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Background: Preplanning of care is necessary for patients with endstage heart failure (HF), but advance care planning (ACP) before the loss of a patient's comprehensive capacity is not yet routine for the public or the medical community. The challenge in accurately predicting a patient's prognosis is a strong barrier to implementing ACP. To address this problem, several models for risk stratification have been proposed and are available in clinical settings. MethodsâandâResults: We randomized the procedure to provide estimated patient survival information to attending physicians and then assessed whether there was a change in (1) the frequency of ACP initiation occurred (physician-side evaluation), and/or (2) the patients' quality of life, including mental state (patient-side evaluation). Conclusions: This multicenter, open-label, single-blinded randomized clinical trial aims to assess the hypothesis that providing information on the estimated survival of a patient to the attending physicians will improve the frequency of ACP initiation and quality of life in patients with HF.
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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.
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Doença de Alzheimer/fisiopatologia , Córtex Cerebral/fisiopatologia , Transtornos Cognitivos/fisiopatologia , Magnetoencefalografia , Memória de Curto Prazo/fisiologia , Idoso , Feminino , Humanos , MasculinoRESUMO
AIM: The aim of this study was to investigate whether magnetoencephalographic oscillations underlying working memory dysfunction in the dorsolateral prefrontal cortex (DLPFC) are related to psychopathological disturbance in patients with schizophrenia-like psychosis of epilepsy (SLPE). METHODS: Twelve patients with SLPE and 14 non-psychotic epilepsy controls participated in this study. Magnetoencephalography was recorded while patients performed a visual working memory (WM) task. Psychopathology was assessed using a four-factor structure of the Brief Psychiatric Rating Scale, and regression analyses were carried out to examine the relative impact of severity of psychopathology on WM-induced activation of the DLPFC. RESULTS: We found that activation of the WM-compromising DLPFC, as indicated by increased alpha desynchronization in patients with SLPE compared with their non-psychotic counterparts, showed a positive linear correlation with disorganization symptom scores. This association remained significant after controlling for confounding factors, including age, task performance, IQ, and duration of psychosis. CONCLUSION: Our results indicate that abnormal activation in prefrontal areas engaged during working memory may be critical to domains of psychopathology, in particular disorganized thought-processing in patients with SLPE.
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Epilepsia/fisiopatologia , Magnetoencefalografia/métodos , Transtornos da Memória/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Transtornos Psicóticos/fisiopatologia , Adulto , Mapeamento Encefálico/métodos , Ondas Encefálicas/fisiologia , Epilepsia/complicações , Feminino , Humanos , Masculino , Transtornos da Memória/complicações , Estimulação Luminosa , Desempenho Psicomotor/fisiologia , Transtornos Psicóticos/complicaçõesRESUMO
Working memory (WM) deficits are considered a core cognitive dysfunction in schizophrenia. To determine cognitive abnormalities in chronic interictal psychosis (CIP), and to assess whether these abnormalities are distinguishable from those seen in schizophrenia in terms of WM deficits, we used magnetoencephalography during a WM task performed by patients with CIP, nonpsychotic epilepsy, and schizophrenia and by healthy subjects. Multiple Source Beamformer and Brain-Voyager were used for analysis. In both patients with CIP and those with schizophrenia, we found dorsolateral prefrontal hyperactivation and left inferior temporal hypoactivation, as indicated by alpha event-related desynchronization and synchronization, respectively. Patients with schizophrenia also showed alpha2 event-related desynchronization in the mid-prefrontal cortex relative to healthy controls. Direct comparison of patients with CIP and schizophrenia rendered no difference in source-power changes. Our findings indicate similar functional cognitive abnormalities in CIP and schizophrenia in the prefrontal and left temporal cortex, which supports the possibility that these disorders share common underlying pathophysiological mechanisms.
