Increased amygdala reactivity following early life stress: a potential resilience enhancer role.

BACKGROUND: Amygdala hyper-reactivity is sometimes assumed to be a vulnerability factor that predates depression; however, in healthy people, who experience early life stress but do not become depressed, it may represent a resilience mechanism. We aimed to test these hypothesis examining whether increased amygdala activity in association with a history of early life stress (ELS) was negatively or positively associated with depressive symptoms and impact of negative life event stress in never-depressed adults. METHODS: Twenty-four healthy participants completed an individually tailored negative mood induction task during functional magnetic resonance imaging (fMRI) assessment along with evaluation of ELS. RESULTS: Mood change and amygdala reactivity were increased in never-depressed participants who reported ELS compared to participants who reported no ELS. Yet, increased amygdala reactivity lowered effects of ELS on depressive symptoms and negative life events stress. Amygdala reactivity also had positive functional connectivity with the bilateral DLPFC, motor cortex and striatum in people with ELS during sad memory recall. CONCLUSIONS: Increased amygdala activity in those with ELS was associated with decreased symptoms and increased neural features, consistent with emotion regulation, suggesting that preservation of robust amygdala reactions may reflect a stress buffering or resilience enhancing factor against depression and negative stressful events.

Effectiveness of group cognitive behavioral therapy for somatoform pain disorder patients in Japan: A preliminary non-case-control study.

AIMS: Somatoform pain disorder is associated with psychosocial dysfunction, and psychotherapies, such as cognitive behavioral therapy (CBT), are thought to provide useful interventions to address such dysfunction as well as the pain itself. However, little is known about whether CBT for somatoform pain disorder is effective, including the long-term course of the illness, in non-Western populations. We therefore tailored such a program based on an existing CBT protocol and examined its effectiveness in Japan. METHODS: Thirty-four Japanese participants (22 women; mean age = 52.5 years) enrolled in a weekly 12-session group treatment, with 32 completing both wait-list and treatment conditions. The primary outcome measure was pain intensity. Secondary outcome measures included pain characteristics, as measured by pain catastrophizing and psychometric evaluations, including depression, anxiety, and quality of life. The patients were followed up for 12 months after treatment. RESULTS: We found that pain intensity, anxiety, depressive symptoms, and social functioning all significantly improved after treatment compared with the wait-list period, and the improvements in pain intensity, depressive symptoms, and social functioning were sustained at 12 months following the completion of CBT. There were strong positive correlations (P < 0.01) among pre- and post-treatment changes in the affective dimension of pain, depression, anxiety, and pain catastrophizing. CONCLUSIONS: These results show that the present CBT program was effective for Japanese patients with somatoform pain disorder and that gains were maintained over the long term. More work is needed to further clarify the effects of CBT interventions on somatoform symptoms, particularly in Japan.

The neurocognitive effects of aripiprazole compared with risperidone in the treatment of schizophrenia.

Aripiprazole is a D2 and D3 receptor partial agonist that is unlike other second generation antipsychotics. The effectiveness of aripiprazole with regard to neurocognitive function and its adverse effects is unclear. The present study evaluates the comparative efficacy, effects on neurocognitive function, and adverse effects of aripiprazole and risperidone in the treatment of hospitalized patients with schizophrenia. This double-blind, cross-over study included 23 patients with schizophrenia who were randomly assigned to be treated first with either aripiprazole or risperidone. After eight weeks on one medication, the patients were switched to the other medication for eight weeks. The patient assessment included the Positive and Negative Syndrome Scale (PANSS), neurocognitive assessments, and adverse events including extrapyramidal symptoms, vital signs, electrocardiogram, and clinical laboratory tests. The study findings indicated that psychopathology assessed with the PANSS, extrapyramidal symptoms and other adverse effects did not differ between aripiprazole and risperidone for the subjects remaining in treatment. In the neurocognitive assessments, the score for disinhibition with aripiprazole was significantly lower than with risperidone (p < 0.05). In addition, serum prolactin levels were significantly lower with aripiprazole (p < 0.001). The treatment drop-out rate was higher for patients receiving aripiprazole than risperidone. In comparing aripiprazole and risperidone, risperidone is better from the viewpoint of treatment continuation. On the other hand, some adverse effects, such as hyperprolactinemia and disinhibition, are less severe with aripiprazole. Thus, for certain applications, aripiprazole may be a beneficial new treatment option for schizophrenia.

