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1.
Int J Mol Sci ; 24(7)2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-37047057

RESUMO

Cerebrospinal fluid (CSF) plays an important role in the homeostasis of the brain. We previously reported that CSF major glycoproteins are biosynthesized in the brain, i.e., lipocalin-type prostaglandin D2 synthase (L-PGDS) and transferrin isoforms carrying unique glycans. Although these glycoproteins are secreted from distinct cell types, their CSF levels have been found to be highly correlated with each other in cases of neurodegenerative disorders. The aim of this study was to examine these marker levels and their correlations in other neurological diseases, such as depression and schizophrenia, and disorders featuring abnormal CSF metabolism, including spontaneous intracranial hypotension (SIH) and idiopathic normal pressure hydrocephalus (iNPH). Brain-derived marker levels were found to be highly correlated with each other in the CSF of depression and schizophrenia patients. SIH is caused by CSF leakage, which is suspected to induce hypovolemia and a compensatory increase in CSF production. In SIH, the brain-derived markers were 2-3-fold higher than in other diseases, and, regardless of their diverse levels, they were found to be correlated with each other. Another abnormality of the CSF metabolism, iNPH, is possibly caused by the reduced absorption of CSF, which secondarily induces CSF accumulation in the ventricle; the excess CSF compresses the brain's parenchyma to induce dementia. One potential treatment is a "shunt operation" to bypass excess CSF from the ventricles to the peritoneal cavity, leading to the attenuation of dementia. After the shunt operation, marker levels began to increase within a week and then further increased by 2-2.5-fold at three, six, and twelve months post-operation, at which point symptoms had gradually attenuated. Notably, the marker levels were found to be correlated with each other in the post-operative period. In conclusion, the brain-derived major glycoprotein markers were highly correlated in the CSF of patients with different neurological diseases, and their correlations were maintained even after surgical intervention. These results suggest that brain-derived proteins could be biomarkers of CSF production.


Assuntos
Demência , Hidrocefalia , Doenças do Sistema Nervoso , Humanos , Encéfalo/metabolismo , Doenças do Sistema Nervoso/metabolismo , Glicoproteínas/metabolismo , Hidrocefalia/metabolismo , Demência/metabolismo , Biomarcadores/metabolismo
2.
Cerebellum ; 21(2): 219-224, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34128209

RESUMO

Objective evaluation of cerebellar dysfunction in neurodegenerative disorders is often difficult because of other overlapping symptoms. Cerebellar inhibition (CBI) tested by dual-coil transcranial magnetic stimulation (TMS) is anticipated as a promising measure to estimate cerebellar function. Cerebellar TMS inhibits the primary motor cortex (M1), which can be measured as the decrease of motor evoked potential (MEP) elicited by a single-pulse TMS over the M1. This study was conducted to quantify cerebellar dysfunction using CBI in cerebellar type multiple system atrophy (MSA-C) patients. First, CBI was measured using MEP elicited from a hand muscle by stimulating the hand motor area of M1. The amount of CBI was defined as the degree of decrease in the MEP amplitude in the presence of cerebellar stimulation compared with the condition of M1 stimulation alone. Results of the MSA-C patients were compared with those of healthy volunteers. Correlation between amounts of CBI and a clinical scale of ataxia, the International Cooperative Ataxia Scale Rating (ICARS), was assessed. Healthy volunteers showed more inhibition than MSA-C patients. Moreover, ICARS showed that the CBI amount in the patients is correlated with the degree of ataxia significantly. Results suggest that CBI can be a good marker of disease progression in MSA-C patients.