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Epilepsia/complicações , Magnetoencefalografia/métodos , Transtornos da Memória/diagnóstico , Transtornos da Memória/etiologia , Memória de Curto Prazo/fisiologia , Transtornos Psicóticos/complicações , Esquizofrenia/complicações , Adulto , Análise de Variância , Mapeamento Encefálico , Epilepsia/psicologia , Potenciais Evocados/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Tempo de Reação/fisiologia , Estatística como Assunto , Fatores de Tempo , Adulto JovemRESUMO
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 Alzheimer's disease (AD). METHODS: Thirteen patients with early AD and 14 age-matched normal controls participated in the present study. Magnetoencephalography activity was acquired during eyes-open and eyes-closed states. Alpha event-related synchronization (ERS) after eye closing was calculated and its cortical sources superimposed on each individual's magnetic resonance imaging (MRI) scan. The resulting functional image was converted into a Talairach-transformed anatomical brain image and group comparisons were made. We also assessed correlations between cortical ERS sources showing significant between-group differences in alpha activity and external clinical parameters, especially measures of cognitive function. RESULTS: The averaged alpha ERS after eye closing appeared dominantly in posterior brain regions in both patients with AD and healthy controls. However, there was a significant increase in alpha ERS in frontal regions, maximal over the prefrontal cortex, in patients with AD relative to controls, indicating a frontal shift of the posterior dominant MEG alpha rhythm in AD patients. This frontal ERS source in the alpha band was negatively correlated with Mini-Mental State Examination scores in the AD patient group. CONCLUSIONS: The findings indicate that a frontal shift of alpha ERS elicited by an eyes-open/eyes-closed paradigm may be an early brain electromagnetic change in patients with AD, probably representing a physiological state marker of the disease. Furthermore, the results confirm that the beamformer with group comparison analysis is a useful tool with which to explore functional processes in the brain, as indicated by oscillatory activity changes.
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Ritmo alfa , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/fisiopatologia , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/fisiopatologia , Lobo Frontal/fisiopatologia , Processamento de Imagem Assistida por Computador/instrumentação , Imageamento Tridimensional/instrumentação , Magnetoencefalografia/instrumentação , Córtex Pré-Frontal/fisiopatologia , Processamento de Sinais Assistido por Computador/instrumentação , Idoso , Idoso de 80 Anos ou mais , Sincronização Cortical/fisiologia , Feminino , Análise de Fourier , Humanos , Masculino , Valores de ReferênciaRESUMO
A recent genome-wide association study showed that a variant (rs1344706) in the ZNF804A gene was associated with schizophrenia and bipolar disorder. Replication studies supported the evidence for association between this variant in the ZNF804A gene and schizophrenia and that this variant is the most likely susceptibility variant. Subsequent functional magnetic resonance imaging studies in healthy subjects demonstrated the association of the high-risk ZNF804A variant with neural activation during a memory task and a theory of mind task. As these cognitive performances are disturbed in patients with schizophrenia, this gene may play a role in cognitive dysfunction in schizophrenia. The aim of the current study was to investigate the potential relationship between this ZNF804A polymorphism and memory function. The effects of the high-risk ZNF804A genotype, diagnosis, and genotype-diagnosis interaction on verbal memory, visual memory (VisM), attention/concentration, and delayed recall (measured by the Wechsler Memory Scale-Revised) were analyzed by two-way analysis of covariance in 113 patients with schizophrenia and 184 healthy subjects. Consistent with previous studies, patients with schizophrenia exhibited poorer performance on all indices as compared to healthy control subjects (P < 0.001). A significant ZNF804A genotype-diagnosis interaction was found for VisM performance (P = 0.0012). Patients with the high-risk T/T genotype scored significantly lower on VisM than G carriers did (P = 0.018). In contrast, there was no genotype effect for any index in the healthy control subjects (P > 0.05). Our data suggest that rs1344706 may be related to memory dysfunction in schizophrenia. © 2010 Wiley-Liss, Inc.
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Transtornos Cognitivos/genética , Fatores de Transcrição Kruppel-Like/genética , Transtornos da Memória/genética , Memória , Esquizofrenia/genética , Adulto , Estudos de Casos e Controles , Transtornos Cognitivos/diagnóstico , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Transtornos da Memória/diagnóstico , Pessoa de Meia-Idade , Testes Neuropsicológicos , Fenótipo , Polimorfismo de Nucleotídeo Único , Esquizofrenia/fisiopatologia , Escalas de WechslerRESUMO
BACKGROUND: In the field of palliative care, morphine is known to be effective for alleviating dyspnea in cancer patients. However, little is known regarding the safety and efficacy of morphine therapy for refractory dyspnea as palliative care in advanced heart failure (HF) patients. METHODS: We retrospectively reviewed consecutive advanced HF patients who were referred to the Palliative Care Team at our institution and administered morphine for refractory dyspnea during hospitalization between September 2013 and December 2018. We investigated the details of morphine usage, vital signs, an 11-point quantitative symptom scale, and adverse events at baseline, 24 h, and 72 h after the start of treatment. RESULTS: Morphine was administered for refractory dyspnea in 43 advanced HF patients [mean age: 73.5 years, male: 28 (65%), New York Heart Association functional class IV: 43 (100%), median left ventricular ejection fraction: 25%, median B-type natriuretic peptide level: 927 pg/ml, concurrent intravenous inotrope: 33 (77%)]. Median initial dose of morphine was 5 mg/day in both oral and intravenous administration and median duration of administration was 5 days. Significant decreases in an 11-point quantitative symptom scale [7 (5, 9) vs. 2 (1, 6); p < 0.01, (data available in 8 patients)] and respiratory rate (22.2 ± 6.1 vs. 19.7 ± 5.2 breaths per minute; p < 0.01) were observed 24 h after the start of morphine administration. Meanwhile, oxygen saturation, blood pressure, and heart rate were not significantly altered after treatment (NS). Common adverse events were delirium (18%) and constipation (8%); however, no lethal adverse event definitely related to morphine therapy occurred during treatment. CONCLUSIONS: This single-center retrospective study revealed the clinical practice of morphine therapy and suggested that morphine therapy might be feasible for refractory dyspnea as palliative care in advanced HF patients.
