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1.
IEEE Int Conf Rehabil Robot ; 2019: 660-664, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31374706

RESUMO

Proprioceptive deficits are common among stroke survivors and are associated with slower motor recovery, poorer upper limb motor function, and decreased self-care ability. Somatosensory feedback augmenting proprioception should enhance motor control after stroke, but available evidence is inconclusive. This study evaluated the effects of a robot-aided, somatosensory-focused training on proprioceptive acuity and motor performance in individuals with sub-acute and chronic stroke. Twelve stroke survivors completed two training sessions on two consecutive days. During training, participants used a haptic robotic wrist exoskeleton and made continuous, goal-directed wrist ab/adduction movements to a visual target while receiving vibro-tactile feedback. Proprioceptive acuity and active movement errors were assessed before, immediately after, and two days after intervention. Results showed significantly improved proprioceptive acuity at posttest and retention. Motor accuracy measures showed improvements, however these were not statistically significant. This study demonstrates the feasibility of robot-aided somatosensory rehabilitation training in stroke survivors.


Assuntos
Atividade Motora/fisiologia , Propriocepção/fisiologia , Robótica , Córtex Sensório-Motor/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Sobreviventes , Adulto , Idoso , Exoesqueleto Energizado , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Punho/fisiopatologia
2.
PLoS One ; 14(7): e0219762, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31295337

RESUMO

Hand function deterioration brings about inconvenience to the daily lives of the chronic kidney disease patients. However, a full spectrum of hand function examination is absent. Therefore, this study aimed to classify the hand sensorimotor functions of the chronic kidney disease patients using the novel sensorimotor assessment tools, manual tactile test (MTT) and pinch-holding-up activity (PHUA) test, and explore the feasibility in comparison with traditional evaluations in the clinical practice. 68 stage-5 chronic kidney disease patients and 50 healthy subjects were recruited in this study. A series of conventional evaluations and two novel hand function tools, manual tactile test and pinch-holding-up activity test were conducted from the perspective of hand dexterity, sensory input threshold, force generation and sensorimotor control. Independent t-test was used to find out group differences and the receiver operating characteristic curve was used to determine accuracy of the tests. In our results, significant reduction of hand dexterity, sensory input, force generation and sensorimotor control was found in patients from an overall perspective. This trend was discovered to be the same when dividing the subjects into the old and young age group. From the receiver operator characteristic curves, nearly all the areas under the curve of all tests were over 0.8. The novel evaluation tools, the manual tactile test and pinch-holding-up activity, were found to have comparable or even better accuracy than the traditional ones. The shape and weight subtests of the manual tactile test displayed the highest accuracy. To sum up, by incorporating the novel and conventional assessment tests, this study built up the fundamental understanding of the hand functions in multiple dimensions and consolidate the clinical merits of applying the two novel tools, manual tactile test and pinch-holding-up activity, on chronic kidney disease patients.


Assuntos
Força da Mão/fisiologia , Mãos/fisiopatologia , Insuficiência Renal Crônica/fisiopatologia , Córtex Sensório-Motor/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Força de Pinça/fisiologia , Diálise Renal , Limiar Sensorial/fisiologia , Polegar/fisiopatologia , Tato/fisiologia
3.
J Headache Pain ; 20(1): 77, 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31288756

RESUMO

BACKGROUND: The migraine brain seems to undergo cyclic fluctuations of sensory processing. For instance, during the preictal phase, migraineurs experience symptoms and signs of altered pain perception as well as other well-known premonitory CNS-symptoms. In the present study we measured EEG-activation to non-painful motor and sensorimotor tasks in the different phases of the migraine cycle by longitudinal measurements of beta event related desynchronization (beta-ERD). METHODS: We recorded electroencephalography (EEG) of 41 migraine patients and 31 healthy controls. Each subject underwent three EEG recordings on three different days with classification of each EEG recording according to the actual migraine phase. During each recording, subjects performed one motor and one sensorimotor task with the flexion-extension movement of the right wrist. RESULTS: Migraine patients had significantly increased beta-ERD and higher baseline beta power at the contralateral C3 electrode overlying the primary sensorimotor cortex in the preictal phase compared to the interictal phase. We found no significant differences in beta-ERD or baseline beta power between interictal migraineurs and controls. CONCLUSION: Increased preictal baseline beta activity may reflect a decrease in pre-activation in the sensorimotor cortex. Altered pre-activation may lead to changes in thresholds for inhibitory responses and increased beta-ERD response, possibly reflecting a generally increased preictal cortical responsivity in migraine. Cyclic fluctuations in the activity of second- and third-order afferent somatosensory neurons, and their associated cortical and/or thalamic interneurons, may accordingly also be a central part of the migraine pathophysiology.


