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1.
PLoS One ; 15(12): e0243535, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33320870

RESUMO

High-frequency oscillations of the frontal cortex are involved in functions of the brain that fuse processed data from different sensory modules or bind them with elements stored in the memory. These oscillations also provide inhibitory connections to neural circuits that perform lower-level processes. Deficit in the performance of these oscillations has been examined as a marker for Alzheimer's disease (AD). Additionally, the neurodegenerative processes associated with AD, such as the deposition of amyloid-beta plaques, do not occur in a spatially homogeneous fashion and progress more prominently in the medial temporal lobe in the early stages of the disease. This region of the brain contains neural circuitry involved in olfactory perception. Several studies have suggested that olfactory deficit can be used as a marker for early diagnosis of AD. A quantitative assessment of the performance of the olfactory system can hence serve as a potential biomarker for Alzheimer's disease, offering a relatively convenient and inexpensive diagnosis method. This study examines the decline in the perception of olfactory stimuli and the deficit in the performance of high-frequency frontal oscillations in response to olfactory stimulation as markers for AD. Two measurement modalities are employed for assessing the olfactory performance: 1) An interactive smell identification test is used to sample the response to a sizable variety of odorants, and 2) Electroencephalography data are collected in an olfactory perception task with a pair of selected odorants in order to assess the connectivity of frontal cortex regions. Statistical analysis methods are used to assess the significance of selected features extracted from the recorded modalities as Alzheimer's biomarkers. Olfactory decline regressed to age in both healthy and mild AD groups are evaluated, and single- and multi-modal classifiers are also developed. The novel aspects of this study include: 1) Combining EEG response to olfactory stimulation with behavioral assessment of olfactory perception as a marker of AD, 2) Identification of odorants most significantly affected in mild AD patients, 3) Identification of odorants which are still adequately perceived by mild AD patients, 4) Analysis of the decline in the spatial coherence of different oscillatory bands in response to olfactory stimulation, and 5) Being the first study to quantitatively assess the performance of olfactory decline due to aging and AD in the Iranian population.


Assuntos
Doença de Alzheimer/diagnóstico , Lobo Frontal/patologia , Percepção Olfatória/fisiologia , Idoso , Doença de Alzheimer/fisiopatologia , Biomarcadores/metabolismo , Encéfalo/patologia , Córtex Cerebral/patologia , Diagnóstico Precoce , Eletroencefalografia/métodos , Feminino , Lobo Frontal/metabolismo , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Odorantes , Olfato/fisiologia , Lobo Temporal/patologia
2.
Nat Commun ; 11(1): 5038, 2020 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028830

RESUMO

Epilepsy is one of the most common neurological disorders, yet its pathophysiology is poorly understood due to the high complexity of affected neuronal circuits. To identify dysfunctional neuronal subtypes underlying seizure activity in the human brain, we have performed single-nucleus transcriptomics analysis of >110,000 neuronal transcriptomes derived from temporal cortex samples of multiple temporal lobe epilepsy and non-epileptic subjects. We found that the largest transcriptomic changes occur in distinct neuronal subtypes from several families of principal neurons (L5-6_Fezf2 and L2-3_Cux2) and GABAergic interneurons (Sst and Pvalb), whereas other subtypes in the same families were less affected. Furthermore, the subtypes with the largest epilepsy-related transcriptomic changes may belong to the same circuit, since we observed coordinated transcriptomic shifts across these subtypes. Glutamate signaling exhibited one of the strongest dysregulations in epilepsy, highlighted by layer-wise transcriptional changes in multiple glutamate receptor genes and strong upregulation of genes coding for AMPA receptor auxiliary subunits. Overall, our data reveal a neuronal subtype-specific molecular phenotype of epilepsy.


Assuntos
Epilepsia Resistente a Medicamentos/genética , Epilepsia do Lobo Temporal/genética , Neurônios/patologia , Lobo Temporal/patologia , Transcriptoma/genética , Adolescente , Adulto , Biópsia , Estudos de Casos e Controles , Núcleo Celular/genética , Núcleo Celular/metabolismo , Conjuntos de Dados como Assunto , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/patologia , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia do Lobo Temporal/diagnóstico , Epilepsia do Lobo Temporal/patologia , Epilepsia do Lobo Temporal/cirurgia , Feminino , Ácido Glutâmico/metabolismo , Humanos , Imagem por Ressonância Magnética , Masculino , Microdissecção , Pessoa de Meia-Idade , Modelos Genéticos , Rede Nervosa/metabolismo , Rede Nervosa/patologia , Neurônios/citologia , Neurônios/metabolismo , RNA-Seq , Receptores de AMPA/genética , Receptores de AMPA/metabolismo , Receptores de Glutamato/genética , Receptores de Glutamato/metabolismo , Transdução de Sinais/genética , Análise de Célula Única , Lobo Temporal/citologia , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/cirurgia , Transcrição Genética , Regulação para Cima , Adulto Jovem
3.
PLoS One ; 15(7): e0236423, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32735611