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Analgésicos Opioides/uso terapêutico , Dispneia/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Morfina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Analgésicos Opioides/efeitos adversos , Dispneia/sangue , Dispneia/fisiopatologia , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Morfina/efeitos adversos , Peptídeo Natriurético Encefálico/sangue , Cuidados Paliativos , Estudos Retrospectivos , Função Ventricular EsquerdaRESUMO
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.
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Hemodinâmica/fisiologia , Córtex Pré-Frontal/irrigação sanguínea , Córtex Pré-Frontal/fisiopatologia , Esquizofrenia/complicações , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Adulto , Análise de Variância , Estudos de Casos e Controles , Feminino , Lateralidade Funcional , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Oxiemoglobinas/análise , Resolução de Problemas/fisiologia , Fluxo Sanguíneo Regional/fisiologia , Esquizofrenia/patologia , Aprendizagem Verbal/fisiologia , Adulto JovemRESUMO
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.
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Povo Asiático/genética , Proteínas de Transporte/genética , Esquizofrenia/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Haplótipos/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Receptores de N-Metil-D-Aspartato/genéticaRESUMO
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.
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Habituação Psicofisiológica/efeitos dos fármacos , Reflexo de Sobressalto/efeitos dos fármacos , Psicologia do Esquizofrênico , Estimulação Acústica , Adulto , Piscadela/efeitos dos fármacos , Interpretação Estatística de Dados , Eletromiografia , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Adulto JovemRESUMO
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.
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Doença de Alzheimer/diagnóstico , Transtornos Cognitivos/diagnóstico , Sincronização Cortical , Magnetoencefalografia , Idoso , Doença de Alzheimer/fisiopatologia , Transtornos Cognitivos/fisiopatologia , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: 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.
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Aprendizagem por Associação/fisiologia , Mapeamento Encefálico/métodos , Discriminação Psicológica/fisiologia , Lobo Frontal/metabolismo , Adulto , Feminino , Humanos , Idioma , Masculino , Testes Neuropsicológicos , Oxiemoglobinas/metabolismo , Espectroscopia de Luz Próxima ao Infravermelho , Adulto JovemRESUMO
Although a nonspecific cephalic sensation, the so-called "cephalic aura," is a common sensory aura, particularly in frontal lobe seizures, but is rarely is the entire sensory seizure event. The unusual presentation of cephalic sensations in isolation representing supplementary motor area (SMA) seizures, which are commonly unaccompanied by ictal electroencephalography (EEG) changes, can easily lead to misdiagnosis of nonepileptic psychogenic seizures. We illustrate the case of a 36-year-old male patient with frontal lobe epilepsy who presented with isolated cephalic auras described as a nonvertiginous sense of head movement without observable clinical signs after his habitual partial motor seizures were controlled with pharmacotherapy. Video/EEG recordings showed no recognizable epileptic discharges time-locked to the onset of the isolated cephalic auras. Ictal magnetoencephalography (MEG) with synthetic aperture magnetometry-kurtosis (SAM(g(2))) analysis demonstrated the SMA onset of the cephalic auras; thus, MEG was essential in differentiating these isolated auras from nonepileptic psychogenic events.
