Children with an anxious temperament (AT) are at risk for developing psychiatric disorders along the internalizing spectrum, including anxiety and depression. Like these disorders, AT is a multidimensional phenotype and children with extreme anxiety show varying mixtures of physiological, behavioral, and other symptoms. Using a well-validated juvenile monkey model of AT, we addressed the degree to which this phenotypic heterogeneity reflects fundamental differences or similarities in the underlying neurobiology. The rhesus macaque is optimal for studying AT because children and young monkeys express the anxious phenotype in similar ways and have similar neurobiology. Fluorodeoxyglucose (FDG)-positron emission tomography (FDG-PET) in 238 freely behaving monkeys identified brain regions where metabolism predicted variation in three dimensions of the AT phenotype: hypothalamic-pituitary-adrenal (HPA) activity, freezing behavior, and expressive vocalizations. We distinguished brain regions that predicted all three dimensions of the phenotype from those that selectively predicted a single dimension. Elevated activity in the central nucleus of the amygdala and the anterior hippocampus was consistently found across individuals with different presentations of AT. In contrast, elevated activity in the lateral anterior hippocampus was selective to individuals with high levels of HPA activity, and decreased activity in the motor cortex (M1) was selective to those with high levels of freezing behavior. Furthermore, activity in these phenotype-selective regions mediated relations between amygdala metabolism and different expressions of anxiety. These findings provide a framework for understanding the mechanisms that lead to heterogeneity in the clinical presentation of internalizing disorders and set the stage for developing improved interventions.
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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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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>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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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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Theories of knowledge such as feature lists, semantic networks, and localist neural nets typically use a single global symbol to represent a property that occurs in multiple concepts. Thus, a global symbol represents mane across HORSE, PONY, and LION. Alternatively, perceptual theories of knowledge, as well as distributed representational systems, assume that properties take different local forms in different concepts. Thus, different local forms of mane exist for HORSE, PONY, and LION, each capturing the specific form that mane takes in its respective concept. Three experiments used the property verification task to assess whether properties are represented globally or locally (e.g., Does a PONY have mane?). If a single global form represents a property, then verifying it in any concept should increase its accessibility and speed its verification later in any other concept. Verifying mane for PONY should benefit as much from having verified mane for LION earlier as from verifying mane for HORSE. If properties are represented locally, however, verifying a property should only benefit from verifying a similar form earlier. Verifying mane for PONY should only benefit from verifying mane for HORSE, not from verifying mane for LION. Findings from three experiments strongly supported local property representation and ruled out the interpretation that object similarity was responsible (e.g., the greater overall similarity between HORSE and PONY than between LION and PONY). The findings further suggest that property representation and verification are complicated phenomena, grounded in sensory-motor simulations.
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Several different models postulate that depression is associated with decreased approach-related behavior. Relatively little has been done to date to specifically investigate this issue. In the present study, a signal-detection analysis was used to examine the response biases of dysphoric and nondysphoric female undergraduates during 3 payoff conditions: neutral, reward, and punishment. As predicted, the dysphoric subjects had a smaller change in bias from the neutral to the reward condition compared with the nondysphoric group. The 2 groups did not differ during the neutral and punishment conditions. These findings are consistent with the hypothesis that the left frontal hypoactivation observed in depression reflects a deficit in approach-related behavior.