Assuntos
Transtornos de Enxaqueca/fisiopatologia , Córtex Sensório-Motor/fisiopatologia , Adulto , Mapeamento Encefálico , Eletroencefalografia , Feminino , Humanos , Estudos Longitudinais , Masculino , Percepção da Dor
4.
Nat Neurosci ; 22(7): 1075-1088, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31209379

RESUMO

Microglia rapidly respond to changes in neural activity and inflammation to regulate synaptic connectivity. The extracellular signals, particularly neuron-derived molecules, that drive these microglial functions at synapses remain a key open question. Here we show that whisker lesioning, known to dampen cortical activity, induces microglia-mediated synapse elimination. This synapse elimination is dependent on signaling by CX3CR1, the receptor for microglial fractalkine (also known as CXCL1), but not complement receptor 3. Furthermore, mice deficient in CX3CL1 have profound defects in synapse elimination. Single-cell RNA sequencing revealed that Cx3cl1 is derived from cortical neurons, and ADAM10, a metalloprotease that cleaves CX3CL1 into a secreted form, is upregulated specifically in layer IV neurons and in microglia following whisker lesioning. Finally, inhibition of ADAM10 phenocopies Cx3cr1-/- and Cx3cl1-/- synapse elimination defects. Together, these results identify neuron-to-microglia signaling necessary for cortical synaptic remodeling and reveal that context-dependent immune mechanisms are utilized to remodel synapses in the mammalian brain.


Assuntos
Proteína ADAM10/fisiologia , Secretases da Proteína Precursora do Amiloide/fisiologia , Receptor 1 de Quimiocina CX3C/fisiologia , Quimiocina CX3CL1/fisiologia , Proteínas de Membrana/fisiologia , Microglia/fisiologia , Córtex Sensório-Motor/fisiopatologia , Tato/fisiologia , Vibrissas/lesões , Proteína ADAM10/antagonistas & inibidores , Proteína ADAM10/genética , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Secretases da Proteína Precursora do Amiloide/genética , Animais , Receptor 1 de Quimiocina CX3C/deficiência , Receptor 1 de Quimiocina CX3C/genética , Contagem de Células , Feminino , Regulação da Expressão Gênica , Masculino , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Técnicas Analíticas Microfluídicas , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Córtex Sensório-Motor/metabolismo , Córtex Sensório-Motor/patologia , Transdução de Sinais/fisiologia , Análise de Célula Única , Transcriptoma , Vibrissas/fisiologia
5.
Neurology ; 93(2): e116-e124, 2019 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-31197032

RESUMO

OBJECTIVE: To assess with magnetoencephalography the developmental vs progressive character of the impairment of spinocortical proprioceptive pathways in Friedreich ataxia (FRDA). METHODS: Neuromagnetic signals were recorded from 16 right-handed patients with FRDA (9 female patients, mean age 27 years, mean Scale for the Assessment and Rating Of ataxia [SARA] score 22.25) and matched healthy controls while they performed right finger movements either actively or passively. The coupling between movement kinematics (i.e., acceleration) and neuromagnetic signals was assessed by the use of coherence at sensor and source levels. Such coupling, that is, the corticokinematic coherence (CKC), specifically indexes proprioceptive afferent inputs to the contralateral primary sensorimotor (cSM1) cortex. Nonparametric permutations and Spearman rank correlation test were used for statistics. RESULTS: In both groups of participants and movement conditions, significant coupling peaked at the cSM1 cortex. Coherence levels were 70% to 75% lower in patients with FRDA than in healthy controls in both movement conditions. In patients with FRDA, coherence levels correlated with genotype alteration (i.e., the size of GAA1 triplet expansion) and the age at symptom onset but not with disease duration or SARA score. CONCLUSION: This study provides electrophysiologic evidence demonstrating that proprioceptive impairment in FRDA is mostly genetically determined and scarcely progressive after symptom onset. It also positions CKC as a reliable, robust, specific marker of proprioceptive impairment in FRDA.


Assuntos
Vias Aferentes/fisiopatologia , Ataxia de Friedreich/fisiopatologia , Propriocepção , Córtex Sensório-Motor/fisiopatologia , Adolescente , Adulto , Idade de Início , Estudos de Casos e Controles , Criança , Feminino , Dedos , Ataxia de Friedreich/genética , Genótipo , Humanos , Proteínas de Ligação ao Ferro/genética , Magnetoencefalografia , Masculino , Pessoa de Meia-Idade , Vias Neurais/fisiopatologia , Índice de Gravidade de Doença , Fatores de Tempo , Expansão das Repetições de Trinucleotídeos , Adulto Jovem
6.
Neuroimage Clin ; 22: 101792, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30928809

