Empirical evidence for discrete neurocognitive subgroups in patients with non-psychotic major depressive disorder: clinical implications.

BACKGROUND: Neuropsychological deficits are present across various cognitive domains in major depressive disorder (MDD). However, a consistent and specific profile of neuropsychological abnormalities has not yet been established. METHODS: We assessed cognition in 170 patients with non-psychotic MDD using the Brief Assessment of Cognition in Schizophrenia and the scores were compared with those of 42 patients with schizophrenia as a reference for severity of cognitive impairment. Hierarchical cluster analysis was conducted to determine whether there are discrete neurocognitive subgroups in MDD. We then compared the subgroups in terms of several clinical factors and social functioning. RESULTS: Three distinct neurocognitive subgroups were found: (1) a mild impairment subgroup with near-normative performance and mild dysfunction in motor speed; (2) a selective impairment subgroup, which exhibited preserved working memory and executive function, but moderate to severe deficits in verbal memory, motor speed, verbal fluency, and attention/information processing speed; and (3) a global impairment subgroup with moderate to severe deficits across all neurocognitive domains, comparable with deficits in schizophrenia. The global impairment subgroup was characterized by lower pre-morbid intelligence quotient (IQ). Moreover, a significant difference between groups was observed in premorbid IQ (p = 0.003), antidepressant dose (p = 0.043), antipsychotic dose (p = 0.013), or anxiolytic dose (p < 0.001). CONCLUSIONS: These results suggest the presence of multiple neurocognitive subgroups in non-psychotic MDD with unique profiles, one of which exhibits deficits comparable to those of schizophrenia. The results of the present study may help guide future efforts to target these disabling symptoms using different treatments.

Association between social functioning and prefrontal cortex function during a verbal fluency task in schizophrenia: A near-infrared spectroscopic study.

AIM: Impaired social functioning is a common characteristic of patients with schizophrenia. Social functioning requires the complex operation of various executive functions. Deficits in the prefrontal cortex (PFC) have been implicated in executive dysfunction. Here we aimed to clarify the relation between subjectively and objectively assessed social functioning, and their associations with PFC function in patients with schizophrenia. METHODS: Twenty-three patients and 22 age- and sex-matched healthy controls (HC) were assessed. In the schizophrenia group, self- and caregiver-rated social functioning were measured using the Specific Level of Functioning Assessment (SLOF). The hemodynamic responses elicited by a verbal fluency task (VFT) in three regions of interest in the frontotemporal area were measured using multi-channel near-infrared spectroscopy (NIRS). We also investigated psychiatric symptoms, neurocognition, and cognitive insight to assess possible confounding factors. RESULTS: Significant positive correlations were found between self- and caregiver-rated SLOF composite scores and three subdomain scores. Self- and caregiver-rated SLOF composite scores were significantly associated with dorsolateral PFC and frontopolar cortex (DLPFC/FPC) activation during the VFT. Psychiatric symptoms, global functioning, neurocognition, and cognitive insight were not associated with NIRS signals. General psychopathology was associated with NIRS signals in the ventrolateral PFC and the anterior temporal cortex. DLPFC and FPC activity may be associated with social functioning in patients with schizophrenia. CONCLUSION: Our results suggest that the two distinct assessments of social functioning were significantly correlated. Moreover, DLPFC and FPC function was strongly associated with social functioning and the ability to carry out daily life in patients with schizophrenia.

Facial expression perception correlates with verbal working memory function in schizophrenia.

AIMS: Facial emotion perception is considered to provide a measure of social cognition. Numerous studies have examined the perception of emotion in patients with schizophrenia, and the majority has reported impaired ability to recognize facial emotion perception. We aimed to investigate the correlation between facial expression recognition and other domains of social cognition and neurocognition in Japanese patients with schizophrenia. METHODS: Participants were 52 patients with schizophrenia and 53 normal controls with no history of psychiatric diseases. All participants completed the Hinting Task and the Social Cognition Screening Questionnaire. The Brief Assessment of Cognition in Schizophrenia was administered only to the patients. Facial emotion perception measured by the Facial Emotion Selection Test (FEST) was compared between the patients and normal controls. RESULTS: Patients performed significantly worse on the FEST compared to normal control subjects. The FEST total score was significantly positively correlated with scores of the Brief Assessment of Cognition in Schizophrenia attention subscale, Hinting Task, Social Cognition Screening Questionnaire Verbal Working Memory and Metacognition subscales. Stepwise multiple regression analysis revealed that verbal working memory function was positively related to the facial emotion perception ability in patients with schizophrenia. CONCLUSIONS: These results point to the concept that facial emotion perception and some types of working memory use common cognitive resources. Our findings may provide implications for cognitive rehabilitation and related interventions in schizophrenia.

