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1.
Nat Commun ; 12(1): 1080, 2021 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-33597538

RESUMO

Clinicians have long been interested in functional brain monitoring, as reversible functional losses often precedes observable irreversible structural insults. By characterizing neonatal functional cerebral networks, resting-state functional connectivity is envisioned to provide early markers of cognitive impairments. Here we present a pioneering bedside deep brain resting-state functional connectivity imaging at 250-µm resolution on human neonates using functional ultrasound. Signal correlations between cerebral regions unveil interhemispheric connectivity in very preterm newborns. Furthermore, fine-grain correlations between homologous pixels are consistent with white/grey matter organization. Finally, dynamic resting-state connectivity reveals a significant occurrence decrease of thalamo-cortical networks for very preterm neonates as compared to control term newborns. The same method also shows abnormal patterns in a congenital seizure disorder case compared with the control group. These results pave the way to infants' brain continuous monitoring and may enable the identification of abnormal brain development at the bedside.


Assuntos
Encéfalo/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Epilepsia/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Algoritmos , Encéfalo/fisiopatologia , Córtex Cerebral/fisiopatologia , Epilepsia/diagnóstico , Epilepsia/fisiopatologia , Feminino , Substância Cinzenta/fisiopatologia , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Imagem por Ressonância Magnética/métodos , Masculino , Modelos Neurológicos , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Ultrassonografia Doppler/métodos , Substância Branca/fisiopatologia
2.
Nat Commun ; 11(1): 4340, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895386

RESUMO

Healthy cognitive ageing is a societal and public health priority. Cerebrovascular risk factors increase the likelihood of dementia in older people but their impact on cognitive ageing in younger, healthy brains is less clear. The UK Biobank provides cognition and brain imaging measures in the largest population cohort studied to date. Here we show that cognitive abilities of healthy individuals (N = 22,059) in this sample are detrimentally affected by cerebrovascular risk factors. Structural equation modelling revealed that cerebrovascular risk is associated with reduced cerebral grey matter and white matter integrity within a fronto-parietal brain network underlying executive function. Notably, higher systolic blood pressure was associated with worse executive cognitive function in mid-life (44-69 years), but not in late-life (>70 years). During mid-life this association did not occur in the systolic range of 110-140 mmHg. These findings suggest cerebrovascular risk factors impact on brain structure and cognitive function in healthy people.


Assuntos
Encéfalo/fisiopatologia , Transtornos Cerebrovasculares/fisiopatologia , Transtornos Cognitivos/fisiopatologia , Envelhecimento Saudável , Adulto , Idoso , Pressão Sanguínea , Mapeamento Encefálico/métodos , Córtex Cerebral/fisiopatologia , Estudos de Coortes , Função Executiva/fisiologia , Feminino , Substância Cinzenta/fisiopatologia , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Substância Branca/fisiopatologia
3.
J Stroke Cerebrovasc Dis ; 29(10): 105152, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32912518

RESUMO

Sirtuins, class III histone deacetylases, are involved in the regulation of tissue repair processes and brain functions after a stroke. The ability of some isoforms of sirtuins to circulate between the nucleus and cytoplasm may have various pathophysiological effects on the cells. In present work, we focused on the role of non-mitochondrial sirtuins SIRT1, SIRT2, and SIRT6 in the restoration of brain cells following ischemic stroke. Here, using a photothrombotic stroke (PTS) model in mice, we studied whether local stroke affects the level and intracellular localization of SIRT1, SIRT2, and SIRT6 in neurons and astrocytes of the intact cerebral cortex adjacent to the ischemic ipsilateral hemisphere and in the analogous region of the contralateral hemisphere at different time points during the recovery period after a stroke. We evaluated the co-localization of sirtuins with growth-associated protein-43 (GAP-43), the presynaptic marker synaptophysin (SYN) and acetylated α-tubulin (Ac-α-Tub), that are associated with brain plasticity and are known to be involved in brain repair after a stroke. The results show that during the recovery period, an increase in SIRT1 and SIRT2 levels occurred. The increase of SIRT1 level was associated with an increase in synaptic plasticity proteins, whereas the increase of SIRT2 level was associated with an acetylated of α-tubulin, that can reduce the mobility of neurites. SIRT6 co-localized with GAP-43, but not with SYN. Moreover, we showed that SIRT1, SIRT2, and SIRT6 are not involved in the PTS-induced apoptosis of penumbra cells. Taken together, our results suggest that sirtuins functions differ depending on cell type, intracellular localization, specificity of sirtuins isoforms to different substrates and nature of post-translational modifications of enzymes.