RESUMO

BACKGROUND: Idiopathic cervical dystonia (CD) is a chronic movement disorder characterized by impressive clinical symptoms and the lack of clear pathological findings in clinical diagnostics and imaging. At present, the injection of botulinum toxin (BNT) in dystonic muscles is an effective therapy to control motor symptoms and pain in CD. OBJECTIVES: We hypothesized that, although it is locally injected to dystonic muscles, BNT application leads to changes in brain and network activity towards normal brain function. METHODS: Using 3 T functional MR imaging along with advanced analysis techniques (functional connectivity, Granger causality, and regional homogeneity), we aimed to characterize brain activity in CD (17 CD patients vs. 17 controls) and to uncover the effects of BNT treatment (at 6 months). RESULTS: In CD, we observed an increased information flow within the basal ganglia, the thalamus, and the sensorimotor cortex. In parallel, some of these structures became less responsive to regulating inputs. Furthermore, our results suggested an altered somatosensory integration. Following BNT administration, we noted a shift towards normal brain function in the CD patients, especially within the motor cortex, the somatosensory cortex, and the basal ganglia. CONCLUSION: The changes in brain function and network activity in CD can be interpreted as related to the underlying cause, the effort to compensate or a mixture of both. Although BNT is applied in the last stage of the cortico-neuromuscular pathway, brain patterns are shifted towards those of healthy controls.


Assuntos
Gânglios da Base/fisiopatologia , Toxinas Botulínicas Tipo A/farmacologia , Rede Nervosa/fisiopatologia , Fármacos Neuromusculares/farmacologia , Córtex Sensório-Motor/fisiopatologia , Tálamo/fisiopatologia , Torcicolo/tratamento farmacológico , Torcicolo/fisiopatologia , Adulto , Idoso , Gânglios da Base/diagnóstico por imagem , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Motor/diagnóstico por imagem , Córtex Motor/fisiopatologia , Rede Nervosa/diagnóstico por imagem , Córtex Sensório-Motor/diagnóstico por imagem , Tálamo/diagnóstico por imagem , Torcicolo/diagnóstico por imagem , Resultado do Tratamento
7.
Restor Neurol Neurosci ; 37(2): 143-153, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30988242

RESUMO

BACKGROUND: Patients with a complex regional pain syndrome (CRPS) in the upper limb show a sensory and motor impairment of the hand. Decreased intra-cortical-inhibition (ICI) of the motor representation of the affected hand muscle and decreased somatosensory hand representation size were related to maladaptive plasticity. OBJECTIVE: To achieve new insights about CRPS we examined whether these alterations were present in a single cohort. METHODS: We used a multi-modal approach comprising behavioral testing, transcranial magnetic stimulation, and high resolution fMRI combined with a new analysis technique for improved neuronal specificity. RESULTS: We found a decreased pinch-grip performance, two-point discrimination on the fingertips, ICI in the motor cortex, and representation size of the hand in Brodmann Area 3b (BA3b) in the somatosensory cortex. Our analysis further showed that correlations with ICI on the non-affected side were absent on the affected side. CONCLUSIONS: This study is the first to gather behavioral, neurophysiologic and imaging measurements for one patient cohort and it therefore enables a comprehensive view of collapsed associations of function and representation focused on the hemisphere contralateral to the affected hand.


Assuntos
Síndromes da Dor Regional Complexa/fisiopatologia , Plasticidade Neuronal , Córtex Sensório-Motor/fisiopatologia , Adulto , Idoso , Mapeamento Encefálico , Estudos de Coortes , Síndromes da Dor Regional Complexa/diagnóstico por imagem , Feminino , Dedos/fisiopatologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Plasticidade Neuronal/fisiologia , Força de Pinça , Córtex Sensório-Motor/diagnóstico por imagem , Percepção do Tato , Estimulação Magnética Transcraniana
8.
Mult Scler Relat Disord ; 31: 1-4, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30875527

RESUMO

The objective of this pilot study was to identify neural descriptors and correlates of participation in a multicomponent walking aid program, the Assistive Device Selection, Training and Education Program (ADSTEP), in people with multiple sclerosis, as reflected by resting state functional MRI. Fourteen people with multiple sclerosis who used a walking aid at baseline and reported falling at least once in the prior year were recruited from the multiple sclerosis clinic in a Veterans Affairs and the surrounding community to participate in a trial of ADSTEP, a multicomponent program of walking aid selection, fitting and six weekly progressive task-oriented walking aid training sessions and undergo resting state functional brain MRI. The functional MRI was performed at baseline and at program completion to assess for changes in neural connectivity of the sensorimotor neural network. Compared to baseline, following ADSTEP participation, functional connectivity between the supplementary motor areas and both the primary somatosensory cortices and the putamen was increased; whereas functional connectivity between the supplementary motor areas and the cerebellum was decreased. This study provides preliminary support for supraspinal sensorimotor neuroplasticity in response to rehabilitation interventions such as task-oriented walking aid training, suggests specific neural targets for future mobility interventions, and supports the need for full-scale randomized controlled trials in this area.


