Ryu Kurimoto

Resting-State EEG Source Localization and Functional Connectivity in Schizophrenia-Like Psychosis of Epilepsy

Background It is unclear whether, like in schizophrenia, psychosis-related disruption in connectivity between certain regions, as an index of intrinsic functional disintegration, occurs in schizophrenia-like psychosis of epilepsy (SLPE). In this study, we sought to determine abnormal patterns of resting-state EEG oscillations and functional connectivity in patients with SLPE, compared with nonpsychotic epilepsy patients, and to assess correlations with psychopathological deficits. Methodology/Principal Findings Resting EEG was recorded in 21 patients with focal epilepsy and SLPE and in 21 clinically-matched non-psychotic epilepsy controls. Source current density and functional connectivity were determined using eLORETA software. For connectivity analysis, a novel nonlinear connectivity measure called “lagged phase synchronization” was used. We found increased theta oscillations in regions involved in the default mode network (DMN), namely the medial and lateral parietal cortex bilaterally in the psychotic patients relative to their nonpsychotic counterparts. In addition, patients with psychosis had increased beta temporo-prefrontal connectivity in the hemisphere with predominant seizure focus. This functional connectivity in temporo-prefrontal circuits correlated with positive symptoms. Additionally, there was increased interhemispheric phase synchronization between the auditory cortex of the affected temporal lobe and the Brocas area correlating with auditory hallucination scores. Conclusions/Significance In addition to dysfunction of parietal regions that are part of the DMN, resting-state disrupted connectivity of the medial temporal cortex with prefrontal areas that are either involved in the DMN or implicated in psychopathological dysfunction may be critical to schizophrenia-like psychosis, especially in individuals with temporal lobe epilepsy. This suggests that DMN deficits might be a core neurobiological feature of the disorder, and that abnormalities in theta oscillations and beta phase synchronization represent the underlying neural activity.

Impaired regional hemodynamic response in schizophrenia during multiple prefrontal activation tasks: A two-channel near-infrared spectroscopy study

In schizophrenia, dysfunction of the prefrontal cortex (PFC), regarded as a core feature of the disease, has been investigated by different neuroimaging methods. Near infrared spectroscopy (NIRS), a novel neurophysiological method, is being increasingly used in the investigation of frontal dysfunction in schizophrenia. However, NIRS measurements during multiple frontal activation tasks have been rarely reported. The purpose of this study was to compare hemodynamic changes in the PFC between patients with schizophrenia and healthy controls during four different types of frontal lobe tasks using a 2-channel NIRS system. Thirty patients with schizophrenia and thirty age- and gender-matched healthy controls were enrolled in this study. In both groups, changes in oxygenated hemoglobin concentration (Delta[oxyHb]) at the bilateral forehead were measured during Verbal fluency test letter version (VFT-letter), VFT category version, Tower of Hanoi (TOH), the Sternberg and Stroop tasks. Regarding Delta[oxyHb] in PFC, a diagnosis group effect was found for VFT-letter and TOH. Significant negative correlation was found between left Delta[oxyHb] during TOH and negative and cognitive symptom scores in schizophrenia patients. Right Delta[oxyHb] during TOH also showed significant negative correlation with cognitive symptoms scores. No significant correlation between Delta[oxyHb] and clinical characteristics were observed during VFT-letter. These findings suggest that among a battery of frontal lobe tasks administered to schizophrenia patients, VFT-letter and TOH are more sensitive to detect PFC activation, as indicated by Delta[oxyHb] using a 2-channel NIRS. Taken together, these findings and those of previous neuroimaging studies suggest that VFT-letter and TOH might represent possible candidate physiological markers of prefrontal dysfunction in schizophrenia, though extensive testing in clinical settings will be necessary.

Impaired prepulse inhibition and habituation of acoustic startle response in Japanese patients with schizophrenia

Prepulse inhibition (PPI) and habituation of the acoustic startle reflex (ASR) are considered to be candidate endophenotypes of schizophrenia. However, to our knowledge, only one group has investigated these startle measures in Asian patients with schizophrenia. In the present study, we evaluated these startle measures in 51 Japanese patients with schizophrenia and compared them with those of 55 healthy age- and sex-matched Japanese controls. A human startle response monitoring system was used to deliver acoustic startle stimuli, and record and score the electromyographic activity of the orbicularis oculi muscle. The startle measures examined were mean magnitude of ASR to pulse alone trials in initial block (SR), habituation of ASR during the session (HAB), and PPI at prepulse intensities of 82 dB (PPI82), 86 dB (PPI86), and 90 dB (PPI90) sound pressure level. SR was not significantly different between the patients and controls. Patients displayed significantly reduced HAB and PPI for all prepulse intensities compared to controls. The greatest statistical difference in PPI between patients and controls was found with PPI86. This did not correlate with any clinical variable in each group. Our results indicate that PPI and habituation of ASR are impaired in Asian patients with schizophrenia.