RESUMO

BACKGROUND: Use of functional MRI (fMRI) in pre-surgical planning is a non-invasive method for pre-operative functional mapping for patients with brain tumors, especially tumors located near eloquent cortex. Currently, this practice predominantly involves task-based fMRI (T-fMRI). Resting state fMRI (RS-fMRI) offers an alternative with several methodological advantages. Here, we compare group-level analyses of RS-fMRI vs. T-fMRI as methods for language localization. PURPOSE: To contrast RS-fMRI vs. T-fMRI as techniques for localization of language function. METHODS: We analyzed data obtained in 35 patients who had both T-fMRI and RS-fMRI scans during the course of pre-surgical evaluation. The RS-fMRI data were analyzed using a previously trained resting-state network classifier. The T-fMRI data were analyzed using conventional techniques. Group-level results obtained by both methods were evaluated in terms of two outcome measures: (1) inter-subject variability of response magnitude and (2) sensitivity/specificity analysis of response topography, taking as ground truth previously reported maps of the language system based on intraoperative cortical mapping as well as meta-analytic maps of language task fMRI responses. RESULTS: Both fMRI methods localized major components of the language system (areas of Broca and Wernicke) although not with equal inter-subject consistency. Word-stem completion T-fMRI strongly activated Broca's area but also several task-general areas not specific to language. RS-fMRI provided a more specific representation of the language system. CONCLUSION: We demonstrate several advantages of classifier-based mapping of language representation in the brain. Language T-fMRI activated task-general (i.e., not language-specific) functional systems in addition to areas of Broca and Wernicke. In contrast, classifier-based analysis of RS-fMRI data generated maps confined to language-specific regions of the brain.


Assuntos
Encéfalo/diagnóstico por imagem , Área de Broca/patologia , Glioblastoma/diagnóstico , Imagem por Ressonância Magnética , Adulto , Idoso , Atenção/fisiologia , Mapeamento Encefálico/métodos , Área de Broca/diagnóstico por imagem , Feminino , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/patologia , Lateralidade Funcional/fisiologia , Glioblastoma/diagnóstico por imagem , Glioblastoma/patologia , Humanos , Idioma , Masculino , Pessoa de Meia-Idade , Descanso/fisiologia , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/patologia , Adulto Jovem
4.
Neurology ; 95(9): e1236-e1243, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32611640

RESUMO

OBJECTIVE: To assess the prevalence of brain MRI abnormalities in people with epilepsy in rural China and to compare it with that of individuals in the United Kingdom. METHODS: Brain MRI scans were obtained in people with epilepsy who participated in a rural community-based program in China between July 2010 and December 2012. Individual epileptogenic lesion types were reviewed and their associations with seizure control examined. The MRI findings were compared with 2 previous similar studies in the United Kingdom. RESULTS: Among the 597 individuals (58% male, median age 38 years) with MRI scans analyzed, 488 (82%) had active epilepsy. The MRI was abnormal in 389 individuals (65%), with potentially epileptogenic lesion in 224 (38%) and nonspecific abnormalities in 165 (28%), and 108 (18%) were potentially resectable. The potentially epileptogenic lesions were less frequently detected in children (<18 years old, 12 of 68, 18%) than in adults (212 of 529, 40%; p < 0.001). In people with potentially epileptogenic lesions, 67% (150 of 224) had failed ≥2 antiseizure medications. They had higher risk of uncontrolled epilepsy than those with normal MRI (risk ratio [RR] 1.25; p < 0.001) and those with nonspecific abnormality (RR 1.15; p = 0.002) after adjustment for age and sex. The diagnostic yield of MRI was similar to that reported in community- and hospital-based studies in the United Kingdom. CONCLUSIONS: More than one-third of people with chronic epilepsy in rural China have potentially epileptogenic lesions identifiable on brain MRI, with two-thirds fulfilling the definition of pharmacoresistance. These findings highlight the magnitude of the unmet needs for epilepsy surgery in China.