Assuntos
Esclerose Múltipla/fisiopatologia , Esclerose Múltipla/reabilitação , Plasticidade Neuronal , Córtex Sensório-Motor/fisiopatologia , Mapeamento Encefálico , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Vias Neurais/fisiopatologia , Projetos Piloto , Resultado do Tratamento , Caminhada
9.
Microbiome ; 7(1): 45, 2019 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-30898151

RESUMO

BACKGROUND AND AIMS: Evidence from preclinical and clinical studies suggests that interactions among the brain, gut, and microbiota may affect the pathophysiology of irritable bowel syndrome (IBS). As disruptions in central and peripheral serotonergic signaling pathways have been found in patients with IBS, we explored the hypothesis that the abundance of serotonin-modulating microbes of the order Clostridiales is associated with functional connectivity of somatosensory brain regions and gastrointestinal (GI) sensorimotor function. METHODS: We performed a prospective study of 65 patients with IBS and 21 healthy individuals (controls) recruited from 2011 through 2013 at a secondary/tertiary care outpatient clinic in Sweden. Study participants underwent functional brain imaging, rectal balloon distension, a nutrient and lactulose challenge test, and assessment of oroanal transit time within a month. They also submitted stool samples, which were analyzed by 16S ribosomal RNA gene sequencing. A tripartite network analysis based on graph theory was used to investigate the interactions among bacteria in the order Clostridiales, connectivity of brain regions in the somatosensory network, and GI sensorimotor function. RESULTS: We found associations between GI sensorimotor function and gut microbes in stool samples from controls, but not in samples from IBS patients. The largest differences between controls and patients with IBS were observed in the Lachnospiraceae incertae sedis, Clostridium XIVa, and Coprococcus subnetworks. We found connectivity of subcortical (thalamus, caudate, and putamen) and cortical (primary and secondary somatosensory cortices) regions to be involved in mediating interactions among these networks. CONCLUSIONS: In a comparison of patients with IBS and controls, we observed disruptions in the interactions between the brain, gut, and gut microbial metabolites in patients with IBS-these involve mainly subcortical but also cortical regions of brain. These disruptions may contribute to altered perception of pain in patients with IBS and may be mediated by microbial modulation of the gut serotonergic system.


Assuntos
Mapeamento Encefálico/métodos , Clostridiaceae/fisiologia , Síndrome do Intestino Irritável/microbiologia , Córtex Sensório-Motor/fisiopatologia , Córtex Somatossensorial/fisiopatologia , Adulto , Estudos de Casos e Controles , Clostridiaceae/isolamento & purificação , Fezes , Feminino , Microbioma Gastrointestinal , Humanos , Síndrome do Intestino Irritável/fisiopatologia , Masculino , Estudos Prospectivos , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Suécia , Adulto Jovem
10.
Brain Behav ; 9(3): e01237, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30790472

RESUMO

INTRODUCTION: Benign epilepsy with centrotemporal spikes (BECTS) is a common form of childhood epilepsy with the majority of those afflicted remitting during their early teenage years. Seizures arise from the lower half of the sensorimotor cortex of the brain (e.g. seizure onset zone) and the abnormal epileptiform discharges observed increase during NREM sleep. To date no clinical factors reliably predict disease course, making determination of ongoing seizure risk a significant challenge. Prior work in BECTS have shown abnormalities in beta band (14.9-30 Hz) oscillations during movement and rest. Oscillations in this frequency band are modulated by state of consciousness and thought to reflect intrinsic inhibitory mechanisms. METHODS: We used high density EEG and source localization techniques to examine beta band activity in the seizure onset zone (sensorimotor cortex) in a prospective cohort of children with BECTS and healthy controls during sleep. We hypothesized that beta power in the sensorimotor cortex would be different between patients and healthy controls, and that beta abnormalities would improve with resolution of disease in this self-limited epilepsy syndrome. We further explored the specificity of our findings and correlation with clinical features. Statistical testing was performed using logistic and standard linear regression models. RESULTS: We found that beta band power in the seizure onset zone is different between healthy controls and BECTS patients. We also found that a longer duration of time spent seizure-free (corresponding to disease remission) correlates with lower beta power in the seizure onset zone. Exploratory spatial analysis suggests this effect is not restricted to the sensorimotor cortex. Exploratory frequency analysis suggests that this phenomenon is also observed in alpha and gamma range activity. We found no relationship between beta power and the presence or rate of epileptiform discharges in the sensorimotor cortex or a test of sensorimotor performance. CONCLUSION: These results provide evidence that cortical beta power in the seizure onset zone may provide a dynamic physiological biomarker of disease in BECTS.


