Shenghong Pu

Neuroimaging-aided differential diagnosis of the depressive state

A serious problem in psychiatric practice is the lack of specific, objective biomarker-based assessments to guide diagnosis and treatment. The use of such biomarkers could assist clinicians in establishing differential diagnosis, which may improve specific individualised treatment. This multi-site study sought to develop a clinically suitable neuroimaging-guided diagnostic support system for differential diagnosis at the single-subject level among multiple psychiatric disorders with depressive symptoms using near-infrared spectroscopy, which is a compact and portable neuroimaging method. We conducted a multi-site, case-control replication study using two cohorts, which included seven hospitals in Japan. The study included 673 patients (women/men: 315/358) with psychiatric disorders (major depressive disorder, bipolar disorder, or schizophrenia) who manifested depressive symptoms, and 1007 healthy volunteers (530/477). We measured the accuracy of the single-subject classification in differential diagnosis among major psychiatric disorders, based on spatiotemporal characteristics of fronto-temporal cortical haemodynamic response patterns induced by a brief (<3 min) verbal fluency task. Data from the initial site were used to determine an optimal threshold, based on receiver-operator characteristics analysis, and to generate the simplest and most significant algorithm, which was validated using data from the remaining six sites. The frontal haemodynamic patterns detected by the near-infrared spectroscopy method accurately distinguished between patients with major depressive disorder (74.6%) and those with the two other disorders (85.5%; bipolar disorder or schizophrenia) that presented with depressive symptoms. These results suggest that neuroimaging-guided differential diagnosis of major psychiatric disorders developed using the near-infrared spectroscopy method can be a promising biomarker that should aid in personalised care in real clinical settings. Potential confounding effects of clinical (e.g., age, sex) and systemic (e.g., autonomic nervous system indices) variables on brain signals will need to be clarified to improve classification accuracy.

Reduced frontopolar activation during verbal fluency task associated with poor social functioning in late‐onset major depression: Multi‐channel near‐infrared spectroscopy study

Aim:  Functional neuroimaging studies to date have indicated prefrontal dysfunction in late‐onset major depression (LOD). The relationships between prefrontal dysfunction and clinical characteristics including social functioning, however, have been unclear. The objective of the present study was to evaluate prefrontal hemodynamic response related to an executive task in LOD and to assess the relationship between activation in the prefrontal regions and clinical characteristics including social functioning.

A multi-channel near-infrared spectroscopy study of prefrontal cortex activation during working memory task in major depressive disorder

Many neuropsychological studies demonstrate impairment of working memory in patients with major depressive disorder (MDD). However, there are not enough functional neuroimaging studies of MDD patients seeking for the underlying brain activity relevant to working memory function. The objective of this study is to evaluate prefrontal hemodynamic response related to working memory function in patients with MDD. Twenty-four subjects with MDD and 26 age- and gender-matched healthy subjects were recruited for the present study. We measured hemoglobin concentration changes in the prefrontal and superior temporal cortical surface areas during the execution of working memory task (WM; 2-back, letter version) using 52-channel near-infrared spectroscopy (NIRS), which enables real-time monitoring of task-related changes in cerebral blood volumes in the cortical surface areas. MDD patients showed a smaller increase in lateral prefrontal and superior temporal cortex activation during the 2-back task and associated poorer task performance than healthy controls. The results coincided with previous findings in terms of working memory deficits and prefrontal cortex dysfunction in MDD patients, but contradicted with some previous fMRI studies that suggested increased cortical activity during the working memory task in patients with depression. The contradiction may, in part, be explained by a relatively low level of cognitive demand imposed on the subjects in the present study.

The relationship between the prefrontal activation during a verbal fluency task and stress-coping style in major depressive disorder: A near-infrared spectroscopy study