Assuntos
Ataxia Cerebelar , Córtex Motor , Atrofia de Múltiplos Sistemas , Cerebelo/fisiologia , Potencial Evocado Motor/fisiologia , Humanos , Córtex Motor/fisiologia , Atrofia de Múltiplos Sistemas/terapia , Estimulação Magnética Transcraniana/métodos
3.
Cerebellum ; 21(6): 1092-1122, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34813040

RESUMO

The cerebellum is involved in multiple closed-loops circuitry which connect the cerebellar modules with the motor cortex, prefrontal, temporal, and parietal cortical areas, and contribute to motor control, cognitive processes, emotional processing, and behavior. Among them, the cerebello-thalamo-cortical pathway represents the anatomical substratum of cerebellum-motor cortex inhibition (CBI). However, the cerebellum is also connected with basal ganglia by disynaptic pathways, and cerebellar involvement in disorders commonly associated with basal ganglia dysfunction (e.g., Parkinson's disease and dystonia) has been suggested. Lately, cerebellar activity has been targeted by non-invasive brain stimulation (NIBS) techniques including transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) to indirectly affect and tune dysfunctional circuitry in the brain. Although the results are promising, several questions remain still unsolved. Here, a panel of experts from different specialties (neurophysiology, neurology, neurosurgery, neuropsychology) reviews the current results on cerebellar NIBS with the aim to derive the future steps and directions needed. We discuss the effects of TMS in the field of cerebellar neurophysiology, the potentials of cerebellar tDCS, the role of animal models in cerebellar NIBS applications, and the possible application of cerebellar NIBS in motor learning, stroke recovery, speech and language functions, neuropsychiatric and movement disorders.


Assuntos
Doença de Parkinson , Estimulação Transcraniana por Corrente Contínua , Animais , Estimulação Transcraniana por Corrente Contínua/métodos , Consenso , Cerebelo/fisiologia , Estimulação Magnética Transcraniana/métodos
4.
J Epidemiol ; 32(1): 34-43, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-34719583

RESUMO

BACKGROUND: Since June 2013, Japan has suspended proactive recommendation of human papillomavirus (HPV) vaccination due to self-reported diverse symptoms, including pain and motor dysfunction, as possible serious adverse events following immunization. Although these symptoms may be seen in adolescents without HPV vaccination, their frequency, taking into account disease severity, has not been examined. METHODS: A two-stage, descriptive, nationwide epidemiological survey was conducted in 2016, with a 6-month target period from July 1 to December 31, 2015, to estimate the prevalence and incidence of diverse symptoms among Japanese adolescents without HPV vaccination. Participants were 11,037 medical departments in hospitals selected nationwide by stratified random sampling. Eligible patients had to satisfy four criteria: (1) aged 12-18 years upon visiting hospital; (2) having at least one of four symptoms/disorders (pain or sensory dysfunction, motor dysfunction, autonomic dysfunction, or cognitive impairment); (3) symptoms/disorders persisting for at least 3 months; and (4) both criteria (2) and (3) influence attendance at school or work. We then extracted data of patients with diverse symptoms similar to those after HPV vaccination while considering opinions of doctors in charge. RESULTS: Estimated 6-month period prevalence of diverse symptoms among girls aged 12-18 years without HPV vaccination was 20.2 per 100,000. Annual incidence was estimated to be 7.3 per 100,000. CONCLUSION: Adolescent Japanese girls without HPV vaccination also visited hospitals with diverse symptoms similar to those following HPV vaccination. Our findings predict the medical demands for coincident diverse symptoms, which are temporally associated with but not caused by HPV vaccination of Japanese adolescents.


Assuntos
Alphapapillomavirus , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Adolescente , Criança , Feminino , Humanos , Incidência , Japão/epidemiologia , Infecções por Papillomavirus/induzido quimicamente , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/efeitos adversos , Prevalência , Vacinação/efeitos adversos
5.
Cogn Behav Neurol ; 34(3): 226-232, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34473675

RESUMO

Marchiafava-Bignami disease (MBD) is a rare complication of chronic alcoholism that typically causes demyelination and necrosis of the corpus callosum. Here, we report a man with probable MBD with callosal and right medial paracentral lesions who presented with abnormal reaching behavior and ideomotor apraxia of the left hand. He exhibited difficulty in reaching with the left hand when a target object was placed on his right-hand side, and he exhibited rightward bias when using his right hand in a line bisection task. These disturbances in reaching suggest disruption of the top-down control of motor intention and spatial attention at the corpus callosum.


