Multivariate sharp-wave ripples in schizophrenia during awake state.

AIMS: Schizophrenia (SZ) is a brain disorder characterized by psychotic symptoms and cognitive dysfunction. Recently, irregularities in sharp-wave ripples (SPW-Rs) have been reported in SZ. As SPW-Rs play a critical role in memory, their irregularities can cause psychotic symptoms and cognitive dysfunction in patients with SZ. In this study, we investigated the SPW-Rs in human SZ. METHODS: We measured whole-brain activity using magnetoencephalography (MEG) in patients with SZ (n = 20) and sex- and age-matched healthy participants (n = 20) during open-eye rest. We identified SPW-Rs and analyzed their occurrence and time-frequency traits. Furthermore, we developed a novel multivariate analysis method, termed "ripple-gedMEG" to extract the global features of SPW-Rs. We also examined the association between SPW-Rs and brain state transitions. The outcomes of these analyses were modeled to predict the positive and negative syndrome scale (PANSS) scores of SZ. RESULTS: We found that SPW-Rs in the SZ (1) occurred more frequently, (2) the delay of the coupling phase (3) appeared in different brain areas, (4) consisted of a less organized spatiotemporal pattern, and (5) were less involved in brain state transitions. Finally, some of the neural features associated with the SPW-Rs were found to be PANSS-positive, a pathological indicator of SZ. These results suggest that widespread but disorganized SPW-Rs underlies the symptoms of SZ. CONCLUSION: We identified irregularities in SPW-Rs in SZ and confirmed that their alternations were strongly associated with SZ neuropathology. These results suggest a new direction for human SZ research.

The Characteristics of Power Spectral Density in Bipolar Disorder at the Resting State.

Bipolar disorder (BD) is a common psychiatric disorder, but its pathophysiology is not fully elucidated. The current study focused on its electrophysiological characteristics, especially power spectral density (PSD). Resting state with eyes opened magnetoencephalography data were collected from 21 patients with BD and 22 healthy controls. The whole brain's PSD was calculated from source reconstructed waveforms at each frequency band (delta: 1-3 Hz, theta: 4-7 Hz, alpha: 8-12 Hz, low beta: 13-19 Hz, high beta: 20-29 Hz, and gamma: 30-80 Hz). We compared PSD values on the marked vertices at each frequency band between healthy and patient groups using a Mann-Whitney rank test to examine the relationship between significantly different PSD and clinical measures. The PSD in patients with BD was significantly decreased in lower frequency bands, mainly in the default mode network (DMN) areas (bilateral medial prefrontal cortex, bilateral precuneus, left inferior parietal lobe, and right temporal cortex in the alpha band) and salience network areas (SAL; left anterior insula [AI] at the delta band, anterior cingulate cortex at the theta band, and right AI at the alpha band). No significant differences in PSD were observed at low beta and high beta. PSD was not correlated with age or other clinical scales. Altered PSDs of the DMN and SAL were observed in the delta, theta, and alpha bands. These alterations contribute to the vulnerability of BD through the disturbance of self-referential mental activity and switching between the default mode and frontoparietal networks.

Disrupted local beta band networks in schizophrenia revealed through graph analysis: A magnetoencephalography study.

AIMS: Schizophrenia (SZ) is characterized by psychotic symptoms and cognitive impairment, and is hypothesized to be a 'dysconnection' syndrome due to abnormal neural network formation. Although numerous studies have helped elucidate the pathophysiology of SZ, many aspects of the mechanism underlying psychotic symptoms remain unknown. This study used graph theory analysis to evaluate the characteristics of the resting-state network (RSN) in terms of microscale and macroscale indices, and to identify candidates as potential biomarkers of SZ. Specifically, we discriminated topological characteristics in the frequency domain and investigated them in the context of psychotic symptoms in patients with SZ. METHODS: We performed graph theory analysis of electrophysiological RSN data using magnetoencephalography to compare topological characteristics represented by microscale (degree centrality and clustering coefficient) and macroscale (global efficiency, local efficiency, and small-worldness) indices in 29 patients with SZ and 38 healthy controls. In addition, we investigated the aberrant topological characteristics of the RSN in patients with SZ and their relationship with SZ symptoms. RESULTS: SZ was associated with a decreased clustering coefficient, local efficiency, and small-worldness, especially in the high beta band. In addition, macroscale changes in the low beta band are closely associated with negative symptoms. CONCLUSIONS: The local networks of patients with SZ may disintegrate at both the microscale and macroscale levels, mainly in the beta band. Adopting an electrophysiological perspective of SZ as a failure to form local networks in the beta band will provide deeper insights into the pathophysiology of SZ as a 'dysconnection' syndrome.