Assuntos
Eletroencefalografia/métodos , Epilepsia Rolândica , Convulsões/diagnóstico , Córtex Sensório-Motor , Adolescente , Criança , Epilepsia Rolândica/diagnóstico , Epilepsia Rolândica/fisiopatologia , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco/métodos , Córtex Sensório-Motor/diagnóstico por imagem , Córtex Sensório-Motor/fisiopatologia
11.
Brain Connect ; 9(4): 365-377, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30799641

RESUMO

The goal of this work was to examine task-dependent functional connectivity of the brain in people with stroke. The work was motivated by prior observations indicating that, during pedaling, cortical activation volume is lower in people with stroke than controls. During paretic foot tapping, activation volume tends to be higher in people with stroke than controls. This study asked whether these differences could be explained by altered network function of the brain. Functional magnetic resonance imaging was used to examine local and global network function of the brain during tapping and pedaling in 15 stroke and 8 control participants. Independent component analysis was used to identify six task regions of interest (ROIs) in the primary sensorimotor cortex (M1S1), anterior lobe of cerebellum (AlCb), and secondary sensory cortex (S2) on the lesioned and non-lesioned sides of the brain (left, right for controls). Global connectivity was calculated as the correlation between mean time series for each ROI. Local connectivity was calculated as the mean correlation between voxels within each ROI. Local efficiency, weighted sum, and clustering coefficient were also calculated. Results suggested that local and global networks of the brain were altered in stroke, but not in the same direction. Detection of both global and local network changes was task-dependent. We found that global network function of the brain was reduced in stroke participants as compared with controls. This effect was detected during pedaling and nonparetic tapping, but not during paretic tapping. Local network function of the brain was elevated in stroke participants during paretic tapping and reduced during pedaling. No between-group differences in local connectivity were seen during nonparetic tapping. Connections involving S2, M1S1, and AlCb were significantly affected. Reduced global connectivity of the brain might contribute to reduced brain activation volume during pedaling poststroke.


Assuntos
Lateralidade Funcional/fisiologia , Extremidade Inferior/fisiologia , Acidente Vascular Cerebral/fisiopatologia , Adulto , Idoso , Mapeamento Encefálico , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Sensório-Motor/fisiopatologia , Acidente Vascular Cerebral/complicações
12.
Artigo em Inglês | MEDLINE | ID: mdl-30711508

RESUMO

BACKGROUND: Resting-state functional magnetic resonance imaging-based studies on functional connectivity in autism spectrum disorder (ASD) have generated inconsistent results. Interpretation of findings is further hampered by small samples and a focus on a limited number of networks, with networks underlying sensory processing being largely underexamined. We aimed to comprehensively characterize ASD-related alterations within and between 20 well-characterized resting-state networks using baseline data from the EU-AIMS (European Autism Interventions-A Multicentre Study for Developing New Medications) Longitudinal European Autism Project. METHODS: Resting-state functional magnetic resonance imaging data was available for 265 individuals with ASD (7.5-30.3 years; 73.2% male) and 218 typically developing individuals (6.9-29.8 years; 64.2% male), all with IQ > 70. We compared functional connectivity within 20 networks-obtained using independent component analysis-between the ASD and typically developing groups, and related functional connectivity within these networks to continuous (overall) autism trait severity scores derived from the Social Responsiveness Scale Second Edition across all participants. Furthermore, we investigated case-control differences and autism trait-related alterations in between-network connectivity. RESULTS: Higher autism traits were associated with increased connectivity within salience, medial motor, and orbitofrontal networks. However, we did not replicate previously reported case-control differences within these networks. The between-network analysis did reveal case-control differences showing on average 1) decreased connectivity of the visual association network with somatosensory, medial, and lateral motor networks, and 2) increased connectivity of the cerebellum with these sensory and motor networks in ASD compared with typically developing subjects. CONCLUSIONS: We demonstrate ASD-related alterations in within- and between-network connectivity. The between-network alterations broadly affect connectivity between cerebellum, visual, and sensory-motor networks, potentially underlying impairments in multisensory and visual-motor integration frequently observed in ASD.


Assuntos
Transtorno do Espectro Autista/fisiopatologia , Cerebelo/fisiopatologia , Córtex Sensório-Motor/fisiopatologia , Córtex Visual/fisiopatologia , Adolescente , Adulto , Mapeamento Encefálico , Estudos de Casos e Controles , Criança , Feminino , Humanos , Estudos Longitudinais , Imagem por Ressonância Magnética , Masculino , Vias Neurais/fisiopatologia , Adulto Jovem
13.
Bull Exp Biol Med ; 166(3): 364-368, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30627904