Post-movement beta rebound abnormality as indicator of mirror neuron system dysfunction in autistic spectrum disorder: an MEG study.

The mu rhythm is regarded as a physiological indicator of the human mirror neuron system (MNS). The dysfunctional MNS hypothesis in patients with autistic spectrum disorder (ASD) has often been tested using EEG and MEG, targeting mu rhythm suppression during action observation/execution, although with controversial results. We explored neural activity related to the MNS in patients with ASD, focusing on power increase in the beta frequency band after observation and execution of movements, known as post-movement beta rebound (PMBR). Multiple source beamformer (MSBF) and BrainVoyager QX were used for MEG source imaging and statistical group analysis, respectively. Seven patients with ASD and ten normal subjects participated in this study. During the MEG recordings, the subjects were asked to observe and later execute object-related hand actions performed by an experimenter. We found that both groups exhibited pronounced PMBR exceeding 20% when observing and executing actions with a similar topographic distribution of maximal activity. However, significantly reduced PMBR was found only during the observation condition in the patients relative to controls in cortical regions within the MNS, namely the sensorimotor area, premotor cortex and superior temporal gyrus. Reduced PMBR during the observation condition was also found in the medial prefrontal cortex. These results support the notion of a dysfunctional execution/observation matching system related to MNS impairment in patients with ASD, and the feasibility of using MEG to detect neural activity, in particular PMBR abnormalities, as an index of MNS dysfunction during performance of motor or cognitive tasks.

Discriminant analysis in schizophrenia and healthy subjects using prefrontal activation during frontal lobe tasks: A near-infrared spectroscopy

While psychiatric disorders such as schizophrenia are largely diagnosed on symptomatology, several studies have attempted to determine which biomarkers can discriminate schizophrenia patients from non-patients with schizophrenia. The objective of this study is to assess whether near-infrared spectroscopy (NIRS) measurement can distinguish schizophrenia patients from healthy subjects. Sixty patients with schizophrenia and sixty age- and gender-matched healthy controls were divided into two sequential groups. The concentration change in oxygenated hemoglobin (Delta[oxy-Hb]) was measured in the bilateral prefrontal areas (Fp1-F7 and Fp2-F8) during the Verbal Fluency Test (VFT) letter version and category version, Tower of Hanoi (TOH), Sternbergs (SBT) and Stroop Tasks. In the first group, schizophrenia patients showed poorer task performance on all tasks and less prefrontal cortex activation during all but the Stroop Task compared to healthy subjects. In the second group, schizophrenia patients showed poorer task performance and less prefrontal cortex activation during VFTs and TOH tasks than healthy subjects. We then performed discriminant analysis by a stepwise method using Delta[oxy-Hb] and task performance measures as independent variables. The discriminant analysis in the first group included task performance of TOH, VFT letter and VFT category and Delta[oxy-Hb] of VFT letter. As a result, 88.3% of the participants were correctly classified as being schizophrenic or healthy subjects in the first analysis. The discriminant function derived from the first group correctly assigned 75% of the subjects in the second group. Our findings suggest that NIRS measurement could be applied to differentiate patients with schizophrenia from healthy subjects.

Association study of the G72 gene with schizophrenia in a Japanese population: A multicenter study

G72 is one of the most widely tested genes for association with schizophrenia. As G72 activates the D-amino acid oxidase (DAO), G72 is termed D-amino acid oxidase activator (DAOA). The aim of this study is to investigate the association between G72 and schizophrenia in a Japanese population, using the largest sample size to date (1774 patients with schizophrenia and 2092 healthy controls). We examined eight single nucleotide polymorphisms (SNPs), which had been associated with schizophrenia in previous studies. We found nominal evidence for association of alleles, M22/rs778293, M23/rs3918342 and M24/rs1421292, and the genotype of M22/rs778293 with schizophrenia, although there was no association of allele or genotype in the other five SNPs. We also found nominal haplotypic association, including M15/rs2391191 and M19/rs778294 with schizophrenia. However, these associations were no longer positive after correction for multiple testing. We conclude that G72 might not play a major role in the risk for schizophrenia in the Japanese population.

