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1.
Nat Commun ; 10(1): 4699, 2019 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619680

RESUMO

Regaining the function of an impaired limb is highly desirable in paralyzed individuals. One possible avenue to achieve this goal is to bridge the interrupted pathway between preserved neural structures and muscles using a brain-computer interface. Here, we demonstrate that monkeys with subcortical stroke were able to learn to use an artificial cortico-muscular connection (ACMC), which transforms cortical activity into electrical stimulation to the hand muscles, to regain volitional control of a paralysed hand. The ACMC induced an adaptive change of cortical activities throughout an extensive cortical area. In a targeted manner, modulating high-gamma activity became localized around an arbitrarily-selected cortical site controlling stimulation to the muscles. This adaptive change could be reset and localized rapidly to a new cortical site. Thus, the ACMC imparts new function for muscle control to connected cortical sites and triggers cortical adaptation to regain impaired motor function after stroke.


Assuntos
Adaptação Fisiológica/fisiologia , Interfaces Cérebro-Computador , Estimulação Elétrica , Córtex Motor/fisiopatologia , Músculo Esquelético/fisiologia , Córtex Somatossensorial/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Animais , Braço , Córtex Cerebral/fisiologia , Córtex Cerebral/fisiopatologia , Eletrocorticografia , Mãos , Macaca mulatta , Córtex Motor/fisiologia , Vias Neurais/fisiopatologia , Paralisia , Córtex Somatossensorial/fisiologia , Reabilitação do Acidente Vascular Cerebral , Punho
2.
Physiol Rev ; 99(4): 2115-2140, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31507244

RESUMO

Drug consumption is driven by a drug's pharmacological effects, which are experienced as rewarding, and is influenced by genetic, developmental, and psychosocial factors that mediate drug accessibility, norms, and social support systems or lack thereof. The reinforcing effects of drugs mostly depend on dopamine signaling in the nucleus accumbens, and chronic drug exposure triggers glutamatergic-mediated neuroadaptations in dopamine striato-thalamo-cortical (predominantly in prefrontal cortical regions including orbitofrontal cortex and anterior cingulate cortex) and limbic pathways (amygdala and hippocampus) that, in vulnerable individuals, can result in addiction. In parallel, changes in the extended amygdala result in negative emotional states that perpetuate drug taking as an attempt to temporarily alleviate them. Counterintuitively, in the addicted person, the actual drug consumption is associated with an attenuated dopamine increase in brain reward regions, which might contribute to drug-taking behavior to compensate for the difference between the magnitude of the expected reward triggered by the conditioning to drug cues and the actual experience of it. Combined, these effects result in an enhanced motivation to "seek the drug" (energized by dopamine increases triggered by drug cues) and an impaired prefrontal top-down self-regulation that favors compulsive drug-taking against the backdrop of negative emotionality and an enhanced interoceptive awareness of "drug hunger." Treatment interventions intended to reverse these neuroadaptations show promise as therapeutic approaches for addiction.


Assuntos
Comportamento Aditivo , Encéfalo/fisiopatologia , Usuários de Drogas/psicologia , Recompensa , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Animais , Encéfalo/metabolismo , Neurônios Dopaminérgicos/metabolismo , Humanos , Vias Neurais/metabolismo , Vias Neurais/fisiopatologia , Plasticidade Neuronal , Fatores de Risco , Transtornos Relacionados ao Uso de Substâncias/metabolismo , Transtornos Relacionados ao Uso de Substâncias/reabilitação
3.
J Clin Neurosci ; 69: 250-256, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31477463

RESUMO

Electroacupuncture (EA) is an adjuvant therapy for peripheral nerve injury (PNI). Both peripheral and central alterations contribute to the rehabilitation process. We employed diffusion tensor imaging (DTI) to investigate the diffusion plasticity of afferent and efferent pathways caused by EA in model of peripheral nerve injury and reparation. Twenty-four rats were divided into three groups: normal group, model group and intervention group. Rats of the model group and the intervention group underwent sciatic nerve transection and anastomosis. EA intervention was performed on the intervention group at ST-36 and GB-30 for three months. Gait assessment and DTI were conducted at days post-operative (DPO) 30, 60 and 90. We selected corticospinal tract, spinothalamic tract and internal capsule as regions of interest and analyzed diffusion metrics including fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD). FA values and RD values displayed significant differences or obvious tendency while AD values maintained a stable level. RD values displayed better indicative performance than FA in internal capsule. The intervention group presented significant correlation between RD values and Regularity Index (RI) during the intervention period. The effect of EA on peripheral nerve injury repairing rats appeared to be accelerated recovery process of sensory and motor neural pathway. We proposed that RD was a potential in vivo indicator for structural plasticity caused by EA and PNI.