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.

Milnacipran influences the indexes of I-metaiodobenzylguanidine scintigraphy in elderly depressed patients.

AIM: This study investigated whether or not and how much milnacipran influences the indexes of I-metaiodobenzylguanidine (I-MIBG) scintigraphy, early heart-to-mediastinum (H/M) ratio, delayed H/M ratio, and wash-out rate. METHODS: Six elderly depressed patients participated in the study. All six patients met the diagnostic criteria for a major depressive disorder. They were taking milnacipran for their depression. They needed differential diagnosis for Lewy body diseases due to their symptomatology. I-MIBG scintigraphy was performed twice for each subject, once under prescription of milnacipran and the other without prescription of milnacipran. RESULTS: Both early and delayed phase H/M ratio were significantly lower when taking milnacipran (early phase H/M ratio, P < 0.01, Cohen's d 1.62; delayed phase H/M ratio, P < 0.005, Cohen's d 1.98) than when not taking the drug. Wash-out rate (%) was significantly higher when taking milnacipran (P < 0.05, Cohen's d 2.31) than when off the drug. CONCLUSION: Taking milnacipran substantially influences the indexes of I-MIBG scintigraphy, indicating that taking the drug possibly causes a false-positive result for Lewy body diseases diagnosis.

New instrument for measuring multiple domains of social cognition: construct validity of the Social Cognition Screening Questionnaire (Japanese version).

AIM: The present study aimed to test the construct validity and internal consistency of the Social Cognition Screening Questionnaire (SCSQ) (Japanese version). METHODS: We first tested whether the subscale scores and the total score of the SCSQ could discriminate patients with schizophrenia from normal controls. Next, we tested the internal consistency. Finally, we investigated the relation between the subscale scores and other measures of social cognition and social functioning that were presumed to correspond to the subscale's scores, including the Hinting Task, the Ambiguous Intentions Hostility Questionnaire (AIHQ), the Beck Cognitive Insight Scale and the Social Functioning Scale. RESULTS: The subscale scores and the total score appeared to show more robust between-group differences than other measures of social cognition, such as the AIHQ and the Hinting Task. The total score distinguished the patients from normal controls with an area under the receiver-operator curve of 0.84, which indicated a high level of discrimination. The Cronbach's alpha for the four subscales was 0.72, which was considered acceptable. In terms of criterion-related validity, theory of mind, metacognition and hostility bias subscale scores showed significant correlations with the Hinting Task, Beck Cognitive Insight Scale and AIHQ, respectively. Moreover, the theory of mind subscale score showed a significant correlation with four domain scores of the Social Functioning Scale. The present results indicated good construct validity and internal consistency of the SCSQ. CONCLUSIONS: Although this is an interim report with a small sample size, the SCSQ holds promise as an efficient measure for social cognition.

Measurement and Treatment Research toImprove Cognition in Schizophrenia Consensus Cognitive Battery: validation of the Japanese version.

AIM: 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). METHODS: The subjects for the present study were 37 patients with schizophrenia. Each subject gave written informed consent to participate in the research. In order to examine the validity of the MCCB-J, the correlation between the MCCB-J and the Japanese-language version of the Brief Assessment of Cognition in Schizophrenia (BACS) was determined. RESULTS: Cronbach's alpha for the MCCB-J was 0.72. The MCCB-J composite score was significantly correlated with all subtests of the MCCB-J. There was a significant correlation between the MCCB-J and the BACS composite score. CONCLUSION: This preliminary study indicates that the MCCB-J has good psychometric properties and validity.

The pilot study of a Neuropsychological Educational Approach to Cognitive Remediation for patients with schizophrenia in Japan.

