Kazutaka Ueda

Rostral anterior cingulate cortex activity mediates the relationship between the depressive symptoms and the medial prefrontal cortex activity

BACKGROUND Depression is characterized by enhanced self-referential processing of negative emotional stimuli. Imaging studies have suggested that activation of both the medial prefrontal (MPFC) and anterior cingulate cortices (ACC) is associated with self-referential processing. However, whether this pattern of activation occurs in depressed individuals during the self-referential processing of the emotional stimuli had not been investigated to date. METHODS Participants were 13 patients with major depressive disorder and 13 normal controls. We used block-designed functional magnetic resonance imaging (fMRI) to investigate neural activity during the self-referential judgments of positive and negative valenced personality trait words. RESULTS Compared with the normal controls, the depressed patients showed hyperactivity in the MPFC and the rostral ACC during the self-referential processing of negative words. In addition, the activity of these regions during self-referential processing of the negative stimuli was correlated with the depressive symptom severity. The rostral ACC activity mediated the correlation between the MPFC activity and the depressive symptoms. Functional connectivity analysis revealed positive connectivities between the MPFC, the rostral ACC, and the amygdala. LIMITATION Small N and antidepressant effect on imaging data limit the stability of reported findings. CONCLUSIONS The relationships between the MPFC, the rostral ACC, and the amygdala appear to reflect an interaction between the self-referential processing and the negative emotional information processing, and we propose that the strong connection between the MPFC and the rostral ACC is associated with depressive symptoms.

Brain activity during expectancy of emotional stimuli : An fMRI study

We studied the neural activation associated with the expectancy of emotional stimuli using whole brain fMRI. Fifteen healthy subjects underwent fMRI scanning during which they performed a warned reaction task using emotional pictures carrying pleasant, unpleasant, or neutral content. The task involved an expected or unexpected condition. Data were analyzed by comparing the images acquired under the different conditions. In the expected condition, compared with the unexpected condition, significant activation was observed in the medial, inferior and dorsolateral prefrontal cortex. Whereas the expectancy of pleasant stimuli produced activation in the left dorsolateral and left medial prefrontal cortex as well as in the right cerebellum, the expectancy of unpleasant stimuli produced activation in the right inferior and right medial prefrontal cortex, the right amygdala, the left anterior cingulate cortex, and bilaterally in the visual cortex. These results suggest that the expectancy of emotional stimuli is mediated by the prefrontal area including the medial, inferior, and dorsolateral prefrontal cortex. Furthermore, our data suggest that left frontal activation is associated with the expectancy of pleasant stimuli and that right frontal activation is associated with the expectancy of unpleasant stimuli. Finally, our findings suggest that the amygdala and anterior cingulate cortex may play an important role in the expectancy of unpleasant stimuli and that the input of this negative information is modulated by these specific brain areas.

Cognitive behavioral therapy for depression changes medial prefrontal and ventral anterior cingulate cortex activity associated with self-referential processing

Cognitive behavioral therapy (CBT), an effective treatment for depression, targets self-referential processing of emotional stimuli. We examined the effects of CBT on brain functioning during self-referential processing in depressive patients using functional magnetic resonance imaging (fMRI). Depressive patients (n = 23) and healthy participants (n = 15) underwent fMRI scans during a self-referential task using emotional trait words. The depressive patients had fMRI scans before and after completing a total of 12 weekly sessions of group CBT for depression, whereas the healthy participants underwent fMRI scans 12 weeks apart with no intervention. Before undergoing CBT, the depressive patients showed hyperactivity in the medial prefrontal cortex (MPFC) during self-referential processing of negative words. Following CBT, MPFC and ventral anterior cingulate cortex (vACC) activity during self-referential processing among depressive patients was increased for positive stimuli, whereas it was decreased for negative stimuli. Improvements in depressive symptoms were negatively correlated with vACC activity during self-referential processing of negative stimuli. These results suggest that CBT-related improvements in depressive symptoms are associated with changes in MPFC and vACC activation during self-referential processing of emotional stimuli.