Assuntos
Astrócitos/enzimologia , Córtex Cerebral/enzimologia , Trombose Intracraniana/complicações , Plasticidade Neuronal , Neurônios/enzimologia , Sirtuína 1/metabolismo , Sirtuína 2/metabolismo , Sirtuínas/metabolismo , Acidente Vascular Cerebral/enzimologia , Animais , Apoptose , Astrócitos/patologia , Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Modelos Animais de Doenças , Masculino , Camundongos , Neurônios/patologia , Recuperação de Função Fisiológica , Transdução de Sinais , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/fisiopatologia , Fatores de Tempo
4.
Rev. neurol. (Ed. impr.) ; 71(6): 225-233, 16 sept., 2020. ilus, graf
Artigo em Espanhol | IBECS | ID: ibc-195516

RESUMO

La epilepsia del lóbulo temporal plus se define como la epilepsia en la cual la zona epileptógena primaria se localiza en el lóbulo temporal y se extiende a regiones vecinas, como la ínsula, la corteza opercular suprasilviana, la corteza orbitofrontal y la unión temporoparietooccipital. El objetivo de esta revisión es proveer una actualización de la información en la epilepsia del lóbulo temporal plus. La historia de traumatismo craneoencefálico, infección cerebral (meningitis-encefalitis) o crisis epiléptica tonicoclónica generalizada está involucrada en su etiología, y permite la generación de redes neuronales complejas hipocámpicas y extrahipocámpicas. Las manifestaciones clínicas dependen de la zona epileptógena involucrada y de su rápida proyección a las estructuras temporales mesiales. El videoelectroencefalograma evidencia actividad interictal extensa e ictal en el lóbulo temporal, pero con rápida propagación perisilviana, orbitofrontal o temporoparietooccipital. La magnetoelectroencefalografía tiene menos contaminación muscular y podría considerarse como un biomarcador de estados tempranos en el proceso diagnóstico. La resonancia cerebral generalmente es negativa o muestra una ligera alteración de señal en la zona mesial temporal en grado variable. El estereoelectroencefalograma es el método invasivo de elección, especialmente guiado por robot. La epilepsia temporal plus se considera la causa más frecuente de fracaso de la cirugía de la epilepsia del lóbulo temporal, hasta un 30%


Temporal plus epilepsy is defined as focal epilepsy in which the primary epileptogenic area extends beyond the temporal lobe. It involves the neighboring regions such as the insula, the suprasilvian opercular cortex, the orbitofrontal cortex and the temporo-parieto-occipital junction. The objective of this review is to provide an update in temporal plus epilepsy. A previous history of brain trauma, a history of tonic clonic seizures, and previous central nervous system infection are risk factors. They likely allowed the generation of complex hippocampal and extrahypocampic neural networks. Clinical manifestations will depend on the location of the epileptogenic zone as well as the rapid propagation into temporal mesial structures. Video-electroencephalography usually shows involvement of the temporal lobe, with rapid propagation into the perisilvian, orbitofrontal or temporo-parieto-occipital regions. The magnetoelectroencephaography has lesser muscle contamination and could be considered as a biomarker of early states in the diagnosis process. Brain MRI is usually negative or shows non-specific mesial temporal abnormalities. Stereoelectroencephalography is the invasive method of choice. Temporal plus epilepsy is considered to be the most common cause of temporal lobe epilepsy surgery failure and represents up to 30%


Assuntos
Humanos , Epilepsia do Lobo Temporal/epidemiologia , Epilepsia do Lobo Temporal/etiologia , Córtex Cerebral/fisiopatologia , Epilepsia do Lobo Temporal/classificação , Córtex Cerebral/cirurgia , Eletroencefalografia/métodos , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/cirurgia , Lobectomia Temporal Anterior
5.
J Stroke Cerebrovasc Dis ; 29(9): 105041, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32807453

RESUMO

BACKGROUND AND PURPOSE: Ischemia-reperfusion injuries (IRIs) can aggravate the condition of some patients with acute occlusion of major intracranial artery (AOMIA) who received endovascular thrombectomy. Here, we provided data confirming the association of Repressor Element-1 Silencing Transcription factor (REST) with the long-term neuroprotective effect of the middle cerebral artery occlusion (MCAO) rats underwent Gradual Flow Restoration (GFR). METHODS: Long term neuroprotective effects of GFR intervention were evaluated on MCAO rats model after 3d and 7d reperfusion. The neurological deficit score and TTC staining were performed to evaluate the degree of brain damage in GFR and other interventions at different time. Differentially expressed genes related to cerebral ischemia reperfusion injury (CIRI) were initially screened and identified using GSE32529 microarray analysis. REST protein expression in rat brain cortex infarction was detected by Western blot analysis. RESULTS: MCAO rats intervened with GFR exhibited reduced neurological deficit (P < 0.05) and alleviated brain infarction volume (P < 0.01). The REST gene with up-regulated expression and its downstream genes with down-regulated expression were screened by Microarray analysis. The brain cortex infarction in MCAO rats produced high levels of REST expression. The GFR intervention inhibited REST expression, and alleviated brain injury on MCAO rats. CONCLUSION: Our results demonstrated that GFR intervention plays a long-term neuroprotective role and reduces brain edema and damage at reperfusion, possibly by inhibiting REST expression.


