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1.
J Vis Exp ; (162)2020 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-32894263

RESUMO

Cannabis is the illicit drug most commonly used worldwide, and its consumption can both induce psychiatric symptoms in otherwise healthy subjects and unmask a florid psychotic picture in patients with a prior psychotic risk. Previous studies suggest that chronic and long-term cannabis exposure may exert significant negative effects in brain areas enriched with cannabinoid receptors. However, whether brain alterations determined by cannabis dependency will lead to a clinically significant phenotype or to a psychotic outbreak at some point of an abuser's life remains unclear. The aim of this study was to investigate morphological brain differences between chronic cannabis users with cannabis-induced psychosis (CIP) and non-psychotic cannabis users (NPCU) without any psychiatric conditions and correlate brain deficits with selective socio-demographic, clinical and psychosocial variables. 3T magnetic resonance imaging (MRI) scans of 10 CIP patients and 12 NPCU were acquired. The type of drug, the frequency, and the duration, as well socio-demographic, clinical and psychosocial parameters of dependency were measured. CIP patients had extensive grey matter (GM) decreases in right superior frontal gyrus, right precentral, right superior temporal gyrus, insula bilaterally, right precuneus, right medial occipital gyrus, right fusiform gyrus, and left hippocampus in comparison to chronic cannabis users without psychosis. Finally, in CIP patients, the results showed a negative correlation between a domain of the Brief Psychiatric Rating Scale (BPRS), BPRS-Activity, and selective GM volumes. Overall, the results suggest that cannabis-induced psychosis is characterized by selective brain reductions that are not present in NPCU. Therefore, neuroimaging studies may provide a potential ground for identifying putative biomarkers associated with the risk of developing psychosis in cannabis users.


Assuntos
Encéfalo/diagnóstico por imagem , Abuso de Maconha/diagnóstico por imagem , Psicoses Induzidas por Substâncias/diagnóstico por imagem , Adulto , Encéfalo/patologia , Feminino , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Abuso de Maconha/epidemiologia , Abuso de Maconha/patologia , Neuroimagem , Projetos Piloto , Psicoses Induzidas por Substâncias/epidemiologia , Psicoses Induzidas por Substâncias/patologia
2.
Medicine (Baltimore) ; 99(31): e21499, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756184

RESUMO

BACKGROUND: Numerous studies using a variety of non-invasive neuroimaging techniques in vivo have demonstrated that chronic pain (CP) is associated with brain alterations. Cortical thickness (CTh) via surface-based morphometry (SBM) analysis of magnetic resonance imaging data is a valid and sensitive method to investigate the structure of brain gray matter. Many studies have employed SBM to measure CTh difference between patients with CP and pain-free controls and provided important insights into the brain basis of CP. However, the findings from these studies were inconsistent and have not been quantitatively reviewed. METHODS: Three major electronic medical databases: PubMed, Web of Science, and Embase were searched for eligible studies published in English on April 3, 2020. This protocol was prepared based on the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols. The Seed-based d Mapping with Permutation of Subject Images software package will be employed to conducted a coordinate-based meta-analysis (CBMA) to identify consistent CTh differences between patients with CP and pain-free controls. Several complementary analyses, including sensitivity analysis, heterogeneity analysis, publication bias, subgroup analysis, and meta-regression analysis, will be further conducted to test the robustness of the results. RESULTS: This CBMA will tell us whether CP with different subtypes shares common CTh alterations and what the pattern of its characterized alterations is. CONCLUSIONS: To the best of our knowledge, this will be the first CBMA of SBM studies that characterizes brain CTh alterations in CP. The CBMA will provide the quantitative evidence of common brain cortical morphometry of CP. The findings will help us to understand the neural basis underlying CP. TRIAL REGISTRATION NUMBER: INPLASY202050069.


Assuntos
Córtex Cerebral/diagnóstico por imagem , Dor Crônica/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Imagem por Ressonância Magnética/estatística & dados numéricos , Neuroimagem/estatística & dados numéricos , Dor Crônica/patologia , Feminino , Substância Cinzenta/patologia , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Metanálise como Assunto , Neuroimagem/métodos , Projetos de Pesquisa , Revisões Sistemáticas como Assunto
3.
J Comput Assist Tomogr ; 44(4): 533-539, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32697523