Self-referential processing of negative stimuli within the ventral anterior cingulate gyrus and right amygdala

Neural activity associated with self-referential processing of emotional stimuli was investigated using whole brain functional magnetic resonance imaging (fMRI). Fifteen healthy subjects underwent fMRI scanning while making judgments about positive and negative trait words in four conditions (self-reference, other-reference, semantic processing, and letter processing). Significant activity was observed in the right ventral anterior cingulate gyrus and the right amygdala in the negative-word/self-reference condition, and in the left amygdala in the positive-word/self-reference condition. Compared with the semantic-processing condition, the self-reference conditions showed significantly more activity in the medial prefrontal and temporal gyri, posterior cingulate gyrus, and precuneus. These results suggest that the medial prefrontal gyrus, posterior cingulate gyrus, and precuneus are associated with a self-referential processing, and the ventral anterior cingulate gyrus is involved in self-referential processing of negative emotional stimuli. The results also suggest that the amygdala is associated with self-referential processing of both positive and negative emotional stimuli.

Anterior cingulate cortex modulates preparatory activation during certain anticipation of negative picture

We studied the neural activation associated with anticipations of emotional pictures using functional magnetic resonance imaging (fMRI) by directly comparing certain with uncertain anticipation conditions. While being scanned with fMRI, healthy participants (n=18) were cued to anticipate and then perceive emotional stimuli having predictable (i.e., certain) emotional valences (i.e., positive and negative), given a preceding cue, as well as cued stimuli of uncertain valence (positive or negative). During anticipation of pictures with certain negative valence, activities of supracallosal anterior cingulate cortex, ventrolateral prefrontal cortex, insula, and amygdala were enhanced relative activity levels that for the uncertain emotional anticipation condition. This result suggests that these brain regions are involved in anticipation of negative images, and that their activity levels may be enhanced by the certainty of anticipation. Furthermore, the supracallosal anterior cingulate cortex showed functional connectivity with the insula, prefrontal cortex, and occipital cortex during the certain negative anticipation. These findings are consistent with an interpretation that top-down modulation, arising from anterior brain regions, is engaged in certain negative anticipation within the occipital cortex. It is thought that the limbic system involving the amygdala, ACC, and insula, engaged emotional processes, and that the input system involving the visual cortex entered an idling state.

Anticipation of affective images and event-related desynchronization (ERD) of alpha activity : An MEG study

We investigated the event-related power decrease (event-related desynchronization: ERD) of the alpha bands associated with the anticipation of affective images. Participants (n=19) were presented with emotionally positive or negative images under different anticipatory conditions, and their brain responses were recorded using magnetoencephalography (MEG). In the Affective Cue conditions, the cue stimulus indicated the emotional valence (positive or negative) of the image. In the Null Cue condition, the cue stimulus did not include any information about the valence of the image, and in the No Cue condition, the affective image was presented without a preceding cue. The cues in the affective and null conditions were followed by emotional images. During the anticipation period for the affective image, the alpha ERD preceding an anticipated negative image was larger than that preceding an anticipated positive image; this effect had an occipital dominance. Furthermore, during the anticipation period, the lower-2-alpha ERD of the right frontal area showed the same result. These results demonstrate that anticipation of negative stimuli induced alpha ERD in both the visual and the right frontal cortex, indicating that top-down modulation may be provided by the right frontal cortex to the visual cortex.

Effects of depression on reward-based decision making and variability of action in probabilistic learning

BACKGROUND AND OBJECTIVES Depression is characterized by low reward sensitivity in behavioral studies applying signal detection theory. We examined deficits in reward-based decision making in depressed participants during a probabilistic learning task, and used a reinforcement learning model to examine learning parameters during the task. METHODS Thirty-six nonclinical undergraduates completed a probabilistic selection task. Participants were divided into depressed and non-depressed groups based on Center for Epidemiologic Studies-Depression (CES-D) cut scores. We then applied a reinforcement learning model to every participants behavioral data. RESULTS Depressed participants showed a reward-based decision making deficit and higher levels of the learning parameter τ, which modulates variability of action selection, as compared to non-depressed participants. Highly variable action selection is more random and characterized by difficulties with selecting a specific course of action. CONCLUSION These results suggest that depression is characterized by deficits in reward-based decision making as well as high variability in terms of action selection.

