Masahiro Takamura

Self-Knowledge Reduces Conflict by Biasing One of Plural Possible Answers

The authors investigated whether self-knowledge has a function to reduce conflict by biasing one of two choices during occupational choice (e.g., Which occupation do you think you could do better?—dancer or chemist). In the three experiments, event-related brain potentials were recorded. Experiment 1 revealed that the amplitude of the conflict-related negativity (CRN) reflects strength of conflict during occupational choice. Results of Experiment 2 demonstrated that the CRN amplitude during occupational choice was smaller when self-knowledge was activated than when other-knowledge was activated. Experiment 3 showed that the CRN amplitude during occupational choice was decreased more when self-knowledge that biases one choice of occupation was activated than when self-knowledge that does not bias was activated. These results suggest that self-knowledge reduces conflict by biasing one of multiple choices in situations where two or more possible correct answers can be given.

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.

Association of thalamic hyperactivity with treatment-resistant depression and poor response in early treatment for major depression: A resting-state fMRI study using fractional amplitude of low-frequency fluctuations

Despite novel antidepressant development, 10–30% of patients with major depressive disorder (MDD) have antidepressant treatment-resistant depression (TRD). Although new therapies are needed, lack of knowledge regarding the neural mechanisms underlying TRD hinders development of new therapeutic options. We aimed to identify brain regions in which spontaneous neural activity is not only altered in TRD but also associated with early treatment resistance in MDD. Sixteen patients with TRD, 16 patients with early-phase non-TRD and 26 healthy control (HC) subjects underwent resting-state functional magnetic resonance imaging. To identify brain region differences in spontaneous neural activity between patients with and without TRD, we assessed fractional amplitude of low-frequency fluctuations (fALFF). We also calculated correlations between the percent change in the Hamilton Rating Scale for Depression (HRSD17) scores and fALFF values in brain regions with differing activity for patients with and without TRD. Patients with TRD had increased right-thalamic fALFF values compared with patients without TRD. The percent change in HRSD17 scores negatively correlated with fALFF values in patients with non-TRD. In addition, patients with TRD showed increased fALFF values in the right inferior frontal gyrus (IFG), inferior parietal lobule (IPL) and vermis, compared with patients with non-TRD and HC subjects. Our results show that spontaneous activity in the right thalamus correlates with antidepressant treatment response. We also demonstrate that spontaneous activity in the right IFG, IPL and vermis may be specifically implicated in the neural pathophysiology of TRD.

Behavioral activation can normalize neural hypoactivation in subthreshold depression during a monetary incentive delay task.

BACKGROUND Late adolescents are under increased risk of developing depressive symptoms. Behavioral activation is an effective treatment for subthreshold depression, which can prevent the development of subthreshold depression into a major depressive disorder. However, the neural mechanisms underlying the efficacy of behavioral activation have not been clearly understood. We investigated neural responses during reward processing by individuals with subthreshold depression to clarify the neural mechanisms of behavioral activation. METHODS Late adolescent university students with subthreshold depression (n=15, age 18-19 years) as indicated by a high score on the Becks Depression Inventory-ll (BDI-ll) and 15 age-matched controls with a low BDI-ll score participated in functional magnetic resonance imaging scanning conducted during a monetary incentive delay task on two occasions. The Individuals in the subthreshold depression group received five, weekly behavioral activation sessions between the two scanning sessions. Moreover, they did not receive any medication until the study was completed. RESULTS Behavioral activation significantly reduced depressive symptoms. Moreover, compared to the changes in brain functions in the control group, the behavioral activation group showed functional changes during loss anticipation in brain structures that mediates cognitive and emotional regulation, including the left ventrolateral prefrontal cortex and angular gyrus. LIMITATIONS Replication of the study with a larger sample size is required to increase the generalizability of these results. CONCLUSIONS Behavioral activation results in improved functioning of the fronto-parietal region during loss anticipation. These results increase our understanding of the mechanisms underlying specific psychotherapies.

Effects of behavioural activation on the neural basis of other perspective self-referential processing in subthreshold depression: a functional magnetic resonance imaging study

Background It has been demonstrated that negatively distorted self-referential processing, in which individuals evaluate ones own self, is a pathogenic mechanism in subthreshold depression that has a considerable impact on the quality of life and carries an elevated risk of developing major depression. Behavioural activation (BA) is an effective intervention for depression, including subthreshold depression. However, brain mechanisms underlying BA are not fully understood. We sought to examine the effect of BA on neural activation during other perspective self-referential processing in subthreshold depression. Method A total of 56 subjects underwent functional magnetic resonance imaging scans during a self-referential task with two viewpoints (self/other) and two emotional valences (positive/negative) on two occasions. Between scans, while the intervention group (n = 27) received BA therapy, the control group (n = 29) did not. Results The intervention group showed improvement in depressive symptoms, increased activation in the dorsal medial prefrontal cortex (dmPFC), and increased reaction times during other perspective self-referential processing for positive words after the intervention. Also, there was a positive correlation between increased activation in the dmPFC and improvement of depressive symptoms. Additionally, there was a positive correlation between improvement of depressive symptoms and increased reaction times. Conclusions BA increased dmPFC activation during other perspective self-referential processing with improvement of depressive symptoms and increased reaction times which were associated with improvement of self-monitoring function. Our results suggest that BA improved depressive symptoms and objective monitoring function for subthreshold depression.