Frequency-Specific Resting Connectome in Bipolar Disorder: An MEG Study.

BACKGROUND: Bipolar disorder (BD) is a serious psychiatric disorder that is associated with a high suicide rate, and for which no clinical biomarker has yet been identified. To address this issue, we investigated the use of magnetoencephalography (MEG) as a new prospective tool. MEG has been used to evaluate frequency-specific connectivity between brain regions; however, no previous study has investigated the frequency-specific resting-state connectome in patients with BD. This resting-state MEG study explored the oscillatory representations of clinical symptoms of BD via graph analysis. METHODS: In this prospective case-control study, 17 patients with BD and 22 healthy controls (HCs) underwent resting-state MEG and evaluations for depressive and manic symptoms. After estimating the source current distribution, orthogonalized envelope correlations between multiple brain regions were evaluated for each frequency band. We separated regions-of-interest into seven left and right network modules, including the frontoparietal network (FPN), limbic network (LM), salience network (SAL), and default mode network (DMN), to compare the intra- and inter-community edges between the two groups. RESULTS: In the BD group, we found significantly increased inter-community edges of the right LM-right DMN at the gamma band, and decreased inter-community edges of the right SAL-right FPN at the delta band and the left SAL-right SAL at the theta band. Intra-community edges in the left LM at the high beta band were significantly higher in the BD group than in the HC group. The number of connections in the left LM at the high beta band showed positive correlations with the subjective and objective depressive symptoms in the BD group. CONCLUSION: We introduced graph theory into resting-state MEG studies to investigate the functional connectivity in patients with BD. To the best of our knowledge, this is a novel approach that may be beneficial in the diagnosis of BD. This study describes the spontaneous oscillatory brain networks that compensate for the time-domain issues associated with functional magnetic resonance imaging. These findings suggest that the connectivity of the LM at the beta band may be a good objective biological biomarker of the depressive symptoms associated with BD.

Decreased cortical reactivity underlies subjective daytime light sleepiness in healthy subjects: a multichannel near-infrared spectroscopy study.

Daytime sleepiness is considered to be one of the main problems in modern society. Of the four aspects of sleepiness, namely, subjective sleepiness, performance decrease, sleep propensity, and arousal decrease, subjective sleepiness is the most difficult to assess. Brain mechanisms underlying subjective light sleepiness in daytime were investigated in healthy subjects using multichannel near-infrared spectroscopy (NIRS), which enables the noninvasive measurement of regional cerebral blood volume (rCBV) changes under natural conditions. Forty right-handed healthy volunteers participated in this study. Relationships were investigated between subjective sleepiness and anxiety, assessed using the Stanford Sleepiness Scale (SSS) and State-Trait Anxiety Inventory (STAI), respectively, and cerebral cortex reactivities assessed as oxygenated and deoxygenated hemoglobin concentration ([oxy-Hb] and [deoxy-Hb], respectively) changes during a verbal fluency task using a 24-channel NIRS machine. SSS score correlated negatively with an [oxy-Hb] increase in the bilateral frontal channels mainly in the middle and last third of the verbal fluency task period. Subjective light daytime sleepiness in healthy subjects is considered to be related to decreased prefrontal reactivities in the later part of cognitive activation.

Time courses of brain activation and their implications for function: a multichannel near-infrared spectroscopy study during finger tapping.