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Epilepsia/fisiopatologia , Magnetoencefalografia , Córtex Motor/fisiopatologia , Adulto , Mapeamento Encefálico , Eletroencefalografia/métodos , Epilepsia/patologia , Lobo Frontal/patologia , Movimentos da Cabeça/fisiologia , Humanos , MasculinoRESUMO
The hallmark of tuberous sclerosis is the presence of multiple cortical tubers. Identifying the epileptogenic tubers is difficult and often requires invasive intracranial electroencephalograph (EEG) monitoring. We report on a patient with tuberous sclerosis upon whom the novel magnetoencephalography (MEG) technique of synthetic aperture magnetometry (SAM) with excess kurtosis (g2) analysis was performed for localization of the epileptogenic tuber. Simultaneous electroencephalography (EEG) was also performed. MEG data, as analyzed by SAM(g2), were superimposed on the patient's MRIs. In the fluid attenuated inversion recovery MRIs, several tubers and subependymal nodules could be identified, with the largest tubers being located in the right frontal and left anteriotemporal regions. Despite multiple cortical lesions existing, the SAM(g2) images showed a single large tuber and surrounding epileptogenic tissue in the left temporal cortex. We suggest that MEG with SAM(g2) analysis may be clinically useful for the accurate identification of epileptogenic tubers in patients with tuberous sclerosis.
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Mapeamento Encefálico , Córtex Cerebral/fisiopatologia , Epilepsia/patologia , Magnetismo , Magnetoencefalografia/métodos , Esclerose Tuberosa/patologia , Adulto , Eletroencefalografia/métodos , Processamento Eletrônico de Dados , Epilepsia/etiologia , Feminino , Humanos , Imageamento Tridimensional , Imageamento por Ressonância Magnética , Esclerose Tuberosa/complicaçõesRESUMO
OBJECTIVES: A meta-analysis of the associations between genetic variants in the AKT1 gene and schizophrenia found that a single nucleotide polymorphism (SNP5; rs2494732) was associated with schizophrenia in Asian populations. METHODS: In this study, we investigated the effects of this SNP on memory and attentional performance and brain structure using magnetic resonance imaging in a Japanese population (117 patients with schizophrenia and 189 healthy subjects). RESULTS: The memory performance, particularly attention/concentration score, measured by the Wechsler Memory Scale-Revised in A carriers of SNP5, which was found to be enriched in patients with schizophrenia, was lower than that in individuals with the G/G genotype. We confirmed the association of the SNP with attentional performance using the Continuous Performance Test, which assessed sustained attention and vigilance of attentional function. Patients with A allele demonstrated lower attentional performance than patients with the G/G genotype. Patients with the A allele had smaller gray matter volumes in the right inferior parietal lobule related to attentional processes and in the frontostriatal region related to different SNPs in AKT1 than patients with the G/G genotype. CONCLUSIONS: Our results suggest that a genetic variant of AKT1 might be associated with attentional deficits and brain morphological vulnerability in patients with schizophrenia.
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Atenção/fisiologia , Memória/fisiologia , Proteínas Proto-Oncogênicas c-akt/genética , Esquizofrenia/genética , Adulto , Encéfalo/metabolismo , Encéfalo/patologia , Feminino , Predisposição Genética para Doença , Humanos , Japão , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tamanho do Órgão/genética , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas c-akt/metabolismo , Escalas de Graduação Psiquiátrica , Esquizofrenia/patologia , Psicologia do EsquizofrênicoRESUMO
Prepulse inhibition (PPI) of acoustic startle reflex (ASR) and personality, such as temperament and character, are considered candidate endophenotypes of schizophrenia. Gene polymorphism studies have provided evidence that both PPI and self-transcendence (ST) are polygenetic traits that involve several neurotransmitters, including the serotonin and dopamine signaling pathways. However, the relationship between PPI and temperament/character has not been properly addressed to date. Here, we investigated the link between PPI and temperament/character in 169 healthy Japanese subjects. A human startle response monitoring system was used to deliver acoustic startle stimuli and to record and score the electromyographic activity of the orbicularis oculi muscle. PPI was evaluated at signal-to-noise ratios (SnRs: intensity difference between background noise and prepulse) of +12, +16, and +20 dB. The lead interval (from prepulse onset to pulse onset) was 120 ms, and Temperament and Character Inventory was used in both groups. Significant correlations at SnR of +16 and +20 dB to ST were identified. Our results suggest that impaired sensorimotor gating, evaluated as lower PPI of ASR, of healthy subjects is correlated with self transcendence, the character which is closely related with schizophrenia and schizotypy.
