Signal Sequence-Dependent Orientation of Signal Peptide Fragments to Exosomes.

Signal peptides (SPs) not only mediate targeting to the endoplasmic reticulum (ER) but also play important roles as biomarkers and substances with physiological activity in extracellular fluids including blood. SPs are thought to be degraded intracellularly, making it unclear how they are transported from the ER to the extracellular fluid. In a recent study, we showed that a C-terminal fragment of the SP of a type I membrane protein, amyloid precursor protein (APP), was secreted into the extracellular fluid via exosomes using transformed HEK293 cells expressing APP SP flanking a reporter protein. In the present study, we demonstrate that a N-terminal fragment of the SP from a type II membrane protein, human placental secreted alkaline phosphatase (SEAP), is contained in exosomes and secreted into the extracellular fluid using HEK-Blue hTLR3 cells, which express both a human toll-like receptor 3 gene and an inducible SEAP reporter gene. When HEK-Blue hTLR3 cells were stimulated with a TLR3 ligand, a N-terminal fragment of SEAP SP in exosomes was increased in parallel with SEAP secretion in a concentration-dependent manner. These results indicated that SP fragments are exosomal components. In addition, migrating SP fragments were determined by characteristics of the signal-anchor sequence of membrane proteins. Furthermore, we found that SP fragments could bind to calmodulin (CALM), which is a cytosolic protein and also a component of exosomes, suggesting its involvement in the transportation of SP fragments from the endoplasmic reticulum to exosomes.

Secretion of signal peptides via extracellular vesicles.

Signal peptides (SPs) consist of short peptide sequences present at the N-terminal of newly synthesizing proteins and act as a zip code for the translocation of the proteins to the endoplasmic reticulum (ER). It was thought that the SPs are intracellularly degraded after translocation to the ER; however, recent studies showed cleaved SPs have diverse roles for controlling cell functions in auto- and/or intercellular manners. In addition, it still remains obscure how SP fragments translocate away from the site where they are produced. Extracellular vesicles (EV) are important for intercellular communication and can transport functional molecules to specific cells. In this study, we show that SPs are involved in EV from T-REx AspALP cells that were transfected with a human APP SP-inducible expression vector. There was no difference in the average particle size or particle concentration of EV collected from T-REx AspALP cells and T-REx Mock cells. When the SP content in the EV was examined by mass spectrometry, the C-terminal fragment of APP SP was identified in the exosomes (SEV) of T-REx AspALP cells. In our preparation of SEV fractions, no ER-specific proteins were detected; therefore, SPs may be included in SEV but not in the debris of degraded ER. This is the first indication that SPs are secreted from cells via EV.

[Hydromorphone in Cancer Patients-A Retrospective Study].

We retrospectively investigated the use of oral hydromorphone for cancer pain. Nineteen patients treated for cancer pain with oral hydromorphone were reviewed in this study. Cancers had occurred in the gastrointestinal (n=4), lung(n=3), breast(n=2), bone and soft tissue(n=2), hematological(n=2), and others(n=6). The administered opioids before switching to hydromorphone were morphine, oxycodone, and tapentadol. The mean oral morphine equivalent daily dose (OMEDD)was 89.3 mg. The average dose of hydromorphone administered was 16.4 mg/day, and average NRS 10(numerical rating scale: 0-10)scores of cancer pain before and after switching were 4.1 and 3.8, respectively, showing no significant differences. In this study, switching from other opioids to oral hydromorphone was feasible with an approved conversion ratio, ie, an oral hydromorphone-to-oral morphine ratio of 1:5. No severe adverse effects were observed. The oral hydromorphone extended-release formulation was administered every 24 h, as a tiny tablet formulation that is preferable owing to easy administration and adherence.

BC-Box Motif-Mediated Neuronal Differentiation of Somatic Stem Cells.