Attenuated prefrontal activation during a verbal fluency task in remitted major depression

The aim of the present study was to investigate whether a functional abnormality in the left prefrontal cortex observed in patients with major depression performing a verbal fluency task is present after remission of depression. Functional magnetic resonance imaging was used to study changes in cerebral blood oxygenation in eight remitted patients with major depression and 10 healthy control subjects during a verbal fluency task. Compared to the control subjects, the patients had a reduced response in the left prefrontal cortex (middle frontal gyrus, Brodmann area 10). These findings suggest the presence of dysfunction in the left prefrontal cortex during remission in major depression.

Gender differences in brain activity toward unpleasant linguistic stimuli concerning interpersonal relationships: an fMRI study

AbstractWomen are more vulnerable to psychosocial stressors such as interpersonal conflicts than men, and are more susceptible to some psychiatric disorders. We hypothesized that there are differences in the brain activity of men and women while perceiving unpleasant linguistic stimuli concerning interpersonal relationships, and that they underlie the different sensitivity toward these stressful stimuli.We carried out a functional magnetic resonance imaging (fMRI) study on 13 young female adults and 13 young male adults who performed an emotional decision task including sets of unpleasant words concerning interpersonal relationships and sets of neutral words.In the women, the unpleasant words more significantly activated the bilateral caudate nuclei and left putamen than the neutral words. However, among the men, there was no difference in the level of activation of any brain area induced by the unpleasant or neutral word stimuli. Upon performing the task, there was a significant gender difference in brain activation. Moreover, among the female subjects, the activation in the bilateral caudate nuclei and left thalamus was negatively correlated with the average rating of pleasantness of the words concerning interpersonal conflicts by the subject.These results demonstrate gender differences in brain activity in processing unpleasant linguistic stimuli related to interpersonal conflicts. Our data suggest that the bilateral caudate nuclei and left putamen play an important role in the perception of words concerning interpersonal conflicts in women. The bilateral caudate nuclei and left thalamus may regulate a woman’s sensitivity to unpleasant information about interpersonal difficulties.

Possible involvement of rumination in gray matter abnormalities in persistent symptoms of major depression: An exploratory magnetic resonance imaging voxel-based morphometry study

BACKGROUND A recent meta-analysis of many magnetic resonance imaging (MRI) studies has identified brain regions with gray matter (GM) abnormalities in patients with major depressive disorder (MDD). A few studies addressing GM abnormalities in patients with treatment-resistant depression (TRD) have yielded inconsistent results. Moreover, although TRD patients tend to exhibit ruminative thoughts, it remains unclear whether rumination is related to GM abnormalities in such patients or not. METHODS We conducted structural MRI scans and voxel-based morphometry (VBM) to identify GM differences among 29 TRD patients and 29 healthy age-matched and sex-matched controls. A response style questionnaire was used to assess the respective degrees of rumination in TRD patients. Structural correlates of rumination were examined. RESULTS TRD patients showed several regions with smaller GM volume than in healthy subjects: the left dorsal anterior cingulate cortex (ACC), right ventral ACC, right superior frontal gyrus, right cerebellum (Crus I), and cerebellar vermis. GM volumes in these regions did not correlate to rumination. However, whole-brain analysis revealed that rumination was positively correlated with the GM volume in the right superior temporal gyrus in TRD patients. LIMITATIONS Structural correlates of rumination were examined only in TRD patients. CONCLUSIONS Our data provide additional evidence supporting the hypothesis that TRD patients show GM abnormalities compared with healthy subjects. Furthermore, this report is the first to describe a study identifying brain regions for which the GM volume is correlated with rumination in TRD patients. These results improve our understanding of the anatomical characteristics of TRD.