the most variance in verbal task performance. Power within individual hemispheres or across hemispheres was unrelated to task performance. The findings indicate robust differences in asymmetrical brain physiology that are produced by well-matched verbal and spatial cognitive tasks.
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Thirty-two participants were tested for both resting electroencephalography (EEG) and neuropsychological function. Eight one-minute trials of resting EEG were recorded from 14 channels referenced to linked ears, which was rederived to an average reference. Neuropsychological tasks included Verbal Fluency, the Tower of London, and Corsi's Recurring Blocks. Asymmetries in EEG alpha activity were correlated with performance on these tasks. Similar patterns were obtained for delta and theta bands. Factor analyses of resting EEG asymmetries over particular regions suggested that asymmetries over anterior scalp regions may be partly independent from those over posterior scalp regions. These results support the notions that resting EEG asymmetries are specified by multiple mechanisms along the rostral/caudal plane, and that these asymmetries predict task performance in a manner consistent with lesion and neuroimaging studies.
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The anterior medial prefrontal (AMPFC) and retrosplenial (RSC) cortices are active during self-referential decision-making tasks such as when participants appraise traits and abilities, or current affect. Other appraisal tasks requiring an evaluative decision or mental representation, such as theory of mind and perspective-taking tasks, also involve these regions. In many instances, these types of decisions involve a subjective opinion or preference, but also a degree of ambiguity in the decision, rather than a strictly veridical response. However, this ambiguity is generally not controlled for in studies that examine self-referential decision-making. In this functional magnetic resonance imaging experiment with 17 healthy adults, we examined neural processes associated with subjective decision-making with and without an overt self-referential component. The task required subjective decisions about colors-regarding self-preference (internal subjective decision) or color similarity (external subjective decision) under conditions where there was no objectively correct response. Results indicated greater activation in the AMPFC, RSC, and caudate nucleus during internal subjective decision-making. The findings suggest that self-referential processing, rather than subjective judgments among ambiguous response alternatives, accounted for the AMPFC and RSC response.
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<p>Many powerful human emotional thoughts are generated in the absence of a precipitating event in the environment. Here, we tested whether we can decode the valence of internally driven, self-generated thoughts during task-free rest based on neural similarities with task-related affective mental states. We acquired functional magnetic resonance imaging (fMRI) data while participants generated positive and negative thoughts as part of an attribution task (Session A) and while they reported the occurrence of comparable mental states during task-free rest periods (Session B). With the use of multivariate pattern analyses (MVPA), we identified response patterns in the medial orbitofrontal cortex (mOFC) that encode the affective content of thoughts that are generated in response to an external experimental cue. Importantly, these task driven response patterns reliably predicted the occurrence of affective thoughts generated during unconstrained rest periods recorded one week apart. This demonstrates that at least certain elements of task-cued and task-free affective experiences rely on a common neural code. Furthermore, our findings reveal the role that the mOFC plays in determining the affective tone of unconstrained thoughts. More generally, our results suggest that MVPA is an important methodological tool for attempts to understand unguided subject driven mental states such as mind-wandering and daydreaming based on neural similarities with task-based experiences.</p>
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Functional neuroimaging research has demonstrated that retrieving information about object-associated colors activates the left fusiform gyrus in posterior temporal cortex. Although regions near the fusiform have previously been implicated in color perception, it remains unclear whether color knowledge retrieval actually activates the color perception system. Evidence to this effect would be particularly strong if color perception cortex was activated by color knowledge retrieval triggered strictly with linguistic stimuli. To address this question, subjects performed two tasks while undergoing fMRI. First, subjects performed a property verification task using only words to assess conceptual knowledge. On each trial, subjects verified whether a named color or motor property was true of a named object (e.g., TAXI-yellow, HAIR-combed). Next, subjects performed a color perception task. A region of the left fusiform gyrus that was highly responsive during color perception also showed greater activity for retrieving color than motor property knowledge. These data provide the first evidence for a direct overlap in the neural bases of color perception and stored information about object-associated color, and they significantly add to accumulating evidence that conceptual knowledge is grounded in the brain's modality-specific systems.
