OBJECTIVE: The purpose of this study was to use functional magnetic resonance imaging (fMRI) to probe the neural circuitry associated with reactivity to negative and positive affective stimuli in patients with major depressive disorder before treatment and after 2 and 8 weeks of treatment with venlafaxine. Relations between baseline neural activation and response to treatment were also evaluated.
METHOD: Patients with major depressive disorder (N=12) and healthy comparison subjects (N=5) were scanned on three occasions, during which trials of alternating blocks of affective and neutral pictorial visual stimuli were presented. Symptoms were evaluated at each testing occasion, and both groups completed self-report measures of mood. Statistical parametric mapping was used to examine the fMRI data with a focus on the group-by-time interactions.
RESULTS: Patients showed a significant reduction in depressive symptoms with treatment. Group-by-time interactions in response to the negative versus neutral stimuli were found in the left insular cortex and the left anterior cingulate. At baseline, both groups showed bilateral activation in the visual cortices, lateral prefrontal cortex, and amygdala in response to the negative versus neutral stimuli, with patients showing greater activation in the visual cortex and less activation in the left lateral prefrontal cortex. Patients with greater relative anterior cingulate activation at baseline in response to the negative versus neutral stimuli showed the most robust treatment response.
CONCLUSIONS: The findings underscore the importance of the neural circuitry activated by negative affect in depression and indicate that components of this circuitry can be changed within 2 weeks of treatment with antidepressant medication.
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OBJECTIVE: Happiness, sadness, and disgust are three emotions that differ in their valence (positive or negative) and associated action tendencies (approach or withdrawal). This study was designed to investigate the neuroanatomical correlates of these discrete emotions.
METHOD: Twelve healthy female subjects were studied. Positron emission tomography and [15O]H2O were used to measure regional brain activity. There were 12 conditions per subject: happiness, sadness, and disgust and three control conditions, each induced by film and recall. Emotion and control tasks were alternated throughout. Condition order was pseudo-randomized and counterbalanced across subjects. Analyses focused on brain activity patterns for each emotion when combining film and recall data.
RESULTS: Happiness, sadness, and disgust were each associated with increases in activity in the thalamus and medial prefrontal cortex (Brodmann's area 9). These three emotions were also associated with activation of anterior and posterior temporal structures, primarily when induced by film. Recalled sadness was associated with increased activation in the anterior insula. Happiness was distinguished from sadness by greater activity in the vicinity of ventral mesial frontal cortex.
CONCLUSIONS: While this study should be considered preliminary, it identifies regions of the brain that participate in happiness, sadness, and disgust, regions that distinguish between positive and negative emotions, and regions that depend on both the elicitor and valence of emotion or their interaction.
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Recent theoretical and empirical work in cognitive science and neuroscience is brought into contact with the concept of the flow experience. After a brief exposition of brain function, the explicit-implicit distinction is applied to the effortless information processing that is so characteristic of the flow state. The explicit system is associated with the higher cognitive functions of the frontal lobe and medial temporal lobe structures and has evolved to increase cognitive flexibility. In contrast, the implicit system is associated with the skill-based knowledge supported primarily by the basal ganglia and has the advantage of being more efficient. From the analysis of this flexibility/efficiency trade-off emerges a thesis that identifies the flow state as a period during which a highly practiced skill that is represented in the implicit system's knowledge base is implemented without interference from the explicit system. It is proposed that a necessary prerequisite to the experience of flow is a state of transient hypofrontality that enables the temporary suppression of the analytical and meta-conscious capacities of the explicit system. Examining sensory-motor integration skills that seem to typify flow such as athletic performance, writing, and free-jazz improvisation, the new framework clarifies how this concept relates to creativity and opens new avenues of research.
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In children, behavioral inhibition (BI) in response to potential threat predicts the development of anxiety and affective disorders, and primate lesion studies suggest involvement of the orbitofrontal cortex (OFC) in mediating BI. Lesion studies are essential for establishing causality in brain-behavior relationships, but should be interpreted cautiously because the impact of a discrete lesion on a complex neural circuit extends beyond the lesion location. Complementary functional imaging methods assessing how lesions influence other parts of the circuit can aid in precisely understanding how lesions affect behavior. Using this combination of approaches in monkeys, we found that OFC lesions concomitantly alter BI and metabolism in the bed nucleus of stria terminalis (BNST) region and that individual differences in BNST activity predict BI. Thus it appears that an important function of the OFC in response to threat is to modulate the BNST, which may more directly influence the expression of BI.