This study aimed to identify coping styles used by patients with major depressive disorder (MDD) in comparison with those used by healthy controls, and to explore their association with prefrontal hemodynamic response related to a cognitive task. Regional hemodynamic changes were monitored during a verbal fluency task (VFT) using a 52-channel near-infrared spectroscopy (NIRS) apparatus in 26 MDD patients in depressive state and 30 matched healthy controls, and their correlation with coping styles assessed by Coping Inventory for Stressful Situations (CISS) were examined. We found the Emotion-oriented coping style was significantly higher, whereas the Task-oriented coping and Avoidance-oriented coping style were lower in the MDD group compared with controls. Emotion-oriented coping style positively correlated with subjective assessment of depression severity. Regional hemodynamic changes were significantly smaller in the MDD group than in the control group in prefrontal and temporal regions, and positively correlated with Task-oriented coping (adaptive coping) in the bilateral ventrolateral and dorsolateral prefrontal cortex, and the midline fronto-polar and bilateral orbitofrontal cortex regions. These findings suggest coping styles may be considered an important source of knowledge for patients who struggle with the illness and for mental health professionals who work with MDD patients, and that hemodynamic response in the ventrolateral and dorsolateral prefrontal cortex, midline fronto-polar, and orbitofrontal cortex regions during a VFT may reflect the adaptive coping (Task-oriented coping) style in MDD patients in depressive state.

Association between cognitive insight and prefrontal function during a cognitive task in schizophrenia: a multichannel near-infrared spectroscopy study.

Insight has been studied mostly from a clinical perspective. Recently, the focus of this research field shifted to cognitive insight or the ability to monitor and correct the erroneous convictions of individuals. In this study, we investigated the relationship between cognitive insight and prefrontal function during a cognitive task in 30 patients with clinically stable schizophrenia and 30 age- and gender-matched healthy controls. We measured the changes in hemoglobin concentration in the prefrontal and temporal cortical regions during a verbal fluency task (VFT) by using 52-channel near-infrared spectroscopy (NIRS). Cognitive insight was measured using the Beck Cognitive Insight Scale (BCIS). Regional hemodynamic changes were significantly smaller in the schizophrenia group than in the control group in prefrontal and temporal regions, and significant positive relationship was observed between the score of the BCIS self-reflectiveness subscale and right ventrolateral prefrontal and right temporal functions during the VFT. These results suggest that the right ventrolateral prefrontal and temporal cortical regions are associated with cognitive insight in clinically stable patients with schizophrenia and that NIRS is an efficient medical tool for monitoring these characteristics.

Suicidal ideation is associated with reduced prefrontal activation during a verbal fluency task in patients with major depressive disorder.

BACKGROUND Despite the known relationship between prefrontal function and increased suicidality during major depressive episodes, the links between prefrontal function and suicidality remain unclear in major depressive disorder (MDD). Suicidal ideation usually precedes a suicide attempt. If prefrontal cortex (PFC) activity is a biomarker for suicidal ideation in depression, monitoring it could be useful for suicide prevention. Therefore, in this study, we assessed the association between prefrontal function and suicidal ideation in MDD. METHODS Prefrontal function in 67 patients with MDD (31 with suicidal ideation and 36 without) and 67 age-, gender-, and intelligence quotient-matched healthy controls (HCs) was evaluated using near-infrared spectroscopy (NIRS) during a verbal fluency task (VFT). Suicidal ideation was assessed using item 3 of the Hamilton Depression Rating Scale (HAMD). RESULTS Regional hemodynamic changes were significantly smaller in patients with MDD than in HCs in prefrontal and temporal regions. Hemodynamic changes in the right dorsolateral PFC (DLPFC), orbitofrontal cortex (OFC), and right frontopolar cortex (FPC) regions in patients with MDD with suicidal ideation were significantly smaller than in those without suicidal ideation. In addition, hemodynamic changes correlated negatively with the severity of suicidal ideation in the DLPFC, OFC, and FPC in patients with MDD. LIMITATIONS Further studies with a larger sample size are required to verify our findings. CONCLUSIONS These results suggest that the DLPFC, OFC, and FPC are brain substrates of suicidal ideation in depressive states in patients with MDD, and that NIRS data can be employed as a clinically useful biomarker for the assessment of suicide risk.