RESUMO

Post-weaning social isolation of male Wistar rats for 10 weeks led to an increase of their aggressiveness, sensorimotor reactivity, and cognitive deficiency, manifesting in training disorders evaluated by the acoustic startle response (amplitude of the response decreasing). Expression of gene encoding serine protease prolyl endopeptidase (EC 3.4.21.26) in the frontal cortex was higher than in control rats kept in groups, while the level of mRNA of the gene encoding dipeptidyl peptidase IV (EC 3.4.14.5) did not differ from the control in any of the brain structures. The levels of serotonin transporter gene mRNA in the striatum and hypothalamus were higher than in the control. No appreciable changes in the expression of genes encoding tryptophan hydroxylase-2 and monoaminoxidase A and B in the frontal cortex, striatum, amygdala, hypothalamus, and hippocampus were detected. The data indicated the involvement of genes associated with the serotoninergic system in the mechanisms of mental disorders induced by post-weaning social isolation and suggest the gene encoding prolyl endopeptidase as a candidate gene involved in the pathogenesis of these disorders.


Assuntos
Disfunção Cognitiva/genética , Serina Endopeptidases/genética , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Isolamento Social/psicologia , Estresse Psicológico/genética , Desmame , Agressão/psicologia , Tonsila do Cerebelo/metabolismo , Tonsila do Cerebelo/fisiopatologia , Animais , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Corpo Estriado/metabolismo , Corpo Estriado/fisiopatologia , Dipeptidil Peptidase 4/genética , Dipeptidil Peptidase 4/metabolismo , Lobo Frontal/metabolismo , Lobo Frontal/fisiopatologia , Regulação da Expressão Gênica , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Hipotálamo/metabolismo , Hipotálamo/fisiopatologia , Isoenzimas/genética , Isoenzimas/metabolismo , Masculino , Monoaminoxidase/genética , Monoaminoxidase/metabolismo , Atividade Motora/fisiologia , Ratos , Ratos Wistar , Reflexo de Sobressalto , Córtex Sensório-Motor/metabolismo , Córtex Sensório-Motor/fisiopatologia , Serina Endopeptidases/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Estresse Psicológico/metabolismo , Estresse Psicológico/fisiopatologia , Triptofano Hidroxilase/genética , Triptofano Hidroxilase/metabolismo
14.
Ann Clin Transl Neurol ; 6(1): 68-82, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30656185

RESUMO

Objective: The objective was to track and compare the progression of neuroplastic changes in a large animal model and humans with spinal cord injury. Methods: A total of 37 individuals with acute traumatic spinal cord injury were followed over time (1, 3, 6, and 12 months post-injury) with repeated neurophysiological assessments. Somatosensory and motor evoked potentials were recorded in the upper extremities above the level of injury. In a reverse-translational approach, similar neurophysiological techniques were examined in a porcine model of thoracic spinal cord injury. Twelve Yucatan mini-pigs underwent a contusive spinal cord injury at T10 and tracked with somatosensory and motor evoked potentials assessments in the fore- and hind limbs pre- (baseline, post-laminectomy) and post-injury (10 min, 3 h, 12 weeks). Results: In both humans and pigs, the sensory responses in the cranial coordinates of upper extremities/forelimbs progressively increased from immediately post-injury to later time points. Motor responses in the forelimbs increased immediately after experimental injury in pigs, remaining elevated at 12 weeks. In humans, motor evoked potentials were significantly higher at 1-month (and remained so at 1 year) compared to normative values. Conclusions: Despite notable differences between experimental models and the human condition, the brain's response to spinal cord injury is remarkably similar between humans and pigs. Our findings further underscore the utility of this large animal model in translational spinal cord injury research.


Assuntos
Modelos Animais de Doenças , Plasticidade Neuronal , Córtex Sensório-Motor/fisiopatologia , Traumatismos da Medula Espinal/fisiopatologia , Adulto , Animais , Potencial Evocado Motor , Potenciais Somatossensoriais Evocados , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Suínos , Porco Miniatura , Pesquisa Médica Translacional , Extremidade Superior/fisiopatologia
15.
Neurorehabil Neural Repair ; 33(1): 70-81, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30595082

RESUMO

BACKGROUND: Passive robot-generated arm movements in conjunction with proprioceptive decision making and feedback modulate functional connectivity (FC) in sensory motor networks and improve sensorimotor adaptation in normal individuals. This proof-of-principle study investigates whether these effects can be observed in stroke patients. METHODS: A total of 10 chronic stroke patients with a range of stable motor and sensory deficits (Fugl-Meyer Arm score [FMA] 0-65, Nottingham Sensory Assessment [NSA] 10-40) underwent resting-state functional magnetic resonance imaging before and after a single session of robot-controlled proprioceptive training with feedback. Changes in FC were identified in each patient using independent component analysis as well as a seed region-based approach. FC changes were related to impairment and changes in task performance were assessed. RESULTS: A single training session improved average arm reaching accuracy in 6 and proprioception in 8 patients. Two networks showing training-associated FC change were identified. Network C1 was present in all patients and network C2 only in patients with FM scores >7. Relatively larger C1 volume in the ipsilesional hemisphere was associated with less impairment ( r = 0.83 for NSA, r = 0.73 for FMA). This association was driven by specific regions in the contralesional hemisphere and their functional connections (supramarginal gyrus with FM scores r = 0.82, S1 with NSA scores r = 0.70, and cerebellum with NSA score r = -0.82). CONCLUSION: A single session of robot-controlled proprioceptive training with feedback improved movement accuracy and induced FC changes in sensory motor networks of chronic stroke patients. FC changes are related to functional impairment and comprise bilateral sensory and motor network nodes.