RESUMO

PURPOSE: The purpose of this study was to investigate the differences of gray matter volume (GMV) alteration patterns between hemodialysis with restless legs syndrome (HD-RLS) and hemodialysis without restless legs syndrome (HD-nRLS) patients using voxel-based morphometry. METHODS: Twenty-three HD-RLS patients, 27 HD-nRLS patients, and 27 age-, sex-, and education-matched healthy controls were included in this study. One-way analysis of covariance and post hoc analyses were used to assess differences in GMV, demographics, and clinical data among the 3 groups. Pearson correlation analysis was conducted between altered GMV in the HD-RLS group and clinical data. RESULTS: Compared with HD-nRLS patients, HD-RLS patients showed decreased GMV in the left primary motor cortex (false discovery rate corrected, P < 0.05). Compared with the healthy controls, both HD subgroups (ie, those with and without RLS) exhibited consistent GMV changes, including decreased GMV in the bilateral anterior cingulate and paracingulate gyrus and left middle temporal gyrus (false discovery rate corrected, P < 0.05). The GMV values in the left precentral gyrus were negatively correlated with the RLS rating scores (r = 0.2138, P = 0.0263). CONCLUSIONS: This abnormal decreased GMV in the sensorimotor cortex provides evidence for a sensory processing disorder in RLS that may be involved in the pathogenesis of RLS in HD patients.


Assuntos
Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Diálise Renal/efeitos adversos , Síndrome das Pernas Inquietas/diagnóstico por imagem , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Motor/diagnóstico por imagem , Córtex Motor/patologia , Tamanho do Órgão , Síndrome das Pernas Inquietas/complicações
4.
Medicine (Baltimore) ; 99(29): e21374, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702936

RESUMO

BACKGROUND: Voxel-based morphometry (VBM) is an objective structural magnetic resonance imaging (MRI) technique which allows researchers to investigate group-level differences in regional gray matter (GM) volume or density over the whole brain. In the last decade, VBM studies in restless leg syndrome (RLS) have exhibited inconsistent and conflicting findings. METHODS: Studies will be identified through a computerized literature search of the following databases: PubMed, Web of Science, and Embase until October 1, 2018 and updated on March 1, 2020. This protocol will be performed in accordance with the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P). In addition, we will follow the recent guidelines and recommendations for coordinate-based meta-analysis (CBMA). This CBMA will be performed with the seed-based d mapping with permutation of subject images (SDM-PSI) software. RESULTS: This CBMA will offer the latest evidence of GM alterations in RLS. CONCLUSIONS: To our knowledge, this will be the first CBMA that pooled VBM findings in RLS. This quantitative evidence of GM alterations will characterize brain morphometry of RLS. PROSPERO REGISTRATION NUMBER: CRD42018117014.


Assuntos
Substância Cinzenta/patologia , Síndrome das Pernas Inquietas/patologia , Substância Cinzenta/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Neuroimagem , Síndrome das Pernas Inquietas/diagnóstico por imagem
5.
J Headache Pain ; 21(1): 89, 2020 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-32652927

RESUMO

Voxel-based morphometry (VBM) is a popular non-invasive magnetic resonance imaging technique to investigate brain gray matter (GM) differences between groups. Recently, two VBM studies in migraine have been published in The Journal of Headache and Pain. Reviewing the two and those previous published VBM studies, we found considerable variations of the results. Spatially diverse brain regions with decreased and increased GM alterations and null findings have been reported. It is interesting to know whether there is a reliable brain morphological signature for migraine. Coordinate-based meta-analysis (CBMA) is increasingly used to quantitatively pool individual neuroimaging studies to identify consistent and reliable findings. Several CBMA have been conducted, however, their results were inconsistent. The algorithms for CBMA have evolved and more eligible VBM studies in migraine have been published. We therefore conducted an updated CBMA using the latest algorithms for CBMA, seed-based d mapping with permutation of subject images (SDM-PSI). The present CBMA of 32 VBM studies (41 datasets comprising 1252 patients and 1025 healthy controls) found no evidence of consistent GM alterations in migraine. Sensitivity analysis, subgroup meta-analyses, and meta-regression analyses revealed that the result was robust. This negative result indicates that there is no reliable brain morphological signature for migraine. VBM investigations in migraine remain a heterogeneous field. Many potential confounding factors, such as underpowered sample sizes, variations in demographic and clinical characteristics, and differences in MRI scanners, head coils, scanning parameters, preprocessing procedures, and statistical strategies may cause the inconsistences of the results. Future VBM studies are warranted to enroll well-characterized and homogeneous subtype samples with appropriate sample sizes, comprehensively assess comorbidities and medication status, and use well-validated and standardized imaging protocols and processing and analysis pipelines to produce robust and replicable results in migraine.