Assuntos
Encefalomalacia/epidemiologia , Epilepsia/epidemiologia , Gliose/epidemiologia , Malformações do Sistema Nervoso/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/epidemiologia , Malformações Vasculares do Sistema Nervoso Central/diagnóstico por imagem , Malformações Vasculares do Sistema Nervoso Central/epidemiologia , Criança , Pré-Escolar , China/epidemiologia , Epilepsia Resistente a Medicamentos , Encefalomalacia/diagnóstico por imagem , Epilepsia/diagnóstico por imagem , Feminino , Gliose/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Malformações do Sistema Nervoso/diagnóstico por imagem , Prevalência , População Rural , Esclerose , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/patologia , Reino Unido/epidemiologia , Adulto Jovem
6.
World Neurosurg ; 140: 46-48, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32479911

RESUMO

BACKGROUND: Reports on neurologic manifestations of coronavirus disease 2019 (COVID-19) have attracted broad attention. We present an unusual case of COVID-19-associated encephalitis mimicking a glial tumor. CASE DESCRIPTION: A 35-year-old woman presented with headache and seizures. T2 fluid-attenuated inverse recovery imaging showed hyperintensities in the left temporal lobe. Magnetic resonance spectroscopy showed an elevated choline peak. Imaging findings were suggestive of high-grade glioma. Antiepileptic medication failed to achieve seizure control. A left anterior temporal lobectomy was performed. The patient had no postoperative deficits, and her symptoms completely improved. Histologic examination revealed encephalitis. Postoperatively, our patient tested positive for COVID-19. CONCLUSIONS: Our case raises awareness of neurologic manifestations of the disease and their potential to mimic glial tumors. For prompt diagnosis and prevention of transmission, clinicians should consider COVID-19 in patients with similar presentation.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/complicações , Diagnóstico Diferencial , Encefalite/virologia , Glioma/diagnóstico , Pneumonia Viral/complicações , Adulto , Infecções por Coronavirus/patologia , Encefalite/diagnóstico , Encefalite/patologia , Feminino , Glioma/patologia , Cefaleia/virologia , Humanos , Pandemias , Pneumonia Viral/patologia , Convulsões/patologia , Convulsões/virologia , Lobo Temporal/patologia , Lobo Temporal/virologia
7.
PLoS One ; 15(6): e0234797, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555735

RESUMO

BACKGROUND: Characteristics of patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and cysteine-sparing NOTCH3 mutations are relatively unknown. This study compared clinical and imaging characteristics between patients with CADASIL and cysteine-sparing NOTCH3 mutations and those with CADASIL and cysteine-involving NOTCH3 mutations. METHODS: We retrospectively reviewed medical records of patients with CADASIL admitted to the Asan Medical Center between September 1999 and September 2017. We compared clinical and brain magnetic resonance imaging (MRI) characteristics based on the presence or absence of cysteine-involving NOTCH3 gene mutations. We compared white matter change frequencies and grades in specific spatial regions between the groups according to age-related white matter change (ARWMC) scores. We evaluated the presence, number, and anatomical distributions of cerebral microbleeds according to the microbleed anatomical rating scale. RESULTS: We reviewed data from 79 patients (55 cysteine-involving, 24 cysteine-sparing NOTCH3 mutations). Clinical symptoms and signs did not differ significantly between the groups. The white matter change frequency and ARWMC scores (adjusted for age and stroke risk factors) in the anterior temporal lobes were lower in cysteine-sparing patients than in cysteine-involving patients. Frequencies and grades of the other brain region's white matter changes and cerebral microbleeds were similar between the groups. CONCLUSIONS: Patients with CADASIL and cysteine-sparing NOTCH3 mutations showed less involvement of the anterior temporal lobes in brain MRI than those with CADASIL and cysteine-involving NOTCH3 mutations, although both groups showed similar clinical characteristics.


Assuntos
CADASIL/patologia , Cisteína/genética , Receptor Notch3/genética , Adulto , Idoso , Encéfalo/diagnóstico por imagem , CADASIL/complicações , CADASIL/genética , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Polimorfismo de Nucleotídeo Único , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Acidente Vascular Cerebral/etiologia , Lobo Temporal/metabolismo , Lobo Temporal/patologia
8.
J Clin Neurosci ; 78: 439-443, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32387256

RESUMO

Calcifying pseudoneoplasms of the neuraxis (CAPNON) are rare benign lesions that can arise anywhere within the central nervous system. The etiology of these lesions remains unknown and diagnosis is made on pathohistological analysis. We present the case of a 35-year-old male patient with a history of epilepsy since childhood who was evaluated for refractory seizures. MRI revealed a small lesion in the left-posterior temporal lobe suspected to be a cavernoma. A gross total resection of the lesion was achieved via a left temporal craniotomy and pathological analysis revealed CAPNON. At 6 months follow-up, the patient remained neurologically intact and his seizures had ceased.