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Positive affect elicited in a mother toward her newborn infant may be one of the most powerful and evolutionarily preserved forms of positive affect in the emotional landscape of human behavior. This study examined the neurobiology of this form of positive emotion and in so doing, sought to overcome the difficulty of eliciting robust positive affect in response to visual stimuli in the physiological laboratory. Six primiparous human mothers with no indications of postpartum depression brought their infants into the laboratory for a photo shoot. Approximately 6 weeks later, they viewed photographs of their infant, another infant, and adult faces during acquisition of functional magnetic resonance images (fMRI). Mothers exhibited bilateral activation of the orbitofrontal cortex (OFC) while viewing pictures of their own versus unfamiliar infants. While in the scanner, mothers rated their mood more positively for pictures of their own infants than for unfamiliar infants, adults, or at baseline. The orbitofrontal activation correlated positively with pleasant mood ratings. In contrast, areas of visual cortex that also discriminated between own and unfamiliar infants were unrelated to mood ratings. These data implicate the orbitofrontal cortex in a mother's affective responses to her infant, a form of positive emotion that has received scant attention in prior human neurobiological studies. Furthermore, individual variations in orbitofrontal activation to infant stimuli may reflect an important dimension of maternal attachment.
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There is mounting evidence that prefrontal cortex (PFC) is activated during mnemonic operations such as working memory maintenance and also during response-related operations. In the current study, we examine the neural organization of mnemonic and response operations with respect to each other within PFC. Stimulus-evoked and sustained functional MRI activity was recorded during performance of a mental calculation task. The presence or absence of mnemonic and response demands was manipulated in a 2 x 2 factorial design with conditions requiring: (1) memory encoding and maintenance (M+); (2) response selection and execution (R+); (3) encoding, maintenance, and response execution (M+R+); (4) neither mnemonic nor response-related processes (M-R-). The first step of the analyses identified PFC voxels exhibiting differential activity during (M+) vs. (R+) trials. Within these voxels, we then examined activity during multiple phases of (M+R+) trials. Greater stimulus-evoked and sustained activity was observed within the anterior extent of dorsolateral prefrontal cortex (BA 46) during R+ vs. M+ trials. In contrast, greater activity was observed in the posterior extent of dorsolateral PFC during M+ vs. R+ trials. Importantly, both regions were activated during (M+R+) trials. Activity levels during all of these conditions exceeded levels observed during (M-R-) control trials. These results suggest that integrative functions of PFC that allow past information to guide future actions may emerge from communication between discrete subregions supporting mnemonic and response operations.
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Pain can be modulated by several cognitive techniques, typically involving increased cognitive control and decreased sensory processing. Recently, it has been demonstrated that pain can also be attenuated by mindfulness. Here, we investigate the underlying brain mechanisms by which the state of mindfulness reduces pain. Mindfulness practitioners and controls received unpleasant electric stimuli in the functional magnetic resonance imaging scanner during a mindfulness and a control condition. Mindfulness practitioners, but not controls, were able to reduce pain unpleasantness by 22% and anticipatory anxiety by 29% during a mindful state. In the brain, this reduction was associated with decreased activation in the lateral prefrontal cortex and increased activation in the right posterior insula during stimulation and increased rostral anterior cingulate cortex activation during the anticipation of pain. These findings reveal a unique mechanism of pain modulation, comprising increased sensory processing and decreased cognitive control, and are in sharp contrast to established pain modulation mechanisms.
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The purpose of the present study was twofold: (1) to obtain information on central mechanisms underlying cardiac self-regulation by comparing changes in cerebral asymmetry during self-control of heart rate with changes observed during the production of affective imagery; and (2) to explore sex differences in hemispheric function during performance of these two tasks. Heart rate (HR) and bilateral parietal EEG filtered for alpha were recorded from 20 right-handed males and females during two discrete experimental phases: cardiac control and image self-generation. HR showed significant effects between up versus down in prefeedback and feedback, and between anger versus relaxing imagery in the image phase. The EEG data indicated similar patterns of hemispheric asymmetry in both sexes during prefeedback. However, with the introduction of feedback, females shifted to greater relative right hemisphere activation comparable to what they show when specifically instructed to think emotional thoughts; males showed little differentiation between conditions. These data indicate that the Self-regulation of HR with biofeedback in males and females may be accomplished by the utilization of strategies involving different underlying patterns of neuropsychological processes.