Sex differences in neural activation to ambiguous facial expression in happy and sad context.

Functional magnetic resonance imaging (fMRI) was used to investigate brain activation associated with a facial expression identification task (stimuli were full emotional, half emotional, or ambiguous in both happy and sad context) in 10 men and 10 women, fMRI assessment revealed significant interaction of sex x context in the right putamen for the ambiguous faces. Women showed a greater BOLD response to ambiguous facial expression in the sad context than in the happy context, while men showed a greater response in the happy context. Further, women showed a greater BOLD response than did men to ambiguous facial expression in the sad context, while men showed a greater response than women in the happy context. These results suggest that sad and happy context differentially modulate right putamen activation related to processing of ambiguous facial expression in men and women.

[Cognition, behavior and emotion in psychotherapy--an example of cognitive behavioral therapy for depression].

The development of neuroimaging methods has enabled significant advances toward elucidating the mechanism of cognition, behavior and emotion. This article first reviews recent human neuroimaging studies that examined the neurocircuitry of emotion and emotion regulation. Next, we review the neuroimaging literature of the effects of cognitive behavioral therapy for depression. Lastly, we provide the brain mechanism that the emotional support regulates psychological pain in ostracism, and then discuss a biological model of psychotherapy. We hope that the present review can help us, not only to better understand the biological basis of cognition, behavior and emotion in psychotherapy, but also to be aware of effects of psychotherapy on brain.

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.

Psychosocial functioning in patients with Treatment-Resistant Depression after group cognitive behavioral therapy.

BACKGROUND: Although patients with Treatment Resistant Depression (TRD) often have impaired social functioning, few studies have investigated the effectiveness of psychosocial treatment for these patients. We examined whether adding group cognitive behavioral therapy (group-CBT) to medication would improve both the depressive symptoms and the social functioning of patient with mild TRD, and whether any improvements would be maintained over one year. METHODS: Forty-three patients with TRD were treated with 12 weekly sessions of group-CBT. Patients were assessed with the Global Assessment of Functioning scale (GAF), the 36-item Short-Form Health Survey (SF-36), the Hamilton Rating Scale for Depression (HRSD), the Dysfunctional Attitudes Scale (DAS), and the Automatic Thought Questionnaire-Revised (ATQ-R) at baseline, at the termination of treatment, and at the 12-month follow-up. RESULTS: Thirty-eight patients completed treatment; five dropped out. For the patients who completed treatment, post-treatment scores on the GAF and SF-36 were significantly higher than baseline scores. Scores on the HRSD, DAS, and ATQ-R were significantly lower after the treatment. Thus patients improved on all measurements of psychosocial functioning and mood symptoms. Twenty patients participated in the 12-month follow-up. Their improvements for psychosocial functioning, depressive symptoms, and dysfunctional cognitions were sustained at 12 months following the completion of group-CBT. CONCLUSIONS: These findings suggest a positive effect that the addition of cognitive behavioural group therapy to medication on depressive symptoms and social functioning of mildly depressed patients, showing treatment resistance.

The effect of induced optimism on the optimistic update bias.

BACKGROUND: Individuals tend to have an optimism bias, processing desirable information more frequently than undesirable information. However, people who have been diagnosed with depression often have a more pessimistic view of the future. A recent study suggests that future expectations in individuals with dysphoria become more optimistic when asked to make optimistic future predictions about the future. In the present study, we investigated the differential effects of induced optimism training which making optimistic future prediction to change future beliefs in normal participants with various levels of dysphoria (low, mild, high). METHODS: We recruited normal participants (n = 69) from a local university students and divided participants into three groups (low, mild, high dysphoria) by measuring dysphoric mood. These three groups were assigned to the induced optimism training or control condition. After the training, participants performed the two-stage belief updating task. In the first stage, participants estimated their personal probability of experiencing adverse events while being presented with the average probability of the event occurring to a living person. This information could be desirable for participants(when presented with a probability that was below their estimation) or undesirable (when presented with a probability that was above their estimation). To assess how desirable versus undesirable information influenced beliefs, participants estimated their personal probability of experiencing the events again in the second stage. The amount of update error was calculated as the difference between the estimates in the first stage and the second stage. The difference between the errors was classified as the update bias. RESULTS: After the induced optimism training, individuals with the mild dysphoria demonstrated a higher update bias than low (p < .001) and the high dysphoria (p < .05) group in induced optimism condition. Significant differences were not found in control group. Results indicates that individuals in the mild dysphoria group showed an increased update bias after being exposed to the induced optimism training Dysphoric mood and trait optimism remained unchanged in both the experimental and control groups. CONCLUSIONS: Results suggest that induced optimism training has potential to change individuals with mild dysphoria perceptions' about the future.

