Keiichi Onoda

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.

Does low self-esteem enhance social pain? The relationship between trait self-esteem and anterior cingulate cortex activation induced by ostracism

According to sociometer theory, self-esteem serves as a barometer of the extent to which individuals are socially included or excluded by others. We hypothesized that trait self-esteem would be related to social pain responsiveness, and we used functional magnetic resonance imaging to experimentally investigate this potential relationship. Participants (n = 26) performed a cyberball task, a computerized game of catch during which the participants were excluded from the game. Participants then rated the degree of social pain experienced during both inclusion in and exclusion from the game. Individuals with lower trait self-esteem reported increased social pain relative to individuals with higher trait self-esteem, and such individuals also demonstrated a greater degree of dorsal anterior cingulate cortex activation. A psychophysiological interaction analysis revealed a positive connectivity between the dorsal anterior cingulate and prefrontal cortices for the lower trait self-esteem group, and a corresponding negative connectivity for the higher trait self-esteem group. Heightened dorsal anterior cortex activity and a corresponding connection with the prefrontal cortex might be one possible explanation for the greater levels of social pain observed experienced by individuals with low trait self-esteem.

Decreased functional connectivity by aging is associated with cognitive decline

Aging is related to cognitive decline, and it has been reported that aging disrupts some resting state brain networks. However, most studies have focused on the default mode network and ignored other resting state networks. In this study, we measured resting state activity using fMRI and explored whether cognitive decline with aging is related to disrupted resting state networks. Independent component analysis was used to evaluate functional connectivity. Notably, the connectivity within the salience network that consisted of the bilateral insula and the anterior cingulated cortex decreased with aging; the impairment of functional connectivity was correlated with measured decreases in individual cognitive abilities. Furthermore, certain internetwork connectivities (salience to auditory, default mode to visual, etc.) also decreased with aging. These results suggest that (1) aging affects not only the default mode network but also other networks, specifically the salience network; (2) aging affects internetwork connectivity; and (3) disruption of the salience network is related to cognitive decline in elderly people.

Decreased ventral anterior cingulate cortex activity is associated with reduced social pain during emotional support

Abstract People feel psychological pain when they are excluded, and this pain is often attenuated when emotional support is received. It is therefore likely that a specific neural mechanism underlies the detection of social exclusion. Similarly, specific neural mechanisms may underlie the beneficial effects of emotional support. Although neuroimaging researchers have recently examined the neural basis of social pain, there is presently no agreement as to which part of the anterior cingulate cortex (ACC) is involved in the perception and modulation of social pain. We hypothesized that activity in those brain regions that are associated with social pain would be correlated with decrements in social pain induced by emotional support. To examine the effects of emotional support on social pain caused by exclusion, we conducted an fMRI study in which participants played a virtual ball-tossing game. Participants were initially included and later excluded from the game. In the latter half of the session from which participants were excluded, participants received emotionally supportive text messages. We found that emotional support led to increased activity in the left lateral/medial prefrontal cortices and some temporal regions. Those individuals who experienced greater attenuation of social pain exhibited lower ventral ACC and higher left lateral prefrontal cortex activation. These results suggest that the ventral ACC underlies social pain, and that emotional support enhances prefrontal cortex activity, which in turn may lead to a weakened affective response.

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.

Personality traits and the amplitude of spontaneous low-frequency oscillations during resting state.

Recently, neural substrates of the Big Five personality model were investigated using neuroimaging. We examined the relationships between the amplitude of spontaneous low-frequency oscillations (LFO) and the Big Five traits using resting-state functional magnetic resonance imaging (R-fMRI). Twenty-four healthy right-handed undergraduates (23.13±1.87 years, 9 males and 15 females) participated in 5-min R-fMRI and completed the NEO Five-Factor Inventory. We observed that Neuroticism correlated negatively with regional activity of the middle frontal gyrus and precuneus; Extraversion correlated positively with regional activity of the striatum, precuneus, and superior frontal gyrus; Openness correlated positively with the thalamus and amygdala, and negatively with the superior frontal gyrus; Conscientiousness correlated positively with regional activity of the middle frontal gyrus and correlated negatively with the cerebellum. Our results revealed the neural substrates of Extraversion, Neuroticism, Openness, and Conscientiousness in the amplitude of spontaneous LFO.

