Hippocampal activation during associative encoding of word pairs and its relation to symptomatic improvement in depression: a functional and volumetric MRI study.

BACKGROUND: Altered emotional memory is one of the core cognitive functions that causes and maintains depression. Although many studies have investigated the relationship between hippocampal volume, depression and treatment response, no studies have investigated the relationship for hippocampal activity. Additionally, few studies have examined the relationship between functional and structural abnormalities in depression. METHODS: We conducted a functional and volumetric MRI study investigating associative encoding of positive, negative and neutral word pairs in 13 healthy controls, and 14 untreated depressives. We carried out fMRI during a memory-encoding task at baseline. Treatment response was clinically assessed six weeks after pharmacotherapy began. Then, we explored the relation between brain activation during encoding of each word pair and symptomatic improvement. RESULTS: Relative to controls, depressives exhibited decreased activity in the left hippocampus during encoding positive word pairs and, in contrast, increased activity in the right hippocampus during encoding negative or neutral word pairs. Poor response to treatment was associated with smaller activation within the left hippocampus during the memory encoding of positive word pairs. Overall results were not confounded by hippocampal volume. LIMITATIONS: We could not appreciate any disease alteration during the retrieving phase. CONCLUSION: We found qualitative differences in hippocampus functioning between depressives and healthy controls. In addition, the left hippocampus could have an effect on treatment response in depression by contributing to the dysfunctional encoding of positive information.

Distinctive neural responses to pain stimuli during induced sadness in patients with somatoform pain disorder: An fMRI study.

Pain is a multidimensional phenomenon. Patients with somatoform pain disorder suffer from long-lasting pain, with the pathology being closely associated with cognitive-emotional components. Differences between these patients and controls in cerebral responses to pain stimuli have been reported. However, to our knowledge, no studies of somatoform pain disorder have evaluated altered pain-related brain activation as modulated by emotional dysregulation. We examined the distinct neural mechanism that is engaged in response to two different pain intensities in a sad emotional condition, performing functional magnetic resonance imaging (fMRI) on a group of 11 somatoform pain patients and an age-matched control group. Our results showed that the ratio for low-pain intensity ratings between the sad and neutral conditions in patients was higher than in controls. They also showed significant increased activation in the anterior/posterior insula in the low pain sadness condition. Furthermore, there was specific functional connectivity between the anterior insula and the parahippocampus in patients during presentation of low-pain stimuli in the sad context. These findings suggest that a negative emotional context such as sadness contributes to dysfunctional pain processing in somatoform pain disorder. Greater sensitivity to low levels of pain in an emotional context of sadness might be an important aspect of the psychopathology of somatoform pain disorder.

Automatic and intentional brain responses during evaluation of face approachability: correlations with trait anxiety.

BACKGROUND: The judgment of the approachability of others based on their facial appearance often precedes social interaction. Whether we ultimately approach or avoid others may depend on such judgments. METHOD: We used functional magnetic resonance imaging to determine the neural basis for such approachability judgments and the relationship between these judgments and trait anxiety. Participants viewed ambiguous (i.e. neutral) or relatively unambiguous (i.e. angry, happy) faces, assessing either the approachability or the sex of the person depicted. RESULTS: Neutral faces elicited more inconsistent responses within participants only during approachability judgment, suggesting ambiguous property as signals. The contrast pertaining to the interaction between task and face valence demonstrated activation in several areas, such that the left amygdala and medial, middle and inferior frontal gyri were responsive to angry faces when subjects were asked to recognize the sex (implicit task) and to neutral faces when required to discern the approachability (explicit task). Moreover, the blood oxygenation level-dependent change within the left amygdala in response to neutral faces during the judgment of approachability was positively correlated with participant trait anxiety. CONCLUSIONS: These findings extend a proposed model of social cognition by highlighting the functional engagement of the amygdala in approachability judgments, which underlie an individual's sensitivity to ambiguous sources of probable threat.

[Effects of serotonin on delay discounting for rewards--an application for understanding of pathophysiology in psychiatric disorders].

In our daily life, we constantly make such choices between actions leading to rewards of various sizes after different delays. "Delay discounting" is a theoretical concept in which the "value" of reward R after delay. A steep rate of discounting results in impulsive choice, defined by an abnormally frequent choice of the more immediate reward. Our behavioral and neuroimaging results suggest that serotonin may adjust the rate of delayed reward discounting via the modulation of striatum in cortico-basal ganglia circuits in human. Our proposed role of serotonin may explain certain aspects of impulsivity in psychiatric disorders such as major depression, panic disorder or obsessive-compulsive disorder, that are known to effectively relieve symptoms by selective serotonin reuptake inhibitors. Future experiments using delayed reward paradigms could be designed to study impulsivity in these patients.