Assuntos
Edema Encefálico/prevenção & controle , Córtex Cerebral/metabolismo , Circulação Cerebrovascular , Infarto da Artéria Cerebral Média/terapia , Traumatismo por Reperfusão/prevenção & controle , Reperfusão/métodos , Proteínas Repressoras/metabolismo , Animais , Edema Encefálico/metabolismo , Edema Encefálico/patologia , Edema Encefálico/fisiopatologia , Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/fisiopatologia , Masculino , Ratos Sprague-Dawley , Reperfusão/efeitos adversos , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/fisiopatologia , Proteínas Repressoras/genética , Transdução de Sinais , Fatores de Tempo , Regulação para Cima
6.
Medicine (Baltimore) ; 99(31): e21403, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756136

RESUMO

BACKGROUND: A growing number of studies have used surface-based morphometry (SBM) analyses to investigate gray matter cortical thickness (CTh) abnormalities in Parkinson disease (PD). However, the results across studies are inconsistent and have not been systematically reviewed. A clear picture of CTh alterations in PD remains lacked. Coordinate-based meta-analysis (CBMA) is a powerful tool to quantitatively integrate the results of individual voxel-based neuroimaging studies to identify the functional or structural neural substrates of particular neuropsychiatric disorders. Recently, CBMA has been updated for integrating SBM studies. METHODS: The online databases PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang, and SinoMed were comprehensively searched without language limitations from the database inception to February 2, 2020. We will include all SBM studies that compared regional CTh between patients with idiopathic PD and healthy control subjects at the whole-cortex level using Seed-based d Mapping with Permutation of Subject Images (SDM-PSI). In addition to the main CBMA, we will conduct several supplementary analyses to test the robustness of the results, such as jackknife analyses, subgroup analyses, heterogeneity analyses, publication bias analyses, and meta-regression analyses. RESULTS: This CBMA will offer the latest evidence of CTh alterations in PD. CONCLUSIONS: Consistent and robust evidence of CTh alterations will feature brain morphometry of PD and may facilitate biomarker development. PROSPERO REGISTRATION NUMBER: CRD42020148775.


Assuntos
Córtex Cerebral/fisiopatologia , Doença de Parkinson/fisiopatologia , Córtex Cerebral/diagnóstico por imagem , Bases de Dados Factuais , Humanos , Neuroimagem , Doença de Parkinson/diagnóstico por imagem , Análise de Regressão
7.
Nat Commun ; 11(1): 3948, 2020 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769984

RESUMO

Thalamocortical dysrhythmia is a key pathology of chronic neuropathic pain, but few studies have investigated thalamocortical networks in chronic low back pain (cLBP) given its non-specific etiology and complexity. Using fMRI, we propose an analytical pipeline to identify abnormal thalamocortical network dynamics in cLBP patients and validate the findings in two independent cohorts. We first identify two reoccurring dynamic connectivity states and their associations with chronic and temporary pain. Further analyses show that cLBP patients have abnormal connectivity between the ventral lateral/posterolateral nucleus (VL/VPL) and postcentral gyrus (PoCG) and between the dorsal/ventral medial nucleus and insula in the less frequent connectivity state, and temporary pain exacerbation alters connectivity between the VL/VPL and PoCG and the default mode network in the more frequent connectivity state. These results extend current findings on thalamocortical dysfunction and dysrhythmia in chronic pain and demonstrate that cLBP pathophysiology and clinical pain intensity are associated with distinct thalamocortical network dynamics.


Assuntos
Córtex Cerebral/fisiopatologia , Dor Crônica/fisiopatologia , Núcleos Laterais do Tálamo/fisiopatologia , Dor Lombar/fisiopatologia , Núcleos Ventrais do Tálamo/fisiopatologia , Adulto , Mapeamento Encefálico , Estudos de Casos e Controles , Córtex Cerebral/diagnóstico por imagem , Dor Crônica/diagnóstico , Conjuntos de Dados como Assunto , Feminino , Humanos , Núcleos Laterais do Tálamo/diagnóstico por imagem , Dor Lombar/diagnóstico , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Rede Nervosa/fisiopatologia , Medição da Dor , Núcleos Ventrais do Tálamo/diagnóstico por imagem , Adulto Jovem
8.
PLoS One ; 15(8): e0231294, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32853207

