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BACKGROUND: Crossed cerebello-cerebral diaschisis (CCCD) conventionally refers to decreased resting cerebral activity caused by injury to the contralateral cerebellum. We investigated whether functional activation of a contralesional cerebral cortical region controlling a specific task is reduced during task performance in a patient with a unilateral cerebellar lesion. We also examined functional compensation by the corresponding ipsilesional cerebral cortex. It was hypothesized that dysfunction of the primary sensorimotor cortex (SM1) contralateral to the cerebellar lesion would be detected together with a compensatory increase in neural activity of the ipsilesional SM1. To test these possibilities, we conducted non-invasive functional neuroimaging techniques for bilateral SM1 during hand grasping, a task known to activate predominantly the SM1 contralateral to the grasping hand. Activity in SM1 during hand grasping was measured electrophysiologically by magnetoencephalography and hemodynamically by near-infrared spectroscopy in an adult with mild right hemiataxia associated with a large injury of the right cerebellum due to resection of a tumor in early childhood. RESULTS: During left hand grasping, increased neural activity was detected predominantly in the right SM1, the typical developmental pattern. In contrast, neural activity increased in the bilateral SM1 with slight right-side dominance during right (ataxic) hand grasping. CONCLUSIONS: This study reported a case that implied functional CCCD and compensatory neural activity in the SM1 during performance of a simple hand motor task in an adult with unilateral cerebellar injury and mild hemiataxia 24 years prior to the study without rehabilitative interventions. This suggests that unilateral cerebellar injuries in early childhood may result in persistent functional abnormalities in the cerebrum into adulthood. Therapeutic treatments that target functional CCCD and interhemispheric compensation might be effective for treating ataxia due to unilateral cerebellar damage.
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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.
Assuntos
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
OBJECTIVES: A genetic variant (rs3800779; M30) in the KCNH2 gene has been associated with schizophrenia, a lower intelligence quotient (IQ) and processing speed scores, altered brain functions and increased KCNH2-3.1. mRNA levels in the hippocampus. The aims of this study were to investigate whether the KCNH2 polymorphism is associated with schizophrenia-related neurocognitive deficits and to confirm the association between the variant and schizophrenia. METHODS: The effects of the risk genotype on IQ and seven neurocognitive batteries were examined by the analysis of covariance in 191 healthy subjects. We performed a meta-analysis of the association between M30 and schizophrenia using five independent ethnic groups (1,720 cases; 2,418 controls). RESULTS: Consistent with the previous study, we provided evidence that subjects with the risk T carriers had significantly lower IQ scores than those with the G/G genotype (P = 0.048). Of the seven neurocognitive batteries, subjects with the risk genotype demonstrated lower performances on attention/vigilance (P = 0.0079) and working memory (P = 0.0066) relative to subjects with the G/G genotype. Meta-analysis demonstrated evidence for an association between M30 and schizophrenia without showing heterogeneity across studies (odds ratio = 1.18; P = 0.0017). CONCLUSIONS: These data suggest that the KCNH2 polymorphism could be associated with schizophrenia-related neuropsychological deficits and the risk of developing schizophrenia.
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Atenção , Canais de Potássio Éter-A-Go-Go/genética , Deficiência Intelectual/genética , Memória de Curto Prazo , Esquizofrenia/genética , Psicologia do Esquizofrênico , Adulto , Canal de Potássio ERG1 , Etnicidade/genética , Feminino , Predisposição Genética para Doença , Variação Genética , Humanos , Deficiência Intelectual/etiologia , Testes de Inteligência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Polimorfismo de Nucleotídeo Único , Esquizofrenia/complicações , Esquizofrenia/epidemiologiaRESUMO
BACKGROUND: Numerous associations between brain-reactive antibodies and neurological or psychiatric symptoms have been proposed. Serum autoantibody against the muscarinic cholinergic receptor (mAChR) was increased in some patients with chronic fatigue syndrome (CFS) or psychiatric disease. We examined whether serum autoantibody against mAChR affected the central cholinergic system by measuring brain mAChR binding and acetylcholinesterase activity using positron emission tomography (PET) in CFS patients with positive [CFS(+)] and negative [CFS(-)] autoantibodies. METHODOLOGY: Five CFS(+) and six CFS(-) patients, as well as 11 normal control subjects underwent a series of PET measurements with N-[(11)C]methyl-3-piperidyl benzilate [(11)C](+)3-MPB for the mAChR binding and N-[(11)C]methyl-4-piperidyl acetate [(11)C]MP4A for acetylcholinesterase activity. Cognitive function of all subjects was assessed by neuropsychological tests. Although the brain [(11)C](+)3-MPB binding in CFS(-) patients did not differ from normal controls, CFS(+) patients showed significantly lower [(11)C](+)3-MPB binding than CFS(-) patients and normal controls. In contrast, the [(11)C]MP4A index showed no significant differences among these three groups. Neuropsychological measures were similar among groups. CONCLUSION: The present results demonstrate that serum autoantibody against the mAChR can affect the brain mAChR without altering acetylcholinesterase activity and cognitive functions in CFS patients.