Assuntos
Alcoolismo , Doença de Marchiafava-Bignami , Alcoolismo/complicações , Atenção , Corpo Caloso/diagnóstico por imagem , Humanos , Intenção , Masculino , Doença de Marchiafava-Bignami/diagnóstico por imagem
6.
J Neurosci ; 39(13): 2509-2521, 2019 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-30692225

RESUMO

The posterior parietal cortex (PPC) features close anatomical and functional relationships with the prefrontal cortex. However, the necessity of the PPC in executive functions has been questioned. The present study used the stop-signal task to examine response inhibition, an executive function that inhibits prepotent response tendency. The brain activity and resting-state functional connectivity were measured to analyze a parcellation-based network that was aimed at identifying a candidate PPC region essential for response inhibition in humans. The intraparietal sulcus (IPS) was activated during response inhibition and connected with the inferior frontal cortex and the presupplementary motor area, the two frontal regions known to be necessary for response inhibition. Next, transcranial magnetic stimulation (TMS) was used to test the essential role of the IPS region for response inhibition. TMS over the IPS region prolonged the stop-signal reaction time (SSRT), the standard behavioral index used to evaluate stopping performance, when stimulation was applied 30-0 ms before stopping. On the contrary, stimulation over the temporoparietal junction region, an area activated during response inhibition but lacking connectivity with the two frontal regions, did not show changes in SSRT. These results indicate that the IPS identified using the parcellation-based network plays an essential role in executive functions.SIGNIFICANCE STATEMENT Based on the previous neuropsychological studies reporting no impairment in executive functions after lesions in the posterior parietal cortex (PPC), the necessity of PPC in executive functions has been questioned. Here, contrary to the long-lasting view, by using recently developed analysis in functional MRI ("parcellation-based network analysis"), we identified the intraparietal sulcus (IPS) region in the PPC as essential for response inhibition: one executive function to stop actions that are inaccurate in a given context. The necessity of IPS for response inhibition was further tested by an interventional technique of transcranial magnetic stimulation. Stimulation to the IPS disrupted the performance of stopping. Our findings suggest that the IPS plays essential roles in executive functions.


Assuntos
Função Executiva/fisiologia , Inibição Psicológica , Lobo Parietal/fisiologia , Adulto , Mapeamento Encefálico , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Vias Neurais/fisiologia , Estimulação Magnética Transcraniana , Adulto Jovem
7.
Exp Brain Res ; 238(7-8): 1619-1625, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32211927

RESUMO

Quadripulse stimulation (QPS) is a newly developed stimulation method to induce neural plasticity in humans. One stimulation burst consisting of four monophasic pulses is given every 5 s for 30 min. A total of 360 bursts (1440 pulses) are given in one session. Short-interval QPS potentiates the target cortical excitability and long-interval QPS depresses it. QPS at an inter-pulse interval of 5 ms (QPS5) induces long-term potentiation (LTP)-like effects most efficiently and QPS50 induces long-term depression (LTD)-like effects most effectively in the primary motor cortex. In this mini-review, we briefly introduce QPS: (i) principle and cortical plasticity (stimulators and protocols, synaptic plasticity, underlying mechanisms, meta-plasticity, axonal plasticity, and drug effects), (ii) robust and strong neural plasticity induction (variability, influence of phasic muscle contraction, independency of BDNF polymorphism, sensory cortical plasticity, neural plasticity in the contralateral hemisphere, on-line effects on the brain networks, studies of normal brain physiology, and visuomotor sequence learning), (iii) therapeutic applications to neurological and psychiatric disorders (Parkinson's disease, epilepsy, cerebrovascular disease, and major depression), (iv) safety, and (v) future issues. Based on this evidence, we propose that QPS is currently the most powerful and reliable non-invasive brain stimulation method to induce neural plasticity in humans.