Von Hippel-Lindau tumor suppressor protein (pVHL) functions to induce neuronal differentiation of neural stem/progenitor cells (NSCs) and skin-derived precursors (SKPs). Here we identified a neuronal differentiation domain (NDD) in pVHL. Neuronal differentiation of SKPs was induced by intracellular delivery of a peptide composed of the amino-acid sequences encoded by the NDD. Neuronal differentiation mediated by the NDD was caused by the binding between it and elongin C followed by Janus kinase-2 (JAK2) ubiquitination of JAK2 and inhibition of the JAK2/the signal transducer and activator of transcription-3(STAT)3 pathway. The NDD in pVHL contained the BC-box motif ((A,P,S,T)LXXX (A,C) XXX(A,I,L,V)) corresponding to the binding site of elongin C. Therefore, we proposed that other BC-box proteins might also contain an NDD; and subsequently also identified in them an NDD containing the amino-acid sequence encoded by the BC-box motif in BC-box proteins. Furthermore, we showed that different NDD peptide-delivered cells differentiated into different kinds of neuron-like cells. That is, dopaminergic neuron-like cells, cholinergic neuron-like cells, GABAnergic neuron-like cells or rhodopsin-positive neuron-like cells were induced by different NDD peptides. These novel findings might contribute to the development of a new method for promoting neuronal differentiation and shed further light on the mechanism of neuronal differentiation of somatic stem cells.

Usefulness of carer-held records to support informal caregivers of patients with dementia who live at home.

AIM: It is unclear whether carer-held records (CHR) are useful for patients with dementia. In this study, we evaluated the usefulness of the CHR for patients with dementia at the municipal level. METHODS: Candidates for CHR use in this study were informal caregivers of patients with dementia who lived at home in Kawanishi, Japan. CHR users were those who are involved in the patient's care and treatment, such as informal caregivers, family physicians, dementia specialists, care professionals, and care service coordinators, known as ?care managers' in Japan. Collaborative meetings were held every month mainly to help users, especially care managers, learn how to effectively use CHR. We surveyed informal caregivers before and 1.5 years after the start of CHR use to evaluate whether CHR improved collaboration and information provision. The Zarit Caregiver Burden Interview and Dementia Behaviour Disturbance Scale were also administered. We divided the informal caregivers who continued CHR use for 1.5 years into two subgroups based on whether their care manager attended the collaborative meetings at least twice. In addition, we divided informal caregivers into three subgroups depending on their relationship to the patient: spouse, child, or daughter-in-law. RESULTS: The study initially consisted of 201 informal caregivers. Among them, 74 informal caregivers continued CHR use for 1.5 years. The information provision score significantly improved after CHR use for all informal caregivers. The collaboration score significantly improved after CHR use only for informal caregivers whose care managers attended at least two collaborative meetings. The Zarit Caregiver Burden Interview score significantly improved after CHR use for daughter-in-law caregivers. The Dementia Behaviour Disturbance Scale scores did not significantly improve after CHR use. CONCLUSIONS: CHR were useful for informal caregivers of patients with dementia. However, care managers need to teach informal caregivers how to properly use CHR.

Recombinant human IgG antibodies recognizing distinct extracellular domains of EGF receptor exhibit different degrees of growth inhibitory effects on human A431 cancer cells.

Recently, we isolated 4 distinct kinds of single chain antibody against human EGF receptor (EGFR) after screening the Keio phage display scFv library by using two methods of target-guided proximity labeling. In the current study, these monovalent scFv antibodies were converted to bivalent IgGs of humanized forms (hIgGs) by recombinant technology using the specially designed expression vectors followed by protein production in CHO cells. The resulting recombinant hIgGs were examined for their binding specificity using several different transformed human BJ cell lines that express deletion mutants of EGFR, each lacking one of 4 distinct extracellular domains (L1, L2, C1 and C2). Immuno-fluorescent microscopy and immuno-precipitation assay on these cells indicated that 4 distinct kinds of hIgGs bind to one of 3 different domains (L1, C1 and C2). Then, these hIgGs were further examined for biological effects on human A431 cancer cells, which overexpress EGFR. The results indicated that hIgG38 binding to L1 and hIgG45 binding to C2 substantially suppressed the EGF-induced phosphorylation of EGFR, resulting in the growth inhibition of A431 cancer cells. On the contrary, hIgG40 binding to C1 and hIgG42 binding to another site (epitope) of C2 exhibited no such inhibitory effects. Thus, the newly produced four recombinant hIgG antibodies recognize 4 different sites (epitopes) in 3 different extracellular domains of EGFR and exhibit different biological effects on cancer cells. These characteristics are somewhat different from the currently utilized therapeutic anti-EGFR antibodies. Hence, these hIgG antibodies will be invaluable as a research tool for the detailed molecular analysis of the EGFR-mediated signal transduction mechanism and more importantly a possible application as new therapeutic agents to treat certain types of cancers.

Association between milder brain deformation before a shunt operation and improvement in cognition and gait in idiopathic normal pressure hydrocephalus.