The main aim of this study is to demonstrate the feasibility and efficacy of a Neuropsychological Educational Approach to Cognitive Remediation (NEAR) in Japan. This multi-site study used a quasi-experimental design. Fifty-one patients with schizophrenia or schizoaffective disorder participated. The NEAR program consisted of two 1-h computer sessions per week and an additional group meeting session lasting 30 to 60 min once a week. The subjects completed 6 months of NEAR sessions before being assessed. Moreover, taking into consideration the possible practice effect, we assessed 21 control patients twice with an interval of 6 months. We assessed cognitive function by using the Japanese version of the Brief Assessment of Cognition in Schizophrenia (BACS-J). Consequently, the NEAR group showed significant improvement in overall cognitive function, and in comparison with the control group, these findings were generally similar except for motor speed. Although the present study has its limitations, it demonstrates that the NEAR is feasible in Japan as well as it is in Western countries.

[Outcome studies of cognitive remediation for schizophrenia].

Cognitive remediation purports to improve the cognitive dysfunction of schizophrenia, and has many forms. Eighty percent of people with schizophrenia suffer from cognitive dysfunction. The impact of cognitive dysfunction on everyday activity is widespread. Cognitive remediation as a non-pharmaceutical, psychosocial treatment modality for cognitive dysfunction has received attention as medical treatment has been able to make only limited gains. The ultimate goal of cognitive remediation is to improve the functional outcome. The increased interest in cognitive remediation resulted in numerous reports of outcome studies and meta-analysis. This paper reports different methods of cognitive remediation, evaluations of outcome studies, and various outcome indices. Cognitive remediation differs according to whether specific cognitions are targeted, and whether a method takes a compensatory or restorative approach. This paper briefly reviews methods of cognitive remediation which demonstrated their effect through RCT: IPT, NEAR, CET, and NET. Cognitive remediation often includes sessions that aim for transfer of the gained learning, such as verbal sessions or vocational skills training. Cognitive remediation is considered most effective when included as part of a comprehensive rehabilitation program. It is important to note that various studies report different outcome indices, control groups, and effect sizes in evaluating the effect of cognitive remediation.

Stress increases blood beta-hydroxybutyrate levels and prefrontal cortex NLRP3 activity jointly in a rodent model.

AIM: This study aimed to assess the response of endogenous beta-hydroxybutyrate to psychological stress, and its association with nucleotide-binding domain, leucine-rich repeat, pyrin domain-containing 3 (NLRP3) inflammasome, and stress-induced behavior. METHODS: Male C57BL/6J mice were subjected to 1-hour restraint stress to examine changes in the endogenous beta-hydroxybutyrate and active NLRP3 levels in the prefrontal cortex. Subsequently, we created a depression model applying 10-day social defeat stress to the male C57BL/6J mice. RESULTS: One-hour restraint stress rapidly increased beta-hydroxybutyrate levels in the blood. The active NLRP3 levels in the prefrontal cortex also increased significantly. A correlation was found between the increased beta-hydroxybutyrate levels in the blood and the active NLRP3 levels in the prefrontal cortex. The mice exposed to social defeat stress exhibited depression- and anxiety-like behavioral changes in the open field, social interaction, and forced swim tests. There was a correlation between these behavioral changes and endogenous beta-hydroxybutyrate levels. Among the social defeat model mice, those with high beta-hydroxybutyrate levels tended to have more depression- and anxiety-like behavior. CONCLUSIONS: The increased blood beta-hydroxybutyrate levels due to psychological stress correlate with the active NLRP3 levels in the prefrontal cortex, suggesting that the increased beta-hydroxybutyrate levels due to stress may reflect a reaction to brain inflammation. In addition, mice with higher blood beta-hydroxybutyrate levels tend to exhibit increased depression- and anxiety-like behaviors; thus, an increase in blood beta-hydroxybutyrate levels due to stress may indicate stress vulnerability.

The relationship between cognitive distortion, depressive symptoms, and social adaptation: A survey in Japan.