Assuntos
Potencial Evocado Motor , Córtex Motor , Humanos , Potenciação de Longa Duração , Plasticidade Neuronal , Estimulação Magnética Transcraniana
8.
J Neurosci ; 38(45): 9679-9688, 2018 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-30249803

RESUMO

Observing mouth movements has strikingly effects on the perception of speech. Any mismatch between sound and mouth movements will result in listeners perceiving illusory consonants (McGurk effect), whereas matching mouth movements assist with the correct recognition of speech sounds. Recent neuroimaging studies have yielded evidence that the motor areas are involved in speech processing, yet their contributions to multisensory illusion remain unclear. Using functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) in an event-related design, we aimed to identify the functional roles of the motor network in the occurrence of multisensory illusion in female and male brains. fMRI showed bilateral activation of the inferior frontal gyrus (IFG) in audiovisually incongruent trials. Activity in the left IFG was negatively correlated with occurrence of the McGurk effect. The effective connectivity between the left IFG and the bilateral precentral gyri was stronger in incongruent than in congruent trials. The McGurk effect was reduced in incongruent trials by applying single-pulse TMS to motor cortex (M1) lip areas, indicating that TMS facilitates the left IFG-precentral motor network to reduce the McGurk effect. TMS of the M1 lip areas was effective in reducing the McGurk effect within the specific temporal range from 100 ms before to 200 ms after the auditory onset, and TMS of the M1 foot area did not influence the McGurk effect, suggesting topographical specificity. These results provide direct evidence that the motor network makes specific temporal and topographical contributions to the processing of multisensory integration of speech to avoid illusion.SIGNIFICANCE STATEMENT The human motor network, including the inferior frontal gyrus and primary motor cortex lip area, appears to be involved in speech perception, but the functional contribution to the McGurk effect is unknown. Functional magnetic resonance imaging revealed that activity in these areas of the motor network increased when the audiovisual stimuli were incongruent, and that the increased activity was negatively correlated with perception of the McGurk effect. Furthermore, applying transcranial magnetic stimulation to the motor areas reduced the McGurk effect. These two observations provide evidence that the motor network contributes to the avoidance of multisensory illusory perception.


Assuntos
Percepção Auditiva/fisiologia , Ilusões/fisiologia , Córtex Motor/fisiologia , Rede Nervosa/fisiologia , Percepção Visual/fisiologia , Estimulação Acústica/métodos , Adolescente , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Córtex Motor/diagnóstico por imagem , Rede Nervosa/diagnóstico por imagem , Estimulação Luminosa/métodos , Distribuição Aleatória , Percepção da Fala/fisiologia , Estimulação Magnética Transcraniana/métodos , Adulto Jovem
9.
Cogn Affect Behav Neurosci ; 19(1): 88-97, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30306414

RESUMO

Clinicians are increasingly recognizing impulse control disorders (ICDs) as a complication of dopaminergic treatment in Parkinson's disease (PD). Considering the pivotal role of dopamine in reward information processing, ICDs may originate from dysregulation of reward-oriented behavior, and the behavioral changes may be reflected in shifts of psychological risk preference during decision-making. We used a behavioral economics paradigm to evaluate quantitatively the risk preferences of PD patients in levodopa on and off states. We also examined age-matched healthy controls. We found that levodopa increased the subjective value and prolonged the decision time in PD patients. These effects are apparently not explained by kinematic improvements but are attributed to psychological shifts of risk preferences and increased attention during risky decision-making. The risk preferences of healthy controls were similar to those of PD on levodopa treatment. The risk preferences of PD patients were not correlated with the scores of routine cognitive batteries, suggesting that dopamine-sensitive risk preferences are independent of cognitive capacities as measured by conventional batteries, including general intelligence, memory, and frontal functioning. By contrast, apathy and ICD partially predicted the risk attitude in PD patients, suggesting a common background of limbic origin behind these properties. The present results demonstrated that dopamine deficiency in off-state PD leads to risk-avoiding behavior and levodopa treatment increases the risk preferences. Behavioral economics framework is useful to evaluate short-term psychological changes in response to levodopa in PD patients.