Neural processing of negative word stimuli concerning body image in patients with eating disorders: An fMRI study

Eating disorders (EDs) are associated with abnormalities of body image perception. The aim of the present study was to investigate the functional abnormalities in brain systems during processing of negative words concerning body images in patients with EDs. Brain responses to negative words concerning body images (task condition) and neutral words (control condition) were measured using functional magnetic resonance imaging in 36 patients with EDs (12 with the restricting type anorexia nervosa; AN-R, 12 with the binging-purging type anorexia nervosa; AN-BP, and 12 with bulimia nervosa; BN) and 12 healthy young women. Participants were instructed to select the most negative word from each negative body-image word set and to select the most neutral word from each neutral word set. In the task relative to the control condition, the right amygdala was activated both in patients with AN-R and in patients with AN-BP. The left medial prefrontal cortex (mPFC) was activated both in patients with BN and in patients with AN-BP. It is suggested that these brain activations may be associated with abnormalities of body image perception. Amygdala activation may be involved in fearful emotional processing of negative words concerning body image and strong fears of gaining weight. One possible interpretation of the finding of mPFC activation is that it may reflect an attempt to regulate the emotion invoked by the stimuli. These abnormal brain functions may help provide better accounts of the psychopathological mechanisms underlying EDs.

Sadness enhances the experience of pain via neural activation in the anterior cingulate cortex and amygdala: An fMRI study

Pain is a multidimensional experience. Human pain perception can be modulated by subjective emotional responses. We examined this association within the context of a neuroimaging study, using functional MRI to examine neural responses to electrical pain-inducing stimuli in 15 healthy subjects (6 females; age range=20-30 years). Pain-inducing stimuli were presented during different emotional contexts, which were induced via the continuous presentation (5 s) of sad, happy, or neutral pictures of faces. We found that subjective pain ratings were higher in the sad emotional context than in the happy and neutral contexts, and that pain-related activation in the ACC was more pronounced in the sad context relative to the happy and neutral contexts. Psychophysiological interaction (PPI) and dynamic causal modeling (DCM) analyses demonstrated amygdala to ACC connections during the experience of pain in the sad context. These findings serve to highlight the neural mechanisms that may be relevant to understanding the broader relationship between somatic complaints and negative emotion.

Modulation of default-mode network activity by acute tryptophan depletion is associated with mood change: A resting state functional magnetic resonance imaging study

Recently, resting-state fMRI (R-fMRI) has attracted interest based on its ability to detect the default mode network. We examined the effect of acute tryptophan depletion (ATD) on the fractional amplitude of low-frequency fluctuation (fALFF) during the resting state, and the correlation between changes of mood and fALFF following ATD. We manipulated the central serotonergic levels of 21 right-handed healthy males (mean age=21.57±1.83 years) following ATD. A within-subjects, double-blind, placebo-controlled, and counter-balanced design was employed. Following ATD or sham depletion, subjects completed the Profile of Mood States (POMS) and underwent 5-min R-fMRI scans. Our findings show that the fALFF of the middle orbitofrontal cortex and precuneus was significantly decreased and the fALFF of the superior parietal lobule, paracentral lobule and precentral gyrus was significantly increased after ATD. The fALFF of the orbitofrontal cortex was negatively correlated with depressive mood. The fALFF of the superior parietal lobule was positively correlated with anger-hostility and the fALFF of the paracentral lobule was negatively correlated with vigor-activity. The middle orbitofrontal cortex plays a key role in serotonin depletion-induced brain changes and individual differences in depressive mood change. These results serve to further elucidate the mechanism of ATD-induced relapse in remitted MDD patients.

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.