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.

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 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.

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.

Residual Symptoms Were Differentially Associated with Brain Function in Remitted Patients with Major Depressive Disorders.

BACKGROUND: The desirable goals of the treatment of major depressive disorder (MDD) are considered both to achieve symptom remission and to help the patients be restored to their premorbid levels of functioning. Remission has often been defined clinically as a threshold using standardized scales. Such a definition, however, allows several residual symptoms to be present in the remitted state. The aim of this study was to examine the relationship between the levels of residual symptoms and social functioning and also the relationship between residual symptoms and brain function. METHODS: The subjects were 21 patients with MDD in remission, defined operationally using clinician-rated 17-item Hamilton Depression Scale. Depressive symptoms and social functioning were self-assessed with the Japanese versions of the Center for Epidemiologic Studies Depression Scale (CES-D) and the Social Adaptation Self-evaluation Scale (SASS), respectively. Brain function was measured by the changes in concentration of oxy-hemoglobin ([oxy-Hb]) in the prefrontal and temporal cortices during verbal fluency task using near-infrared spectroscopy (NIRS). RESULTS: The mean CES-D total score was 18.0, s = 13.2, indicating that they have on average mild depression. Scores of CES-D total and those of its four factors showed a significantly negative correlation with the SASS total score. Among the four factors, "Interpersonal problems" factor showed the strongest correlation with it. CES-D total score and those of its three factors, "Depressed affect", "Somatic and retarded activity" and "Positive affect", showed significantly negative correlations with the mean [oxy-Hb] changes mainly in the left hemisphere, whereas "Interpersonal problems" factor showed a significantly positive correlation with the size of NIRS activation predominantly in right prefrontal regions. CONCLUSION: Our results indicate that remitted patients with MDD possibly have residual symptoms which are most likely to impair their social functioning and that these symptoms are differentially associated with brain function measured with NIRS.

Social cognition and prefrontal hemodynamic responses during a working memory task in schizophrenia.

Social cognition is an important determinant of functional impairment in schizophrenia, but its relationship with the prefrontal functional abnormalities associated with the condition is still unclear. The present study aimed to explore the relationship between social cognition and prefrontal function in patients with schizophrenia using 52-channel near-infrared spectroscopy (NIRS). Twenty-six patients with schizophrenia and 26 age-, gender-, and intelligence quotient-matched healthy controls (HCs) participated in the study. Hemodynamic responses in the prefrontal and superior temporal cortical regions were assessed during a working memory task using NIRS. Social cognition was assessed using the Social Cognition Screening Questionnaire (SCSQ). The observed hemodynamic responses were significantly reduced in the lateral prefrontal cortex (PFC), the frontopolar cortex, and temporal regions in subjects with schizophrenia compared to HCs. Additionally, lateral PFC hemodynamic responses assessed during the working memory task demonstrated a strong positive correlation with the SCSQ theory of mind (ToM) subscale score even after controlling for working memory performance. These results suggest that ToM integrity is closely related to lateral PFC functional abnormalities found in patients with schizophrenia. In addition, this study provides evidence to suggest that NIRS could be used to identify biomarkers of social cognition function in subjects with schizophrenia.

The association between cognitive deficits and prefrontal hemodynamic responses during performance of working memory task in patients with schizophrenia.

Schizophrenia-associated cognitive deficits are resistant to treatment and thus pose a lifelong burden. The Brief Assessment of Cognition in Schizophrenia (BACS) provides reliable and valid assessments across cognitive domains. However, because the prefrontal functional abnormalities specifically associated with the level of cognitive deficits in schizophrenia have not been examined, we explored this relationship. Patients with schizophrenia (N=87) and matched healthy controls (N=50) participated in the study. Using near-infrared spectroscopy (NIRS), we measured the hemodynamic responses in the prefrontal and superior temporal cortical surface areas during a working memory task. Correlation analyses revealed a relationship between the hemodynamics and the BACS composite and domain scores. Hemodynamic responses of the left dorsolateral prefrontal cortex (DLPFC) and left frontopolar cortex (FPC) in the higher-level-of-cognitive-function schizophrenia group were weaker than the responses of the controls but similar to those of the lower-level-of-cognitive-function schizophrenia group. However, hemodynamic responses in the right DLPFC, bilateral ventrolateral PFC (VLPFC), and right temporal regions decreased with increasing cognitive deficits. In addition, the hemodynamic response correlated positively with the level of cognitive function (BACS composite scores) in the right DLPFC, bilateral VLPFC, right FPC, and bilateral temporal regions in schizophrenia. The correlation was driven by all BACS domains. Our results suggest that the linked functional deficits in the right DLPFC, bilateral VLPFC, right FPC, and bilateral temporal regions may be related to BACS-measured cognitive impairments in schizophrenia and show that linking the neurocognitive deficits and brain abnormalities can increase our understanding of schizophrenia pathophysiology.

Self-reported social functioning and prefrontal hemodynamic responses during a cognitive task in schizophrenia.

Impaired social functioning is a characteristic of schizophrenia that affects patients' quality of life. The aim of the study was to assess prefrontal hemodynamic responses during a cognitive task and establish its influence on psychiatric symptoms, cognitive function, global functioning, and self-reported social functioning in patients with schizophrenia. Thirty-three patients with schizophrenia and 30 age-and sex-matched healthy controls participated in the study. We measured hemodynamic responses in the prefrontal and superior temporal cortical surface areas with 52-channel near-infrared spectroscopy (NIRS) during a verbal fluency task (VFT). Self-reported social functioning was assessed using the Social Functioning Scale (SFS). Regional hemodynamic responses were significantly smaller in the prefrontal and temporal regions in subjects with schizophrenia than in the controls, and prefrontal hemodynamic responses during the VFT showed a strong correlation with SFS total scores. These results suggest an association between self-reported social functioning and prefrontal activation in subjects with schizophrenia. The present study provides evidence that NIRS imaging could be helpful in understanding the neural basis of social functioning.

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.