Assuntos
Agonistas de Dopamina/farmacologia , Dopamina/deficiência , Doença de Parkinson/fisiopatologia , Recompensa , Idoso , Cognição/efeitos dos fármacos , Cognição/fisiologia , Tomada de Decisões/efeitos dos fármacos , Tomada de Decisões/fisiologia , Transtornos Disruptivos, de Controle do Impulso e da Conduta/genética , Transtornos Disruptivos, de Controle do Impulso e da Conduta/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/genética , Análise e Desempenho de Tarefas
10.
BMC Neurol ; 19(1): 301, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31775676

RESUMO

BACKGROUND: McLeod syndrome is a rare X-linked recessive acanthocytosis associated with neurological manifestations including progressive chorea, cognitive impairment, psychiatric disturbances, seizures, and sensorimotor axonal polyneuropathy. However, no studies have investigated the functioning of central sensorimotor tracts in patients with McLeod syndrome. CASE PRESENTATION: A 66-year-old man had experienced slowly progressive chorea and gait disturbance due to lower limb muscle weakness since his early fifties. Blood examinations showed erythrocyte acanthocytosis and the reduction of Kell antigens in red blood cells. Brain magnetic resonance imaging showed atrophy of the bilateral caudate nuclei and putamen. The diagnosis of McLeod syndrome was confirmed by the presence of a mutation of the XK gene on the X chromosome. Somatosensory-evoked potential and transcranial magnetic stimulation studies demonstrated that the central sensory and motor conduction times were abnormally prolonged for the lower extremity but normal for the upper extremity. CONCLUSIONS: This is the first report of the involvement of the central sensorimotor tracts for the legs in a patient with McLeod syndrome. The clinical neurophysiological technique revealed the central sensorimotor tracts involvements clinically masked by neuropathy.


Assuntos
Neuroacantocitose/diagnóstico , Idoso , Atrofia , Humanos , Imageamento por Ressonância Magnética , Masculino , Transtornos dos Movimentos/etiologia , Debilidade Muscular/etiologia , Mutação
11.
Exp Brain Res ; 237(3): 647-651, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30535949

RESUMO

Caffeine, an adenosine receptor antagonist, is known to affect sleep-awake cycles, the stress response, and learning and memory. It has been suggested that caffeine influences synaptic plasticity, but the effects of caffeine on synaptic plasticity in the human brain remain unexplored. The present study aimed to investigate the effects of caffeine on long-term potentiation (LTP)-like effects in the primary motor cortex of healthy humans. Twelve healthy participants (six women and six men; mean age: 44.8 ± 1.5 years) underwent quadripulse magnetic stimulation with an inter-stimulus interval of 5 ms (QPS5) to induce LTP-like effects, 2 h after administration of either a caffeine (200 mg) or placebo tablet in a double-blind crossover design. We recorded motor-evoked potentials (MEPs) before and after QPS5. The degree of MEP enhancement was compared between the placebo and caffeine conditions. Neither active nor resting motor thresholds were influenced by caffeine administration. Following caffeine administration, the degree of potentiation significantly decreased in "significant responders", whose average MEP ratios were greater than 1.24 in the placebo condition. The observed reduction in potentiation following caffeine administration is consistent with the A2A receptor antagonistic effect of caffeine. This is the first report of an effect of caffeine on neural synaptic plasticity in the human brain, which is consistent with the caffeine-induced plasticity reduction observed in primate studies. Because we studied only a small number of subjects, we cannot firmly conclude that caffeine reduces LTP in humans. The present results will, however, be helpful when considering further or new clinical uses of caffeine.