Assuntos
Retroalimentação Sensorial/fisiologia , Atividade Motora/fisiologia , Rede Nervosa/fisiopatologia , Propriocepção/fisiologia , Robótica , Córtex Sensório-Motor/fisiopatologia , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/terapia , Idoso , Isquemia Encefálica/complicações , Doença Crônica , Conectoma , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Estudo de Prova de Conceito , Robótica/instrumentação , Córtex Sensório-Motor/diagnóstico por imagem , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/fisiopatologia , Reabilitação do Acidente Vascular Cerebral/instrumentação , Resultado do Tratamento
16.
J Autism Dev Disord ; 49(2): 788-793, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30159694

RESUMO

The perception of subsecond durations in adults with autism spectrum disorder (hereafter 'autism'; n = 25 Experiment 1, n = 21 Experiment 2) and matched typical adults (n = 24 Experiment 1, n = 22 Experiment 2) was examined by requiring participants to perform an action in time with auditory (Experiment 1) or visual (Experiment 2) events. Individuals with autism performed comparably to typical participants in the auditory task and exhibited less temporal error relative to their typical counterparts in the visual task. These findings suggest that perception of subsecond intervals is intact in autism, if not enhanced. Results support recent Bayesian theories of enhanced visual-perceptual precision in people with autism, and extend empirical support into the precision of subsecond temporal estimates.


Assuntos
Percepção Auditiva , Transtorno do Espectro Autista/fisiopatologia , Desempenho Psicomotor , Percepção do Tempo , Percepção Visual , Adulto , Feminino , Humanos , Masculino , Córtex Sensório-Motor/fisiopatologia
17.
Neurosci Bull ; 35(1): 133-144, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30311072

RESUMO

Autonomic disturbances often occur in patients with acute cerebrovascular disease due to damage of the central autonomic network. We summarize the structures of the central autonomic network and the clinical tests used to evaluate the functions of the autonomic nervous system. We review the clinical and experimental findings as well as management strategies of post-stroke autonomic disturbances including electrocardiographic changes, cardiac arrhythmias, myocardial damage, thermoregulatory dysfunction, gastrointestinal dysfunction, urinary incontinence, sexual disorders, and hyperglycemia. The occurrence of autonomic disturbances has been associated with poor outcomes in stroke patients. Autonomic nervous system modulation appears to be an emerging therapeutic strategy for stroke management in addition to treatments for sensorimotor dysfunction.


Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Transtornos Cerebrovasculares/fisiopatologia , Rede Nervosa/lesões , Córtex Sensório-Motor/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Doença Aguda , Animais , Transtornos Cerebrovasculares/complicações , Humanos
18.
Int J Neurosci ; 129(4): 337-343, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30311827

RESUMO

BACKGROUND: The beneficial effects of the combination therapy of low-frequency repetitive transcranial magnetic stimulation of nonlesional hemisphere and intensive occupational therapy (LF-rTMS/OT) on upper limb hemiparesis have been well established in poststroke patients. However, there is no information on the effect of brain activity on LF-rTMS/OT treatment outcome. METHOD: A total of 59 poststroke patients with upper limb hemiparesis received 15-day LF-rTMS/OT. Motor function of the affected upper limb was evaluated before and after the treatment. We also conducted functional near-infrared spectroscopy (fNIRS) before the treatment and calculated the laterality index (LI) based on the change in oxy-hemoglobin in the primary sensorimotor cortex and supplementary motor cortex. The correlation between LI before LF-rTMS/OT and observed improvement in upper limb motor function was analyzed. RESULTS: Motor recovery was significantly more pronounced in patients with unaffected hemisphere dominance in both hemispheres (LI of -1 to 0) than in those with affected hemisphere dominance in the lesional hemisphere (LI of 0 to 1). There was a significant negative correlation between LI and improvement in upper limb motor function. DISCUSSION: The results demonstrated that patients with a shift in brain activity to the noninjured cerebral cortex exhibited better motor recovery following LF-rTMS/OT. The findings suggest that evaluation of brain asymmetry before LF-rTMS/OT with fNIRS can help predict the response to LF-rTMS/OT.