Assuntos
Algoritmos , Encéfalo/patologia , Transtornos de Enxaqueca/patologia , Mapeamento Encefálico , Feminino , Substância Cinzenta/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Neuroimagem
6.
Clinics (Sao Paulo) ; 75: e1505, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555945

RESUMO

OBJECTIVES: Parkinson's disease (PD) and the parkinsonian variant of multiple system atrophy (MSA-P) are distinct neurodegenerative disorders that share similar clinical features of parkinsonism. The morphological alterations of these diseases have yet to be understood. The purpose of this study was to evaluate gray matter atrophy in PD and MSA-P using regions of interest (ROI)-based measurements and voxel-based morphometry (VBM). METHODS: We studied 41 patients with PD, 20 patients with MSA-P, and 39 controls matched for age, sex, and handedness using an improved T1-weighted sequence that eased gray matter segmentation. The gray matter volumes were measured using ROI and VBM. RESULTS: ROI volumetric measurements showed significantly reduced bilateral putamen volumes in MSA-P patients compared with those in PD patients and controls (p<0.05), and the volumes of the bilateral caudate nucleus were significantly reduced in both MSA-P and PD patients compared with those in the controls (p<0.05). VBM analysis revealed multifocal cortical and subcortical atrophy in both MSA-P and PD patients, and the volumes of the cerebellum and temporal lobes were remarkably reduced in MSA-P patients compared with the volumes in PD patients (p<0.05). CONCLUSIONS: Both PD and MSA-P are associated with gray matter atrophy, which mainly involves the bilateral putamen, caudate nucleus, cerebellum, and temporal lobes. ROI and VBM can be used to identify these morphological alterations, and VBM is more sensitive and repeatable and less time-consuming, which may have potential diagnostic value.


Assuntos
Atrofia/patologia , Substância Cinzenta/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Atrofia de Múltiplos Sistemas/patologia , Doença de Parkinson/classificação , Doença de Parkinson/diagnóstico por imagem , Estudos de Casos e Controles , Feminino , Substância Cinzenta/patologia , Humanos , Masculino , Transtornos Parkinsonianos/patologia , Curva ROC
7.
Am J Cardiol ; 129: 102-108, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32576368

RESUMO

Evidence on the relations between heart rate, brain morphology, and cognition is limited. We examined the associations of resting heart rate (RHR), visit-to-visit heart rate variation (VVHRV), brain volumes and cognitive impairment. The study sample consisted of postmenopausal women enrolled in the Women's Health Initiative Memory Study and its ancillary MRI sub-studies (WHIMS-MRI 1 and WHIMS-MRI 2) without a history of cardiovascular disease, including 493 with one and 299 women with 2 brain magnetic resonance imaging (MRI) scans. HR readings were acquired annually starting from baseline visit (1996-1998). RHR was calculated as the mean and VVHRV as standard deviation of all available HR readings. Brain MRI scans were performed between 2005 and 2006 (WHIMS-MRI 1), and approximately 5 years later (WHIMS-MRI 2). Cognitive impairment was defined as incident mild cognitive impairment or probable dementia until December 30, 2017. An elevated RHR was associated with greater brain lesion volumes at the first MRI exam (7.86 cm3 [6.48, 9.24] vs 4.78 cm3 [3.39, 6.17], p-value <0.0001) and with significant increases in lesion volumes between brain MRI exams (6.20 cm3 [4.81, 7.59] vs 4.28 cm3 [2.84, 5.73], p-value = 0.0168). Larger ischemic lesion volumes were associated with a higher risk for cognitive impairment (Hazard Ratio [95% confidence interval], 2.02 [1.18, 3.47], p-value = 0.0109). Neither RHR nor VVHRV were related to cognitive impairment. In sensitivity analyses, we additionally included women with a history of cardiovascular disease to the study sample. The main results were consistent to those without a history of cardiovascular disease. In conclusion, these findings show an association between elevated RHR and ischemic brain lesions, probably due to underlying subclinical disease processes.


Assuntos
Isquemia Encefálica/epidemiologia , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/epidemiologia , Demência/epidemiologia , Frequência Cardíaca/fisiologia , Idoso , Encéfalo/patologia , Isquemia Encefálica/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Demência/diagnóstico por imagem , Terapia de Reposição de Estrogênios , Feminino , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Humanos , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Tamanho do Órgão , Pós-Menopausa , Modelos de Riscos Proporcionais , Substância Branca/diagnóstico por imagem , Substância Branca/patologia
8.
Braz J Med Biol Res ; 53(6): e9275, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32428131