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Autoanticorpos/sangue , Mapeamento Encefálico , Síndrome de Fadiga Crônica , Receptores Muscarínicos , Acetilcolinesterase/metabolismo , Adulto , Autoanticorpos/imunologia , Radioisótopos de Carbono , Síndrome de Fadiga Crônica/sangue , Síndrome de Fadiga Crônica/imunologia , Síndrome de Fadiga Crônica/patologia , Feminino , Humanos , Lisina/análogos & derivados , Imageamento por Ressonância Magnética , Masculino , Maleimidas , Receptores Muscarínicos/sangue , Receptores Muscarínicos/imunologia , Tomografia Computadorizada de EmissãoRESUMO
The pathogenesis of schizophrenia is thought to involve aberrant immune and inflammatory responses. Nuclear factor kappa B (NF-κB) has important roles in the immune and inflammatory responses. The v-rel avian reticuloendotheliosis viral oncogene homolog A (RELA) gene encodes the major component of the NF-κB complex. We genotyped four single-nucleotide polymorphisms (SNPs) in the RELA gene and performed a gene-based association analysis using 1224 patients with schizophrenia and 1663 controls. We found significant associations of three SNPs (rs11820062: p=0.00011, rs2306365: p=0.0031, and rs7119750: p=0.0080) with schizophrenia and stronger evidence for association in a multi-marker sliding window haplotype analysis (the lowest p=0.00006). The association between this gene and schizophrenia was evident in male subjects but not in female subjects, when separately analyzed by gender. In silico genotype-gene expression analysis using web database and the WGAViewer software revealed that these three schizophrenia-associated SNPs might be related to RELA mRNA expression in immortalized B-lymphocytes. In silico analysis also suggested the putative promoter SNP, rs11820062, might disrupt the consensus transcription factor binding sequence of the androgen receptor. The impact of four RELA polymorphisms on pre-pulse inhibition (PPI) was investigated in 53 patients with schizophrenia. We provided evidence that at risk genotypes of three SNPs were associated with deficits in PPI; however, there was no effect of the one non-risk SNP on PPI. These findings suggest that variants of the RELA gene are associated with risk for schizophrenia and PPI deficits in a Japanese population.
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Predisposição Genética para Doença/genética , Variação Genética/genética , Reflexo de Sobressalto/genética , Esquizofrenia/genética , Fator de Transcrição RelA/genética , Adulto , Idoso , Feminino , Predisposição Genética para Doença/etnologia , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Inibição Neural/genética , Polimorfismo de Nucleotídeo Único/genética , Esquizofrenia/etnologia , Esquizofrenia/fisiopatologiaRESUMO
Prepulse inhibition (PPI) of the acoustic startle reflex (ASR) is the most common psychophysiological index of sensorimotor gating. Several studies have investigated the relationship of PPI of ASR to schizotypy in Caucasians. However, little has been reported on this relationship in Asians. We investigated a possible relationship between PPI of ASR and schizotypy in 79 healthy Japanese subjects. Schizotypy was assessed by the Schizotypal personality Questionnaire (SPQ). PPI was evaluated at signal-to-noise ratios (SnRs: difference between background noise intensity and prepulse intensity) of +12, +16, and +20 dB. The total SPQ score, cognitive/perceptual score, and interpersonal score correlated negatively with PPI at SnR of +16 and +20 dB. We conclude that PPI is associated with the trait of schizotypy in healthy Asian subjects.
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Reflexo de Sobressalto/fisiologia , Transtorno da Personalidade Esquizotípica/fisiopatologia , Transtorno da Personalidade Esquizotípica/psicologia , Estimulação Acústica , Adulto , Piscadela/fisiologia , Eletromiografia , Feminino , Humanos , Japão , Masculino , Testes de Personalidade , Filtro Sensorial , Fumar/psicologia , Inquéritos e QuestionáriosRESUMO
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
This study was carried out to evaluate Synthetic Aperture Magnetometry-kurtosis (SAM(g(2))), a spatially filtered source localization technique in magnetoencephalography (MEG), for identification of epileptogenic areas of focal cortical dysplasia (FCD). Three children with FCD were investigated to localize the ictal onset zone (IOZ). All patients subsequently had extraoperative electrocorticography (ECoG) for intractable epilepsy and surgical resection. SAM(g(2)) analysis showed overlapping of interictal MEG spike sources with the IOZ on ECoG in all children. We recommend MEG-SAM(g(2)) and MEG interictal spike source localization in patients with epileptogenic FCD.