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<p>Subregional analyses of the hippocampus have suggested a selective role for the CA1 subregion in intermediate/long-term spatial memory and consolidation, but not short-term acquisition or encoding processes. It remains unclear how the direct cortical projection to CA1 via the perforant path (pp) contributes to these CA1-dependent processes. It has been suggested that dopamine selectively modulates the pp projection to CA1 while having little to no effect on the Schaffer collateral (SC) projection to CA1. This series of behavioral and electrophysiological experiments takes advantage of this pharmacological dissociation to demonstrate that the direct pp inputs to CA1 are critical in CA1-dependent intermediate-term retention and retrieval function. Here we demonstrate that local infusion of the nonselective dopamine agonist, apomorphine (10, 15 microg), into the CA1 subregion of awake animals produces impairments in between-day retention and retrieval, sparing within-day encoding of a modified Hebb-Williams maze and contextual conditioning of fear. In contrast, apomorphine produces no deficits when infused into the CA3 subregion. To complement the behavioral analyses, electrophysiological data was collected. In anesthetized animals, local infusion of the same doses of apomorphine significantly modifies evoked responses in the distal dendrites of CA1 following angular bundle stimulation, but produces no significant effects in the more proximal dendritic layer following stimulation of the SC. These results support a modulatory role for dopamine in the EC-CA1, but not CA3-CA1 circuitry, and suggest the possibility of a more fundamental role for EC-CA1 synaptic transmission in terms of intermediate-term, but not short-term spatial memory.</p>
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We investigate the hypothesis that those subregions of the prefrontal cortex (PFC) found to support proactive interference resolution may also support delay-spanning distractor interference resolution. Ten subjects performed delayed-recognition tasks requiring working memory for faces or shoes during functional MRI scanning. During the 15-sec delay interval, task-irrelevant distractors were presented. These distractors were either all faces or all shoes and were thus either congruent or incongruent with the domain of items in the working memory task. Delayed-recognition performance was slower and less accurate during congruent than during incongruent trials. Our fMRI analyses revealed significant delay interval activity for face and shoe working memory tasks within both dorsal and ventral PFC. However, only ventral PFC activity was modulated by distractor category, with greater activity for congruent than for incongruent trials. Importantly, this congruency effect was only present for correct trials. In addition to PFC, activity within the fusiform face area was investigated. During face distraction, activity was greater for face relative to shoe working memory. As in ventrolateral PFC, this congruency effect was only present for correct trials. These results suggest that the ventrolateral PFC and fusiform face area may work together to support delay-spanning interference resolution.
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BACKGROUND: Excessive behavioral inhibition during childhood marks anxious temperament and is a risk factor for the development of anxiety and affective disorders. Studies in nonhuman primates can provide important information related to the expression of this risk factor, since threat-induced freezing in rhesus monkeys is a trait-like characteristic analogous to human behavioral inhibition. The orbitofrontal cortex (OFC) and amygdala are part of a circuit involved in the processing of emotions and associated physiological responses. Earlier work demonstrated involvement of the primate central nucleus of the amygdala (CeA) in mediating anxious temperament. This study assessed the role of the primate OFC in mediating anxious temperament and its involvement in fear responses.
METHODS: Twelve adolescent rhesus monkeys were studied (six lesion and six control monkeys). Lesions were targeted at regions of the OFC that are most interconnected with the amygdala. Behavior and physiological parameters were assessed before and after the lesions.
RESULTS: The OFC lesions significantly decreased threat-induced freezing and marginally decreased fearful responses to a snake. The lesions also resulted in a leftward shift in frontal brain electrical activity consistent with a reduction in anxiety. The lesions did not significantly decrease hypothalamic-pituitary-adrenal (HPA) activity or cerebrospinal fluid (CSF) concentrations of corticotrophin-releasing factor (CRF).
CONCLUSIONS: These findings demonstrate a role for the OFC in mediating anxious temperament and fear-related responses in adolescent primates. Because of the similarities between rhesus monkey threat-induced freezing and childhood behavioral inhibition, these findings are relevant to understanding mechanisms underlying anxious temperament in humans.
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Selective attention has been shown to bias sensory processing in favor of relevant stimuli and against irrelevant or distracting stimuli in perceptual tasks. Increasing evidence suggests that selective attention plays an important role during working memory maintenance, possibly by biasing sensory processing in favor of to-be-remembered items. In the current study, we investigated whether selective attention may also support working memory by biasing processing against irrelevant and potentially distracting information. Event-related potentials (ERPs) were recorded while subjects (n = 22) performed a delayed-recognition task for faces and shoes. The delay period was filled with face or shoe distractors. Behavioral performance was impaired when distractors were congruent with the working memory domain (e.g., face distractor during working memory for faces) relative to when distractors were incongruent with the working memory domain (e.g., face distractor during shoe working memory). If attentional biasing against distractor processing is indeed functionally relevant in supporting working memory maintenance, perceptual processing of distractors is predicted to be attenuated when distractors are more behaviorally intrusive relative to when they are nonintrusive. As such, we predicted that perceptual processing of distracting faces, as measured by the face-sensitive N170 ERP component, would be reduced in the context of congruent (face) working memory relative to incongruent (shoe) working memory. The N170 elicited by distracting faces demonstrated reduced amplitude during congruent versus incongruent working memory. These results suggest that perceptual processing of distracting faces may be attenuated due to attentional biasing against sensory processing of distractors that are most behaviorally intrusive during working memory maintenance.