Assuntos
Calcinose/patologia , Sistema Nervoso Central/patologia , Convulsões/etiologia , Adulto , Calcinose/complicações , Calcinose/diagnóstico por imagem , Cefalometria , Humanos , Imagem por Ressonância Magnética , Masculino , Lobo Temporal/patologia , Lobo Temporal/cirurgia , Resultado do Tratamento
9.
Nat Commun ; 11(1): 2595, 2020 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-32444620

RESUMO

The anterior temporal lobes (ATL) have become a key brain region of interest in cognitive neuroscience founded upon neuropsychological investigations of semantic dementia (SD). The purposes of this investigation are to generate a single unified model that captures the known cognitive-behavioural variations in SD and map these to the patients' distribution of frontotemporal atrophy. Here we show that the degree of generalised semantic impairment is related to the patients' total, bilateral ATL atrophy. Verbal production ability is related to total ATL atrophy as well as to the balance of left > right ATL atrophy. Apathy is found to relate positively to the degree of orbitofrontal atrophy. Disinhibition is related to right ATL and orbitofrontal atrophy, and face recognition to right ATL volumes. Rather than positing mutually-exclusive sub-categories, the data-driven model repositions semantics, language, social behaviour and face recognition into a continuous frontotemporal neurocognitive space.


Assuntos
Reconhecimento Facial , Demência Frontotemporal/diagnóstico por imagem , Demência Frontotemporal/psicologia , Idoso , Atrofia , Estudos de Casos e Controles , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Modelos Neurológicos , Testes Neuropsicológicos , Análise de Componente Principal , Comportamento Social , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/patologia
10.
Psychiatry Res Neuroimaging ; 300: 111083, 2020 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-32298948

RESUMO

There has been a growing interest in the abnormality of networks across the brain in major depressive disorder (MDD). We aimed to investigate the structural covariance networks in patients with first-episode and drug-naïve MDD using structural imaging. A total of 77 patients with first-episode and drug-naïve MDD and 79 healthy subjects (HS) were recruited, from whom high-resolution T1-weighted images were analysed. Incident component analysis was used to calculate the brain networks based on grey matter volume covariance. There were significant differences in salience network, medial temporal lobe network, default mode network and central executive network between MDD and HS (p < 0.05). Further, the disturbance of medial temporal lobe network was significantly correlated with the severity of depressive symptoms (p < 0.05). In conclusion, we found a novel abnormality in the brain network in the medial temporal lobe primarily involving the hippocampus and parahippocampal gyrus in patients with first-episode and treatment-naïve MDD.


Assuntos
Transtorno Depressivo Maior/patologia , Imagem por Ressonância Magnética , Rede Nervosa/patologia , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Mapeamento Encefálico , Estudos de Casos e Controles , Transtorno Depressivo Maior/diagnóstico por imagem , Feminino , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Humanos , Masculino , Rede Nervosa/diagnóstico por imagem , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/patologia
11.
J Clin Neurosci ; 76: 246-248, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32278517

RESUMO

The incidence of paediatric glioblastoma is uncommon in comparison to their adult counterpart. Even more infrequent are extraneural metastases in glioblastoma. A previously well 14-year-old female presented with progressive right hemiparesis secondary to a left fronto-temporal lobe glioblastoma (WHO IV). She underwent successful gross total resection for her brain tumour. Prior to commencement of her adjuvant treatment, she developed tumour recurrence associated with intra-lesional haemorrhage. Although she underwent a second surgery, the patient developed bilateral malignant pleural effusion secondary to extraneural pulmonary metastases. Early awareness of its existence enables prompt diagnosis for this devastating disease. The authors emphasize the urgent need for international collaborations to work together for children affected by this challenging brain tumour.


Assuntos
Glioblastoma/patologia , Neoplasias Pulmonares/secundário , Recidiva Local de Neoplasia/patologia , Adolescente , Neoplasias Encefálicas/cirurgia , Feminino , Humanos , Lobo Temporal/patologia
12.
Brain ; 143(4): 1233-1248, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32252068

RESUMO

Human episodic memory critically depends on subregions of the medial temporal lobe, which are part of functional brain systems such as the anterior-temporal and the posterior-medial system. Here we analysed how Alzheimer's pathology affects functional connectivity within these systems. Data from 256 amyloid-ß-negative cognitively unimpaired, 103 amyloid-ß-positive cognitively unimpaired, and 83 amyloid-ß-positive individuals with mild cognitive impairment were analysed. Amyloid-ß and tau pathology were measured using the CSF amyloid-ß42/40 ratio and phosphorylated tau, respectively. We found that amyloid-ß-positive cognitively unimpaired individuals were mainly characterized by decreased functional connectivity between the medial temporal lobe and regions in the anterior-temporal system, most prominently between left perirhinal/entorhinal cortices and medial prefrontal cortex. Furthermore, correlation analysis in this group revealed decreasing functional connectivity between bilateral perirhinal/entorhinal cortices, anterior hippocampus and posterior-medial regions with increasing levels of phosphorylated tau. The amyloid-ß-positive individuals with mild cognitive impairment mostly exhibited reduced connectivity between the medial temporal lobe and posterior-medial regions, predominantly between the anterior hippocampus and posterior cingulate cortex. In addition, they showed hyperconnectivity within the medial temporal lobe and its immediate proximity. Lower medial temporal-cortical functional connectivity networks resulting from the group comparisons of cognitively unimpaired individuals were associated with reduced memory performance and more rapid longitudinal memory decline as shown by linear mixed-effects regression analysis. Finally, we found that reduced medial temporal-cortical connectivity in mildly cognitively impaired individuals was related to reduced entorhinal thickness and white matter integrity of the parahippocampal cingulum and the fornix. No such relationships were found in cognitively unimpaired individuals. In conclusion, our findings show that the earliest changes in preclinical Alzheimer's disease might involve decreased connectivity within the anterior-temporal system, and early changes in connectivity might be related to memory impairment, but not to structural changes. With disease progression and increased tau pathology, medial temporal functional connectivity with posterior-medial regions seems to be increasingly impaired. In individuals with mild cognitive impairment, reduced functional connectivity is associated with structural brain changes as well as the emergence of locally increased connectivity patterns. Thus, functional connectivity between the medial temporal lobe and the anterior-temporal and posterior-medial system could serve as stage-specific functional markers in early Alzheimer's disease.