BACKGROUND: In the treatment of depression, improvements in both clinical symptoms and social adaptation are important. Previous studies have shown that cognitive distortion and depressive symptoms are mutually related, and that depressive symptoms and social adaptation are related to each other. However, it is unknown how these three factors interrelate. Therefore, this study examined the relationship between cognitive distortion, depressive symptoms, and social adaptation. METHODS: The final analyzed sample consisted of 430 employees of a manufacturing company in Japan (74.2% male, 24.7% female, 1.2% unknown). Participants completed the Worker's Cognitive Distortion Scale (WCDS), Beck Depression Inventory-Second Edition (BDI-II), and Social Adaptation Self-Evaluation Scale (SASS). The WCDS was further divided into two subscales: self-contained cognitive distortion (WCDS-S) and environment-dependent cognitive distortion (WCDS-E). We used a covariance structure analysis for the main analysis and examined the relationship between these three variables' scores. RESULTS: The results revealed that both the WCDS-S and WCDS-E affected social adaptation indirectly via depressive symptoms, and that the WCDS-S additionally affected social adaptation directly. It was further revealed that the WCDS-S exerted a greater effect on depressive symptoms than the WCDS-E. LIMITATIONS: The participants were healthy cases. As such, one must be cautious about applying the results of healthy cases to clinical cases. CONCLUSIONS: This study indicates that cognitive distortion affects social adaptation directly and that it is indirectly mediated by depressive symptoms. Thus, professionals are required to attempt to treat depressive symptoms and improve social adaptation by considering that interventions in cognitive distortion may be effective.

Prefrontal cortex infusion of beta-hydroxybutyrate, an endogenous NLRP3 inflammasome inhibitor, produces antidepressant-like effects in a rodent model of depression.

AIMS: Neuroinflammation is deeply related to the pathophysiology of depression. Beta-hydroxybutyrate (BHB), which is an endogenous ketone body, exerts anti-inflammatory effects, and peripheral administration of BHB induces antidepressant effects in an animal model of depression; however, it is unclear whether BHB specifically mediates these actions in the brain. Thus, we administered BHB directly into the brain in a rodent model of depression using a chronic unpredictable stress (CUS) paradigm. METHODS: BHB was continuously microinjected into the prefrontal cortex (PFC) using osmotic pumps for 21 days. Behavioral testing included the forced swim test (FST) and the open field test (OFT); the levels of pro-inflammatory cytokines, such as interleukin 1ß (IL-1ß) and tumor necrosis factor α (TNF-α), were quantified in the PFC, and the concentration of corticosterone in blood serum was measured. RESULTS: BHB administration into the PFC significantly decreased immobility time in the FST, without significantly altering locomotor activity assessed in the OFT. Also, CUS significantly increased the levels of TNF-α in the PFC and decreased serum corticosterone levels; these changes were attenuated by BHB administration. These findings suggest that a small amount of BHB administered into the PFC directly produces antidepressant effects, possibly through anti-inflammatory mechanisms, and can improve hypothalamus-pituitary-adrenal axis responses. CONCLUSION: BHB may be a novel therapeutic candidate for the treatment of depression based on the neuro-inflammatory hypothesis, and the PFC is a region implicated in the antidepressant action of BHB.

Comparison of prefrontal hemodynamic responses and cognitive deficits between adult patients with autism spectrum disorder and schizophrenia.

Autism spectrum disorder (ASD) and schizophrenia share many phenotypic characteristics, but their association with prefrontal function have not been directly compared. The aim of this study is to compare cognitive profiles and their association with the prefrontal function between the two groups. We explored prefrontal dysfunction among adult individuals with ASD (n = 32), schizophrenia (n = 87), and healthy controls (HCs; n = 50). We assessed cognitive function in all participants using the Brief Assessment of Cognition in Schizophrenia (BACS). The BACS data of patients with schizophrenia were entered into hierarchical cluster analyses to assign subjects to a specific subgroup based on individual profiles. Using near-infrared spectroscopy, we measured hemodynamic responses in the fronto-temporal regions during a working memory task. Among the patients with schizophrenia, we defined 4 neurocognitive subgroups, including a global impairment, a mild impairment, and 2 selective impairment groups. Compared to the HCs, the ASD and schizophrenia groups had much weaker hemodynamic responses in the left DLPFC, left frontopolar cortex (FPC), and left inferior frontal gyrus. The ASD group showed a similar level of cognitive impairment with the mild level subgroup of schizophrenia. Additionally, the two groups shared reduced activity in the left DLPFC and left FPC during the task compared to HCs. Moreover, the BACS composite scores correlated positively with hemodynamic responses in a broad area involving fronto-temporal regions in the total patient sample. This research indicates considerable similarity in the left PFC dysfunction and its association with cognitive deficits between the disorders. These findings may guide future studies that investigate pathophysiological similarities between ASD and schizophrenia.