RESUMO

Evidence from previous voxel-based morphometry (VBM) studies indicates that widespread brain regions are involved in Parkinson's disease with mild cognitive impairment (PD-MCI). However, the spatial localization reported for gray matter (GM) abnormalities is heterogeneous. The aim of the present study was to quantitatively integrate studies on GM abnormalities observed in PD-MCI in order to determine whether a pattern exists. Eligible whole-brain VBM studies were identified by a systematic search of articles in PubMed and EMBASE databases spanning from 1995 to January 1, 2019. A meta-analysis was performed to investigate regional GM abnormalities in PD-MCI. The anisotropic effect size version of seed-based d mapping (AES-SDM) meta-analysis was conducted to explore the GMV differences of PD-MCI compared with PD patients with normal cognitive function (PD-NC). A total of 12 studies comprising 243 PD-MCI patients and 326 PD-NC were included in the meta-analysis. PD-MCI patients showed a robust GM decrease in the left insula and left superior temporal gyrus. Moreover, meta-regression analysis demonstrated that age, PD duration and stage, and Unified Parkinson's Disease Rating Scale III and Mini-Mental State Examination scores might be partly correlated with the GM abnormalities observed in PD-MCI patients. The convergent findings of this quantitative meta-analysis revealed a characteristic neuroanatomical pattern in PD-MCI. The findings provide some evidence that MCI in PD may result in the breakdown of the insula and temporal gyrus, which may serve as specific regions of interest for further investigations.


Assuntos
Disfunção Cognitiva/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Doença de Parkinson/diagnóstico por imagem , Disfunção Cognitiva/fisiopatologia , Feminino , Substância Cinzenta/patologia , Substância Cinzenta/fisiopatologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/fisiopatologia
9.
PLoS One ; 15(5): e0232826, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32379845

RESUMO

This study aimed to investigate abnormalities in the gray matter and white matter (GM and WM, respectively) that are shared between schizophrenia (SZ) and bipolar disorder (BD). We used 3T-magnetic resonance imaging to examine patients with SZ, BD, or healthy control (HC) subjects (aged 20-50 years, N = 65 in each group). We generated modulated GM maps through voxel-based morphometry (VBM) for T1-weighted images and skeletonized fractional anisotropy, mean diffusion, and radial diffusivity maps through tract-based special statistics (TBSS) methods for diffusion tensor imaging (DTI) data. These data were analyzed using a generalized linear model with pairwise comparisons between groups with a family-wise error corrected P < 0.017. The VBM analysis revealed widespread decreases in GM volume in SZ compared to HC, but patients with BD showed GM volume deficits limited to the right thalamus and left insular lobe. The TBSS analysis showed alterations of DTI parameters in widespread WM tracts both in SZ and BD patients compared to HC. The two disorders had WM alterations in the corpus callosum, superior longitudinal fasciculus, internal capsule, external capsule, posterior thalamic radiation, and fornix. However, we observed no differences in GM volume or WM integrity between SZ and BD. The study results suggest that GM volume deficits in the thalamus and insular lobe along with widespread disruptions of WM integrity might be the common neural mechanisms underlying the pathologies of SZ and BD.


Assuntos
Transtorno Bipolar/patologia , Substância Cinzenta/patologia , Esquizofrenia/patologia , Substância Branca/patologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
10.
PLoS One ; 15(5): e0232975, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32392241

RESUMO

Finite element models combined with animal experimental models of spinal cord injury provides the opportunity for investigating the effects of the injury mechanism on the neural tissue deformation and the resulting tissue damage. Thus, we developed a finite element model of the mouse cervical spinal cord in order to investigate the effect of morphological, experimental and mechanical factors on the spinal cord mechanical behavior subjected to transverse contusion. The overall mechanical behavior of the model was validated with experimental data of unilateral cervical contusion in mice. The effects of the spinal cord material properties, diameter and curvature, and of the impactor position and inclination on the strain distribution were investigated in 8 spinal cord anatomical regions of interest for 98 configurations of the model. Pareto analysis revealed that the material properties had a significant effect (p<0.01) for all regions of interest of the spinal cord and was the most influential factor for 7 out of 8 regions. This highlighted the need for comprehensive mechanical characterization of the gray and white matter in order to develop effective models capable of predicting tissue deformation during spinal cord injuries.