Assuntos
Doença de Alzheimer/patologia , Memória Episódica , Vias Neurais/patologia , Lobo Temporal/patologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/fisiopatologia , Cognição/fisiologia , Progressão da Doença , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Lobo Temporal/fisiopatologia
13.
Cogn Behav Neurol ; 33(1): 63-66, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32132404

RESUMO

Individuals with a hemispheric infarction often reveal inattention to, or neglect of, contralesional lateral space (ie, hemispatial neglect). Individuals with a bilateral ventral temporal-occipital lesion have been shown to demonstrate upper vertical neglect, and those with a bilateral parietal-occipital lesion have been shown to demonstrate lower vertical neglect. However, to our knowledge, there have been no reports of individuals with vertical neglect from a unilateral hemispheric lesion. We report on a 72-year-old, right-handed male who developed transient left hemiparesis. On examination, he had left facial weakness and he bisected horizontal lines to the left of the midline (ie, ipsilesional neglect). In addition, on a line bisection test involving nine vertical line bisections, he demonstrated downward deviation in the majority of the trials; healthy individuals deviate upward. On brain imaging, our patient revealed a cerebral infarction, primarily affecting the right temporal lobe; the temporal lobes contain the ventral attentional network that allocates attention upward. There is also some evidence that, whereas the right hemisphere mediates attention upward, the left mediates attention downward. Therefore, injury to the right temporal lobe may account for our patient's upward neglect with downward deviation. However, further studies are needed to better understand the pathophysiology of vertical neglect.


Assuntos
Encéfalo/patologia , Lateralidade Funcional/fisiologia , Transtornos da Percepção/fisiopatologia , Acidente Vascular Cerebral/complicações , Lobo Temporal/patologia , Idoso , Humanos , Masculino , Acidente Vascular Cerebral/patologia
14.
Brain ; 143(3): 862-876, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32155246

RESUMO

Humans are uniquely able to retrieve and combine words into syntactic structure to produce connected speech. Previous identification of focal brain regions necessary for production focused primarily on associations with the content produced by speakers with chronic stroke, where function may have shifted to other regions after reorganization occurred. Here, we relate patterns of brain damage with deficits to the content and structure of spontaneous connected speech in 52 speakers during the acute stage of a left hemisphere stroke. Multivariate lesion behaviour mapping demonstrated that damage to temporal-parietal regions impacted the ability to retrieve words and produce them within increasingly complex combinations. Damage primarily to inferior frontal cortex affected the production of syntactically accurate structure. In contrast to previous work, functional-anatomical dissociations did not depend on lesion size likely because acute lesions were smaller than typically found in chronic stroke. These results are consistent with predictions from theoretical models based primarily on evidence from language comprehension and highlight the importance of investigating individual differences in brain-language relationships in speakers with acute stroke.


Assuntos
Lobo Frontal/patologia , Lobo Parietal/patologia , Distúrbios da Fala/patologia , Acidente Vascular Cerebral/patologia , Lobo Temporal/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Lateralidade Funcional , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Distúrbios da Fala/complicações , Acidente Vascular Cerebral/complicações , Adulto Jovem
15.
Psychiatry Res Neuroimaging ; 299: 111069, 2020 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-32203897

RESUMO

Eating disorders (EDs) have a possible neurodevelopmental pathogenesis. Our study aim was to assess regional cortical thickness (CT), local gyrification index (lGI) and fractal dimensionality (FD), as specific markers of cortical neurodevelopment in ED females. Twenty-two women with acute anorexia nervosa (acuAN), 10 with recovered anorexia nervosa (recAN), 24 with bulimia nervosa (BN) and 35 female healthy controls (HC) underwent a 3T MRI scan. All data were processed by FreeSurfer. Compared to recAN group women with acuAN showed a lower CT in multiple areas, while compared to HC they showed lower CT in temporal regions. BN group showed higher CT values in temporal and paracentral areas compared to HC. In multiple cortical areas, AcuAN group showed greater values of lGI compared to recAN group and lower values of lGI compared to HC. The BN group showed lower lGI in left medial orbitofrontal cortex compared to HC. No significant differences were found in FD among the groups. Present results provide evidence of CT and lGI alterations in patients with AN and, for the first time, in those with BN. Although these alterations could be state-dependent phenomena, they may underlie psychopathological aspects of EDs.


