Katsutoshi Yokoyama

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.

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.

Relationship between prefrontal function during a cognitive task and social functioning in male Japanese workers: A multi-channel near-infrared spectroscopy study

To investigate whether prefrontal function during a cognitive task reflects the social functioning of male Japanese workers, prefrontal function during a working memory task in 181 male workers was measured by multi-channel near-infrared spectroscopy (NIRS). Social functioning was assessed using the Social Adaptation Self-Evaluation Scale (SASS). The results indicated that cortical oxygenation level increases in dorsolateral prefrontal region showed significant positive correlations with the interest and motivation factor scores on the SASS. These results suggest that dorsolateral prefrontal function is associated with the interest and motivation factor in social functioning in male workers and that NIRS could be an addition to the medical tools for monitoring these characteristics on mental health examination.

Association between subjective well-being and prefrontal function during a cognitive task in schizophrenia: a multi-channel near-infrared spectroscopy study.

The purpose of this study was to examine the relationship between subjective well-being and prefrontal function during a cognitive task in schizophrenia. Twenty-four patients with clinically stable schizophrenia participated in the study. We measured the change in hemoglobin concentration in the prefrontal region during a verbal fluency task (VFT) by using 52-channel near-infrared spectroscopy (NIRS). The subjective well-being of participants was assessed using the Subjective Well-being under Neuroleptic drug treatment Short form (SWNS). A significant positive relationship was observed between the SWNS score and frontopolar, left ventrolateral, and bilateral dorsolateral prefrontal function during the VFT. These results suggest that the frontopolar and left ventrolateral and bilateral dorsolateral prefrontal cortical regions are associated with the subjective well-being of clinically stable patients with schizophrenia and that NIRS may be an efficient medical tool for monitoring these characteristics.

Relationship between hypothalamic-pituitary-adrenal axis dysregulation and insulin resistance in elderly patients with depression

Cortisol dysregulation has been proposed to be involved in depression. Hypothalamic-pituitary-adrenal (HPA) axis dysregulation associated with major depressive disorder (MDD) was previously reported to be higher in the elderly. Furthermore, insulin resistance and the prevalence of type 2 diabetes are known to increase with aging. The aim of the present study was to determine whether a relationship existed between plasma cortisol levels following the dexamethasone/corticotrophin-releasing hormone (DEX/CRH) test and insulin resistance evaluated by the homeostasis model assessment of insulin resistance (HOMA-R) in elderly MDD subjects. Fifteen unmedicated MDD inpatients and 17 age- and sex-matched healthy controls participated in this study. After overnight fasting, blood samples were collected to measure plasma glucose and insulin concentrations, estimate HOMA-R, and perform the DEX/CRH test to evaluate HPA axis function. The value of the area under the time curve of plasma cortisol concentrations (CortAUC) and peak cortisol values (Cortpeak) following the administration of DEX/CRH both correlated with HOMA-R in MDD group. In contrast, neither CortAUC nor Cortpeak correlated with HOMA-R in controls. This is the first study to directly demonstrate the relationship between HPA axis dysregulation assessed with the DEX/CRH test and the index of insulin resistance estimated as HOMA-R in elderly MDD patients.

Association between social functioning and prefrontal hemodynamic responses in elderly adults.

Social functioning has received widespread attention as one of the most important outcomes in psychiatric disorders and has been related to cognitive functioning and the underlying brain activity. Cognitive decline, however, appears not only in the psychiatric population but also in aged individuals. In our previous study, we demonstrated a significant relationship between social functioning and prefrontal cortex (PFC) activity in patients with depression. However, it has not been shown whether the above relationship could be extended to healthy populations. The purpose of the present study was to investigate a possible association between social functioning and prefrontal hemodynamic responses in healthy elderly adults by using a non-invasive and low-constraint functional neuroimaging technique, near-infrared spectroscopy (NIRS). Study subjects included 55 healthy, elderly volunteers. We measured hemodynamic responses over prefrontal cortical (PFC) areas during the verbal fluency task by using multi-channel NIRS and analyzed the relationship between task-associated hemodynamic responses and social functioning as measured by the social adaptation self-evaluation scale (SASS). A significant positive relationship was observed between the SASS total score and PFC activation. Our findings suggest that PFC activation is associated with social functioning in healthy elderly adults. Furthermore, hemodynamic responses assessed using non-invasive NIRS could be a useful biological marker of these characteristics.

Effects of donepezil and serotonin reuptake inhibitor on acute regression during adolescence in Down syndrome

A 14-year-old boy with Down syndrome (DS) showed a gradual decline in his daily activities and feeding capacities, and a marked deterioration triggered by a streptococcal infection was observed at the age of 15 years. He became bedridden, accompanied by sleep disturbance, sustained upward gaze, and generalized rigidity. Magnetic resonance imaging showed unremarkable findings, but antiglutamate receptor autoantibodies were positive in his cerebrospinal fluid. Treatment with thiamine infusion and steroid pulse therapy showed little effect, but gross motor dysfunction and appetite loss were ameliorated by the administration of l-DOPA and serotonin reuptake inhibitors. Thereafter, autistic behaviors predominated, including loss of social interaction, oral tendency, water phobia, and aggressiveness. Initiation of donepezil, an acetylcholinesterase inhibitor, resulted in the disappearance of these symptoms and total recovery of the patient to his previous psychosocial levels. We hypothesize that the acute regression in adolescence represents a process closely related to the defects of serotonergic and cholinergic systems that are innate to DS brains and not just a nonspecific comorbidity of depression or limbic encephalitis.

Association between Fish Consumption and Prefrontal Function during a Cognitive Task in Male Japanese Workers: A Multi-Channel Near-Infrared Spectroscopy Study

The purpose of this study was to examine the relationship between fish consumption and prefrontal function during a cognitive task in male Japanese workers. The study included 208 male workers who underwent medical health examinations 3 months after a change in their work assignment. We measured the hemoglobin concentration changes in the prefrontal region during working memory tasks using 52-channel near-infrared spectroscopy. The frequency of fish consumption was calculated on the basis of the subjects’ self-reported customary intake frequency over the previous 3 months. A significant positive relationship was observed between fish consumption and left dorsolateral prefrontal function during a working memory task. To our knowledge, this is the first study to report an association between fish consumption and functional cortical activity with an ample sample size, suggesting that fish consumption modulates functional activity in the left dorsolateral prefrontal cortex.