Altered emotional and locomotor responses in mice deficient in the transcription factor CREM.
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Various transcription factors act as nuclear effectors of the cAMP-dependent signaling pathway. These are the products of three genes in the mouse, CREB, CRE modulator (CREM), and ATF-1. CREM proteins are thought to play important roles within the hypothalamic-pituitary axis and in the control of rhythmic functions in the pineal gland. We have generated CREM-mutant mice and investigated their response in a variety of behavioral tests. CREM-null mice show a drastic increase in locomotion. In contrast to normal mice, the CREM-deficient mice show equal locomotor activity during the circadian cycle. The anatomy of the hypothalamic suprachiasmatic nuclei, the center of the endogenous pacemaker, is normal in mutant mice. Remarkably, CREM mutant mice also elicit a different emotional state, revealed by a lower anxiety in two different behavioral models, but they preserve the conditioned reactiveness to stress. These results demonstrate the high degree of functional specificity of each cAMP-responsive transcription factor in behavioral control. (+info)
Emotional outcomes after stroke: factors associated with poor outcome.
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OBJECTIVES: The impact of stroke on the emotional outcome of patients is large. The aim was to describe the emotional outcomes among a cohort of patients which was of sufficient size to provide a precise estimate of their frequency and help identify those factors which are associated with poor outcomes after an acute stroke. METHODS: 372 surviving patients, who had been referred to a hospital and entered into a randomised trial to evaluate a stroke family care worker, were asked to complete questionnaires at a 6 month follow up. These included measures of emotional distress (general health questionnaire 30 item, hospital anxiety and depression scale) and physical functioning (modified Rankin, Barthel index). A regression analysis was used to identify factors which were independently associated with poor outcomes. RESULTS: 184 (60%) surviving patients scored more than 4 on the GHQ-30, 55 (22%) more than 8 on the HAD anxiety subscale, and 49 (20%) more than 8 on the HAD depression subscale. Patients with severe strokes resulting in physical disability were more likely to be depressed whereas there was a less strong relation between disability and anxiety. Patients with posterior circulation strokes had consistently better emotional outcomes than those with anterior circulation strokes. CONCLUSIONS: These data may help identify those patients at greatest risk of poor emotional outcomes and thus help in planning trials and delivering appropriate interventions. (+info)
Statistical methods for characterizing similarities and differences between semantic structures.
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This paper describes a variety of statistical methods for obtaining precise quantitative estimates of the similarities and differences in the structures of semantic domains in different languages. The methods include comparing mean correlations within and between groups, principal components analysis of interspeaker correlations, and analysis of variance of speaker by question data. Methods for graphical displays of the results are also presented. The methods give convergent results that are mutually supportive and equivalent under suitable interpretation. The methods are illustrated on the semantic domain of emotion terms in a comparison of the semantic structures of native English and native Japanese speaking subjects. We suggest that, in comparative studies concerning the extent to which semantic structures are universally shared or culture-specific, both similarities and differences should be measured and compared rather than placing total emphasis on one or the other polar position. (+info)
Not if, but how: one way to talk with patients about forgoing life support.
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May the common clinical conversation be used to explore whether or not seriously ill patients want to talk about possible limitations of life support? In order to answer this question, a series of 20 seriously ill patients took part in an interview. The clinical conversations were taped and transcribed, and recurrent themes were identified and organised into categories. After talking about their diagnosis and prognosis, most patients said it was natural to talk about possible limitations of life support, and a substantial number immediately indicated that they did not want any life-sustaining treatment. Although their emotional reactions were different, no one seemed to be upset by talking about such issues. Many but not all patients said that they wanted a family member and possibly also a nurse to participate in the conversation. Every doctor learns to conduct a clinical conversation and this approach may be applied when talking with seriously ill patients about difficult treatment decisions. (+info)
Tryptophan enhancement/depletion and reactions to failure on a cooperative computer game.
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Twenty-eight high trait hostility male volunteers played a "cooperative" computer game 4.5 hours after an amino acid drink enhanced with, or depleted of, tryptophan. Each trial involved steering a tank through minefields following directions from an unknown "partner." Failure was experienced when the tank hit a mine or when time ran out. Subjects' moods, verbal aggression, attributions of blame, vocal acoustics, and blood pressure were assessed. Differences between tryptophan groups were not significant for primary measures of anger and verbal aggression. However, depleted subjects reported greater increases in feelings of restlessness and incompetence, were less successful in avoiding mines and showed greater increases in blood pressure during the game. Subjects in both groups sent more negative ratings when they lost the game by virtue of hitting a mine rather than losing by running out of time. However, ratings of the depleted group were less influenced by the reason for losing the game. Also, vocal acoustics showed a group X reason-for-losing interaction in the high-frequency band. Tryptophan-depleted subjects with high scores on Behavioral-Activation-System-Drive were most likely to send negative ratings and those scoring high on Buss-Durkee Hostility Inventory Assault and Guilt to report increased anger after the game. (+info)
Serotonin reuptake inhibition by citalopram in rat strains differing for their emotionality.