Assuntos
Anorexia Nervosa/patologia , Bulimia Nervosa/patologia , Córtex Cerebral/patologia , Feminino , Fractais , Lobo Frontal/patologia , Humanos , Imagem por Ressonância Magnética , Lobo Temporal/patologia
16.
Sci Rep ; 10(1): 3869, 2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-32123248

RESUMO

Neurofibrillary tangles are a pathological hallmark of Alzheimer's disease, and their levels correlate with the severity of cognitive dysfunction in humans. However, experimental evidence suggests that soluble tau species cause cognitive deficits and memory impairment. Our recent study suggests that caspase-2 (Casp2)-catalyzed tau cleavage at aspartate 314 mediates synaptic dysfunction and memory impairment in mouse and cellular models of neurodegenerative disorders. Δtau314, the C-terminally-truncated cleavage products, are soluble and present in human brain. In addition, levels of Δtau314 proteins are elevated in the brain of the cognitively impaired individuals compared to the cognitively normal individuals, indicating a possible role for Δtau314 proteins in cognitive deterioration. Here we show that (1) Δtau314 proteins are present in the inferior temporal gyrus of human brains; (2) Δtau314 proteins are generated from all six tau splicing isoforms, (3) levels of both Casp2 and Δtau314 proteins are elevated in cognitively impaired individuals compared to cognitively normal individuals, and (4) levels of Δtau314 proteins show a modest predictive value for dementia. These findings advance our understanding of the characteristics of Δtau314 proteins and their relevance to cognitive dysfunction and shed light on the contribution of Casp2-mediated Δtau314 production to cognitive deterioration.


Assuntos
Doença de Alzheimer/metabolismo , Disfunção Cognitiva/metabolismo , Lobo Temporal/metabolismo , Proteínas tau/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Animais , Caspase 2/genética , Caspase 2/metabolismo , Disfunção Cognitiva/genética , Disfunção Cognitiva/patologia , Cisteína Endopeptidases/genética , Cisteína Endopeptidases/metabolismo , Feminino , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Lobo Temporal/patologia , Proteínas tau/genética
17.
Cochrane Database Syst Rev ; 3: CD009628, 2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-32119112