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Test-retest reliability of resting regional cerebral metabolic rate of glucose (rCMR) was examined in selected subcortical structures: the amygdala, hippocampus, thalamus, and anterior caudate nucleus. Findings from previous studies examining reliability of rCMR suggest that rCMR in small subcortical structures may be more variable than in larger cortical regions. We chose to study these subcortical regions because of their particular interest to our laboratory in its investigations of the neurocircuitry of emotion and depression. Twelve normal subjects (seven female, mean age = 32.42 years, range 21-48 years) underwent two FDG-PET scans separated by approximately 6 months (mean = 25 weeks, range 17-35 weeks). A region-of-interest approach with PET-MRI coregistration was used for analysis of rCMR reliability. Good test-retest reliability was found in the left amygdala, right and left hippocampus, right and left thalamus, and right and left anterior caudate nucleus. However, rCMR in the right amygdala did not show good test-retest reliability. The implications of these data and their import for studies that include a repeat-test design are considered.
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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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We investigated the top-down influence of working memory (WM) maintenance on feedforward perceptual processing within occipito-temporal face processing structures. During event-related potential (ERP) recordings, subjects performed a delayed-recognition task requiring WM maintenance of faces or houses. The face-sensitive N170 component elicited by delay-spanning task-irrelevant grayscale noise probes was examined. If early feedforward perceptual activity is biased by maintenance requirements, the N170 ERP component elicited by probes should have a greater N170 amplitude response during face relative to house WM trials. Consistent with this prediction, N170 elicited by probes presented at the beginning, middle, and end of the delay interval was greater in amplitude during face relative to house WM. Thus, these results suggest that WM maintenance demands may modulate early feedforward perceptual processing for the entirety of the delay duration. We argue based on these results that temporally early biasing of domain-specific perceptual processing may be a critical mechanism by which WM maintenance is achieved.
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In the present study, we examined the stability of one measure of emotion, the emotion-modulated acoustic startle response, in an undergraduate sample. Using the acoustic startle paradigm on two different occasions, we measured stability of affective modulation of the startle response during and following the presentation of pictures selected to be of positive, negative, or neutral emotional valence. The two assessments were separated by 4 weeks. Two groups of subjects were compared: one group that viewed the same pictures at each assessment and a second group that viewed different pictures at the second assessment. We found that viewing different pictures at two assessments separated by 4 weeks yielded moderate stability of the emotion modulation of startle magnitude, whereas subjects who viewed the same pictures at both assessments showed poor stability. Furthermore, this difference was due to the stability of responses to high versus low arousal pictures, not to differences in valence.
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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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Spatial working memory is a cognitive brain mechanism that enables the temporary maintenance and manipulation of spatial information. Recent neuroimaging and behavioral studies have led to the proposal that directed spatial attention is the mechanism by which location information is maintained in spatial working memory. Yet it is unclear whether attentional involvement is required throughout the period of active maintenance or is only invoked during discrete task-phases such as mnemonic encoding. In the current study, we aimed to track the time-course of attentional involvement during spatial working memory by recording event-related brain potentials (ERPs) from healthy volunteers. In Experiment 1, subjects performed a delayed-recognition task. Each trial began with the presentation of a brief stimulus (S1) that indicated the relevant location that subjects were to maintain in working memory. A 4.8-5.3 sec delay interval followed during which a single task-irrelevant probe was presented. The delay interval concluded with a test item (S2) to which subjects made a response indicating whether the S2-location was the same as the S1-memory location. To determine if attention was differentially engaged during discrete phases of the trial, task-irrelevant probes were presented early (400-800 msec following S1-offset) or late (2600-3000 msec following S1-offset) during the delay interval. Sensory-evoked ERPs (P1 and N1) elicited by these irrelevant probes showed attention-like modulations with greater amplitude responses for probes occurring at the S1-memory locations in comparison to probes presented at other locations. This pattern was obtained for both early- and late-delay probes. Probe-evoked activity during delayed-recognition trials was similar to activity observed when spatial attention was explicitly focused on a location in visual space (Experiment 2). These results are consistent with a model of spatial working memory in which perceptual level selective attention is utilized throughout the entire period of active maintenance to keep relevant spatial information in mind.