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Motion correction of fMRI data is a widely used step prior to data analysis. In this study, a comparison of the motion correction tools provided by several leading fMRI analysis software packages was performed, including AFNI, AIR, BrainVoyager, FSL, and SPM2. Comparisons were performed using data from typical human studies as well as phantom data. The identical reconstruction, preprocessing, and analysis steps were used on every data set, except that motion correction was performed using various configurations from each software package. Each package was studied using default parameters, as well as parameters optimized for speed and accuracy. Forty subjects performed a Go/No-go task (an event-related design that investigates inhibitory motor response) and an N-back task (a block-design paradigm investigating working memory). The human data were analyzed by extracting a set of general linear model (GLM)-derived activation results and comparing the effect of motion correction on thresholded activation cluster size and maximum t value. In addition, a series of simulated phantom data sets were created with known activation locations, magnitudes, and realistic motion. Results from the phantom data indicate that AFNI and SPM2 yield the most accurate motion estimation parameters, while AFNI's interpolation algorithm introduces the least smoothing. AFNI is also the fastest of the packages tested. However, these advantages did not produce noticeably better activation results in motion-corrected data from typical human fMRI experiments. Although differences in performance between packages were apparent in the human data, no single software package produced dramatically better results than the others. The "accurate" parameters showed virtually no improvement in cluster t values compared to the standard parameters. While the "fast" parameters did not result in a substantial increase in speed, they did not degrade the cluster results very much either. The phantom and human data indicate that motion correction can be a valuable step in the data processing chain, yielding improvements of up to 20% in the magnitude and up to 100% in the cluster size of detected activations, but the choice of software package does not substantially affect this improvement.
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Divides the study of human attention into 3 components: alertness, selectivity, and processing capacity. Experimental techniques designed to separate these components and examine their interrelations within comparable tasks are outlined. It is shown that a stimulus may be used to increase alertness for processing all external information, to improve selection of particular stimuli, or to do both simultaneously. Development of alertness and selectivity are separable, but may go on together without interference. Moreover, encoding a stimulus may proceed without producing interference with other signals. Thus, the contact between an external stimulus and its representation in memory does not appear to require processing capacity. Limited capacity results are obtained when mental operations, E.g., response selection or rehearsal, must be performed on the encoded information. (45 ref.)

We present a novel data smoothing and analysis framework for cortical thickness data defined on the brain cortical manifold. Gaussian kernel smoothing, which weights neighboring observations according to their 3D Euclidean distance, has been widely used in 3D brain images to increase the signal-to-noise ratio. When the observations lie on a convoluted brain surface, however, it is more natural to assign the weights based on the geodesic distance along the surface. We therefore develop a framework for geodesic distance-based kernel smoothing and statistical analysis on the cortical manifolds. As an illustration, we apply our methods in detecting the regions of abnormal cortical thickness in 16 high functioning autistic children via random field based multiple comparison correction that utilizes the new smoothing technique.
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Many investigators have hypothesized that brain response to cortisol is altered in depression. However, neural activation in response to exogenously manipulated cortisol elevations has not yet been directly examined in depressed humans. Animal research shows that glucocorticoids have robust effects on hippocampal function, and can either enhance or suppress neuroplastic events in the hippocampus depending on a number of factors. We hypothesized that depressed individuals would show 1) altered hippocampal response to exogenous administration of cortisol, and 2) altered effects of cortisol on learning. In a repeated-measures design, 19 unmedicated depressed and 41 healthy individuals completed two fMRI scans. Fifteen mg oral hydrocortisone (i.e., cortisol) or placebo (order randomized and double-blind) was administered 1 h prior to encoding of emotional and neutral words during fMRI scans. Data analysis examined the effects of cortisol administration on 1) brain activation during encoding, and 2) subsequent free recall for words. Cortisol affected subsequent recall performance in depressed but not healthy individuals. We found alterations in hippocampal response to cortisol in depressed women, but not in depressed men (who showed altered response to cortisol in other regions, including subgenual prefrontal cortex). In both depressed men and women, cortisol's effects on hippocampal function were positively correlated with its effects on recall performance assessed days later. Our data provide evidence that in depressed compared to healthy women, cortisol's effects on hippocampal function are altered. Our data also show that in both depressed men and women, cortisol's effects on emotional memory formation and hippocampal function are related.
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How does language reliably evoke emotion, as it does when people read a favorite novel or listen to a skilled orator? Recent evidence suggests that comprehension involves a mental simulation of sentence content that calls on the same neural systems used in literal action, perception, and emotion. In this study, we demonstrated that involuntary facial expression plays a causal role in the processing of emotional language. Subcutaneous injections of botulinum toxin-A (BTX) were used to temporarily paralyze the facial muscle used in frowning. We found that BTX selectively slowed the reading of sentences that described situations that normally require the paralyzed muscle for expressing the emotions evoked by the sentences. This finding demonstrates that peripheral feedback plays a role in language processing, supports facial-feedback theories of emotional cognition, and raises questions about the effects of BTX on cognition and emotional reactivity. We account for the role of facial feedback in language processing by considering neurophysiological mechanisms and reinforcement-learning theory.