Assuntos
Cafeína/farmacologia , Potencial Evocado Motor/efeitos dos fármacos , Potenciação de Longa Duração/efeitos dos fármacos , Córtex Motor/efeitos dos fármacos , Antagonistas de Receptores Purinérgicos P1/farmacologia , Adulto , Estudos Cross-Over , Método Duplo-Cego , Eletromiografia , Feminino , Humanos , Masculino , Estimulação Magnética Transcraniana
12.
Bioelectromagnetics ; 40(3): 150-159, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30920674

RESUMO

The purpose of the study involves measuring the threshold for electric currents (i.e., current perception threshold or CPT) under several stimulating current frequencies. Specifically, current perception threshold (CPT) was measured in 53 healthy volunteers between the ages of 21 and 67. The stimulation currents were applied on the right index finger with stimulus frequencies in the range of 50 Hz - 300 kHz. The method of limits and method of constant stimuli were combined to measure the CPT. In a manner consistent with the findings obtained by previous studies, the results indicated that CPT was higher in men than in women and in older individuals than in young subjects. Bioelectromagnetics. 9999:XX-XX, 2019. © 2019 Bioelectromagnetics Society.


Assuntos
Estimulação Elétrica , Voluntários Saudáveis , Adulto , Idoso , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Limiar Sensorial , Adulto Jovem
14.
Cerebellum ; 22(4): 542-543, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-35661101
15.
Eur J Neurosci ; 46(11): 2684-2701, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29044874

RESUMO

To understand how the information derived from different motor cortical areas representing different body parts is organized in the basal ganglia, we examined the neuronal responses in the subthalamic nucleus (STN), and the external (GPe) and internal (GPi) segments of the globus pallidus (input, relay and output nuclei, respectively) to stimulation of the orofacial, forelimb and hindlimb regions of the primary motor cortex (MI) and supplementary motor area (SMA) in macaque monkeys under the awake state. Most STN and GPe/GPi neurons responded exclusively to stimulation of either the MI or SMA, and one-fourth to one-third of neurons responded to both. STN neurons responding to the hindlimb, forelimb and orofacial regions of the MI were located along the medial-lateral axis in the posterolateral STN, while neurons responding to the orofacial region of the SMA were located more medially than the others in the anteromedial STN. GPe/GPi neurons responding to the hindlimb, forelimb and orofacial regions of the MI were found along the dorsal-ventral axis in the posterolateral GPe/GPi, and neurons responding to the corresponding regions of the SMA were similarly but less clearly distributed in more anteromedial regions. Moreover, neurons responding to the distal and proximal forelimb MI regions were found along the lateral-medial axis in the STN and the ventral-dorsal axis in the GPe/GPi. Most STN and GPe/GPi neurons showed kinaesthetic responses with similar somatotopic maps. These observations suggest that the somatotopically organized inputs from the MI and SMA are well preserved in the STN and GPe/GPi with partial convergence.


Assuntos
Globo Pálido/fisiologia , Córtex Motor/fisiologia , Núcleo Subtalâmico/fisiologia , Potenciais de Ação/fisiologia , Animais , Estimulação Elétrica , Eletrodos Implantados , Feminino , Macaca mulatta , Vias Neurais/fisiologia
16.
BMC Neurol ; 17(1): 93, 2017 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-28506261

RESUMO

BACKGROUND: Chronic graft-versus-host disease (GVHD) appears several months following allogenic hematopoietic stem cell transplantation (HSCT) and is clinically analogous to autoimmune disorder. Polymyositis is a common neuromuscular disorder in chronic GVHD, but myasthenia gravis (MG) is extremely rare. Hence, its pathophysiology and treatment have not been elucidated. CASE PRESENTATION: A 63-year-old man with a history of chronic GVHD presented with ptosis, dropped head, and dyspnea on exertion, which had worsened over the previous several months. He showed progressive decrement of compound muscle action potential in the deltoid muscle evoked by 3-Hz repetitive nerve stimulation, a positive edrophonium test, and elevated levels of serum anti-acetylcholine receptor antibodies, which suggested a diagnosis of generalized MG. No thymoma was found. Flow cytometric analysis revealed a remarkable depletion of peripheral Tregs (CD4+CD25highFOXP3+ cells, 0.24% of the total lymphocytes). Administration of prednisolone and tacrolimus was insufficient to alleviate his symptoms; however, the use of rituximab successfully improved his condition. CONCLUSIONS: Myasthenic symptoms appeared in the process of tapering prednisolone for the treatment of chronic GVHD, supporting the diagnosis of MG associated with chronic GVHD. The present case proposes a possibility that reduction of Tregs might contribute to the pathogenesis of MG underlying chronic GVHD. Immunotherapy with rituximab is beneficial for treatment of refractory MG and GVHD.