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Increasing research indicates that concepts are represented as distributed circuits of property information across the brain's modality-specific areas. The current study examines the distributed representation of an important but under-explored category, foods. Participants viewed pictures of appetizing foods (along with pictures of locations for comparison) during event-related fMRI. Compared to location pictures, food pictures activated the right insula/operculum and the left orbitofrontal cortex, both gustatory processing areas. Food pictures also activated regions of visual cortex that represent object shape. Together these areas contribute to a distributed neural circuit that represents food knowledge. Not only does this circuit become active during the tasting of actual foods, it also becomes active while viewing food pictures. Via the process of pattern completion, food pictures activate gustatory regions of the circuit to produce conceptual inferences about taste. Consistent with theories that ground knowledge in the modalities, these inferences arise as reenactments of modality-specific processing.
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The experience of pain arises from both physiological and psychological factors, including one's beliefs and expectations. Thus, placebo treatments that have no intrinsic pharmacological effects may produce analgesia by altering expectations. However, controversy exists regarding whether placebos alter sensory pain transmission, pain affect, or simply produce compliance with the suggestions of investigators. In two functional magnetic resonance imaging (fMRI) experiments, we found that placebo analgesia was related to decreased brain activity in pain-sensitive brain regions, including the thalamus, insula, and anterior cingulate cortex, and was associated with increased activity during anticipation of pain in the prefrontal cortex, providing evidence that placebos alter the experience of pain.
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<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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We examined whether resting anterior electroencephalographic (EEG) asymmetry in the alpha frequency band has psychometric properties that would be expected of a measure assessing individual differences. In each of two experimental sessions, separated by three weeks, resting EEG in midfrontal and anterior temporal sites was recorded from 85 female adults during eight 60-s baselines. Resting alpha asymmetry demonstrated acceptable test-retest stability and excellent internal consistency reliability. Analyses including other frequency bands indicated that degree of stability varied somewhat as a function of band and region. In addition, asymmetry was less stable than absolute power. Discussion focuses on the implications of the present findings for the measurement and conceptualization of resting anterior asymmetry.
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Differences between dyslexics and controls in the unimanual and bimanual conditions of the peg placement section of the Purdue Pegboard Test were examined. Twenty-three disabled and twenty-three normal readers were studied. The groups were carefully screened on a neuropsychological battery. The disabled readers were comprised of a relatively homogeneous language-disordered subgroup exhibiting deficits in naming. Significant Group X Condition interactions were obtained for both raw and percentile scores and indicated that disabled readers performed worse than controls in the unimanual compared to bimanual conditions. The dyslexics performed particularly poorly compared with controls on the left hand condition. The implications of these data for hypotheses which argue for left hemisphere dysfunction, as well as those which posit interhemispheric transfer deficits in reading disabled children, are discussed.
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This experiment was designed to assess the differential impact of initially presenting affective information to the left versus right hemisphere on both the perception of and response to the input. Nineteen right-handed subjects were presented with faces expressing happiness and sadness. Each face was presented twice to each visual field for an 8-sec duration. The electro-oculogram (EOG) was monitored and fed back to subjects to train them to keep their eyes focused on the central fixation point as well as to eliminate trials confounded by eye movement artifact. Following each slide presentation, subjects rated the intensity of the emotional expression depicted in the face and their emotional reaction to the face on a series of 7-point rating scales. Subjects reported perceiving more happiness in response to stimuli initially presented to the left hemisphere (right visual field) compared to presentations of the identical faces to the right hemisphere (left visual field). This effect was predominantly a function of ratings on sad faces. A similar, albeit less robust, effect was found on self-ratings of happiness (the degree to which the face elicited the emotion in the viewer). These data challenge the view that the right hemisphere is uniquely involved in all emotional behavior. The implications of these findings for theories concerning the lateralization of emotional behavior are discussed.