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Eletroencefalografia , Epilepsia/patologia , Epilepsia/fisiopatologia , Magnetoencefalografia , Adolescente , Mapeamento Encefálico , Criança , Epilepsia/etiologia , Feminino , Humanos , Masculino , Malformações do Desenvolvimento Cortical/complicaçõesRESUMO
Antipsychotic polypharmacy and excessive dosing still prevail worldwide in the treatment of schizophrenia, while their possible association with cognitive function has not well been examined. We examined whether the "non-standard" use of antipsychotics (defined as antipsychotic polypharmacy or dosage >1,000 mg/day of chlorpromazine equivalents) is associated with cognitive function. Furthermore, we compared cognitive function between patients taking only atypical antipsychotics and those taking only conventionals. Neurocognitive functions were assessed in 67 patients with chronic schizophrenia and 92 controls using the Wechsler Memory Scale-Revised (WMS-R), the Wechsler Adult Intelligence Scale-Revised (WAIS-R), the Wisconsin Card Sorting Test (WCST), and the Advanced Trail Making Test (ATMT). Patients showed markedly poorer performance than controls on all these tests. Patients on non-standard antipsychotic medication demonstrated poorer performance than those on standard medication on visual memory, delayed recall, performance IQ, and executive function. Patients taking atypical antipsychotics showed better performance than those taking conventionals on visual memory, delayed recall, and executive function. Clinical characteristics such as duration of medication, number of hospitalizations, and concomitant antiparkinsonian drugs were different between the treatment groups (both dichotomies of standard/non-standard and conventional/atypical). These results provide evidence for an association between antipsychotic medication and cognitive function. This association between antipsychotic medication and cognitive function may be due to differential illness severity (e.g., non-standard treatment for severely ill patients who have severe cognitive impairment). Alternatively, poorer cognitive function may be due in part to polypharmacy or excessive dosing. Further investigations are required to draw any conclusions.
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Antipsicóticos/uso terapêutico , Cognição/efeitos dos fármacos , Esquizofrenia/tratamento farmacológico , Adulto , Análise de Variância , Feminino , Humanos , Testes de Inteligência/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos/estatística & dados numéricosRESUMO
To assess the involvement of serotonin in the symptoms of chronic fatigue syndrome, we investigated the serotonergic neurotransmitter system of chronic fatigue syndrome patients by the positron emission tomography (PET). Here we show that the density of serotonin transporters (5-HTTs) in the brain, as determined by using a radiotracer, [C](+)McN5652, was significantly reduced in the rostral subdivision of the anterior cingulate as compared with that in normal volunteers. This subdivision is different from that in the dorsal anterior cingulate in which binding potential values of individual patient showed a weak negative correlation with self-reported pain score of the patients. Therefore, an alteration of serotonergic system in the rostral anterior cingulate plays a key role in pathophysiology of chronic fatigue syndrome.
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Síndrome de Fadiga Crônica/metabolismo , Giro do Cíngulo/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Adulto , Mapeamento Encefálico , Isótopos de Carbono/metabolismo , Estudos de Casos e Controles , Síndrome de Fadiga Crônica/patologia , Feminino , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/patologia , Humanos , Isoquinolinas/metabolismo , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Medição da Dor/métodos , Tomografia por Emissão de Pósitrons/métodos , Proteínas da Membrana Plasmática de Transporte de SerotoninaRESUMO
Fatigue is an indispensable sense for ordering rest. However, the neuronal and molecular mechanisms of fatigue remain unclear. Chronic fatigue syndrome (CFS) with long-lasting fatigue sensation seems to be a good model for studying these mechanisms underlying fatigue sensation. Recently, we found that most patients with CFS showed a low level of serum acetylcarnitine, which well correlated with the rating score of fatigue, and that a considerable amount of acetyl moiety of serum acetylcarnitine is taken up into the brain. Here we show by metabolite analysis of the mouse brain that an acetyl moiety taken up into the brain through acetylcarnitine is mainly utilized for the biosynthesis of glutamate. When we studied the cerebral uptake of acetylcarnitine by using [2-(11)C]acetyl-L-carnitine in 8 patients with CFS and in 8 normal age- and sex-matched controls, a significant decrease was found in several regions of the brains of the patient group, namely, in the prefrontal (Brodmann's area 9/46d) and temporal (BA21 and 41) cortices, anterior cingulate (BA24 and 33), and cerebellum. These findings suggest that the levels of biosynthesis of neurotransmitters through acetylcarnitine might be reduced in some brain regions of chronic fatigue patients and that this abnormality might be one of the keys to unveiling the mechanisms of the chronic fatigue sensation.