Assuntos
Modelos Neurológicos , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia , Animais , Fenômenos Biomecânicos , Simulação por Computador , Modelos Animais de Doenças , Análise de Elementos Finitos , Substância Cinzenta/patologia , Substância Cinzenta/fisiopatologia , Humanos , Imageamento Tridimensional , Camundongos , Traumatismos da Medula Espinal/etiologia , Substância Branca/patologia , Substância Branca/fisiopatologia
11.
BMC Neurol ; 20(1): 185, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32404188

RESUMO

BACKGROUND: To explore the feasibility of the metrics of diffusion kurtosis imaging (DKI) for investigations of the microstructural changes of spinal cord injury in patients with degenerative cervical myelopathy (DCM) and the correlation between Japan Orthopaedic Association (JOA) scores and DKI metrics. METHODS: Fifty-seven patients with DCM and 38 healthy volunteers underwent 3.0 T magnetic resonance (MR) imaging with routine MRI sequences and DKI from echo-planar imaging sequence. Based on the JOA score, DCM patients were divided into four subgroups. DKI metrics of the DCM group and control group were obtained and compared, separately for the white matter (WM) and the gray matter (GM). RESULTS: The FA values in WM were significantly lower (P = 0.020) in the DCM group than in the control group. The MK values in GM were lower (P = 0.011) in the DCM group than in the control group. The MD values in WM were significantly higher (P = 0.010) in the DCM group than in the control group. In GM, the JOA score was positively correlated with the MK values (r = 0.768, P < 0.05). In the WM, the JOA score was positively correlated with the FA values (r = 0.612, P < 0.05). CONCLUSION: DKI provides quantitive evaluation to the characters of microstructure of the spinal cord damage in patients with DCM compared to conventional MR. MK values can reflect microstructural abnormalities of gray matter of the cervical spinal cord and provide more information beyond that obtained with routine diffusion metrics. In addition, MK values of GM and FA values of WM may as a be highly sensitive biomarker for the degree of cervical spinal cord damage.


Assuntos
Medula Cervical/diagnóstico por imagem , Imagem Ecoplanar/métodos , Neuroimagem/métodos , Doenças da Medula Espinal/diagnóstico por imagem , Adulto , Medula Cervical/patologia , Feminino , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Humanos , Japão , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Doenças da Medula Espinal/patologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia
12.
Neurology ; 94(24): e2592-e2604, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32414878

RESUMO

OBJECTIVE: To understand the progressive nature of amyotrophic lateral sclerosis (ALS) by investigating differential brain patterns of gray and white matter involvement in clinically or genetically defined subgroups of patients using cross-sectional, longitudinal, and multimodal MRI. METHODS: We assessed cortical thickness, subcortical volumes, and white matter connectivity from T1-weighted and diffusion-weighted MRI in 292 patients with ALS (follow-up: n = 150) and 156 controls (follow-up: n = 72). Linear mixed-effects models were used to assess changes in structural brain measurements over time in patients compared to controls. RESULTS: Patients with a C9orf72 mutation (n = 24) showed widespread gray and white matter involvement at baseline, and extensive loss of white matter integrity in the connectome over time. In C9orf72-negative patients, we detected cortical thinning of motor and frontotemporal regions, and loss of white matter integrity of connections linked to the motor cortex. Patients with spinal onset displayed widespread white matter involvement at baseline and gray matter atrophy over time, whereas patients with bulbar onset started out with prominent gray matter involvement. Patients with unaffected cognition or behavior displayed predominantly motor system involvement, while widespread cerebral changes, including frontotemporal regions with progressive white matter involvement over time, were associated with impaired behavior or cognition. Progressive loss of gray and white matter integrity typically occurred in patients with shorter disease durations (<13 months), independent of progression rate. CONCLUSIONS: Heterogeneity of phenotype and C9orf72 genotype relates to distinct patterns of cerebral degeneration. We demonstrate that imaging studies have the potential to monitor disease progression and early intervention may be required to limit cerebral degeneration.


Assuntos
Esclerose Amiotrófica Lateral/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Idoso , Esclerose Amiotrófica Lateral/genética , Esclerose Amiotrófica Lateral/patologia , Comportamento , Encéfalo/patologia , Proteína C9orf72/genética , Cognição , Estudos Transversais , Imagem de Difusão por Ressonância Magnética , Progressão da Doença , Feminino , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Humanos , Estudos Longitudinais , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Mutação , Estudos Prospectivos , Substância Branca/diagnóstico por imagem , Substância Branca/patologia
13.
Am J Psychiatry ; 177(9): 844-854, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32375536