Assuntos
Lateralidade Funcional/fisiologia , Terapia Ocupacional/métodos , Paresia/terapia , Córtex Sensório-Motor/diagnóstico por imagem , Córtex Sensório-Motor/fisiopatologia , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/terapia , Estimulação Magnética Transcraniana/métodos , Extremidade Superior/fisiopatologia , Idoso , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Motor/diagnóstico por imagem , Córtex Motor/fisiopatologia , Paresia/etiologia , Paresia/fisiopatologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/fisiopatologia
19.
Eur J Pain ; 23(3): 483-494, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30288850

RESUMO

BACKGROUND: Sensorimotor conflicts are well known to induce sensory disturbances. However, explanations as to why patients with chronic pain are more sensitive to sensorimotor conflicts remain elusive. The main objectives of this study were (a) to assess and compare the sensory disturbances induced by sensorimotor conflict in complex regional pain syndrome (n = 38), fibromyalgia (n = 36), arthritis (n = 34) as well as in healthy volunteers (HV) (n = 32); (b) to assess whether these disturbances were related to the intensity and duration of pain, or to other clinical variables assessed using questionnaires (abnormalities in sensory perception, depression and anxiety); and (c) to categorize different subgroups of conflict-induced sensory disturbances. METHODS: One hundred and forty participants performed in phase or anti-phase movements with their arms while viewing a reflection of one arm in a mirror (and the other arm obscured). They were asked to report changes in sensory disturbances using a questionnaire. RESULTS: First, results showed that patients with complex regional pain syndrome and fibromyalgia were more prone to report sensory disturbances than arthritis patients and HV in response to conflicts (small effect size). Second, conflict-induced sensory disturbances were correlated with pain intensity (large effect size) and abnormalities in sensory perception (only in the CRPS group) but were not related to the duration of the disease or psychological factors. Finally, we identified two distinct subgroups of conflict-induced sensory disturbances. CONCLUSIONS: Our results suggest that pain lowers the threshold for the detection of sensorimotor conflicts, a phenomenon that could contribute to the maintenance of pain in clinical populations. SIGNIFICANCE: Individuals with complex regional pain syndrome and fibromyalgia were more sensitive to sensorimotor conflicts than arthritis patients and controls. Moreover, conflict-induced sensory disturbances were specific to higher pain intensity and higher sensory abnormalities in all groups, suggesting that pain lowers the threshold for the detection of sensorimotor conflicts.


Assuntos
Artrite/complicações , Síndromes da Dor Regional Complexa/complicações , Fibromialgia/complicações , Dor/etiologia , Sensação/fisiologia , Córtex Sensório-Motor/fisiopatologia , Adulto , Artrite/fisiopatologia , Estudos de Casos e Controles , Síndromes da Dor Regional Complexa/diagnóstico , Síndromes da Dor Regional Complexa/fisiopatologia , Feminino , Fibromialgia/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Movimento , Dor/fisiopatologia , Dor/psicologia , Inquéritos e Questionários
20.
Clin Genet ; 95(1): 182-186, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30298599

RESUMO

MPV17 encodes a putative channel-forming protein of the inner mitochondrial membrane and is involved in mitochondrial deoxynucleotide homeostasis. MPV17 mutations were first reported in patients with Navajo neurohepatopathy, an autosomal recessive mitochondrial DNA depletion syndrome, characterized by early-onset liver failure, failure to thrive as well as central and peripheral neurological involvement. Recently, two patients with juvenile-onset peripheral sensorimotor neuropathy associated with an MVP17 c.122G>A (p.Arg41Gln) variant have been reported. Here, we describe five additional patients from two unrelated families with sensorimotor axonal neuropathy without hepatocerebral affection caused by homozygous MPV17 variants. Patients of the first family carried the known c.122G>A variant and affected individuals of the second family had a novel c.376-9T>G near-splice variant, which was shown to result in an in-frame deletion of 11 amino acids. This report provides further evidence that MPV17 mutations should be considered in patients with pure, non-syndromic axonal neuropathy.


Assuntos
Predisposição Genética para Doença , Proteínas de Membrana/genética , Proteínas Mitocondriais/genética , Doenças do Sistema Nervoso Periférico/genética , Polineuropatias/genética , Adolescente , Adulto , Idade de Início , Axônios/patologia , Criança , Insuficiência de Crescimento/genética , Insuficiência de Crescimento/fisiopatologia , Feminino , Transtornos Heredodegenerativos do Sistema Nervoso/genética , Transtornos Heredodegenerativos do Sistema Nervoso/fisiopatologia , Humanos , Hepatopatias/genética , Hepatopatias/fisiopatologia , Falência Hepática/genética , Falência Hepática/fisiopatologia , Masculino , Doenças Mitocondriais/genética , Doenças Mitocondriais/fisiopatologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Polineuropatias/fisiopatologia , Córtex Sensório-Motor/fisiopatologia , Adulto Jovem
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