RESUMO

BACKGROUND: Mild cognitive impairment (MCI) due to Alzheimer's disease is the symptomatic predementia phase of Alzheimer's disease dementia, characterised by cognitive and functional impairment not severe enough to fulfil the criteria for dementia. In clinical samples, people with amnestic MCI are at high risk of developing Alzheimer's disease dementia, with annual rates of progression from MCI to Alzheimer's disease estimated at approximately 10% to 15% compared with the base incidence rates of Alzheimer's disease dementia of 1% to 2% per year. OBJECTIVES: To assess the diagnostic accuracy of structural magnetic resonance imaging (MRI) for the early diagnosis of dementia due to Alzheimer's disease in people with MCI versus the clinical follow-up diagnosis of Alzheimer's disease dementia as a reference standard (delayed verification). To investigate sources of heterogeneity in accuracy, such as the use of qualitative visual assessment or quantitative volumetric measurements, including manual or automatic (MRI) techniques, or the length of follow-up, and age of participants. MRI was evaluated as an add-on test in addition to clinical diagnosis of MCI to improve early diagnosis of dementia due to Alzheimer's disease in people with MCI. SEARCH METHODS: On 29 January 2019 we searched Cochrane Dementia and Cognitive Improvement's Specialised Register and the databases, MEDLINE, Embase, BIOSIS Previews, Science Citation Index, PsycINFO, and LILACS. We also searched the reference lists of all eligible studies identified by the electronic searches. SELECTION CRITERIA: We considered cohort studies of any size that included prospectively recruited people of any age with a diagnosis of MCI. We included studies that compared the diagnostic test accuracy of baseline structural MRI versus the clinical follow-up diagnosis of Alzheimer's disease dementia (delayed verification). We did not exclude studies on the basis of length of follow-up. We included studies that used either qualitative visual assessment or quantitative volumetric measurements of MRI to detect atrophy in the whole brain or in specific brain regions, such as the hippocampus, medial temporal lobe, lateral ventricles, entorhinal cortex, medial temporal gyrus, lateral temporal lobe, amygdala, and cortical grey matter. DATA COLLECTION AND ANALYSIS: Four teams of two review authors each independently reviewed titles and abstracts of articles identified by the search strategy. Two teams of two review authors each independently assessed the selected full-text articles for eligibility, extracted data and solved disagreements by consensus. Two review authors independently assessed the quality of studies using the QUADAS-2 tool. We used the hierarchical summary receiver operating characteristic (HSROC) model to fit summary ROC curves and to obtain overall measures of relative accuracy in subgroup analyses. We also used these models to obtain pooled estimates of sensitivity and specificity when sufficient data sets were available. MAIN RESULTS: We included 33 studies, published from 1999 to 2019, with 3935 participants of whom 1341 (34%) progressed to Alzheimer's disease dementia and 2594 (66%) did not. Of the participants who did not progress to Alzheimer's disease dementia, 2561 (99%) remained stable MCI and 33 (1%) progressed to other types of dementia. The median proportion of women was 53% and the mean age of participants ranged from 63 to 87 years (median 73 years). The mean length of clinical follow-up ranged from 1 to 7.6 years (median 2 years). Most studies were of poor methodological quality due to risk of bias for participant selection or the index test, or both. Most of the included studies reported data on the volume of the total hippocampus (pooled mean sensitivity 0.73 (95% confidence interval (CI) 0.64 to 0.80); pooled mean specificity 0.71 (95% CI 0.65 to 0.77); 22 studies, 2209 participants). This evidence was of low certainty due to risk of bias and inconsistency. Seven studies reported data on the atrophy of the medial temporal lobe (mean sensitivity 0.64 (95% CI 0.53 to 0.73); mean specificity 0.65 (95% CI 0.51 to 0.76); 1077 participants) and five studies on the volume of the lateral ventricles (mean sensitivity 0.57 (95% CI 0.49 to 0.65); mean specificity 0.64 (95% CI 0.59 to 0.70); 1077 participants). This evidence was of moderate certainty due to risk of bias. Four studies with 529 participants analysed the volume of the total entorhinal cortex and four studies with 424 participants analysed the volume of the whole brain. We did not estimate pooled sensitivity and specificity for the volume of these two regions because available data were sparse and heterogeneous. We could not statistically evaluate the volumes of the lateral temporal lobe, amygdala, medial temporal gyrus, or cortical grey matter assessed in small individual studies. We found no evidence of a difference between studies in the accuracy of the total hippocampal volume with regards to duration of follow-up or age of participants, but the manual MRI technique was superior to automatic techniques in mixed (mostly indirect) comparisons. We did not assess the relative accuracy of the volumes of different brain regions measured by MRI because only indirect comparisons were available, studies were heterogeneous, and the overall accuracy of all regions was moderate. AUTHORS' CONCLUSIONS: The volume of hippocampus or medial temporal lobe, the most studied brain regions, showed low sensitivity and specificity and did not qualify structural MRI as a stand-alone add-on test for an early diagnosis of dementia due to Alzheimer's disease in people with MCI. This is consistent with international guidelines, which recommend imaging to exclude non-degenerative or surgical causes of cognitive impairment and not to diagnose dementia due to Alzheimer's disease. In view of the low quality of most of the included studies, the findings of this review should be interpreted with caution. Future research should not focus on a single biomarker, but rather on combinations of biomarkers to improve an early diagnosis of Alzheimer's disease dementia.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Disfunção Cognitiva/complicações , Imagem por Ressonância Magnética , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Atrofia/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Disfunção Cognitiva/patologia , Progressão da Doença , Córtex Entorrinal/diagnóstico por imagem , Córtex Entorrinal/patologia , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Humanos , Ventrículos Laterais/diagnóstico por imagem , Ventrículos Laterais/patologia , Pessoa de Meia-Idade , Neuroimagem/métodos , Tamanho do Órgão , Estudos Prospectivos , Sensibilidade e Especificidade , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/patologia
18.
J Neuroinflammation ; 17(1): 43, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32005256