Assuntos
Autoanticorpos , Transplante de Medula Óssea , Antagonistas Colinérgicos , Doença Enxerto-Hospedeiro , Miastenia Gravis , Linfócitos T Reguladores/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/imunologia , Miastenia Gravis/fisiopatologia , Miastenia Gravis/terapia
17.
Exp Brain Res ; 235(7): 2103-2108, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28386713

RESUMO

The reduction of plasticity with age has been shown by many previous papers in animal experiments. This issue can be studied in humans because several non-invasive brain stimulation techniques induce synaptic plasticity in the human brain. We investigated the influence of individuals' age on the responder rate of the long-term potentiation (LTP)-like effect induced by quadripulse magnetic stimulation (QPS). The participants were 107 healthy volunteers: 53 older participants (Mean ± SD 65.0 ± 1.5 years) and 54 younger participants (37.2 ± 8.7). The quadripulse stimulation with 5-ms inter-pulse interval (QPS5) was applied over the primary motor cortex (M1). We measured motor evoked potentials (MEPs) before QPS, and at five time points after QPS for up to 25 min. In each participant, average MEP amplitude (size) ratios were quantified. We first classified participants as responders and non-responders simply by comparing the size ratio with 1.0 for consistency with previous studies, then as "significant responders", "non-responders", and "opposite responders" for more detailed analysis by comparing the size ratio with the mean and standard deviation of the MEP size ratios of the sham condition. The degree of LTP-like effects induced by QPS5 was significantly smaller in the older group compared to the younger group. Also, the rates of responders and significant responders were lower in the older group (58 and 47%, respectively) compared to the younger group (80 and 76%, respectively). The age of the participants significantly affected the LTP-like effect induced by QPS5, which suggests that brain plasticity decreases with age.


Assuntos
Envelhecimento/fisiologia , Potencial Evocado Motor/fisiologia , Potenciação de Longa Duração/fisiologia , Córtex Motor/fisiologia , Músculo Esquelético/fisiologia , Adulto , Fatores Etários , Idoso , Análise de Variância , Eletromiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/inervação , Psicofísica , Estimulação Magnética Transcraniana
18.
Bioelectromagnetics ; 38(6): 466-473, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28628221

RESUMO

The purpose of this study was to evaluate the effects of 3rd-generation (3G) cellular phone radiofrequency-electromagnetic wave (RF-EMW) exposure on fertilization and embryogenesis in mice. Oocytes and spermatozoa were exposed to 3G cellular phone RF-EMWs, 1.95 GHz wideband code division multiple access, at a specific absorption rate of 2 mW/g for 60 min, or to sham exposure. After RF-EMW exposure, in vitro fertilization and intracytoplasmic sperm injection were performed. Rates of fertilization, embryogenesis (8-cell embryo, blastocyst), and chromosome aberration were compared between the combined spermatozoa and oocyte groups: both exposed, both non-exposed, one exposed, and the other non-exposed. Rates of fertilization, embryogenesis, and blastocyst formation did not change significantly across the four groups. Considering that the degree of exposure in the present study was ≥100 times greater than daily exposure of human spermatozoa and even greater than daily exposure of oocytes, the present results indicate safety of RF-EMW exposure in humans. Bioelectromagnetics. 38:466-473, 2017. © 2017 Wiley Periodicals, Inc.