Assuntos
Eletroacupuntura , Cápsula Interna/fisiopatologia , Vias Neurais/fisiopatologia , Plasticidade Neuronal/fisiologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Animais , Imagem de Tensor de Difusão/métodos , Modelos Animais de Doenças , Masculino , Ratos , Ratos Sprague-Dawley , Nervo Isquiático/lesões
4.
Postgrad Med ; 131(7): 523-532, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31478421

RESUMO

Objectives: Many people affected by multiple sclerosis (MS) experience cognitive impairment, especially decreases in information processing speed (PS). Neural disconnection is thought to represent the neural marker of this symptom, although the role played by alterations of specific functional brain networks still remains unclear. The aim is to investigate and compare patterns of association between PS-demanding cognitive performance and functional connectivity across two MS phenotypes. Methods: Forty patients with relapsing-remitting MS (RRMS) and 25 with secondary progressive MS (SPMS) had neuropsychological and MRI assessments. Multiple regression models were used to investigate the relationship between performance on tests of visuomotor and verbal PS, and on the verbal fluency tests, and functional connectivity of four cognitive networks, i.e. left and right frontoparietal, salience and default-mode, and two control networks, i.e. visual and sensorimotor. Results: Patients with SPMS were older and had longer disease history than patients with RRMS and presented with worse overall clinical conditions: higher disease severity, total lesion volume, and cognitive impairment rates. However, in both patient samples, cognitive performance across tests was negatively correlated with functional connectivity of the salience and default-mode networks, and positively with connectivity of the left frontoparietal network. Only the visuomotor PS scores of the RRMS group were also associated with connectivity of the sensorimotor network. Conclusions: PS-demanding cognitive performance in patients with MS appears mainly associated with strength of functional connectivity of frontal networks involved in the evaluation and manipulation of information, as well as the default mode network. These results are in line with the hypothesis that multiple neural networks are needed to support normal cognitive performance across MS phenotypes. However, different PS measures showed partially different patterns of association with functional connectivity. Therefore, further investigations are needed to clarify the contribution of inter-network communication to specific cognitive deficits due to MS.


Assuntos
Encéfalo/diagnóstico por imagem , Esclerose Múltipla Crônica Progressiva/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Adulto , Idoso , Encéfalo/fisiopatologia , Cerebelo/diagnóstico por imagem , Cerebelo/fisiopatologia , Feminino , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/fisiopatologia , Neuroimagem Funcional , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/fisiopatologia , Esclerose Múltipla/psicologia , Esclerose Múltipla Crônica Progressiva/fisiopatologia , Esclerose Múltipla Crônica Progressiva/psicologia , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Esclerose Múltipla Recidivante-Remitente/psicologia , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Testes Neuropsicológicos , Lobo Parietal/diagnóstico por imagem , Lobo Parietal/fisiopatologia , Desempenho Psicomotor
5.
J Autism Dev Disord ; 49(11): 4498-4514, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31473949

RESUMO

There is growing evidence of altered connectivity in autism spectrum disorders (ASD) between the cerebellum and cortex. Three intrinsic connectivity networks (ICNs) are especially important to cognitive processing in ASD: the default mode network (DMN), executive control network (ECN), and salience networks (SNs). The goal of this study was to compare resting-state functional connectivity between the cerebellum and the DMN, ECN, and SN in ASD and typically developing children (n = 74, ages 7-12 years). Children with ASD showed stronger connectivity between the ventral DMN and left cerebellar lobules I-IV. No meaningful relationships were observed between ICN-cerebellar functional connectivity and ASD symptoms. These results suggest that the cerebellum contributes to altered network connectivity in ASD.