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. METHODS: Twenty-four subjects with LOD and 30 age- and gender-matched healthy subjects were recruited for the present study. Hemoglobin concentration changes in the prefrontal and superior temporal cortical surface area were measured during verbal fluency task (VFT) using 52-channel near-infrared spectroscopy (NIRS), which enables real-time monitoring of cerebral blood volume (CBV) in the cortical surface area. RESULTS: The two groups had a distinct spatiotemporal pattern of oxy-hemoglobin concentration change; LOD patients had less activation in a broad area covering both prefrontal and superior temporal cortices than healthy controls. In addition, reduced activation of the frontopolar region had a significant positive correlation with lower self-assessment of social functioning scores in the patient group. CONCLUSION: Reduced frontopolar cortical activation was associated with social functioning impairment in patients with LOD, and NIRS may be an efficient clinical tool for monitoring these characteristics.

Right Frontotemporal Cortex Mediates the Relationship between Cognitive Insight and Subjective Quality of Life in Patients with Schizophrenia.

Although prior studies identified a relationship between cognitive insight and subjective quality of life (QOL) in patients with schizophrenia, the brain regions mediating this relationship remain unknown. Recent studies have shown that the ventrolateral prefrontal cortex may be particularly important for cognitive insight in individuals with schizophrenia. Here, we examined whether frontotemporal function mediates the relationship between cognitive insight and QOL in 64 participants, including 32 patients with schizophrenia and 32 healthy controls. Cognitive insight was measured using the Beck Cognitive Insight Scale (BCIS), while participants' subjective QOL was assessed using the Medical Outcomes Study 36-item Short-form Health Survey. Frontotemporal function was evaluated during a verbal fluency task using multichannel near-infrared spectroscopy. Consistent with previous findings, we found that frontotemporal function was impaired in patients with schizophrenia. Interestingly, our data also revealed that the right ventrolateral PFC and the right anterior part of the temporal cortex significantly mediated the relationship between the self-reflectiveness (SR) subscale of the BCIS and subjective QOL. These findings suggest that cognitive insight, particularly SR, is associated with subjective QOL in patients with schizophrenia via right frontotemporal function. The findings of this study provide important insight into a QOL model of schizophrenia, which may guide the development of cost-effective interventions that target frontotemporal function in patients with schizophrenia.

Association between cognitive deficits and suicidal ideation in patients with major depressive disorder.

The role of cognitive function in suicidal ideation in patients with major depressive disorder (MDD) has not been adequately explored. This research sought to measure the relationship between suicidal ideation and cognitive function. Therefore, in this study, the association between cognitive function and suicidal ideation in patients with MDD was assessed. Cognitive function was evaluated in 233 patients with MDD using the Japanese version of the Brief Assessment of Cognition in Schizophrenia (BACS). Suicidal ideation was assessed using item 3 of the Hamilton Depression Rating Scale. Approximately 59.2% of the patients (138/233) expressed suicidal ideation. Among the BACS subtests, only the executive function scores were significantly lower in patients with MDD with than in those without (p < 0.005). In addition, the executive function, motor speed function, and composite scores correlated negatively with the severity of suicidal ideation in these patients. These results suggest that executive function, motor speed function, and global neuropsychological function are associated with suicidal ideation in patients with MDD and that the BACS neuropsychological battery is an efficient instrument for monitoring these characteristics. Moreover, specific BACS scores can potentially serve as cognitive biomarkers of suicide risk in patients with MDD.

Association of fronto-temporal function with cognitive ability in schizophrenia.

Deficits in neuropsychological performance are common in schizophrenia, but their relationship with the fronto-temporal functional abnormalities associated with this condition remains unclear. We explored the relationship between neuropsychological performance as measured using the Brief Assessment of Cognition in Schizophrenia (BACS) and the Social Cognition Screening Questionnaire theory of mind (ToM) subscale and fronto-temporal function in 23 patients with schizophrenia and 23 age- and gender-matched healthy controls (HCs), using 52-channel near-infrared spectroscopy (NIRS). Regional hemodynamic changes were significantly smaller in the schizophrenia group than in the HCs group in the ventro-lateral prefrontal cortex and the anterior part of the temporal cortex (VLPFC/aTC) and dorso-lateral prefrontal cortex and frontopolar cortex (DLPFC/FPC) regions. To dissect the effect of variance in BACS cognitive domains from the relationship between ToM function and fronto-temporal function, we performed additional partial correlation analyses between ToM and NIRS data, using BACS composite score as a control variable. The correlation between ToM and NIRS data remained significant only in the DLPFC/FPC region. This finding is important to models of recovery, as it suggests that intervention programs focusing on enhancing fronto-temporal function may have a greater impact on social and occupational outcomes than traditional rehabilitation programs focusing on neuropsychological performance.