Assuntos
Telefone Celular , Desenvolvimento Embrionário/efeitos da radiação , Ondas de Rádio/efeitos adversos , Injeções de Esperma Intracitoplásmicas/efeitos da radiação , Animais , Aberrações Cromossômicas/efeitos da radiação , Feminino , Masculino , Camundongos , Oócitos/fisiologia , Oócitos/efeitos da radiação , Espermatozoides/fisiologia , Espermatozoides/efeitos da radiação
19.
J Neurosci ; 35(4): 1411-22, 2015 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-25632119

RESUMO

Models propose an auditory-motor mapping via a left-hemispheric dorsal speech-processing stream, yet its detailed contributions to speech perception and production are unclear. Using fMRI-navigated repetitive transcranial magnetic stimulation (rTMS), we virtually lesioned left dorsal stream components in healthy human subjects and probed the consequences on speech-related facilitation of articulatory motor cortex (M1) excitability, as indexed by increases in motor-evoked potential (MEP) amplitude of a lip muscle, and on speech processing performance in phonological tests. Speech-related MEP facilitation was disrupted by rTMS of the posterior superior temporal sulcus (pSTS), the sylvian parieto-temporal region (SPT), and by double-knock-out but not individual lesioning of pars opercularis of the inferior frontal gyrus (pIFG) and the dorsal premotor cortex (dPMC), and not by rTMS of the ventral speech-processing stream or an occipital control site. RTMS of the dorsal stream but not of the ventral stream or the occipital control site caused deficits specifically in the processing of fast transients of the acoustic speech signal. Performance of syllable and pseudoword repetition correlated with speech-related MEP facilitation, and this relation was abolished with rTMS of pSTS, SPT, and pIFG. Findings provide direct evidence that auditory-motor mapping in the left dorsal stream causes reliable and specific speech-related MEP facilitation in left articulatory M1. The left dorsal stream targets the articulatory M1 through pSTS and SPT constituting essential posterior input regions and parallel via frontal pathways through pIFG and dPMC. Finally, engagement of the left dorsal stream is necessary for processing of fast transients in the auditory signal.


Assuntos
Vias Auditivas/fisiologia , Córtex Cerebral/fisiologia , Lateralidade Funcional , Fonética , Fala/fisiologia , Adulto , Vias Auditivas/irrigação sanguínea , Mapeamento Encefálico , Córtex Cerebral/irrigação sanguínea , Potencial Evocado Motor/fisiologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Lábio/inervação , Masculino , Modelos Neurológicos , Músculo Esquelético/fisiologia , Oxigênio/sangue , Estimulação Luminosa , Tempo de Reação , Percepção da Fala , Adulto Jovem
20.
J Neurosci ; 35(12): 4813-23, 2015 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-25810512

RESUMO

Stop-signal task (SST) has been a key paradigm for probing human brain mechanisms underlying response inhibition, and the inhibition observed in SST is now considered to largely depend on a fronto basal ganglia network consisting mainly of right inferior frontal cortex, pre-supplementary motor area (pre-SMA), and basal ganglia, including subthalamic nucleus, striatum (STR), and globus pallidus pars interna (GPi). However, causal relationships between these frontal regions and basal ganglia are not fully understood in humans. Here, we partly examined these causal links by measuring human fMRI activity during SST before and after excitatory/inhibitory repetitive transcranial magnetic stimulation (rTMS) of pre-SMA. We first confirmed that the behavioral performance of SST was improved by excitatory rTMS and impaired by inhibitory rTMS. Afterward, we found that these behavioral changes were well predicted by rTMS-induced modulation of brain activity in pre-SMA, STR, and GPi during SST. Moreover, by examining the effects of the rTMS on resting-state functional connectivity between these three regions, we showed that the magnetic stimulation of pre-SMA significantly affected intrinsic connectivity between pre-SMA and STR, and between STR and GPi. Furthermore, the magnitudes of changes in resting-state connectivity were also correlated with the behavioral changes seen in SST. These results suggest a causal relationship between pre-SMA and GPi via STR during response inhibition, and add direct evidence that the fronto basal ganglia network for response inhibition consists of multiple top-down regulation pathways in humans.


Assuntos
Gânglios da Base/fisiologia , Lobo Frontal/fisiologia , Inibição Psicológica , Córtex Motor/fisiologia , Estimulação Magnética Transcraniana , Adulto , Mapeamento Encefálico , Humanos , Imageamento por Ressonância Magnética , Masculino , Vias Neurais/fisiologia , Desempenho Psicomotor/fisiologia
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