RESUMO

BACKGROUND: A hallmark of temporal lobe epilepsy (TLE) is brain inflammation accompanied by neuronal demise. Accumulating evidence demonstrates that Rev-Erbα is involved in regulating neuroinflammation and determining the fate of neurons. Therefore, we studied the expression and cellular distribution of Rev-Erbα in the epileptogenic zone of TLE and the effect of treatment with the Rev-Erbα specific agonist SR9009 in the pilocarpine model. METHODS: The expression pattern of Rev-Erbα was investigated by western blotting, immunohistochemistry, and immunofluorescence labeling in patients with TLE. Next, the effects of SR9009 on neuroinflammation, neuronal apoptosis, and neuronal loss in the mouse hippocampus 7 days after status epilepticus (SE) were assessed by western blotting, immunofluorescence labeling staining, and TUNEL staining. RESULTS: The western blotting, immunohistochemistry, and immunofluorescence labeling results revealed that Rev-Erbα was downregulated in the epileptogenic zone of TLE patients and mainly localized in neurons, astrocytes, and presumably microglia. Meanwhile, the expression of Rev-Erbα was decreased in the hippocampus and temporal neocortex of mice treated with pilocarpine in the early post-SE and chronic phases. Interestingly, the expression of Rev-Erbα in the normal hippocampus showed a 24-h rhythm; however, the rhythmicity was disturbed in the early phase after SE, and this disturbance was still present in epileptic animals. Our further findings revealed that treatment with SR9009 inhibited NLRP3 inflammasome activation, inflammatory cytokine (IL-1ß, IL-18, IL-6, and TNF-α) production, astrocytosis, microgliosis, and neuronal damage in the hippocampus after SE. CONCLUSIONS: Taken together, these results suggested that a decrease in Rev-Erbα in the epileptogenic zone may contribute to the process of TLE and that the activation of Rev-Erbα may have anti-inflammatory and neuroprotective effects.


Assuntos
Anti-Inflamatórios/farmacologia , Encefalite/genética , Encefalite/prevenção & controle , Epilepsia do Lobo Temporal/induzido quimicamente , Epilepsia do Lobo Temporal/metabolismo , Fármacos Neuroprotetores , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/biossíntese , Pirrolidinas/farmacologia , Tiofenos/farmacologia , Adolescente , Adulto , Animais , Convulsivantes , Citocinas/metabolismo , Encefalite/patologia , Epilepsia do Lobo Temporal/patologia , Regulação da Expressão Gênica , Gliose/patologia , Gliose/prevenção & controle , Hipocampo/patologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/agonistas , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/genética , Pilocarpina , Estado Epiléptico/patologia , Estado Epiléptico/prevenção & controle , Lobo Temporal/patologia , Adulto Jovem
20.
Brain ; 143(3): 844-861, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32068789

RESUMO

The loss and recovery of language functions are still incompletely understood. This longitudinal functional MRI study investigated the neural mechanisms underlying language recovery in patients with post-stroke aphasia putting particular emphasis on the impact of lesion site. To identify patterns of language-related activation, an auditory functional MRI sentence comprehension paradigm was administered to patients with circumscribed lesions of either left frontal (n = 17) or temporo-parietal (n = 17) cortex. Patients were examined repeatedly during the acute (≤1 week, t1), subacute (1-2 weeks, t2) and chronic phase (>6 months, t3) post-stroke; healthy age-matched control subjects (n = 17) were tested once. The separation into two patient groups with circumscribed lesions allowed for a direct comparison of the contributions of distinct lesion-dependent network components to language reorganization between both groups. We hypothesized that activation of left hemisphere spared and perilesional cortex as well as lesion-homologue cortex in the right hemisphere varies between patient groups and across time. In addition, we expected that domain-general networks serving cognitive control independently contribute to language recovery. First, we found a global network disturbance in the acute phase that is characterized by reduced functional MRI language activation including areas distant to the lesion (i.e. diaschisis) and subsequent subacute network reactivation (i.e. resolution of diaschisis). These phenomena were driven by temporo-parietal lesions. Second, we identified a lesion-independent sequential activation pattern with increased activity of perilesional cortex and bilateral domain-general networks in the subacute phase followed by reorganization of left temporal language areas in the chronic phase. Third, we observed involvement of lesion-homologue cortex only in patients with frontal but not temporo-parietal lesions. Fourth, irrespective of lesion location, language reorganization predominantly occurred in pre-existing networks showing comparable activation in healthy controls. Finally, we detected different relationships of performance and activation in language and domain-general networks demonstrating the functional relevance for language recovery. Our findings highlight that the dynamics of language reorganization clearly depend on lesion location and hence open new perspectives for neurobiologically motivated strategies of language rehabilitation, such as individually-tailored targeted application of neuro-stimulation.


Assuntos
Afasia/fisiopatologia , Lobo Frontal/fisiopatologia , Idioma , Lobo Parietal/fisiopatologia , Recuperação de Função Fisiológica/fisiologia , Acidente Vascular Cerebral/fisiopatologia , Lobo Temporal/fisiopatologia , Estudos de Casos e Controles , Lobo Frontal/patologia , Neuroimagem Funcional , Humanos , Testes de Linguagem , Estudos Longitudinais , Imagem por Ressonância Magnética , Vias Neurais/fisiopatologia , Lobo Parietal/patologia , Acidente Vascular Cerebral/complicações , Lobo Temporal/patologia
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