We investigated the association between the degree of deformation of the brain before shunt operation and improvement of gait and cognitive impairment after shunt operation in 16 patients with idiopathic normal pressure hydrocephalus (iNPH). We evaluated gait and cognitive impairment and measured the cerebrospinal fluid volume in the ventricles/sylvian fissure (vVS) and the subarachnoid space at high convexity/midline areas (vHCM) using MR images with voxel-based morphometry before and 3 months after shunt operation. We used the ratio of vVS to vHCM (vVS/vHCM) as an index of the severity of brain deformation. After shunt operation, improvements were observed in gait, as shown by the Timed Up and Go (TUG) test and 10-meter reciprocating walking test (WT), and in cognitive function, as shown by the Mini-Mental State Examination, Alzheimer Disease Assessment Scale, Frontal Assessment battery (FAB), and Trail Making test A (TMT-A). The vVS/vHCM ratio was negatively correlated with improvement of the FAB, TMT-A and TUG. Preoperative vVS/vHCM was not significantly correlated with preoperative clinical assessments. The rate of change of vVS/vHCM was positively correlated with improvement in the WT. The improvements of gait and cognitive function were larger in iNPH patients with milder deformation of the brain before shunt operation.

Reversibility of brain morphology after shunt operations and preoperative clinical symptoms in patients with idiopathic normal pressure hydrocephalus.

AIM: Brain deformations might prevent clinical symptoms from worsening in patients with idiopathic normal pressure hydrocephalus (iNPH). We investigated the relationship between reversibility of brain morphology after shunt operations and preoperative clinical symptoms in iNPH patients. METHODS: Using head magnetic resonance images with voxel-based morphometry, we measured the cerebrospinal fluid volume in the combined areas of the lateral and third ventricles and Sylvian fissure (the volume of the ventricles and Sylvian fissure (vVS)) and the volume of the subarachnoid space at high convexity and midline areas (vHCM) before and 1 year after lumboperitoneal shunt operations in 12 patients with shunt-responsive iNPH. We used the ratio of normalized vVS to normalized vHCM (nvVS/nvHCM) as an index of the severity of the brain deformation. The degree of reversibility of the brain morphology after the shunt operation was defined as the change ratio of the preoperative nvVS/nvHCM to the postoperative nvVS/nvHCM (CR-nvVS/nvHCM). Higher CR-nvVS/nvHCM values indicated more improvement in the brain deformation. In addition, we rated the severity of the white matter lesions on the preoperative magnetic resonance images based on the Fazekas scale. Dependency in activities of daily living, gait and cognition were evaluated before and 1 year after the shunt operations. RESULTS: After the shunt operations, the nvVS/nvHCM and nvVS decreased significantly, and nvHCM increased significantly. The CR-nvVS/nvHCM negatively correlated with the preoperative severity of dependency in activities of daily living, gait and cognitive impairments. The CR-nvVS/nvHCM negatively correlated with the Fazekas scale, but not with age, duration of the disease and cerebrospinal fluid pressure. CONCLUSIONS: Reversibility of brain morphology, which varied among iNPH patients, would prevent clinical symptoms from worsening in iNPH patients. The presence of white matter lesions reduced the degree of reversibility of the brain deformations in iNPH patients.

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 Sternberg's memory recognition task performed by patients with early Alzheimer's 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.

Calmodulin as a Key Regulator of Exosomal Signal Peptides.

Signal peptides (SPs) and their fragments play important roles as biomarkers and substances with physiological functions in extracellular fluid. We previously reported that SP fragments were released into extracellular fluid via exosomes and bound to calmodulin (CaM), an exosomal component, in a cell-free system. However, it currently remains unclear whether CaM intracellularly interacts with SP fragments or is involved in the trafficking of these fragments to exosomes. Therefore, the present study examined the binding of CaM to SP fragments in T-REx AspALP cells, transformed HEK293 cells expressing amyloid precursor protein (APP) SP flanking a reporter protein, and their exosomes. APP SP fragments were detected in exosomes from T-REx AspALP cells in the absence of W13, a CaM inhibitor, but were present in lower amounts in exosomes from W13-treated cells. Cargo proteins, such as Alix, CD63, and CD81, were increased in W13-treated T-REx AspALP cells but were decreased in their exosomes. Furthermore, CaM interacted with heat shock protein 70 and CD81 in T-REx AspALP cells and this increased in the presence of W13. APP SP fragments were detected in intracellular CaM complexes in the absence of W13, but not in its presence. These results indicate that CaM functions as a key regulator of the transport of SP fragments into exosomes and plays novel roles in the sorting of contents during exosomal biogenesis.

