Near-infrared spectroscopy (NIRS) is an optimal imaging modality used to examine spontaneous brain activity because it can quietly measure blood flow changes with less physical restriction during the resting state. Here, NIRS was used at rest to measure spontaneous activity in the medial prefrontal cortex (mPFC), a main locus of default mode network. Consistent with previous fMRI studies, magnitude of the spontaneous activity in this region declined with increasing age in healthy subjects. The magnitude reduced in the mPFC of patients with schizophrenia. Additionally, in the mPFC of patients with schizophrenia, the spontaneous activity did not show any age-related decline; the activity was already low in younger patients. Further analysis using fractional amplitude of low-frequency fluctuations confirmed the reduction of spontaneous activity in the mPFC of patients with schizophrenia, consistent with the findings of fMRI studies. Our findings demonstrate the ability of NIRS to evaluate the spontaneous activity in the mPFC of patients with schizophrenia, particularly younger patients. Considering the safety and ease of the NIRS measurements, the current NIRS study of the resting-state activity indicates its utility for clinical applications to schizophrenia, which may facilitate chronological assessment of larger cohorts of patients with schizophrenia in further studies.

in functional imaging, accumulating evidence suggests that spontaneous activity decreases during the resting state in the core brain regions of the default-mode network [e.g. medial prefrontal cortex (mPFC)] in schizophrenia. However, the significance of this decreased activity has not been clarified in relation to its clinical symptoms. in this study, near-infrared spectroscopy (niRS), which is a simple imaging modality suitable for resting state paradigm, was used to evaluate the intensity of the spontaneous activity during the resting state in chronic schizophrenia. Consistent with previous findings of fMRi studies, spontaneous activity decreased in the mpfc of patients with schizophrenia. in addition, the decreased spontaneous activity was associated with severe hallucinations in this region where reality monitoring is fundamentally engaged. these results may encourage additional application of niRS with the resting state paradigm into daily clinical settings for addressing the broad phenotypes and unstable course of schizophrenia. Since default-mode activity was termed for the brain regional activity that is enhanced during the resting state 1,2 , numerous research fields have been opened up to identify the significance of this activity in human brains and brain diseases 3-5. The default-mode activity is characterized by spontaneous low-frequency (<0.1 Hz) fluctuations of the brain blood flow 6. Such fluctuations are synchronized among specific brain regions called the default-mode network whose core regions consist of the medial prefrontal cortex (mPFC) and PCC/precuneus 1,4. While most of the recent studies about disturbances of this activity have examined the impact on the network changes in psychiatric illnesses, less attention has been paid to quantify the intensity of this activity, which may provide an additional valid marker for mental illnesses. An index to measure the intensity of the resting-state activity in functional MRI (fMRI) is the amplitude of low-frequency fluctuations (ALFF), which appear dominantly in the core regions of the default-mode network 7,8. The ALFF indicates the sum of the power across low-frequency range (0.01-0.08 Hz) fluctuations of the brain blood flow, whereas the fractional ALFF (fALFF) indicates the ratio of the ALFF to the total power. Although previous fMRI studies have shown that both the ALFF and fALFF have reliable signals from the grey matter of the brain, the ALFF is believed to be more sensitive to the differences among groups and individuals owing to its higher test-retest reliability 8. On the other hand, the fALFF is reported to generate lesser noise from physiological sources 7,8. Therefore, it is recommended to use both analyses to maximize the reliability of examining spontaneous regional brain activity during the resting state 8. Several lines of evidence using fMRI suggest that the ALFF or fALFF is decreased during the resting state in the core regions of the default-mode network in schizophrenia 9-16. However, the extended analysis to explore the releva...

Impaired gamma oscillations found in a 40-Hz auditory steady-state response (ASSR) in patients with schizophrenia are the robust findings that can be used for future biomarker-based therapeutics. To apply these significant observations into the clinical practice, a clinical system for evoked response audiometry (ERA) may be available. In this study, the delayed 40-Hz ASSR, which was reported as a potent biomarker for schizophrenia, was examined using the ERA system in patients with schizophrenia and its clinical relevance was investigated. The phase of ASSR was significantly delayed in patients with schizophrenia compared with the healthy subjects. The delayed phase was associated with severity of the disease symptoms in the patients. A phase delay with aging was found in healthy subjects, but not in patients with schizophrenia. These findings show availability of the ERA system to identify the delayed 40-Hz ASSR and its clinical implication in patients with schizophrenia. Further applications of the ERA system in clinical psychiatry are warranted in developing biological assessments of schizophrenia with 40-Hz ASSR.

Gamma oscillations probed using auditory steady-state response (ASSR) are promising clinical biomarkers that may give rise to novel therapeutic interventions for schizophrenia. Optimizing clinical settings for these biomarker-driven interventions will require a quick and easy assessment system for gamma oscillations in psychiatry. ASSR has been used in clinical otolaryngology for evoked response audiometry (ERA) in order to judge hearing loss by focusing on the phase-locked response detectability via an automated analysis system. Herein, a standard ERA system with 40- and 46-Hz ASSRs was applied to evaluate the brain pathophysiology of patients with schizophrenia. Both ASSRs in the ERA system showed excellent detectability regarding the phase-locked response in healthy subjects and sharply captured the deficits of the phase-locked response caused by aberrant gamma oscillations in individuals with schizophrenia. These findings demonstrate the capability of the ERA system to specify patients who have aberrant gamma oscillations. The ERA system may have a potential to serve as a real-world clinical medium for upcoming biomarker-driven therapeutics in psychiatry.

Gamma oscillations probed using auditory steady-state response (ASSR) are promising clinical biomarkers that may address novel therapeutic interventions for schizophrenia. Optimizing clinical settings for these biomarker-driven interventions will require a quick and easy assessment system of gamma oscillations in psychiatry. ASSR has been used in clinical otolaryngology for evoked response audiometry (ERA) to judge hearing loss by focusing on the phase-locked response detectability in an automated analysis system. Herein, a standard ERA system was applied to evaluate the brain pathophysiology of patients with schizophrenia with 40-Hz ASSR. The 40-Hz ASSR in the ERA system showed excellent detectability of the phase-locked response in healthy subjects, which sharply captured the deficits of the phase-locked response caused by aberrant gamma oscillations in individuals with schizophrenia. These findings reveal the availability of the ERA system in specifying patients who have aberrant 40-Hz gamma oscillations. The ERA system may have a potential to serve as a real-world clinical setting for upcoming biomarker-driven therapeutics in psychiatry.