RESUMO

Eigenvector alignment, introduced herein to investigate human brain functional networks, is adapted from methods developed to detect influential nodes and communities in networked systems. It is used to identify differences in the brain networks of subjects with Alzheimer's disease (AD), amnestic Mild Cognitive Impairment (aMCI) and healthy controls (HC). Well-established methods exist for analysing connectivity networks composed of brain regions, including the widespread use of centrality metrics such as eigenvector centrality. However, these metrics provide only limited information on the relationship between regions, with this understanding often sought by comparing the strength of pairwise functional connectivity. Our holistic approach, eigenvector alignment, considers the impact of all functional connectivity changes before assessing the strength of the functional relationship, i.e. alignment, between any two regions. This is achieved by comparing the placement of regions in a Euclidean space defined by the network's dominant eigenvectors. Eigenvector alignment recognises the strength of bilateral connectivity in cortical areas of healthy control subjects, but also reveals degradation of this commissural system in those with AD. Surprisingly little structural change is detected for key regions in the Default Mode Network, despite significant declines in the functional connectivity of these regions. In contrast, regions in the auditory cortex display significant alignment changes that begin in aMCI and are the most prominent structural changes for those with AD. Alignment differences between aMCI and AD subjects are detected, including notable changes to the hippocampal regions. These findings suggest eigenvector alignment can play a complementary role, alongside established network analytic approaches, to capture how the brain's functional networks develop and adapt when challenged by disease processes such as AD.


Assuntos
Doença de Alzheimer/fisiopatologia , Mapeamento Encefálico/métodos , Disfunção Cognitiva/fisiopatologia , Idoso , Amnésia/fisiopatologia , Encéfalo/fisiopatologia , Córtex Cerebral/fisiopatologia , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Modelos Teóricos , Rede Nervosa/fisiopatologia , Vias Neurais/fisiopatologia
9.
PLoS Comput Biol ; 16(7): e1007996, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32667909

RESUMO

Cortical spreading depression (CSD) is the propagation of a relatively slow wave in cortical brain tissue that is linked to a number of pathological conditions such as stroke and migraine. Most of the existing literature investigates the dynamics of short term phenomena such as the depolarization and repolarization of membrane potentials or large ion shifts. Here, we focus on the clinically-relevant hour-long state of neurovascular malfunction in the wake of CSDs. This dysfunctional state involves widespread vasoconstriction and a general disruption of neurovascular coupling. We demonstrate, using a mathematical model, that dissolution of calcium that has aggregated within the mitochondria of vascular smooth muscle cells can drive an hour-long disruption. We model the rate of calcium clearance as well as the dynamical implications on overall blood flow. Based on reaction stoichiometry, we quantify a possible impact of calcium phosphate dissolution on the maintenance of F0F1-ATP synthase activity.


Assuntos
Depressão Alastrante da Atividade Elétrica Cortical , Potenciais da Membrana , Mitocôndrias/metabolismo , Vasoconstrição , Trifosfato de Adenosina/química , Cálcio/química , Fosfatos de Cálcio/química , Córtex Cerebral/fisiopatologia , Circulação Cerebrovascular , Citosol/química , Retículo Endoplasmático/química , Substância Cinzenta/fisiopatologia , Humanos , Modelos Teóricos , Acoplamento Neurovascular , Oscilometria , Oxigênio/química , Fosforilação , ATPases Translocadoras de Prótons/química , Acidente Vascular Cerebral/fisiopatologia
10.
J Vis Exp ; (160)2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32597838

RESUMO

It has been more than a decade since the first functional magnetic resonance imaging (fMRI)-based neurofeedback approach was successfully implemented. Since then, various studies have demonstrated that participants can learn to voluntarily control a circumscribed brain region. Consequently, real-time fMRI (rtfMRI) provided a novel opportunity to study modifications of behavior due to manipulation of brain activity. Hence, reports of rtfMRI applications to train self-regulation of brain activity and the concomitant modifications in behavioral and clinical conditions such as neurological and psychiatric disorders [e.g., schizophrenia, obsessive compulsive Disorder (OCD), stroke] have rapidly increased. Neuroimaging studies in addiction research have shown that the anterior cingulate cortex, orbitofrontal cortex, and insular cortex are activated during the presentation of drug-associated cues. Also, activity in both left and right insular cortices have been shown to be highly correlated with drug urges when participants are exposed to craving-eliciting cues. Hence, the bilateral insula is of particular importance in researching drug urges and addiction due to its role in the representation of bodily (interoceptive) states. This study explores the use of rtfMRI neurofeedback for the reduction in blood oxygen-level dependent (BOLD) activity in bilateral insular cortices of nicotine-addicted participants. The study also tests if there are neurofeedback training-associated modifications in the implicit attitudes of participants towards nicotine-craving cues and explicit-craving behavior.