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Caráter , Reflexo de Sobressalto/fisiologia , Filtro Sensorial/fisiologia , Temperamento/fisiologia , Adulto , Povo Asiático , Eletromiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esquizofrenia/fisiopatologia , Adulto JovemRESUMO
Several studies have identified the possible involvement of sigma non-opioid intracellular receptor 1 (SIGMAR1) in the pathogenesis of schizophrenia. The Gln2Pro polymorphism in the SIGMAR1 gene has been extensively examined for an association with schizophrenia. However, findings across multiple studies have been inconsistent. We performed a meta-analysis of the association between the functional Gln2Pro polymorphism and schizophrenia using combined samples (1254 patients with schizophrenia and 1574 healthy controls) from previously published studies and our own additional samples (478 patients and 631 controls). We then used near-infrared spectroscopy to analyze the effects of the Gln2Pro genotype, a schizophrenia diagnosis and the interaction between genotype and diagnosis on activation of the prefrontal cortex (PFC) during a verbal fluency task (127 patients and 216 controls). The meta-analysis provided evidence of an association between Gln2Pro and schizophrenia without heterogeneity across studies (odds ratio=1.12, p=0.047). Consistent with previous studies, patients with schizophrenia showed lower bilateral activation of the PFC when compared to controls (p<0.05). We provide evidence that Pro carriers, who are more common among patients with schizophrenia, have significantly lower activation of the right PFC compared to subjects with the Gln/Gln genotype (p=0.013). These data suggest that the SIGMAR1 polymorphism is associated with an increased risk of schizophrenia and differential activation of the PFC.
Assuntos
Córtex Pré-Frontal/metabolismo , Receptores sigma/genética , Esquizofrenia/genética , Adulto , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Glutamina/genética , Humanos , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Córtex Pré-Frontal/patologia , Córtex Pré-Frontal/fisiopatologia , Prolina/genética , Receptores sigma/metabolismo , Esquizofrenia/epidemiologia , Esquizofrenia/fisiopatologia , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Distúrbios da Fala/metabolismo , Distúrbios da Fala/patologia , Receptor Sigma-1RESUMO
Alpha rhythm is one of the most prominent electromagnetic changes in the brain, and electroencephalography (EEG) alpha reactivity disturbance may sometimes represent an early sign of cerebral dysfunction. Although magnetoencephalography (MEG) has a better spatial resolution than EEG, it has not extensively been used to explore alpha-power change deficits in schizophrenia as a possible neurophysiological marker of the disease. The purpose of this study was to use MEG to identify abnormalities in alpha synchronization induced by eye-closing in schizophrenia patients compared to healthy controls, and to investigate whether alpha reactivity deficits correlate with clinical features of the disorder. MEG data were recorded in 22 schizophrenia patients and 20 age- and gender-matched controls during eyes-open/eyes-closed resting states. Cortical sources of event-related synchronization (ERS) were estimated using multiple source beamformer, and BrainVoyager was used for statistic group analysis. A significant decrease in ERS in the upper alpha band (10-13 Hz) was found in the left posterior temporal region in schizophrenia patients relative to controls, and this activity showed correlation with visual memory scores. This upper alpha ERS deficit may indicate left temporal dysfunction and visual-information processing impairment in schizophrenia, and upon further confirmation it might represent a neurophysiological state marker of the disorder.
Assuntos
Ritmo alfa/fisiologia , Sincronização Cortical/fisiologia , Magnetoencefalografia/métodos , Esquizofrenia/diagnóstico , Esquizofrenia/fisiopatologia , Lobo Temporal/fisiopatologia , Adulto , Biomarcadores , Piscadela/fisiologia , Mapeamento Encefálico/métodos , Feminino , Lateralidade Funcional/fisiologia , Humanos , Masculino , Transtornos da Memória/diagnóstico , Transtornos da Memória/etiologia , Transtornos da Memória/fisiopatologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Lobo Temporal/anatomia & histologia , Percepção Visual/fisiologiaRESUMO
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.
Assuntos
Lobo Frontal/fisiologia , Memória de Curto Prazo/fisiologia , Percepção Espacial/fisiologia , Teste de Sequência Alfanumérica , Percepção Visual/fisiologia , Adulto , Atenção/fisiologia , Mapeamento Encefálico , Feminino , Humanos , Masculino , Desempenho Psicomotor/fisiologia , Tempo de Reação/fisiologia , Espectroscopia de Luz Próxima ao InfravermelhoRESUMO
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), Sternberg's (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.