Induced oscillatory responses during the Sternberg's visual memory task in patients with Alzheimer's disease and mild cognitive impairment.

In this study we used magnetoencephalography during a modified version of the Sternbergs memory recognition task performed by patients with early Alzheimers disease (AD), mild cognitive impairment (MCI), and by age-matched healthy controls to identify differences in induced oscillatory responses. For analyses, we focused on the retention period of the working memory task. Multiple-source beamformer and Brain Voyager were used for localization of source-power changes across the cortex and for statistic group analyses, respectively. We found significant differences in oscillatory response during the task, specifically in beta and gamma frequency bands: patients with AD showed reduced beta event-related desynchronization (ERD) in the right central area compared to controls, and reduced gamma ERD in the left prefrontal and medial parietal cortex compared to patients with MCI. Our findings suggest that reduced oscillatory responses over certain brain regions in high frequency bands (i.e., beta, gamma), and especially in the beta band that was significantly different between AD patients and healthy subjects, may represent brain electromagnetic changes underlying visual-object working memory dysfunction in early AD, and a neurophysiological indicator of cognitive decline.

Frontal cortex activation associated with speeded processing of visuospatial working memory revealed by multichannel near-infrared spectroscopy during Advanced Trail Making Test performance

Although visuospatial working memory (VSWM) is commonly used during speeded and unconscious memory processing in daily life, most neuroimaging studies on VSWM use tasks that impose motor restrictions onto the examinees to avoid movement-related artifacts. Multichannel near-infrared spectroscopy (NIRS), however, can measure cortical activation during cognitive processing without interfering with task procedure. The purpose of this study is to determine whether multichannel NIRS can detect VSWM-induced frontal cortex activation similar to that seen in VSWM performance in daily-life activity. Using NIRS, we measured relative changes in the concentration of oxygenated hemoglobin as an index of frontal activation in 52 measurement points (channels) on the frontal area during the Advanced Trail Making Test (ATMT), a tool used to assess VSWM. The ATMT consists of two tasks, R and F, with the former assessing motor factors and the latter relating to both motor and cognitive factors involved in speeded and unconscious VSWM operations. Twenty-six healthy volunteers were enrolled in this study. Channel activation during Task F performance was observed bilaterally over the dorsolateral and ventrolateral prefrontal cortex. This distribution may reflect central executive function of working memory. Channel activation during Task R was circumscribed to part of the left ventrolateral prefrontal cortex partially overlapping with areas active during Task F performance, likely representing task-related motor factor activation. Our findings suggest that multichannel NIRS during ATMT performance is an appropriate means of measuring cortical activation induced by VSWM operations during daily activity.

Frontal Activity during the Digit Symbol Substitution Test Determined by Multichannel Near-Infrared Spectroscopy

Backgrounds: The digit symbol substitution test (DSST) is a clinically useful and widely accepted tool for the detection of various psychiatric disorders. Investigating neural activity during the DSST is useful when considering the relationship between the poor performance on the DSST and neurocognitive deficits. However, obtaining reliable functional imaging of the neural mechanisms associated with this test is challenging due to motion artifacts. Aims: To circumvent this problem, we examined frontal lobe activity during the DSST using multichannel near-infrared spectroscopy, a noninvasive functional imaging technique that does not interfere with the DSST procedure. Methods: Twenty-five healthy volunteers were enrolled in this study. Changes in the concentration of oxygenated hemoglobin (oxyHb) during the DSST were determined bilaterally in 52 measurement points (channels) on the frontal area. Results: We found significant increases in oxyHb in more than 70% of the channels, with the intensity of the increase being more pronounced in the left hemisphere. Several channels showed significant positive correlations between changes in oxyHb and DSST performance. Some of the channels with a significant increase in oxyHb during the DSST did not show a correlation with the DSST performance. Conclusions: Our findings indicate that the DSST could prove useful as a frontal lobe stimulating task. Further examinations of DSST/near-infrared spectroscopy analyses of neural mechanisms in patients with psychiatric and neurological diseases are necessary to assess its effectiveness in clinical practice for the evaluation of neuropsychopathology.

Frontal shift of posterior alpha activity is correlated with cognitive impairment in early Alzheimer's disease: a magnetoencephalography-beamformer study.

Background:  Induced‐oscillatory activity is considered a key factor for understanding functional processes in the brain. Magnetoencephalography (MEG) can measure oscillatory activity non‐invasively with higher spatial resolution than electroencephalography (EEG). However, MEG has rarely been used to explore functional abnormalities that may represent state markers in patients with Alzheimers disease (AD).