Assuntos
Córtex Cerebral/diagnóstico por imagem , Regulação para Baixo , Imagem por Ressonância Magnética , Neurorretroalimentação , Nicotina/efeitos adversos , Fumantes , Tabagismo/diagnóstico por imagem , Tabagismo/fisiopatologia , Córtex Cerebral/fisiopatologia , Fissura/fisiologia , Seguimentos , Humanos , Oxigênio/sangue , Inquéritos e Questionários
11.
Rinsho Shinkeigaku ; 60(7): 473-478, 2020 Jul 31.
Artigo em Japonês | MEDLINE | ID: mdl-32536664

RESUMO

An 82-year-old female suffered from head trauma, and developed acute consciousness disturbance 6 days after the event. Head CT showed the acute subdural hematoma in the left temporooccipital area and the patient underwent emergency hematoma evacuation and decompression. However, her consciousness disturbance became worse after surgery. Intermittent large negative infraslow shifts (lasting longer than 40 seconds) were recorded in the right posterior quadrant by scalp EEG with TC of 2 sec, that was defined as cortical spreading depolarizations (CSDs). Clinically consciousness disturbance sustained poor until 1 month after surgery in spite of treatment by anti-epileptic drugs. CSDs were observed on the right side where head injury most likely occurred. It may explain the sustained consciousness disturbance associated with significant prolonged ischemia. Once scalp EEG could record CSDs in this particular patient, the degree and its prognosis of traumatic head injury were estimated.


Assuntos
Lesões Encefálicas Traumáticas/diagnóstico , Lesões Encefálicas Traumáticas/fisiopatologia , Lesões Encefálicas/diagnóstico , Lesões Encefálicas/fisiopatologia , Córtex Cerebral/fisiopatologia , Eletroencefalografia/métodos , Couro Cabeludo/fisiologia , Doença Aguda , Idoso , Lesões Encefálicas/cirurgia , Lesões Encefálicas Traumáticas/cirurgia , Córtex Cerebral/diagnóstico por imagem , Transtornos da Consciência/etiologia , Descompressão Cirúrgica , Feminino , Humanos , Trombectomia , Fatores de Tempo , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada por Raios X
12.
J Neurosci ; 40(28): 5495-5509, 2020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32527982

RESUMO

Neurofibromatosis type 1 (NF1) is a common monogenic neurodevelopmental disorder associated with physical and cognitive problems. The cognitive issues are thought to arise from increased release of the neurotransmitter GABA. Modulating the signaling pathways causing increased GABA release in a mouse model of NF1 reverts deficits in hippocampal learning. However, clinical trials based on these approaches have so far been unsuccessful. We therefore used a combination of slice electrophysiology, in vivo two-photon calcium imaging, and optical imaging of intrinsic signal in a mouse model of NF1 to investigate whether cortical development is affected in NF1, possibly causing lifelong consequences that cannot be rescued by reducing inhibition later in life. We find that, in NF1 mice of both sexes, inhibition increases strongly during the development of the visual cortex and remains high. While this increase in cortical inhibition does not affect spontaneous cortical activity patterns during early cortical development, the critical period for ocular dominance plasticity is shortened in NF1 mice due to its early closure but unaltered onset. Notably, after environmental enrichment, differences in inhibitory innervation and ocular dominance plasticity between NF1 mice and WT littermates disappear. These results provide the first evidence for critical period dysregulation in NF1 and suggest that treatments aimed at normalizing levels of inhibition will need to start at early stages of development.SIGNIFICANCE STATEMENT Neurofibromatosis type 1 is associated with cognitive problems for which no treatment is currently available. This study shows that, in a mouse model of neurofibromatosis type 1, cortical inhibition is increased during development and critical period regulation is disturbed. Rearing the mice in an environment that stimulates cognitive function overcomes these deficits. These results uncover critical period dysregulation as a novel mechanism in the pathogenesis of neurofibromatosis type 1. This suggests that targeting the affected signaling pathways in neurofibromatosis type 1 for the treatment of cognitive disabilities may have to start at a much younger age than has so far been tested in clinical trials.


Assuntos
Córtex Cerebral/fisiopatologia , Neurofibromatose 1/fisiopatologia , Plasticidade Neuronal/fisiologia , Neurônios/fisiologia , Animais , Período Crítico Psicológico , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Imagem Óptica , Córtex Visual/fisiopatologia
13.
Eur J Paediatr Neurol ; 27: 30-36, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32473849

RESUMO

AIM: Little is known about acute febrile status epilepticus-induced injury of extrahippocampal structures. To clarify the presence and clinical significance of acute extrahippocampal injuries, we performed diffusion-weighted imaging (DWI) in children immediately after prolonged febrile seizure (PFS). METHOD: We performed a retrospective cohort study in children younger than 6 years old who visited one of two hospitals due to PFSs between January 2013 and October 2018. PFS was defined as a febrile seizure that persisted for 15 min or longer. We collected brain DWI data within 6 h of the end of PFS. When the initial DWI detected an abnormality, a follow-up DWI was performed a few days later. RESULTS: The study population consisted of 101 patients with PFSs. DWI was performed within 6 h in 51 patients, while the remaining 50 patients did not undergo imaging because of good recovery of consciousness. Restricted cortical diffusion was evident in 9 (18%) patients on initial DWI. All of them underwent DWI within 100 min after PFS. Restricted cortical diffusion was associated with male sex, asymmetrical PFS symptoms, and a shorter duration between the end of the seizure and DWI, but was not associated with seizure duration. All cortical abnormalities had resolved on follow-up DWI of these patients within 72 h after the initial imaging, but ipsilateral hippocampal hyperintensity appeared in one patient. All 9 patients with restricted cortical diffusion were finally diagnosed with PFS and discharged without sequelae. CONCLUSIONS: Some children with PFSs exhibit transient restricted diffusion in the regional cortex on DWI performed immediately after the end of PFS. These transient diffusion changes were not associated with unfavorable epileptic sequelae or neuroimaging in the short-term.