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.

Cognitive behavioral therapy changes functional connectivity between medial prefrontal and anterior cingulate cortices.

BACKGROUND: Depression is characterized by negative self-cognition. Our previous study (Yoshimura et al. 2014) revealed changes in brain activity after cognitive behavioral therapy (CBT) for depression, but changes in functional connectivity were not assessed. METHOD: This study included 29 depressive patients and 15 healthy control participants. Functional Magnetic Resonance Imaging was used to investigate possible CBT-related functional connectivity changes associated with negative emotional self-referential processing. Depressed and healthy participants (overlapping with our previous study, Yoshimura et al. 2014) were included. We defined a seed region (medial prefrontal cortex) and coupled region (ACC) based on our previous study, and we examined changes in MPFC-ACC functional connectivity from pretreatment to posttreatment. RESULTS: CBT was associated with reduced functional connectivity between the MPFC and ACC. Symptom change with CBT was positively correlated with change in MPFC-ACC functional connectivity. LIMITATIONS: Patients received pharmacotherapy including antidepressant. The present sample size was quite small and more study is needed. Statistical threshold in fMRI analysis was relatively liberal. CONCLUSIONS: CBT for depression may disrupt MPFC-ACC connectivity, with associated improvements in depressive symptoms and dysfunctional cognition.

Toward Probabilistic Diagnosis and Understanding of Depression Based on Functional MRI Data Analysis with Logistic Group LASSO.

Diagnosis of psychiatric disorders based on brain imaging data is highly desirable in clinical applications. However, a common problem in applying machine learning algorithms is that the number of imaging data dimensions often greatly exceeds the number of available training samples. Furthermore, interpretability of the learned classifier with respect to brain function and anatomy is an important, but non-trivial issue. We propose the use of logistic regression with a least absolute shrinkage and selection operator (LASSO) to capture the most critical input features. In particular, we consider application of group LASSO to select brain areas relevant to diagnosis. An additional advantage of LASSO is its probabilistic output, which allows evaluation of diagnosis certainty. To verify our approach, we obtained semantic and phonological verbal fluency fMRI data from 31 depression patients and 31 control subjects, and compared the performances of group LASSO (gLASSO), and sparse group LASSO (sgLASSO) to those of standard LASSO (sLASSO), Support Vector Machine (SVM), and Random Forest. Over 90% classification accuracy was achieved with gLASSO, sgLASSO, as well as SVM; however, in contrast to SVM, LASSO approaches allow for identification of the most discriminative weights and estimation of prediction reliability. Semantic task data revealed contributions to the classification from left precuneus, left precentral gyrus, left inferior frontal cortex (pars triangularis), and left cerebellum (c rus1). Weights for the phonological task indicated contributions from left inferior frontal operculum, left post central gyrus, left insula, left middle frontal cortex, bilateral middle temporal cortices, bilateral precuneus, left inferior frontal cortex (pars triangularis), and left precentral gyrus. The distribution of normalized odds ratios further showed, that predictions with absolute odds ratios higher than 0.2 could be regarded as certain.

fMRI Study of Social Anxiety during Social Ostracism with and without Emotional Support.