Comparison of neurocognitive function in major depressive disorder, bipolar disorder, and schizophrenia in later life: A cross-sectional study of euthymic or remitted, non-demented patients using the Japanese version of the Brief Assessment of Cognition in Schizophrenia (BACS-J).

Major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ) are associated with cognitive dysfunction both in adulthood and in later life. In this study, we directly compared neurocognitive function between these three conditions in later life, employing stringent definitions of euthymia and symptomatic remission. Cognitive function in 60 elderly outpatients with MDD, BD, or SZ (20 patients per group) was assessed using the Japanese version of the Brief Assessment of Cognition in Schizophrenia. Patients with MDD had significantly higher z scores than both the other groups with large or moderately large effect sizes, for verbal fluency, attention and speed of information processing, and composite scores. In contrast, there were no significant differences in the degree of neurocognitive impairment between patients with BD and SZ. In later life, patients with BD and SZ showed a similar degree of neurocognitive impairment, while patients with MDD showed smaller impairments in several neurocognitive domains compared to patients with either of the other two disorders.

Aberrant Spatial and Temporal Prefrontal Activation Patterns in Medication-Naïve Adults with ADHD.

Previous near-infrared spectroscopy (NIRS) studies using a verbal fluency task (VFT) have consistently reported that adults with attention-deficit hyperactivity disorder (ADHD) showed significantly smaller oxygenated-hemoglobin [oxy-Hb] activations in the prefrontal cortex (PFC) compared to those in healthy controls (HC). Despite this consistent evidence of brain dysfunction in ADHD, ADHD is currently diagnosed based only on subjective clinical and scoring measures, which are often unreliable. Hence, it is necessary to establish objective neuroimaging biomarkers for ADHD. While most NIRS studies have utilized averaged [oxy-Hb] values during the whole task period for group comparisons, we used a cluster-based non-parametric randomization test to compare the [oxy-Hb] time-course changes with a 0.1-s time resolution between drug-naïve adults with ADHD and HC, which may provide us with more details regarding abnormal prefrontal activation patterns in ADHD. A total of 101 participants, consisting of 63 drug-naïve adult individuals with ADHD and 38 HC, were included in this study. We identified that adults with ADHD showed significantly smaller [oxy-Hb] activations than those in HC at spatially and temporally connected clusters located in the bilateral PFC (more prominent on the left) and temporal brain region (more prominent on the left). We further found that aberrant [oxy-Hb] activation differs according to the time period during the task or according to brain location. Our findings indicate more detailed aberrant prefrontal and temporal activation patterns of ADHD compared with those in previous studies, possibly representing a biological marker for ADHD.

Frontal and temporal cortical functional recovery after electroconvulsive therapy for depression: A longitudinal functional near-infrared spectroscopy study.

While the efficacy and tolerability of electroconvulsive therapy (ECT) for depression has been well established, the acute effects of ECT on brain function remain unclear. Particularly, although cognitive dysfunction has been consistently observed after ECT, little is known about the extent and time course of ECT-induced brain functional changes, as observed during cognitive tasks. Considering the acute antidepressant effects of ECT on depression, aberrant brain functional responses during cognitive tasks in patients with depression may improve immediately after this treatment. To clarify changes in cortical functional responses to cognitive tasks following ECT, we used task-related functional near-infrared spectroscopy (NIRS) to assess 30 patients with major depressive disorder or bipolar depression before and after an ECT series, as well as 108 healthy controls. Prior to ECT, patients exhibited significantly smaller [oxy-Hb] values in the bilateral frontal cortex during a letter verbal fluency task (VFT) compared with healthy controls. We found a significant increase in [oxy-Hb] values in the bilateral frontal cortex during the VFT after ECT in the patient group. A decrease in depression severity was significantly correlated with an increase in [oxy-Hb] values in the right ventrolateral prefrontal cortex following ECT. This is the first NIRS study to evaluate brain functional changes before vs. after ECT. Impaired functional responses, observed during the cognitive task in depressed patients, were normalized after ECT. Thus, recovery from abnormal functional responses to cognitive tasks in the frontal brain regions may be associated with the acute therapeutic effects of ECT for depression.