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In rodents, theta rhythm has been linked to the hippocampal formation, as well as other regions, including the anterior cingulate cortex (ACC). To test the role of the ACC in theta rhythm, concurrent measurements of brain electrical activity (EEG) and glucose metabolism (PET) were performed in 29 subjects at baseline. EEG data were analyzed with a source localization technique that enabled voxelwise correlations of EEG and PET data. For theta, but not other bands, the rostral ACC (Brodmann areas 24/32) was the largest cluster with positive correlations between current density and glucose metabolism. Positive correlations were also found in right fronto-temporal regions. In control but not depressed subjects, theta within ACC and prefrontal/orbitofrontal regions was positively correlated. The results reveal a link between theta and cerebral metabolism in the ACC as well as disruption of functional connectivity within frontocingulate pathways in depression.
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Cyclic AMP (cAMP) is a second messenger involved in many processes including mnemonic processing and anxiety. Memory deficits and anxiety are noted in the phenotype of fragile X (FX), the most common heritable cause of mental retardation and autism. Here we review reported observations of altered cAMP cascade function in FX and autism. Cyclic AMP is a potentially useful biochemical marker to distinguish autism comorbid with FX from autism per se and the cAMP cascade may be a viable therapeutic target for both FX and autism.
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Sensitivity, specificity, and reproducibility are vital to interpret neuroscientific results from functional magnetic resonance imaging (fMRI) experiments. Here we examine the scan-rescan reliability of the percent signal change (PSC) and parameters estimated using Dynamic Causal Modeling (DCM) in scans taken in the same scan session, less than 5 min apart. We find fair to good reliability of PSC in regions that are involved with the task, and fair to excellent reliability with DCM. Also, the DCM analysis uncovers group differences that were not present in the analysis of PSC, which implies that DCM may be more sensitive to the nuances of signal changes in fMRI data.
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Individual variation in the experience and expression of pleasure may relate to differential patterns of lateral frontal activity. Brain electrical measures have been used to study the asymmetric involvement of lateral frontal cortex in positive emotion, but the excellent time resolution of these measures has not been used to capture second-by-second changes in ongoing emotion until now. The relationship between pleasure and second-by-second lateral frontal activity was examined with the use of hierarchical linear modeling in a sample of 128 children ages 6-10 years. Electroencephalographic activity was recorded during "pop-out toy," a standardized task that elicits pleasure. The task consisted of 3 epochs: an anticipation period sandwiched between 2 play periods. The amount of pleasure expressed during the task predicted the pattern of nonlinear change in lateral frontal activity. Children who expressed increasing amounts of pleasure during the task exhibited increasing left lateral frontal activity during the task, whereas children who expressed contentment exhibited increasing right/decreasing left activity. These findings indicate that task-dependent changes in pleasure relate to dynamic, nonlinear changes in lateral frontal activity as the task unfolds.
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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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OBJECTIVES: Randomized controlled studies on the effectiveness of body-oriented methods of treatment for children with attention-deficit hyperactivity disorder (ADHD) are lacking. Our aim was to compare the effectiveness of two methods of treatment (yoga for children vs. conventional motor exercises) in a randomized controlled pilot study. METHODS: Nineteen children with a clinical diagnosis of ADHD (according to ICD-10 criteria) were included and randomly assigned to treatment conditions according to a 2x2 cross-over design. Effects of treatment were analyzed by means of an analysis of variance for repeated measurements. RESULTS: For all outcome measures (test scores on an attention task, and parent ratings of ADHD symptoms) the yoga training was superior to the conventional motor training, with effect sizes in the medium-to-high range (0.60-0.97). All children showed sizable reductions in symptoms over time, and at the end of the study, the group means for the ADHD scales did not differ significantly from those for a representative control group. Furthermore, the training was particularly effective for children undergoing pharmacotherapy (MPH). CONCLUSIONS: The findings from this pilot study demonstrate that yoga can be an effective complementary or concomitant treatment for attention-deficit hyperactivity disorder. The study advocates further research into the impact of yoga or body-oriented therapies on the prevention and treatment of ADHD.
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This study describes the effects of an 8-week course in Mindfulness-Based Stress Reduction (MBSR; J. Kabat-Zinn, 1982, 1990) on affective symptoms (depression and anxiety), dysfunctional attitudes, and rumination. Given the focus of mindfulness meditation (MM) in modifying cognitive processes, it was hypothesized that the primary change in MM practice involves reductions in ruminative tendencies. We studied a sample of individuals with lifetime mood disorders who were assessed prior to and upon completion of an MBSR course. We also compared a waitlist sample matched with a subset of the MBSR completers. Overall, the results suggest that MM practice primarily leads to decreases in ruminative thinking, even after controlling for reductions in affective symptoms and dysfunctional beliefs.

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