Assuntos
Transtorno do Espectro Autista/fisiopatologia , Cerebelo/fisiopatologia , Córtex Cerebral/fisiopatologia , Estudos de Casos e Controles , Criança , Função Executiva , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Motivação , Vias Neurais/fisiopatologia , Neuroimagem
6.
World Neurosurg ; 132: 314-320, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31449994

RESUMO

BACKGROUND: Whereas transient, self-limiting seizures are an infrequent but known complication of deep brain stimulation (DBS) implantation surgery, stimulation itself has occasionally been reported to result in seizure activity at delayed time points. The neural circuitry implicated in stimulation-induced seizures is unknown. CASE DESCRIPTION: A 47-year-old woman underwent chronic subcallosal cingulate DBS for treatment of refractory anorexia nervosa and experienced seizure with stimulation onset. Supratherapeutic voltage caused a generalized seizure. The patient subsequently experienced a full recovery. We reviewed the literature for other cases of delayed postoperative DBS seizures associated with stimulation. We also investigated whether the higher voltage may have recruited networks implicated in epilepsy. The supratherapeutic voltage stimulated a larger area and engaged vulnerable networks, including bilateral hippocampi, cingulate gyrus, and temporal lobes. Literature review identified 20 studies reporting delayed seizure after DBS surgery, 13 of which demonstrated a robust association with mostly nonmotor DBS stimulation. CONCLUSIONS: Nonmotor DBS targets, particularly in patients with epilepsy, may be more vulnerable to stimulation-induced seizures; as such, extra caution should be used when programming stimulation parameters at these DBS targets.


Assuntos
Anorexia Nervosa/terapia , Encéfalo/fisiopatologia , Estimulação Encefálica Profunda/efeitos adversos , Convulsões/etiologia , Anticonvulsivantes/uso terapêutico , Encéfalo/diagnóstico por imagem , Feminino , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/fisiopatologia , Hipocampo/diagnóstico por imagem , Hipocampo/fisiopatologia , Humanos , Lamotrigina/uso terapêutico , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Convulsões/diagnóstico por imagem , Convulsões/tratamento farmacológico , Convulsões/fisiopatologia , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/fisiopatologia
7.
J Autism Dev Disord ; 49(12): 4751-4760, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31444629

RESUMO

Evidence on neurophysiological correlates of coexisting autism spectrum disorders (ASD) and overweight/obesity may elucidate mechanisms leading to the observed greater risk of obesity in children with ASD. An exploratory secondary data analysis was performed on resting state functional magnetic resonance imaging (rs-fMRI) data of children downloaded from the ABIDE Preprocessed database (n = 81). Children with isolated ASD showed hypo-connectivity between anterior and posterior default mode network (DMN) (p = 0.003; FWER). Children with coexisting ASD and overweight/obesity showed hyper-connectivity between anterior and posterior DMN (p = 0.015; FWER). More evidence is needed to confirm these contrasting rs-fMRI connectivity profiles and to explicate causal inferences regarding neurophysiological mechanisms associated with coexisting ASD and overweight/obesity.


Assuntos
Transtorno do Espectro Autista/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Rede Nervosa/diagnóstico por imagem , Obesidade Pediátrica/diagnóstico por imagem , Adolescente , Transtorno do Espectro Autista/epidemiologia , Transtorno do Espectro Autista/fisiopatologia , Encéfalo/fisiopatologia , Mapeamento Encefálico/métodos , Criança , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Rede Nervosa/fisiopatologia , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Sobrepeso/diagnóstico por imagem , Sobrepeso/epidemiologia , Sobrepeso/fisiopatologia , Obesidade Pediátrica/epidemiologia , Obesidade Pediátrica/fisiopatologia
8.
J Integr Neurosci ; 18(2): 133-139, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31321954

RESUMO

The dynamic process of epilepsy is modeled as a cascading failure model in functional networks derived from graph theory. The aim is to test whether cascading failure identified from functional magnetic resonance imaging data could simulate epileptic discharges in 18 subjects with generalized tonic-clonic seizure and 17 demographically matched healthy controls. A cascading failure model was used to simulate the neural networks underlying generalized tonic-clonic seizure and healthy controls by stimulation of the node with the greatest number of connections. Results showed that the efficiency of generalized tonic-clonic seizure dropped significantly when compared to controls. Particular nodes whose efficiency altered significantly showed a correlation with the symptoms of generalized tonic-clonic seizure. Results also indicated that the left middle frontal lobe may be a potential focal area in the initiation of generalized tonic-clonic seizure.