Assuntos
Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiopatologia , Convulsões Febris/diagnóstico por imagem , Convulsões Febris/fisiopatologia , Pré-Escolar , Estudos de Coortes , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Humanos , Lactente , Masculino , Neuroimagem/métodos , Estudos Retrospectivos
14.
Psychiatry Res Neuroimaging ; 301: 111082, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32438277

RESUMO

Attention-deficit hyperactive disorder (ADHD) is characterized by inattention and increased impulsive and hypermotoric behaviors.Despite the high prevalence and impact of ADHD, little is known about the underlying neurophysiology of ADHD. The main inhibitory and excitatory neurotransmitters γ-aminobutyric acid (GABA) and glutamate are receiving increased attention in ADHD and can be measured using Magnetic Resonance Spectroscopy (MRS). However, MRS studies in ADHD are limited. We measured GABA and glutamate in young unmedicated participants, utilizing high magnetic field strength. Fifty unmedicated children (26 with ADHD, 24 controls) aged 5-9 years completed MRS at 7T and behavioral testing. GABA and glutamate were measured in dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), premotor cortex (PMC), and striatum, and estimated using LCModel. Children with ADHD showed poorer inhibitory control and significantly reduced GABA/Cr in the striatum, but not in ACC, DLPFC, or PMC regions. There were no significant group differences for Glu/Cr levels, or correlations with behavioral manifestations of ADHD. The primary finding of this study is a reduction of striatal GABA levels in unmedicated children with ADHD at 7T. These findings provide guidance for future studies or interventions. Reduced striatal GABA may be a marker for specific GABA-related treatment for ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Ácido Glutâmico/análise , Espectroscopia de Ressonância Magnética/métodos , Ácido gama-Aminobutírico/análise , Córtex Cerebral/fisiopatologia , Criança , Pré-Escolar , Corpo Estriado/fisiopatologia , Humanos , Comportamento Impulsivo/fisiologia , Masculino , Transmissão Sináptica
15.
Nat Commun ; 11(1): 2441, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32415109

RESUMO

KIF21B is a kinesin protein that promotes intracellular transport and controls microtubule dynamics. We report three missense variants and one duplication in KIF21B in individuals with neurodevelopmental disorders associated with brain malformations, including corpus callosum agenesis (ACC) and microcephaly. We demonstrate, in vivo, that the expression of KIF21B missense variants specifically recapitulates patients' neurodevelopmental abnormalities, including microcephaly and reduced intra- and inter-hemispheric connectivity. We establish that missense KIF21B variants impede neuronal migration through attenuation of kinesin autoinhibition leading to aberrant KIF21B motility activity. We also show that the ACC-related KIF21B variant independently perturbs axonal growth and ipsilateral axon branching through two distinct mechanisms, both leading to deregulation of canonical kinesin motor activity. The duplication introduces a premature termination codon leading to nonsense-mediated mRNA decay. Although we demonstrate that Kif21b haploinsufficiency leads to an impaired neuronal positioning, the duplication variant might not be pathogenic. Altogether, our data indicate that impaired KIF21B autoregulation and function play a critical role in the pathogenicity of human neurodevelopmental disorder.


Assuntos
Cinesina/genética , Atividade Motora , Mutação/genética , Transtornos do Neurodesenvolvimento/genética , Transtornos do Neurodesenvolvimento/fisiopatologia , Animais , Axônios/metabolismo , Movimento Celular , Proliferação de Células , Córtex Cerebral/embriologia , Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Células HEK293 , Humanos , Masculino , Camundongos , Mutação de Sentido Incorreto/genética , Rede Nervosa/patologia , Rede Nervosa/fisiopatologia , Neurônios/metabolismo , Tamanho do Órgão , Organogênese/genética , Linhagem , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Peixe-Zebra/anatomia & histologia , Peixe-Zebra/genética
16.
Neurology ; 94(22): e2323-e2336, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32371448