The time courses of brain activation were monitored during a finger tapping task using multichannel near-infrared spectroscopy with a time resolution of 0.1s in 30 healthy volunteers. Task-induced brain activations were demonstrated as significant increases in oxygenated hemoglobin concentration ([oxy-Hb]) in a broad area around the motor cortex and significant decreases in deoxygenated hemoglobin concentration ([deoxy-Hb]) in a more restricted area, with a large degree of activation in the contralateral hemisphere. The time courses of the [oxy-Hb] changes varied depending on channel location: sustained activation across the task period in the motor cortex, transient activation during the initial segments of the task period in the somatosensory cortex, and accumulating activation along the task period in the frontal lobe. These characteristics are assumed to reflect the functional roles of the brain structures during the task period, that is, the execution, sensory monitoring, and maintenance of finger tapping.

Frontal lobe function in bipolar disorder: a multichannel near-infrared spectroscopy study.

Frontal lobe dysfunction has been implicated as one of the pathophysiological bases of bipolar disorder. Detailed time courses of brain activation in the bipolar disorder group were investigated using multichannel near-infrared spectroscopy (NIRS), a recently developed functional neuroimaging technology with a high time resolution, and were compared with those in the major depression and healthy control groups. Seventeen patients with bipolar disorder, 11 equally depressed patients with major depression, and 17 healthy controls participated in the study. Changes in oxy hemoglobin concentration ([oxy-Hb]) during cognitive and motor tasks were monitored using frontal and temporal probes of two sets of 24-channel NIRS machines. [oxy-Hb] increases in the bipolar disorder group were smaller than those in the healthy control group during the early period of a verbal fluency task, larger than those in the major depression and healthy control groups during the late period of this task, and were smaller than those in the major depression group during a finger-tapping task. Depressive symptoms and antidepressant dosages did not correlate with [oxy-Hb] changes in the two patient groups. Bipolar disorder and major depression were characterized by preserved but delayed and reduced frontal lobe activations, respectively, in the present high-time-resolution study by multichannel NIRS.

Increased and decreased cortical reactivities in novelty seeking and persistence: a multichannel near-infrared spectroscopy study in healthy subjects.

BACKGROUND: Near-infrared spectroscopy (NIRS) has enabled completely noninvasive measurements of regional cerebral blood volume (rCBV) changes in cortices. In the present study, we investigated the relationships between rCBV changes assessed with NIRS and two dimensions of personality, novelty seeking and persistence. METHODS: Thirty right-handed healthy volunteers participated in the study. Their personality traits were assessed using the Temperament and Character Inventory (TCI), and changes in oxy- and deoxy-hemoglobin concentrations were monitored during 40 s unilateral finger tapping tasks over the subjects' bilateral temporal regions using a 24-channel NIRS machine. RESULTS: The oxy-hemoglobin concentration increases were significantly correlated positively with novelty seeking scores and negatively with persistence scores in the TCI during the initial time segment of the left-finger tapping task. CONCLUSION: Increased and decreased brain activations demonstrated using multichannel NIRS were assumed to characterize the cortical reactivities underlying novelty seeking and persistence temperament, respectively.

Multichannel near-infrared spectroscopy in depression and schizophrenia: cognitive brain activation study.

BACKGROUND: Recent developments in near-infrared spectroscopy (NIRS) have enabled the noninvasive clarification of brain functions in psychiatric disorders with measurement of hemoglobin concentrations as cerebral blood volume. METHODS: Ten patients with depression, 13 patients with schizophrenia, and 16 age- and gender-matched healthy control subjects participated in the study after giving consent. The relative concentrations of oxyhemoglobin [oxyHb] were measured with frontal and temporal probes every.1 sec during word fluency and unilateral finger tapping tasks, with two 24-channel NIRS machines. RESULTS: The [oxyHb] increase patterns during the word fluency task varied among the three groups, although their task performances were similar: the depression group was characterized by a smaller [oxyHb] increase during the first half of the task period and the schizophrenic group by a small trough of [oxyHb] at the start of the task period and [oxyHb] re-increase in the posttask period. [OxyHb] increases during the finger-tapping task were rather larger in the patient groups than in the control group. CONCLUSIONS: The characteristic time courses of [oxyHb] changes in the frontal lobe were elucidated for depression and schizophrenia. Near-infrared spectroscopy, with its noninvasiveness and high time resolution, can be a useful tool for research and clinical purposes in psychiatry.