Assuntos
Encéfalo/fisiopatologia , Modelos Neurológicos , Convulsões/fisiopatologia , Adulto , Criança , Simulação por Computador , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vias Neurais/fisiopatologia , Convulsões/etiologia , Adulto Jovem
9.
Handb Clin Neurol ; 161: 167-186, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31307598

RESUMO

We review the motor cortical and basal ganglia involvement in two important movement disorders: Parkinson's disease (PD) and dystonia. Single and paired pulse transcranial magnetic stimulation studies showed altered excitability and cortical circuits in PD with decreased silent period, short interval intracortical inhibition, intracortical facilitation, long afferent inhibition, interhemispheric inhibition, and cerebellar inhibition, and increased long interval intracortical inhibition and short interval intracortical facilitation. In dystonia, there is decreased silent period, short interval intracortical inhibition, long afferent inhibition, interhemispheric inhibition, and increased intracortical facilitation. Plasticity induction protocols revealed deficient plasticity in PD and normal and exaggerated plasticity in dystonia. In the basal ganglia, there is increased ß (14-30Hz) rhythm in PD and characteristic 5-18Hz band synchronization in dystonia. These motor cortical circuits, cortical plasticity, and oscillation profiles of the basal ganglia are altered with medications and deep brain stimulation treatment. There is considerable variability in these measures related to interindividual variations, different disease characteristics, and methodological considerations. Nevertheless, these pathophysiologic studies have expanded our knowledge of cortical excitability, plasticity, and oscillations in PD and dystonia, improved our understanding of disease pathophysiology, and helped to develop new treatments for these conditions.


Assuntos
Distonia/fisiopatologia , Córtex Motor/fisiopatologia , Vias Neurais/fisiopatologia , Doença de Parkinson/fisiopatologia , Humanos
10.
Front Neural Circuits ; 13: 42, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31275116

RESUMO

Leukoaraiosis (LA) is associated with cognitive impairment in the older people which can be demonstrated in functional connectivity (FC) based on resting-state functional magnetic resonance imaging (rs-fMRI). This study is to explore the FC changes in LA patients with different cognitive status by three network models. Fifty-three patients with LA were divided into three groups: the normal cognition (LA-NC; n = 14, six males), mild cognitive impairment (LA-MCI; n = 27, 13 males), and vascular dementia (LA-VD; n = 12, six males), according to the Mini Mental State Exam (MMSE) and Clinical Dementia Rating (CDR). The three groups and 30 matched healthy controls (HCs; 11 males) underwent rs-fMRI. The data of rs-fMRI were analyzed by independent components analysis (ICA) and region of interest (ROI) analysis by the REST toolbox. Then the FC was respectively analyzed by the default-mode network (DMN), salience networks (SNs) and the central executive network (CEN) with their results compared among the different groups. For inter-brain network analysis, there were negative FC between the SN and DMN in LA groups, and the FC decreased when compared with HC group. While there were enhanced inter-brain network FC between the SN and CEN as well as within the SN. The FC in patients with LA can be detected by different network models of rs-fMRI. The multi-model analysis is helpful for the further understanding of the cognitive changes in those patients.


Assuntos
Encéfalo/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Leucoaraiose/fisiopatologia , Vias Neurais/fisiopatologia , Idoso , Disfunção Cognitiva/etiologia , Feminino , Humanos , Leucoaraiose/complicações , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
11.
Neuropsychology ; 33(6): 893-910, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31192652