Reduced prefrontal cortex activation during the working memory task associated with poor social functioning in late-onset depression: Multi-channel near-infrared spectroscopy study

A number of studies have demonstrated impairment of working memory (WM) in patients with major depressive disorder (MDD). However, the relationship between the underlying brain activity associated with impairment of WM function in MDD patients and their clinical characteristics is not yet clear. The objective of this study is to evaluate prefrontal hemodynamic response related to a WM task in patients with late-onset depression (LOD) and to assess the relationship between activation in the prefrontal cortex and clinical characteristics. Thirty-six patients with LOD and 35 age- and gender-matched healthy controls were recruited for the present study. We measured hemoglobin concentration changes in the prefrontal and temporal regions during a WM (2-back, letter version) task using 52-channel near-infrared spectroscopy (NIRS). LOD patients were associated with reduced increase in prefrontal and temporal activation compared with healthy controls. Moreover, reduced activation in the prefrontal and temporal regions was significantly related to lower scores on the Social Adaptation Self-Evaluation Scale (SASS) in the patient group. More specifically, the reduced hemodynamic response in the frontopolar region was associated with functional impairment related to interpersonal relationship factor scores on the SASS. These findings suggest that hemodynamic response in prefrontal and temporal regions during a WM task may act as a biological marker of social functioning in LOD patients.

A Longitudinal Functional Neuroimaging Study in Medication-Naïve Depression after Antidepressant Treatment

Recent studies have indicated the potential clinical use of near infrared spectroscopy (NIRS) as a tool in assisting the diagnosis of major depressive disorder (MDD); however, it is still unclear whether NIRS signal changes during cognitive task are state- or trait-dependent, and whether NIRS could be a neural predictor of treatment response. Therefore, we conducted a longitudinal study to explore frontal haemodynamic changes following antidepressant treatment in medication-naïve MDD using 52-channel NIRS. This study included 25 medication-naïve individuals with MDD and 62 healthy controls (HC). We performed NIRS scans before and after antidepressant treatment and measured changes of [oxy-Hb] activation during a verbal fluency task (VFT) following treatment. Individuals with MDD showed significantly decreased [oxy-Hb] values during a VFT compared with HC in the bilateral frontal and temporal cortices at baseline. There were no [oxy-Hb] changes between pre- and post-antidepressant treatment time points in the MDD cohort despite significant improvement in depressive symptoms. There was a significant association between mean [oxy-Hb] values during a VFT at baseline and improvement in depressive symptoms following treatment in the bilateral inferior frontal and middle temporal gyri in MDD. These findings suggest that hypofrontality response to a VFT may represent a potential trait marker for depression rather than a state marker. Moreover, the correlation analysis indicates that the NIRS signals before the initiation of treatment may be a biological marker to predict patient’s clinical response to antidepressant treatment. The present study provides further evidence to support a potential application of NIRS for the diagnosis and treatment of depression.

A pilot study on the effects of cognitive remediation on hemodynamic responses in the prefrontal cortices of patients with schizophrenia: A multi-channel near-infrared spectroscopy study

The regional neuronal changes taking place between before and after cognitive rehabilitation are still not characterized in schizophrenia patients. In addition, it is not known whether these regional changes are predictive or correlated with treatment response. We conducted a preliminary quasi-experimental study to investigate the effects of a Neuropsychological Educational Approach to Cognitive Remediation (NEAR), one of the cognitive remediation therapies, on neurocognitive functioning assessed by the Japanese version of the Brief Assessment of Cognition in Schizophrenia (BACS-J), and on prefrontal and temporal hemodynamic responses during working memory (WM) task (2-back, letter version) using 52-channel near-infrared spectroscopy (NIRS). We assessed 19 patients with schizophrenia or schizoaffective disorder twice with an interval of 6months. Moreover, taking into consideration the possible practice effect, we assessed 12 control patients twice with an interval of 6months. The NEAR group, in comparison with the control group, showed significant improvement in two subcomponents of BACS-J, that is, motor speed and executive function along with the composite scores. The NEAR group also showed a significant increase in brain activation in the bilateral cortical regions associated with WM, and in comparison with the control group the between-group differences were restricted to the right frontopolar area. In addition, the amount of enhancement in some cognitive subcomponents was positively correlated with the magnitude of an increase in hemodynamic response during WM task predominantly in the right hemispheres. These findings suggest that neurocognitive deficits in schizophrenia and their neural dysfunction may be improved by NEAR, and NIRS may be a useful tool to assess the changes of the neural activity underlying the improvement of neurocognitive functioning elicited by neurocognitive rehabilitation.

Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery: Validation of the Japanese version

This preliminary study was performed to test the reliability and validity of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB), developed by the National Institute of Mental Health MATRICS initiative, as an assessment tool in a Japanese‐language version (MCCB‐J).