RESUMO

OBJECTIVE: The dual-pathway model has been proposed to explain the heterogeneity in symptoms of attention deficit hyperactivity disorder (ADHD) by two independent psychological pathways based on distinct brain circuits. The authors sought to test whether the hypothesized cognitive and motivational pathways have separable neural correlates. METHODS: In a longitudinal community-based cohort of 1,963 adolescents, the neuroanatomical correlates of ADHD were identified by a voxel-wise association analysis and then validated using an independent clinical sample (99 never-medicated patients with ADHD, 56 medicated patients with ADHD, and 267 healthy control subjects). The cognitive and motivational pathways were assessed by neuropsychological tests of working memory, intrasubject variability, stop-signal reaction time, and delay discounting. The associations were tested between the identified neuroanatomical correlates and both ADHD symptoms 2 years later and the polygenic risk score for ADHD. RESULTS: Gray matter volumes of both a prefrontal cluster and a posterior occipital cluster were negatively associated with inattention. Compared with healthy control subjects, never-medicated patients, but not medicated patients, had significantly lower gray matter volumes in these two clusters. Working memory and intrasubject variability were associated with the posterior occipital cluster, and delay discounting was independently associated with both clusters. The baseline gray matter volume of the posterior occipital cluster predicted the inattention symptoms in a 2-year follow-up and was associated with the genetic risk for ADHD. CONCLUSIONS: The dual-pathway model has both shared and separable neuroanatomical correlates, and the shared correlate in the occipital cortex has the potential to serve as an imaging trait marker of ADHD, especially the inattention symptom domain.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Sintomas Comportamentais , Cognição/fisiologia , Técnicas de Rastreamento Neuroanatômico/métodos , Lobo Occipital , Córtex Pré-Frontal , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Sintomas Comportamentais/diagnóstico , Sintomas Comportamentais/fisiopatologia , Ciências Biocomportamentais , Feminino , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Humanos , Estudos Longitudinais , Masculino , Motivação/fisiologia , Neuroimagem/métodos , Testes Neuropsicológicos , Lobo Occipital/diagnóstico por imagem , Lobo Occipital/patologia , Tamanho do Órgão , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/patologia , Medição de Risco/métodos
14.
AJNR Am J Neuroradiol ; 41(5): 804-808, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32381540

RESUMO

BACKGROUND AND PURPOSE: Recent studies showed thalamic atrophy in the early stages of MS. We investigated the impact of intracortical lesions on the volumes of subcortical structures (especially the thalamus) compared with other lesions in MS. MATERIALS AND METHODS: Seventy-one patients with MS were included. The volumes of intracortical lesions and white matter lesions were identified on double inversion recovery and FLAIR, respectively, by using 3D Slicer. Volumes of white matter T1 hypointensities and subcortical gray matter, thalamus, caudate, putamen, and pallidum volumes were calculated using FreeSurfer. Age, MS duration, and the Expanded Disability Status Scale score were assessed. RESULTS: Patients with intracortical lesions were older (P = .003), had longer disease duration (P < .001), and higher Expanded Disability Status Scale scores (P = .02). The presence of intracortical lesions was associated with a significant decrease of subcortical gray matter volume (P = .02). In our multiple regression model, intracortical lesion volume was the only predictor of thalamic volume (R 2 = 0.4, b* = -0.28, P = .03) independent of white matter lesion volume and T1 hypointensity volume. White matter lesion volume showed an impact on subcortical gray matter volume in patients with relapsing-remitting MS (P = .04) and those with disease duration of <5 years (P = .04) and on thalamic volume in patients with Expanded Disability Status Scale scores of <4.0 (P = .01). By contrast, intracortical lesion volume showed an impact on subcortical gray matter and thalamic volumes in the secondary-progressive MS subgroup (P = .02 and P < .001) in patients with a long-standing disease course (P < .001 and P = .001) and more profound disability (P < .001 and P < .001). CONCLUSIONS: Thalamic atrophy was explained better by intracortical lesions than by white matter lesion and T1 hypointensity volumes, especially in patients with more profound disability.


Assuntos
Córtex Cerebral/patologia , Esclerose Múltipla/patologia , Tálamo/patologia , Adulto , Atrofia/diagnóstico por imagem , Atrofia/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Córtex Cerebral/diagnóstico por imagem , Estudos Transversais , Progressão da Doença , Feminino , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico por imagem , Estudos Retrospectivos , Tálamo/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Substância Branca/patologia
15.
Neurobiol Aging ; 91: 112-124, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32224068

RESUMO

Higher levels of body fat have shown adverse effects on multiple aspects of health, including cognitive and neuroanatomical changes. We tested the relationships of body fat levels and cholesterol to longitudinal age trajectories of subcortical gray matter volume (SCV), hippocampal volume (HCV), and episodic memory. Body fat was indexed by a concerted factor of BMI, visceral adipose tissue, percentage body fat, and total fat mass and was included in the analyses as a cross-sectional measure. We hypothesized that higher level of body fat would be related to steeper age trajectories of SCV, HCV, and memory. The sample consisted of 581 participants (20-83 years) with 942 magnetic resonance imaging and 945 memory examinations. Using generalized additive mixed models, a negative effect of body fat was found on SCV, HCV, and memory. Age and body fat interacted in their association with brain volume change. The results suggest that among cognitively healthy adults, there is a negative effect of higher body fat on SCV, HCV, and memory decline, an effect that increased with age for the neuroanatomical volumes.