RESUMO

OBJECTIVE: Functional brain networks converge on areas of heteromodal processing such as lateral posterior parietal cortex (PPC). Traumatic brain injury (TBI) alters global connectivity patterns secondary to both focal and diffuse damage, but little is known about how it impacts regional environments. We examined local PPC functioning in individuals with moderate-severe TBI and controls during resting-state functional magnetic resonance imaging (rs-fMRI). METHOD: Eighteen individuals with moderate-severe TBI and 19 healthy controls underwent rs-fMRI and neurocognitive testing. Seed-based analyses characterized remote connectivity of PPC subregions. Voxelwise graph theoretical approaches were used to probe local PPC connectivity and modularity within and between groups, and to examine relationships between local functioning and cognition. RESULTS: Seed-based findings included increased connectivity from left and right hemispheric subregions to right-lateralized default mode and frontoparietal control networks in TBI compared to controls. Graph theoretical analyses revealed increased connection strength within right PPC relative to the contralateral region in TBI. Across groups, right PPC also showed decreased betweenness centrality compared with left PPC. Groups did not differ in the extent of modularity within left or right PPC, but there was less interindividual variability in modular structure within the TBI group. Right PPC modularity significantly predicted individual differences in cognitive performance. CONCLUSIONS: Our findings substantiate hyperconnectivity on both local and global levels after TBI and propose a special role for local right hemispheric functioning in supporting cognition independent of neurologic status. Hyperconnectivity does not appear to result from breakdown in local modular organization and may reflect shared responses to neurologic disruption among those with TBI. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Lesões Encefálicas Traumáticas/fisiopatologia , Lobo Parietal/fisiopatologia , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Estudos de Casos e Controles , Cognição , Feminino , Neuroimagem Funcional , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Testes Neuropsicológicos , Lobo Parietal/diagnóstico por imagem , Adulto Jovem
12.
Brain Struct Funct ; 224(6): 2087-2101, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31161472

RESUMO

Despite the common co-occurrence of cognitive impairment and brain structural deficits in alcoholism, demonstration of relations between regional gray matter volumes and cognitive and motor processes have been relatively elusive. In pursuit of identifying brain structural substrates of impairment in alcoholism, we assessed executive functions (EF), episodic memory (MEM), and static postural balance (BAL) and measured regional brain gray matter volumes of cortical, subcortical, and cerebellar structures commonly affected in individuals with alcohol dependence (ALC) compared with healthy controls (CTRL). ALC scored lower than CTRL on all composite scores (EF, MEM, and BAL) and had smaller frontal, cingulate, insular, parietal, and hippocampal volumes. Within the ALC group, poorer EF scores correlated with smaller frontal and temporal volumes; MEM scores correlated with frontal volume; and BAL scores correlated with frontal, caudate, and pontine volumes. Exploratory analyses investigating relations between subregional frontal volumes and composite scores in ALC yielded different patterns of associations, suggesting that different neural substrates underlie these functional deficits. Of note, orbitofrontal volume was a significant predictor of memory scores, accounting for almost 15% of the variance; however, this relation was evident only in ALC with a history of a non-alcohol substance diagnosis and not in ALC without a non-alcohol substance diagnosis. The brain-behavior relations observed provide evidence that the cognitive and motor deficits in alcoholism are likely a result of different neural systems and support the hypothesis that a number of identifiable neural systems rather than a common or diffuse neural pathway underlies cognitive and motor deficits observed in chronic alcoholism.


Assuntos
Alcoolismo , Cognição/fisiologia , Substância Cinzenta/patologia , Córtex Motor/patologia , Vias Neurais/patologia , Adulto , Idoso , Alcoolismo/patologia , Alcoolismo/fisiopatologia , Cerebelo/patologia , Cerebelo/fisiopatologia , Função Executiva/fisiologia , Feminino , Substância Cinzenta/fisiopatologia , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Memória Episódica , Pessoa de Meia-Idade , Córtex Motor/fisiopatologia , Vias Neurais/fisiopatologia
13.
Nat Commun ; 10(1): 2372, 2019 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-31147546

RESUMO

Only a minority of individuals experiencing trauma subsequently develop post-traumatic stress disorder (PTSD). However, whether differences in vulnerability to PTSD result from a predisposition or trauma exposure remains unclear. A major challenge in differentiating these possibilities is that clinical studies focus on individuals already exposed to trauma without pre-trauma conditions. Here, using the predator scent model of PTSD in rats and a longitudinal design, we measure pre-trauma brain-wide neural circuit functional connectivity, behavioral and corticosterone responses to trauma exposure, and post-trauma anxiety. Freezing during predator scent exposure correlates with functional connectivity in a set of neural circuits, indicating pre-existing circuit function can predispose animals to differential fearful responses to threats. Counterintuitively, rats with lower freezing show more avoidance of the predator scent, a prolonged corticosterone response, and higher anxiety long after exposure. This study provides a framework of pre-existing circuit function that determines threat responses, which might directly relate to PTSD-like behaviors.