Exosome-derived small non-coding RNAs reveal immune response upon grafting transplantation in Pinctada fucata (Mollusca).

Exosomes, a subset of small extracellular vesicles, carry various nucleic acids, proteins, lipids, amino acids and metabolites. They function as a mode of intercellular communication and molecular transfer. Exosome cargo molecules, including small non-coding RNAs (sncRNAs), are involved in the immune response in various organisms. However, the role of exosome-derived sncRNAs in immune responses in molluscs remains unclear. Here, we aimed to reveal the sncRNAs involved in the immune response during grafting transplantation by the pearl oyster Pinctada fucata. Exosomes were successfully extracted from the P. fucata haemolymph during graft transplantation. Abundant microRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs) were simultaneously discovered in P. fucata exosomes by small RNA sequencing. The expression patterns of the miRNAs and piRNAs at the grafting and initial stages were not substantially different, but varied significantly between the initial and later stages. Target prediction and functional analysis indicate that these miRNAs and piRNAs are related to immune response upon grafting transplantation, whereas piRNAs may also be associated with transposon silencing by targeting with genome transposon elements. This work provides the basis for a functional understanding of exosome-derived sncRNAs and helps to gain further insight into the PIWI/piRNA pathway function outside of germline cells in molluscs.

Protein synthesis in the posterior cingulate cortex in Alzheimer's disease.

BACKGROUND: Neuroimaging studies using (18) F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) and single photon emission computed tomography (SPECT) have shown that the posterior cingulate cortex (PCC) is the primary and most prominent area of cerebral metabolic and perfusional decrement in early Alzheimer's disease (AD). We carried out the present preliminary study to investigate whether a decline of cerebral blood flow (CBF) in the PCC in early to moderate AD was accompanied with that of cerebral protein synthesis (CPS). METHODS: We carried out both N-isopropyl-p-[123I] iodoamphetamine SPECT (IMP-SPECT) and L-[methyl-11C] methionine positron emission tomography (MET-PET) in eight AD patients with apolipoprotein E epsilon 4 allele in the early to moderate stage. We also carried out IMP-SPECT in eight healthy controls (HC). We located 32 regions of interest (ROI), and values of regional MET or IMP uptakes were averaged in five regions; the frontal lobe (FL), the parietal lobe (PL), the medial temporal lobe (MTL), PCC and the occipital lobe. Furthermore, the values in the FL, PL, MTL and PCC were divided by values in the occipital areas, and normalized values of regional CBF (rCBF) and CPS (rCPS) were calculated. Then, the rCBF in the FL, PL, MTL and PCC were compared between AD and HC. In addition, the rCBF and rCPS were compared in the FL, PL, MTL and PCC of AD. RESULTS: The rCBF in the PCC, but not in the other three regions, was significantly lower in AD than in HC. The rCBF was significantly lower than rCPS in the PCC, but rCBF and rCPS were comparable in the other three regions in AD. CONCLUSIONS: The CBF reduction in the PCC in AD was partly caused by neuronal loss in the PCC and partly supported the hypothesis that CBF reduction in the PCC was a result of functional deafferentation by neural degeneration in areas other than the PCC.

Environmental pH stress influences cellular secretion and uptake of extracellular vesicles.

Exosomes (extracellular vesicles/EVs) participate in cell-cell communication and contain bioactive molecules, such as microRNAs. However, the detailed characteristics of secreted EVs produced by cells grown under low pH conditions are still unknown. Here, we report that low pH in the cell culture medium significantly affected the secretion of EVs with increased protein content and zeta potential. The intracellular expression level and location of stably expressed GFP-fused CD63 (an EV tetraspanin) in HeLa cells were also significantly affected by environmental pH. In addition, increased cellular uptake of EVs was observed. Moreover, the uptake rate was influenced by the presence of serum in the cell culture medium. Our findings contribute to our understanding of the effect of environmental conditions on EV-based cell-cell communication.

KIBRA genetic polymorphism influences episodic memory in Alzheimer's disease, but does not show association with disease in a Japanese cohort.