Assuntos
Tecido Adiposo/metabolismo , Envelhecimento/metabolismo , Envelhecimento/patologia , Índice de Massa Corporal , Hipocampo/patologia , Transtornos da Memória/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Atrofia , Estudos Transversais , Feminino , Substância Cinzenta/patologia , Humanos , Masculino , Memória Episódica , Pessoa de Meia-Idade , Tamanho do Órgão , Adulto Jovem
16.
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
17.
Psychiatry Res Neuroimaging ; 300: 111067, 2020 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-32298949

RESUMO

We aimed to study the correlations between gray matter volume and the motor subscores of NSS in first-episode psychosis patients with both, whole brain and region of interest analyses. The structural MRIs of 81 first-episode psychosis patients were analyzed by using voxel-based morphometry (VBM) for SPM. NSS were assessed using the Heidelberg scale. Significant decreases of gray matter volume were correlated to high NSS total scores and, more specifically, frontal, subcortical and cerebellar areas were significantly correlated with increased scores of the subscores Motor Coordination (MoCo) and Complex Motor Tasks (CMT). When applying a stricter statistical correction, only the frontal gyrus and caudate nucleus survived for MoCo; whereas the precentral and superior frontal gyri survived for CMT. When doing regional analyses, using as masks the structures deemed as significant by the whole brain analyses and applying the FWE-correction, the superior frontal gyrus, thalamus and caudate nucleus correlated negatively with MoCo; and the precentral and superior frontal gyri, thalamus and caudate nucleus showed inverse correlations with CMT. These results suggest that cerebral cortex, subcortical structures (thalamus and striatum) and cerebellum are inversely correlated to both motor NSS subscores, the first time a study describes this relationship for all the relevant structures simultaneously. For its part, ROI proves to be effective demonstrating that subcortical structures (thalamus and caudate) are the most affected by motor NSS.


Assuntos
Substância Cinzenta/patologia , Imagem por Ressonância Magnética , Transtornos Psicóticos/patologia , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Masculino , Córtex Motor/diagnóstico por imagem , Córtex Motor/patologia , Destreza Motora , Tamanho do Órgão , Transtornos Psicóticos/diagnóstico por imagem
18.
Brain ; 143(3): 993-1009, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32203580

RESUMO

Alzheimer's disease neurodegeneration is thought to spread across anatomically and functionally connected brain regions. However, the precise sequence of spread remains ambiguous. The prevailing model used to guide in vivo human neuroimaging and non-human animal research assumes that Alzheimer's degeneration starts in the entorhinal cortices, before spreading to the temporoparietal cortex. Challenging this model, we previously provided evidence that in vivo markers of neurodegeneration within the nucleus basalis of Meynert (NbM), a subregion of the basal forebrain heavily populated by cortically projecting cholinergic neurons, precedes and predicts entorhinal degeneration. There have been few systematic attempts at directly comparing staging models using in vivo longitudinal biomarker data, and none to our knowledge testing if comparative evidence generalizes across independent samples. Here we addressed the sequence of pathological staging in Alzheimer's disease using two independent samples of the Alzheimer's Disease Neuroimaging Initiative (n1 = 284; n2 = 553) with harmonized CSF assays of amyloid-ß and hyperphosphorylated tau (pTau), and longitudinal structural MRI data over 2 years. We derived measures of grey matter degeneration in a priori NbM and the entorhinal cortical regions of interest. To examine the spreading of degeneration, we used a predictive modelling strategy that tests whether baseline grey matter volume in a seed region accounts for longitudinal change in a target region. We demonstrated that predictive spread favoured the NbM→entorhinal over the entorhinal→NbM model. This evidence generalized across the independent samples. We also showed that CSF concentrations of pTau/amyloid-ß moderated the observed predictive relationship, consistent with evidence in rodent models of an underlying trans-synaptic mechanism of pathophysiological spread. The moderating effect of CSF was robust to additional factors, including clinical diagnosis. We then applied our predictive modelling strategy to an exploratory whole-brain voxel-wise analysis to examine the spatial specificity of the NbM→entorhinal model. We found that smaller baseline NbM volumes predicted greater degeneration in localized regions of the entorhinal and perirhinal cortices. By contrast, smaller baseline entorhinal volumes predicted degeneration in the medial temporal cortex, recapitulating a prior influential staging model. Our findings suggest that degeneration of the basal forebrain cholinergic projection system is a robust and reliable upstream event of entorhinal and neocortical degeneration, calling into question a prevailing view of Alzheimer's disease pathogenesis.