Assuntos
Comportamento Animal , Encéfalo/fisiopatologia , Corticosterona/metabolismo , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Animais , Ansiedade/diagnóstico por imagem , Ansiedade/metabolismo , Ansiedade/fisiopatologia , Aprendizagem da Esquiva , Encéfalo/diagnóstico por imagem , Modelos Animais de Doenças , Reação de Congelamento Cataléptica , Neuroimagem Funcional , Estudos Longitudinais , Imagem por Ressonância Magnética , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Odorantes , Trauma Psicológico/diagnóstico por imagem , Trauma Psicológico/metabolismo , Trauma Psicológico/fisiopatologia , Ratos , Transtornos de Estresse Pós-Traumáticos/diagnóstico por imagem , Transtornos de Estresse Pós-Traumáticos/metabolismo
14.
Lancet Psychiatry ; 6(7): 610-619, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31196794

RESUMO

Catatonia is a psychomotor syndrome associated with several psychiatric and medical conditions. Psychomotor signs range from stupor to agitation, and include pathognomonic features such as verbigeration and waxy flexibility. Disturbances of volition led to the classification of catatonia as a subtype of schizophrenia, but changes in nosology now recognise the high prevalence in mood disorders, overlap with delirium, and comorbidity with medical conditions. Initial psychometric studies have revealed three behavioural factors, but the structure of catatonia is still unknown. Evidence from brain imaging studies of patients with psychotic disorders indicates increased neural activity in premotor areas in patients with hypokinetic catatonia. However, whether this localised hyperactivity is due to corticocortical inhibition or excess activity of inhibitory corticobasal ganglia loops is unclear. Current treatment of catatonia relies on benzodiazepines and electroconvulsive therapy-both effective, yet unspecific in their modes of action. Longitudinal research and treatment studies, with neuroimaging and brain stimulation techniques, are needed to advance our understanding of catatonia.


Assuntos
Encéfalo/fisiopatologia , Catatonia/fisiopatologia , Rede Nervosa/fisiopatologia , Catatonia/diagnóstico , Humanos , Vias Neurais/fisiopatologia
15.
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
16.
Nature ; 570(7761): 326-331, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31189958

RESUMO

Mutation or disruption of the SH3 and ankyrin repeat domains 3 (SHANK3) gene represents a highly penetrant, monogenic risk factor for autism spectrum disorder, and is a cause of Phelan-McDermid syndrome. Recent advances in gene editing have enabled the creation of genetically engineered non-human-primate models, which might better approximate the behavioural and neural phenotypes of autism spectrum disorder than do rodent models, and may lead to more effective treatments. Here we report CRISPR-Cas9-mediated generation of germline-transmissible mutations of SHANK3 in cynomolgus macaques (Macaca fascicularis) and their F1 offspring. Genotyping of somatic cells as well as brain biopsies confirmed mutations in the SHANK3 gene and reduced levels of SHANK3 protein in these macaques. Analysis of data from functional magnetic resonance imaging revealed altered local and global connectivity patterns that were indicative of circuit abnormalities. The founder mutants exhibited sleep disturbances, motor deficits and increased repetitive behaviours, as well as social and learning impairments. Together, these results parallel some aspects of the dysfunctions in the SHANK3 gene and circuits, as well as the behavioural phenotypes, that characterize autism spectrum disorder and Phelan-McDermid syndrome.