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<p>This experiment was designed to test whether reading disabled boys differ from matched controls on behavioral measures of interhemispheric transfer time (IHTT). Specifically, we proposed that language-disordered reading disabled children who had deficits in naming would show either faster or slower IHTTs compared with controls. From an initial group of 118 right-handed males, we selected a group of 25 disabled and 25 normal readers, matched on age. All subjects had to obtain a full scale IQ of 90 or above, a PIQ score of 85 or above, and a scaled score of 7 or above on the Block Design Subtest of the WISC-R. After meeting additional criteria for group assignment, manual reaction time (RT) measures of IHTT were obtained in response to simple visual and tactile stimuli during two laboratory testing sessions. Half the trials were conducted with the hands in an uncrossed orientation and half with the hands crossed in order to examine the effects of spatial compatibility on estimates of IHTT. The results revealed no overall group differences in IHTT for any of the conditions. However, correlations between IHTT measures and indices of cognitive performance indicated that faster IHTTs were significantly correlated with poorer performance on measures of reading and language function in the dyslexic group. These data are discussed within the context of a model of interhemispheric transfer deficits in disabled readers.</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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Working memory (WM) comprises operations whose coordinated action contributes to our ability to maintain focus on goal-relevant information in the presence of distraction. The present study investigated the nature of distraction upon the neural correlates of WM maintenance operations by presenting task-irrelevant distracters during the interval between the memoranda and probes of a delayed-response WM task. The study used a region of interest (ROIs) approach to investigate the role of anterior (e.g., lateral and medial prefrontal cortex--PFC) and posterior (e.g., parietal and fusiform cortices) brain regions that have been previously associated with WM operations. Behavioral results showed that distracters that were confusable with the memorandum impaired WM performance, compared to either the presence of non-confusable distracters or to the absence of distracters. These different levels of distraction led to differences in the regional patterns of delay interval activity measured with event-related functional magnetic resonance imaging (fMRI). In the anterior ROIs, dorsolateral PFC activation was associated with WM encoding and maintenance, and in maintaining a preparatory state, and ventrolateral PFC activation was associated with the inhibition of distraction. In the posterior ROIs, activation of the posterior parietal and fusiform cortices was associated with WM and perceptual processing, respectively. These findings provide novel evidence concerning the neural systems mediating the cognitive and behavioral responses during distraction, and places frontal cortex at the top of the hierarchy of the neural systems responsible for cognitive control.
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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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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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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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Given the central role of the amygdala in fear perception and expression and its likely abnormality in affective disorders and autism, there is great demand for a technique to measure differences in neurochemistry of the human amygdala. Unfortunately, it is also a technically complex target for magnetic resonance spectroscopy (MRS) due to a small volume, high field inhomogeneity and a shared boundary with hippocampus, which can undergo opposite changes in response to stress. We attempted to achieve reliable PRESS-localized single-voxel MRS at 3T of the isolated human amygdala by using anatomy to guide voxel size and location. We present data from 106 amygdala-MRS sessions from 58 volunteers aged 10 to 52 years, including two tests of one-week stability and a feasibility study in an adolescent sample. Our main outcomes were indices of spectral quality, repeated measurement variability (within- and between-subject standard deviations), and sensitivity to stable individual differences measured by intra-class correlation (ICC). We present metrics of amygdala-MRS reliability for n-acetyl-aspartate, creatine, choline, myo-Inositol, and glutamate+glutamine (Glx). We found that scan quality suffers an age-related difference in field homogeneity and modified our protocol to compensate. We further identified an effect of anatomical inclusion near the endorhinal sulcus, a region of high synaptic density, that contributes up to 29% of within-subject variability across 4 sessions (n=14). Remaining variability in line width but not signal-to-noise also detracts from reliability. Statistical correction for partial inclusion of these strong neurochemical gradients decreases n-acetyl-aspartate reliability from an intraclass correlation of 0.84 to 0.56 for 7-minute acquisitions. This suggests that systematic differences in anatomical inclusion can contribute greatly to apparent neurochemical concentrations and could produce false group differences in experimental studies. Precise, anatomically-based prescriptions that avoid age-related sources of inhomogeneity and use longer scan times may permit study of individual differences in neurochemistry throughout development in this late-maturing structure.
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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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