Assuntos
Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Prosencéfalo Basal/patologia , Progressão da Doença , Degeneração Neural/patologia , Proteínas tau/líquido cefalorraquidiano , Idoso , Doença de Alzheimer/líquido cefalorraquidiano , Núcleo Basal de Meynert/patologia , Biomarcadores , Bases de Dados Factuais , Córtex Entorrinal/patologia , Feminino , Substância Cinzenta/patologia , Humanos , Estudos Longitudinais , Imagem por Ressonância Magnética , Masculino , Neuroimagem , Fosforilação
19.
Nat Med ; 26(3): 387-397, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32123386

RESUMO

With the potential development of new disease-modifying Alzheimer's disease (AD) therapies, simple, widely available screening tests are needed to identify which individuals, who are experiencing symptoms of cognitive or behavioral decline, should be further evaluated for initiation of treatment. A blood-based test for AD would be a less invasive and less expensive screening tool than the currently approved cerebrospinal fluid or amyloid ß positron emission tomography (PET) diagnostic tests. We examined whether plasma tau phosphorylated at residue 181 (pTau181) could differentiate between clinically diagnosed or autopsy-confirmed AD and frontotemporal lobar degeneration. Plasma pTau181 concentrations were increased by 3.5-fold in AD compared to controls and differentiated AD from both clinically diagnosed (receiver operating characteristic area under the curve of 0.894) and autopsy-confirmed frontotemporal lobar degeneration (area under the curve of 0.878). Plasma pTau181 identified individuals who were amyloid ß-PET-positive regardless of clinical diagnosis and correlated with cortical tau protein deposition measured by 18F-flortaucipir PET. Plasma pTau181 may be useful to screen for tau pathology associated with AD.


Assuntos
Doença de Alzheimer/sangue , Doença de Alzheimer/diagnóstico , Degeneração Lobar Frontotemporal/sangue , Degeneração Lobar Frontotemporal/diagnóstico , Proteínas tau/sangue , Idoso , Doença de Alzheimer/líquido cefalorraquidiano , Amiloide/metabolismo , Peptídeos beta-Amiloides/sangue , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Cognição , Feminino , Degeneração Lobar Frontotemporal/genética , Degeneração Lobar Frontotemporal/patologia , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Proteínas de Neurofilamentos/sangue , Fosforilação , Tomografia por Emissão de Pósitrons , Índice de Gravidade de Doença , Proteínas tau/líquido cefalorraquidiano , Proteínas tau/genética
20.
Neurology ; 94(16): e1716-e1725, 2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32209649

RESUMO

OBJECTIVE: To test the hypothesis that neuroinflammation is a key process in adult Niemann-Pick type C (NPC) disease, we undertook PET scanning utilizing a ligand binding activated microglia on 9 patients and 9 age- and sex-matched controls. METHOD: We scanned all participants with the PET radioligand 11C-(R)-PK-11195 and undertook structural MRI to measure gray matter volume and white matter fractional anisotropy (FA). RESULTS: We found increased binding of 11C-(R)-PK-11195 in total white matter compared to controls (p < 0.01), but not in gray matter regions, and this did not correlate with illness severity or duration. Gray matter was reduced in the thalamus (p < 0.0001) in patients, who also showed widespread reductions in FA across the brain compared to controls (p < 0.001). A significant correlation between 11C-(R)-PK11195 binding and FA was shown (p = 0.002), driven by the NPC patient group. CONCLUSIONS: Our findings suggest that neuroinflammation-particularly in white matter-may underpin some structural and degenerative changes in patients with NPC.


Assuntos
Encéfalo/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Inflamação/diagnóstico por imagem , Doença de Niemann-Pick Tipo C/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Adulto , Anisotropia , Encéfalo/metabolismo , Estudos de Casos e Controles , Estudos Transversais , Feminino , Substância Cinzenta/metabolismo , Substância Cinzenta/patologia , Humanos , Inflamação/metabolismo , Isoquinolinas , Imagem por Ressonância Magnética , Masculino , Doença de Niemann-Pick Tipo C/metabolismo , Tamanho do Órgão , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Substância Branca/metabolismo , Adulto Jovem
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