Assuntos
Comportamento Animal , Encéfalo/fisiopatologia , Macaca fascicularis/genética , Macaca fascicularis/psicologia , Mutação , Proteínas do Tecido Nervoso/genética , Vias Neurais/fisiopatologia , Animais , Encéfalo/patologia , Movimentos Oculares/genética , Feminino , Mutação em Linhagem Germinativa/genética , Hereditariedade/genética , Relações Interpessoais , Imagem por Ressonância Magnética , Masculino , Tono Muscular/genética , Vias Neurais/patologia , Sono/genética , Vocalização Animal
17.
Brain Connect ; 9(6): 464-474, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31219308

RESUMO

Due to technological advances, spatially indexed objects, such as blood oxygen level-dependent time series or electroencephalography data, are commonly observed across different scientific disciplines. Such object data are typically high dimensional and therefore challenging to handle. We propose a new approach for spatially indexed object data by mapping their spatial locations to a targeted one-dimensional interval so objects that are similar are placed near each other on the new target space. The proposed alignment not only provides a visualization tool for such complex object data but also facilitates a new way to study brain functional connectivity. Specifically, we introduce a new concept of path length to quantify the functional connectivity and a new community detection method. The advantages of the proposed methods are illustrated by simulations and in a study of functional connectivity for Alzheimer's disease.


Assuntos
Mapeamento Encefálico/métodos , Conectoma/métodos , Adulto , Doença de Alzheimer/fisiopatologia , Encéfalo/fisiopatologia , Simulação por Computador , Interpretação Estatística de Dados , Eletroencefalografia/métodos , Feminino , Neuroimagem Funcional/métodos , Humanos , Aprendizado de Máquina , Imagem por Ressonância Magnética/métodos , Masculino , Vias Neurais/fisiopatologia , Oxigênio/análise , Oxigênio/sangue
18.
BMC Neurosci ; 20(1): 30, 2019 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-31208340

RESUMO

BACKGROUND: Distinctive patterns of functional connectivity (FC) abnormalities in neural circuitry has been reported in patients with bipolar depression (BD) and unipolar depression (UD). However, it is unclear that whether this distinct functional connectivity patterns are diagnosis specific between BD and UD. This study aimed to compare patterns of functional connectivity among BD, UD and healthy controls (HC) and determine the distinct functional connectivity patterns which can differentiate BD from UD. METHOD: Totally 23 BD, 22 UD, and 24 HC were recruited to undergo resting-state fMRI scanning. FC between each pair of brain regions was calculated and compared among the three groups, the associations of FC with depressive symptom were also analyzed. RESULTS: Both patient groups showed significantly decreased cerebral-limbic FC located between the default mode network [posterior cingulated gyrus (PCG) and precuneus] and limbic regions (hippocampus, amygdala and thalamus) than HC. Moreover, the BD group exhibited more decreased FC mainly in the cortical regions (middle temporal gyrus, PCG, medial superior frontal gyrus, inferior occipital gyrus and superior temporal gyrus), but the UD group is more associated with limbic alterations. These decreased FCs were negatively correlated with HAMD scores in both BD and UD patients. CONCLUSIONS: BD and UD patients demonstrate different patterns of abnormal cerebral-limbic FC, reflected by decreased FC within cerebral cortex and limbic regions in BD and UD, respectively. The distinct FC abnormal pattern of the cerebral-limbic circuit might be applied as biomarkers to differentiate these two depressive patient groups.


Assuntos
Transtorno Bipolar/fisiopatologia , Córtex Cerebral/fisiopatologia , Transtorno Depressivo/fisiopatologia , Sistema Límbico/fisiopatologia , Adulto , Estudos de Casos e Controles , Feminino , Neuroimagem Funcional , Humanos , Imagem por Ressonância Magnética , Masculino , Vias Neurais/fisiopatologia , Índice de Gravidade de Doença , Adulto Jovem
19.
Hypertension ; 74(2): 349-358, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31203727