RESUMO

OBJECTIVE: To identify which cortical regions are associated with direct electrical stimulation (DES)-induced alteration of breathing significant enough to impair pulse oximetry (SpO2). METHODS: Evolution of SpO2 after 1,352 DES was analyzed in 75 patients with refractory focal epilepsy who underwent stereo-EEG recordings. For each DES, we assessed the change in SpO2 from 30 seconds prior to DES onset to 120 seconds following the end of the DES. The primary outcome was occurrence of stimulation-induced transient hypoxemia as defined by decrease of SpO2 ≥5% within 60 seconds after stimulation onset as compared to pre-DES SpO2 or SpO2 nadir <90% during at least 5 seconds. Localization of the stimulated contacts was defined according to MarsAtlas brain parcellation and Freesurfer segmentation. RESULTS: A stimulation-induced transient hypoxemia was observed after 16 DES (1.2%) in 10 patients (13%), including 6 in whom SpO2 nadir was <90%. Among these 16 DES, 7 (44%) were localized within the perisylvian cortex. After correction for individual effects and the varying number of DES contributed by each person, significant decrease of SpO2 was significantly associated with the localization of DES (p = 0.019). CONCLUSION: Though rare, a significant decrease of SpO2 could be elicited by cortical direct electrical stimulation outside the temporo-limbic structures, most commonly after stimulation of the perisylvian cortex.


Assuntos
Mapeamento Encefálico/métodos , Córtex Cerebral/fisiopatologia , Eletroencefalografia/métodos , Hipóxia/fisiopatologia , Adulto , Córtex Cerebral/metabolismo , Estimulação Elétrica/métodos , Feminino , Humanos , Hipóxia/metabolismo , Masculino , Oximetria/métodos , Estudos Prospectivos , Adulto Jovem
17.
Medicine (Baltimore) ; 99(16): e19835, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32312005

RESUMO

RATIONALE: Pusher syndrome is a disorder of postural control. It is associated with unilateral lesions on central vestibular system. In the current study, we attempted to identify and investigate neural connectivity of the parieto-insular vestibular cortex in a patient with pusher syndrome, using diffusion tensor imaging. PATIENT CONCERNS: A 60-year-old male patient had left hemiplegia due to an infarction on right premotor cortex, primary motor cortex, corona radiata and temporal and occipital lobe. The patient had severe motor weakness in left upper and lower limb, left side neglect and significant pusher syndrome. DIAGNOSIS: Patient was diagnosed with left hemiplegia due to an infarction in the right middle cerebral artery territory at the neurology department of a university hospital. INTERVENTIONS: One patient and 5 control subjects of similar age participated. Diffusion tensor imaging data were acquired at 4-month and 12-month after the initial injury. OUTCOMES: Fractional anisotropy, mean diffusivity, and tract volume (TV) were measured. TV values in both affected and unaffected hemispheres of the patient were significantly decreased at 4-month compared to those of control subjects. In the unaffected hemisphere of the patient, TV value showed significant increase at 12-month compared to that at 4-month. Although the TV value at 12-month of the affected hemisphere was out of reference range, TV was considerably increased compared to that at 4-month. Mean values for fractional anisotropy or mean diffusivity in 2 hemispheres did not show significant difference compared to those of control subjects regardless of month. LESSONS: Restoration of an injured projection pathway between the vestibular nuclei and parieto-insular vestibular cortex with recovery of pusher syndrome was found in a patient with stroke.


Assuntos
Imagem de Tensor de Difusão/métodos , Hemiplegia/diagnóstico , Sistema Nervoso/diagnóstico por imagem , Equilíbrio Postural/fisiologia , Anisotropia , Infarto Encefálico , Córtex Cerebral/fisiopatologia , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Hemiplegia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média/diagnóstico por imagem , Artéria Cerebral Média/patologia , Córtex Motor/diagnóstico por imagem , Córtex Motor/patologia , Sistema Nervoso/fisiopatologia , Lobo Occipital/diagnóstico por imagem , Lobo Occipital/patologia , Lobo Parietal/fisiopatologia , Córtex Somatossensorial/fisiopatologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia
18.
Epilepsia ; 61(5): 984-994, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32314372

RESUMO

OBJECTIVE: Insulo-opercular seizures are characterized by diverse semiology, related to the insula's multiple functional roles and extensive connectivity. We aimed to identify semiologic subgroups and correlate these with insulo-opercular subregions based on connectional architecture. METHODS: We retrospectively collected a large series of 37 patients with insulo-opercular seizures explored by stereoelectroencephalography (SEEG) from three epilepsy centers. A new human brain atlas (Brainnetome Atlas, BNA) based on both anatomic and functional connections was employed to segment insulo-opercular cortex. Semiology and SEEG changes were carefully reviewed and quantified. Principal component analysis and cluster analysis were used to correlate semiologic characteristics with insulo-opercular subregions. RESULTS: Four main semiologic subgroups were identified, organized along an anteroventral to posterodorsal axis based on BNA. Group 1 was characterized by epigastric sensation and/or integrated gestural motor behaviors with or without feelings of fear or rage, involving the anteroventral insular regions and mesial temporal lobes. Group 2 was characterized by auditory sensations and symmetric proximal/axial tonic signs involving the posteroventral temporal operculum. The characteristics of group 3 were orofacial and laryngeal signs, involving the intermediate insulo-opercular regions. The features of group 4 were somatosensory signs followed by nonintegrated gestural motor behaviors and/or asymmetric tonic signs involving the posterodorsal insulo-opercular regions with propagation to the mesial frontal lobes. Thus anteroventral seizure organizations predominantly showed limbic system semiology, whereas more posterodorsal regions were associated with semiology involving mainly the sensorimotor system. Subjective symptoms proved to be particularly discriminating factors. SIGNIFICANCE: Insulo-opercular seizures can be categorized in terms of clinical semiology and correlate with connectional architecture subregions along an anteroventral-posterodorsal axis in line with the cytoarchitectonic gradient rather than the gyral anatomy of the insula cortex. This provides new insights into facilitating differential diagnosis and presurgical localization but also highlights the importance of considering connectional architecture in determining neural correlates of complex semiologic patterns.