BACKGROUND/AIMS: A single-nucleotide polymorphism (SNP) in the KIBRA gene, rs17070145, was reported to be significantly associated with episodic memory in cognitively normal cohorts. This observation has expanded genetic studies on KIBRA to Alzheimer's disease (AD). Importantly, the association between KIBRA and episodic memory in AD has never been addressed. In this study, we investigated whether the KIBRA rs17070145 SNP influences AD episodic memory and the disease in a Japanese cohort. METHODS: Blood samples from 346 AD patients and 375 normal cognitive controls were collected and genotyped for rs17070145. Episodic memory was measured in 32 AD patients, diagnosed for the first time, by use of the Rivermead Behavioral Memory Test (RBMT). RESULTS: We found that KIBRA C allele carriers scored significantly lower than KIBRA non-C carriers on both RBMT total profile score (p = 0.042, effect size = 0.84) and RBMT total screening score (p < 0.001, effect size = 1.42). The KIBRA gene did not show association with AD in our Japanese cohort. CONCLUSION: Our results evidence a strong association between the KIBRA gene and episodic memory impairment in AD, but show no influence on AD in our Japanese cohort. We propose that KIBRA might have an effect similar to cognitive reserve.

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.

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.

Neuroimaging studies in patients with Charles Bonnet Syndrome.

Charles Bonnet Syndrome (CBS) is characterized by complex formed and recurrent visual hallucinations in psychologically normal people, and is often associated with eye pathology. Many psychiatrists have taken an interest in CBS because this syndrome could provide clues to the mechanisms underlying visual hallucinations. In the present paper, we review previous neuroimaging studies in patients with CBS and summarize the results of these studies. There could be a fundamental dysfunction in the primary and secondary visual cortices in some patients with CBS, and transient cortical activation occurs in the inferior lateral temporal cortex during the appearance of visual hallucinations in CBS patients. External visual stimuli are perceived in the retina and are transmitted to the primary visual cortex (Brodmann area (BA) 17). The stimuli are transmitted from BA 17 to the secondary visual cortex (BA 18) and then to the visual association cortices (BA 19 and BA 37). In general, our perception of external visual stimuli normally has an inhibitory effect on the endogenous activation of the visual cortex. Visual loss due to certain conditions, of which eye pathology is the most commonly postulated in CBS patients, produces a state of sensory deprivation that releases the visual cortex from regulation by external stimuli, resulting in visual hallucinations (cortical release phenomenon). The results of previous neuroimaging studies suggest that the cortical release phenomenon hypothesis for the occurrence of visual hallucinations in patients with CBS is plausible. In addition, the results indicate that not only eye pathology, but also dysfunction in the primary and secondary visual cortices could result in deprivation of external visual stimuli.

[A case of unresectable advanced pancreatic cancer treated by gemcitabine-based chemotherapy following cancer pain alleviation by low-dose matrix-type transdermal fentanyl].

Cancer pain often makes patient's performance status worsen and is one of the difficulties in anti-cancer therapy. We report a case of unresectable advanced pancreatic cancer with cancer pain, which was treated by matrix-type transdermal fentanyl following slow-releasing oxycodone, which caused severe constipation. Rotation to matrix-type transdermal fentanyl (Durotep MT 2.1 mg) releaved severe constipation as well as cancer pain. The patient could take gemcitabine-based chemotherapy. Low-dose matrix-type transdermal fentanyl (Durotep MT 2.1 mg) is useful for opioid rotation from low-dose morphine or oxycodone with uncontrolled side effects, and it contributes to continuation of anti-cancer therapy.

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.

Event-related synchronization of alpha activity in early Alzheimer's disease and mild cognitive impairment: an MEG study combining beamformer and group comparison.

In patients with Alzheimer's disease (AD), it is sometimes challenging to identify typical findings in electroencephalography (EEG) or magnetoencephalography (MEG) such as a slowing of the posterior dominant activity or an increase in slow activity. In this MEG study, we evaluated the event-related synchronization (ERS) of alpha activity after eye closing in patients with early AD and mild cognitive impairment (MCI) who presented no slow MEG pattern. Thirteen patients with probable AD and thirteen patients with MCI, who met NINCDS-ADRDA and Petersen's diagnostic criteria, respectively, were enrolled. We also selected fourteen age-matched normal control subjects. MEG activity was acquired during eye-open and eye-closed states. The ERS after eye closing within 8-15Hz frequency band was calculated and its cortical source was superimposed on the individual's MRI by using the beamformer implemented in Brain Electrical Source Analysis (BESA). The Source image was converted into a standardized image, and group comparisons across patients with AD, MCI and controls were performed using BrainVoyager QX. The averaged ERS was observed dominantly in posterior regions in all three groups. Significant difference in ERS was observed only for the comparison between AD patients and controls, with AD patients showing increased ERS in frontal regions. Frontal shift of posterior alpha activity was observed clearly in AD patients using the combination of beamformer and group comparison.