RESUMO

Nerve traffic recordings (muscle sympathetic nerve traffic [MSNA]) have shown that sympathetic activation may occur in obesity. However, the small sample size of the available studies, presence of comorbidities, heterogeneity of the subjects examined represented major weaknesses not allowing to draw definite conclusions. This is the case for the overweight state. The present meta-analysis evaluated 1438 obese or overweight subjects recruited in 45 microneurographic studies. The analysis was primarily based on MSNA quantification in obesity and overweight, excluding as concomitant conditions hypertension, metabolic syndrome, and other comorbidities. Assessment was extended to the relationships of MSNA with other neuroadrenergic markers, such as plasma norepinephrine and heart rate, anthropometric variables, as body mass index, waist-to-hip ratio, presence/absence of obstructive sleep apnea, and metabolic profile. Compared with normoweights MSNA was significantly greater in overweight and more in obese individuals (37.0±4.1 versus 43.2±3.5 and 50.4±5.0 burts/100 heartbeats, P<0.01). This was the case even in the absence of obstructive sleep apnea. MSNA was significantly directly related to body mass index and waist-to-hip ratio ( r=0.41 and r=0.64, P<0.04 and <0.01, respectively), clinic blood pressure ( r=0.68, P<0.01), total cholesterol, LDL (low-density lipoprotein) cholesterol, and triglycerides ( r=0.91, r=0.94, and r=0.80, respectively, P<0.01) but unrelated to plasma insulin, glucose, and homeostatic model assessment for insulin resistance. No significant correlation was found between MSNA, heart rate, and norepinephrine. Thus, obesity and overweight are characterized by sympathetic overactivity which mirrors the severity of the clinical condition and reflects metabolic alterations, with the exclusion of glucose/insulin profile. Neither heart rate nor norepinephrine appear to represent faithful markers of the muscle sympathetic overdrive.


Assuntos
Índice de Massa Corporal , Músculo Esquelético/inervação , Vias Neurais/fisiopatologia , Obesidade/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Adulto , Idoso , Antropometria , Estudos de Casos e Controles , Feminino , Hemodinâmica/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Sobrepeso/fisiopatologia , Valores de Referência , Medição de Risco
20.
Neurology ; 93(3): e215-e226, 2019 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-31227617

RESUMO

OBJECTIVE: To identify brain regions underlying interictal generalized paroxysmal fast activity (GPFA), and their causal interactions, in children and adults with Lennox-Gastaut syndrome (LGS). METHODS: Concurrent scalp EEG-fMRI was performed in 2 separately analyzed patient groups with LGS: 10 children (mean age 8.9 years) scanned under isoflurane-remifentanil anesthesia and 15 older patients (mean age 31.7 years) scanned without anesthesia. Whole-brain event-related analysis determined GPFA-related activation in each group. Results were used as priors in a dynamic causal modeling (DCM) analysis comparing evidence for different neuronal hypotheses describing initiation and propagation of GPFA between cortex, thalamus, and brainstem. RESULTS: A total of 1,045 GPFA events were analyzed (cumulative duration 1,433 seconds). In both pediatric and older groups, activation occurred in distributed association cortical areas, as well as the thalamus and brainstem (p < 0.05, corrected for family-wise error). Activation was similar across individual patients with structural, genetic, and unknown etiologies of epilepsy, particularly in frontoparietal cortex. In both groups, DCM revealed that GPFA was most likely driven by prefrontal cortex, with propagation occurring first to the brainstem and then from brainstem to thalamus. CONCLUSIONS: We show reproducible evidence of a cortically driven process within the epileptic network of LGS. This network is present early (in children) and late (in older patients) in the course of the syndrome and across diverse etiologies of epilepsy, suggesting that LGS reflects shared "secondary network" involvement. A cortical-to-subcortical hierarchy is postulated whereby GPFA rapidly propagates from prefrontal cortex to the brainstem via extrapyramidal corticoreticular pathways, whereas the thalamus is engaged secondarily.


Assuntos
Encéfalo/diagnóstico por imagem , Síndrome de Lennox Gastaut/diagnóstico por imagem , Adolescente , Adulto , Fatores Etários , Encéfalo/fisiopatologia , Tronco Encefálico/diagnóstico por imagem , Tronco Encefálico/fisiopatologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiopatologia , Criança , Pré-Escolar , Eletroencefalografia , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/fisiopatologia , Neuroimagem Funcional , Humanos , Síndrome de Lennox Gastaut/fisiopatologia , Imagem por Ressonância Magnética , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Lobo Parietal/diagnóstico por imagem , Lobo Parietal/fisiopatologia , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiopatologia , Tálamo/diagnóstico por imagem , Tálamo/fisiopatologia , Adulto Jovem
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