Assuntos
Córtex Cerebral/patologia , Epilepsia do Lobo Frontal/patologia , Vias Neurais/patologia , Convulsões/patologia , Adolescente , Córtex Cerebral/fisiopatologia , Eletroencefalografia , Epilepsia do Lobo Frontal/classificação , Epilepsia do Lobo Frontal/fisiopatologia , Feminino , Humanos , Masculino , Vias Neurais/fisiopatologia , Análise de Componente Principal , Estudos Retrospectivos , Convulsões/classificação , Convulsões/etiologia , Convulsões/fisiopatologia
19.
Psychiatry Res Neuroimaging ; 300: 111081, 2020 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-32344156

RESUMO

Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive, compulsive behaviors. While a cortico-striatal-limbic network has been implicated in the pathophysiology of OCD, the neural correlates of this network in OCD are not well understood. In this study, we examined resting state functional connectivity among regions within the cortico-striatal-limbic OCD neural network, including the rostral anterior cingulate cortex, dorsolateral prefrontal cortex, ventrolateral prefrontal cortex, orbitofrontal cortex, ventromedial prefrontal cortex, amygdala, thalamus and caudate, in 44 OCD and 43 healthy participants. We then examined relationships between OCD neural network connectivity and OCD symptom severity in OCD participants. OCD relative to healthy participants showed significantly greater connectivity between the left caudate and bilateral dorsolateral prefrontal cortex. We also found a positive correlation between left caudate-bilateral dorsolateral prefrontal cortex connectivity and depression scores in OCD participants, such that greater positive connectivity was associated with more severe symptoms. This study makes a significant contribution to our understanding of functional networks and their relationship with depression in OCD.


Assuntos
Imagem por Ressonância Magnética , Rede Nervosa/fisiopatologia , Transtorno Obsessivo-Compulsivo/fisiopatologia , Índice de Gravidade de Doença , Adulto , Tonsila do Cerebelo/fisiopatologia , Estudos de Casos e Controles , Córtex Cerebral/fisiopatologia , Corpo Estriado/diagnóstico por imagem , Corpo Estriado/fisiopatologia , Feminino , Giro do Cíngulo/fisiopatologia , Humanos , Masculino , Rede Nervosa/diagnóstico por imagem , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiopatologia , Tálamo/fisiopatologia , Adulto Jovem
20.
Psychiatry Res Neuroimaging ; 300: 111066, 2020 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-32244111

RESUMO

Glucocorticoids reduce phobic fear in anxiety disorders and enhance psychotherapy, possibly by reducing the retrieval of fear memories and enhancing the consolidation of new corrective memories. Glucocorticoid signaling in the basolateral amygdala can influence connected fear and memory-related cortical regions, but this is not fully understood. Previous studies investigated specific pathways moderated by glucocorticoids, for example, visual-temporal pathways; however, these analyses were limited to a-priori selected regions. Here, we performed whole-brain pattern analysis to localize phobic stimulus decoding related to the fear-reducing effect of glucocorticoids. We reanalyzed functional magnetic resonance imaging (fMRI) data from a previously published study with spider-phobic patients and healthy controls. The patients received glucocorticoids or a placebo before the exposure to spider images. There was moderate evidence that patients with phobia had higher decoding of phobic content in the anterior cingulate cortex (ACC) and the left and right anterior insula compared to controls. Decoding in the ACC and the right insula showed strong evidence for correlation with experienced fear. Patients with cortisol reported a reduction of fear by 10-13%; however, there was only weak evidence for changes in neural decoding compared to placebo which was found in the precuneus, the opercular cortex, and the left cerebellum.


Assuntos
Córtex Cerebral/efeitos dos fármacos , Medo/efeitos dos fármacos , Glucocorticoides/farmacologia , Memória/efeitos dos fármacos , Transtornos Fóbicos/tratamento farmacológico , Adulto , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Córtex Cerebral/fisiopatologia , Feminino , Giro do Cíngulo/efeitos dos fármacos , Giro do Cíngulo/fisiopatologia , Humanos , Imagem por Ressonância Magnética , Masculino , Transtornos Fóbicos/fisiopatologia , Aranhas
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