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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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Four experiments testing right-handed adult males examined interhemispheric transfer time (IHTT) estimation with visual evoked potentials (EPs) elicited in response to hemiretinal presentations of checkerboard-flash stimuli. Experiment 1 was a study of the relation between reaction time (RT) and EP measures of IHTT. EP measures provided more valid estimates than RT measures because more subjects showed IHTT in the direction of anatomical prediction. Experiment 2 showed that EPs derived from lateral occipital sites provided more valid and longer estimates of IHTT compared with EPs from medial occipital sites. Experiment 3 showed no difference between random versus blocked hemiretinal stimuli. Experiment 4 showed that IHTT derived with a linked-ears reference provided more valid estimates than IHTT derived with a mid-frontal reference and that small changes in stimulus eccentricity did not influence IHTT. The findings of these experiments indicate that noninvasive estimates of visual IHTT can be obtained in humans.
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Research on temporal-order judgments, reference frames, discrimination tasks, and links to oculomotor control suggest important differences between inhibition of return (IOR) and attentional costs and benefits. Yet, it is generally assumed that IOR is an attentional effect even though there is little supporting evidence. The authors evaluated this assumption by examining how several factors that are known to influence attentional costs and benefits affect the magnitude of IOR: target modality, target intensity, and response mode. Results similar to those previously reported for attention were observed: IOR was greater for visual than for auditory targets, showed an inverse relationship with target intensity, and was equivalent for manual and saccadic responses. Important parallels between IOR and attentional costs and benefits are indicated, suggesting that, like attention, IOR may in part affect sensory-perceptual processes.
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Dynamic adjustments in cognitive control are well documented in conflict tasks, wherein competition from irrelevant stimulus attributes intensifies selection demands and leads to subsequent performance benefits. The current study investigated whether mnemonic demands, in a working memory (WM) task, can drive similar online control modifications. Demand levels (high vs. low) of WM maintenance (memory load of 2 items vs. 1 item) and delay-spanning distractor interference (confusable vs. not confusable with memoranda) were manipulated using a factorial design during a WM delayed-recognition task. Performance was best subsequent to trials in which both maintenance and distractor interference demands were high, followed by trials with high demand in either of these 2 control domains, and worst following trials with low demand in both domains. These results suggest that dynamic adjustments in cognitive control are not triggered exclusively by conflict-specific contexts but are also triggered by WM demands, revealing a putative mechanism by which this system configures itself for successful task performance.
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In our database of 331 parental narratives of tantrums had by children 18–60 months old, 29% of the tantrums were followed by child-initiated affiliation with parents. Four variables increased the probability of children's post tantrum affiliation (PTA): age, prolonged screaming, physiological stress, and parent-initiated separation from the child during the tantrum. The age effect may be due to increasing post tantrum persistence of negative affect, to the emergence of shame, guilt, and embarrassment over this developmental period, and/or to increasing cognitive ability, empathic capacity, or socialization. Screaming, which may be analogous to the defensive vocalizations of nonhuman primates, increases PTA when prolonged for 6 min or more. Physiological stress (indicated by autonomic activation or respiratory distress) appears linked to prolonged screaming and may mediate its effects by increasing the child's dysphoria and need for consolation. Separation (parents' departure from the scene of the tantrum or their imposition of a time out) also appears linked to prolonged screaming and may reflect parents' response to an aversive auditory stimulus. There was no evidence that PTA was associated with the presence or degree of physically expressed anger in the tantrum. PTA may be associated with distress during the tantrum. The post conflict reconciliation which occurs in several domains of human social life may be first experienced by children in the aftermath of their tantrums. Aggr. Behav. 23:329–341, 1997. © 1997 Wiley-Liss, Inc.
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