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

BackgroundAmygdala 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.MethodsTwenty-four healthy participants completed an individually tailored negative mood induction task during functional magnetic resonance imaging (fMRI) assessment along with evaluation of ELS.ResultsMood 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.ConclusionsIncreased 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.

Disrupted Brain Activation and Deactivation Pattern during Semantic Verbal Fluency Task in Patients with Major Depression

Background: Patients with major depressive disorder (MDD) exhibit cognitive impairment, and evidence suggests that the semantic version of the verbal fluency task is a reliable cognitive marker of the disorder. Here, using functional magnetic resonance imaging (fMRI), we investigated the dysfunction of neural processing in acute depression and examined the effects of a 6-week pharmacological intervention. Methods: Sixteen patients with MDD participated in 2 fMRI sessions, and 16 healthy control (HC) subjects participated in 1 fMRI session. During each fMRI session, the participants performed a semantic verbal fluency task. Brain activity during the task was compared between groups (MDD 1st fMRI vs. HC) and times (MDD 1st fMRI vs. 2nd fMRI). Results: Significant brain hypoactivation was observed in MDD patients at the prefrontal, lateral parietal, and limbic regions compared to HC, and MDD patients exhibited hyperactivation at the left precuneus compared to HC. Hypoactivity of the left dorsolateral prefrontal cortex (DLPFC) and hyperactivity of the precuneus were normalized with treatment. Conclusions: Hypoactivation of the left DLPFC and hyperactivation of the precuneus should be considered as dysregulation of anticorrelated brain networks during a cognitive demanding task. This failure of network regulation may be an important factor in the pathophysiology of MDD.

Prediction of clinical depression scores and detection of changes in whole-brain using resting-state functional MRI data with partial least squares regression

In diagnostic applications of statistical machine learning methods to brain imaging data, common problems include data high-dimensionality and co-linearity, which often cause over-fitting and instability. To overcome these problems, we applied partial least squares (PLS) regression to resting-state functional magnetic resonance imaging (rs-fMRI) data, creating a low-dimensional representation that relates symptoms to brain activity and that predicts clinical measures. Our experimental results, based upon data from clinically depressed patients and healthy controls, demonstrated that PLS and its kernel variants provided significantly better prediction of clinical measures than ordinary linear regression. Subsequent classification using predicted clinical scores distinguished depressed patients from healthy controls with 80% accuracy. Moreover, loading vectors for latent variables enabled us to identify brain regions relevant to depression, including the default mode network, the right superior frontal gyrus, and the superior motor area.

Altruistic People Show No Self-Reference Effect in Memory

ABSTRACT The self-reference effect (SRE), by which encoding of information is done in a self-referential manner (e.g., “Does the word describe you?”), enhances subsequent memory performance. It is thought to reflect that self-reference is a highly practiced task in everyday life. Accordingly, it is expected that the types of tasks that produce memory enhancement vary according to individual differences of past experiences. On the basis of neuroimaging studies, we hypothesized that social desirability reference (“Is this word socially desirable?”) produces memory enhancement as with SRE in people who have chosen altruistic behavior frequently. Participants processed trait adjectives in relation to themselves, social desirability, and meaning. Then they performed a free recall task. The self-report altruism scale was used to assess the frequency of past altruistic behavior. Consistent with our prediction, the social desirability reference yielded the best retention in the high-altruism group. SRE was observed only in the low-altruism group.

Resting state functional connectivity explains individual scores of multiple clinical measures for major depression

Recent studies have revealed that resting state functional connectivity is associated with major depressive disorder (MDD). However, the relationship between functional connectivity and clinical measures for the detailed assessment of depression remains unclear. The objective of our study is thus to associate functional connectivity of depressed patients and healthy controls with their individual clinical measures, using a statistical method called partial least squares analysis (PLS). We demonstrated that this method could predict certain clinical measures based on a limited number of functional connections and provided benefits to the prediction performance through incorporation of the subjects age and the estimation of multiple measures simultaneously. Generalizability of the prediction model was assured through leave one out cross validation. The results showed that for BDI-II and SHAPS the most contributing connections concerned cuneus, precuneus and middle frontal cortex and areas of the cerebellum. While the relationship was similar for PANAS(n), it showed its strongest relation with functional connection between calcarine and insula.