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Acute administration of the selective serotonin (5-HT) reuptake inhibitor (SSRI), citalopram (1-10 mg/kg, i.p. 1 h before an elevated plus-maze test), to Spontaneously Hypertensive rats (SHRs), Lewis (LEW) rats, and Wistar-Kyoto (WKY) rats, i.e., rat strains differing for their emotionality, promoted anxiety, and/or hypoactivity, except in WKY rats. In the three strains, such a pretreatment increased central 5-HT levels and/or decreased 5-hydroxyindoleacetic acid levels. Hippocampal, but not midbrain or striatal, [3H]citalopram binding at 5-HT transporters was lower in WKY rats than in SHRs. However, neither [3H]5-HT reuptake kinetics nor the potencies of citalopram (1-1000 nM) to inhibit [3H]5-HT reuptake into hippocampal and striatal synaptosomes differed between strains. This was confirmed in vivo by means of microdialysis in the hippocampus of freely moving rats. Thus, although LEW rats displayed a 3-4 fold higher baseline level of extracellular 5-HT in the hippocampus, compared with SHRs and WKY rats, local perfusion with 1 microM citalopram promoted relative increases in extracellular 5-HT levels over baseline that were similar in all strains. Lastly, acute i.p. administration of 3.3 mg/kg citalopram (1 h beforehand) decreased to similar extents [3H]5-HT reuptake into hippocampal synaptosomes from SHRs and WKY rats. This study indicates that genetic differences in the behavioural responses to SSRIs may involve 5-HT transporter-independent mechanisms. (+info)
Cognitive response profile of the human fusiform face area as determined by MEG.
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Activation in or near the fusiform gyrus was estimated to faces and control stimuli. Activation peaked at 165 ms and was strongest to digitized photographs of human faces, regardless of whether they were presented in color or grayscale, suggesting that face- and color-specific areas are functionally separate. Schematic sketche evoked approximately 30% less activation than did face photographs. Scrambling the locations of facial features reduced the response by approximately 25% in either hemisphere, suggesting that configurational versus analytic processing is not lateralized at this latency. Animal faces evoked approximately 50% less activity, and common objects, animal bodies or sensory controls evoked approximately 80% less activity than human faces. The (small) responses evoked by meaningless control images were stronger when they included surfaces and shading, suggesting that the fusiform gyrus may use these features in constructing its face-specific response. Putative fusiform activation was not significantly related to stimulus repetition, gender or emotional expression. A midline occipital source significantly distinguished between faces and control images as early as 110 ms, but was more sensitive to sensory qualities. This source significantly distinguished happy and sad faces from those with neutral expressions. We conclude that the fusiform gyrus may selectively encode faces at 165 ms, transforming sensory input for further processing. (+info)
Functional dissociation between medial and lateral prefrontal cortical spatiotemporal activation in negative and positive emotions: a combined fMRI/MEG study.
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The orbitofrontal cortex has been cytoarchitectonically and connectionally subdivided into a medial and a lateral part which are assumed to subserve distinct functions in emotional processing. However the exact spatiotemporal mechanisms of negative and positive emotional processing in medial and lateral orbitofrontal cortex remain unclear. We therefore investigated spatiotemporal orbitofrontal and prefrontal cortical activation patterns during emotional stimulation in a combined fMRI/MEG study. We investigated 10 healthy subjects, 5 women and 5 men. Positive and negative pictures from the International Affective Picture system (IAPS) were used for emotional stimulation, whereas neutral and gray pictures were taken as control conditions. fMRI/MEG measurements covered the whole frontal lobe and a time window between -2000 and +200 ms around motor responses (right index finger extension) associated with each picture. Positively and negatively correlated activities were determined in various prefrontal/frontal cortical regions in fMRI. Isocontour maps and single dipoles in MEG were analyzed in 50 ms time windows ranging from -2000 to +200 ms. Dipoles and fMR images were mapped on three-dimensional anatomical MRI so that anatomical localization of single dipoles and regional fMRI activity could be compared. Both negative and positive emotional conditions differed from non-emotional control conditions by strong orbitofrontal and lateral prefrontal activation as well as by the presence of early magnetic fields (-1700 to +1100 ms). Negative emotional processing was characterized by strong medial orbitofrontal activation and earlier (-1700 ms), stronger and more medially oriented orbitofrontal dipoles. In contrast positive emotional processing showed a rather strong activation in lateral prefrontal cortex with later (-1500 ms), weaker and more laterally oriented orbito and prefrontal dipoles. Negative emotional processing can be characterized by strong and early medial orbitofrontal cortical activation, whereas positive emotional processing showed rather later and weaker activation in lateral orbitofrontal/prefrontal cortex. Such a functional dissociation between medial and lateral orbito-frontal/prefrontal cortex during negative and positive emotional processing lends further support to the assumption of a functional subdivision in the orbitofrontal cortex. (+info)