Social anxiety is characterized by an excessive fear of being embarrassed in social interactions or social performance situations. Emotional support can help to decrease or diminish social distress. Such support may play an important role at different points of social interaction. However, it is unclear how the beneficial effects of social support are represented in the brains of socially anxious individuals. To explore this, we used the same paradigm previously used to examine the effects of emotional support on social pain caused by exclusion. Undergraduates (n = 46) showing a wide range of social anxiety scores underwent functional magnetic resonance imaging (fMRI) while participating in a Cyberball game. Participants were initially included and later excluded from the game. In the latter half of the session in which participants were excluded, they were provided with supportive messages. In line with our previous work, we found that social exclusion led to increased anterior cingulate cortex (ACC) activity, whereas emotional support led to increased left dorsolateral prefrontal cortex (DLPFC) activity. Despite validation of the paradigm, social anxiety was not associated with increased ACC activity during social exclusion, or during perceived emotional support. Instead, fear of negative evaluation as assessed by the Brief Fear of Negative Evaluation (BFNE) scale showed positive associations with left DLPFC activation while receiving emotional support, compared to while being socially excluded. The more socially anxious an individual was, the greater was the left DLPFC activity increased during receipt of messages. This suggests that highly socially anxious people still have the ability to perceive social support, but that they are nevertheless susceptible to negative evaluation by others.

Visual imagery while reading concrete and abstract Japanese kanji words: an fMRI study.

Neuroimaging studies have investigated differences in neural correlates between abstract and concrete concepts but this has not been done with Japanese participants. Concrete words have higher imageability than abstract words, such that they elicit more visual imagery. The present study used functional MRI to investigate brain activity of Japanese participants (N=16) during generation of visual images for written concrete or abstract Japanese kanji words. Concrete words elicited significantly more activation than abstract words in the left middle frontal gyrus (LMFG), bilateral superior frontal gyrus, and left fusiform gyrus (LFG). Psychophysiological interaction (PPI) analyses were performed to assess LMFG and LFG functional connections. LMFG activity was accompanied by increased functional interaction with the left superior parietal lobule (LSPL), and LFG activity was accompanied by increased functional interaction with the LMFG. This finding suggests that the LMFG plays an important role in visual imagery, with interactions between this region and both the LSPL and LFG.

The dorsolateral prefrontal network is involved in pain perception in knee osteoarthritis patients.

Functional MRI (fMRI) studies have been used to investigate how the brain processes noxious stimuli in osteoarthritis (OA) and to identify the cortical location of pain perception. However, no consensus has been reached regarding brain activity associated with pain-induced conditions in OA patients. We examined cerebral responses using intra-epidermal electrical stimulation of the . knee in knee OA patients. To replicate the pain of knee OA in terms of predictability, acute pain generated by electrical stimulation was provided simultaneously with displayed images in this study. We used fMRI to identify differences in response between healthy subjects and knee OA patients and explored the modulating cortico-subcortical and cortico-cortical pathways using psychophysiological interaction (PPI) analysis. Our results show that chronic pain results in a different brain activation profile in the DLPFC and the pain matrix in knee OA patients. Abnormal brain connectivity between the DLPFC and the pain matrix is induced by chronic pain in knee OA patients.

Neural basis of anticipatory anxiety reappraisals.

Reappraisal is a well-known emotion regulation strategy. Recent neuroimaging studies suggest that reappraisal recruits both medial and lateral prefrontal brain regions. However, few studies have investigated neural representation of reappraisals associated with anticipatory anxiety, and the specific nature of the brain activity underlying this process remains unclear. We used functional magnetic resonance imaging (fMRI) to investigate neural activity associated with reappraisals of transient anticipatory anxiety. Although transient anxiety activated mainly subcortical regions, reappraisals targeting the anxiety were associated with increased activity in the medial and lateral prefrontal regions (including the orbitofrontal and anterior cingulate cortices). Reappraisal decreased fear circuit activity (including the amygdala and thalamus). Correlational analysis demonstrated that reductions in subjective anxiety associated with reappraisal were correlated with orbitofrontal and anterior cingulate cortex activation. Reappraisal recruits medial and lateral prefrontal regions; particularly the orbitofrontal and anterior cingulate cortices are associated with successful use of this emotion regulation strategy.

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.

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.

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 spontaneous regional neural activity in patients with somatoform pain disorder: a preliminary resting-state fMRI study.

This resting-state functional magnetic resonance imaging study found that nine patients with somatoform pain disorder exhibited atypical precentral gyrus activation compared with 20 healthy controls. The role of the precentral gyrus in pain-related processing is discussed.