Abnormal Brain Connectivity Patterns in Adults with ADHD: A Coherence Study

Studies based on functional magnetic resonance imaging (fMRI) during the resting state have shown decreased functional connectivity between the dorsal anterior cingulate cortex (dACC) and regions of the Default Mode Network (DMN) in adult patients with Attention-Deficit/Hyperactivity Disorder (ADHD) relative to subjects with typical development (TD). Most studies used Pearson correlation coefficients among the BOLD signals from different brain regions to quantify functional connectivity. Since the Pearson correlation analysis only provides a limited description of functional connectivity, we investigated functional connectivity between the dACC and the posterior cingulate cortex (PCC) in three groups (adult patients with ADHD, n = 21; TD age-matched subjects, n = 21; young TD subjects, n = 21) using a more comprehensive analytical approach - unsupervised machine learning using a one-class support vector machine (OC-SVM) that quantifies an abnormality index for each individual. the median abnormality index for patients with ADHD was greater than for TD age-matched subjects (p = 0.014); the ADHD and young TD indices did not differ significantly (p = 0.480); the median abnormality index of young TD was greater than that of TD age-matched subjects (p = 0.016). Low frequencies below 0.05 Hz and around 0.20 Hz were the most relevant for discriminating between ADHD patients and TD age-matched controls and between the older and younger TD subjects. in addition, we validated our approach using the fMRI data of children publicly released by the ADHD-200 Competition, obtaining similar results. Our findings suggest that the abnormal coherence patterns observed in patients with ADHD in this study resemble the patterns observed in young typically developing subjects, which reinforces the hypothesis that ADHD is associated with brain maturation deficits.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)National Institute of Mental HealthNovartisJanssen-CilagAbbottEli-LillyShireBristol-Myers SquibbUniv Fed ABC, Ctr Math Computat & Cognit, Santo Andre, BrazilUniversidade Federal de São Paulo, Lab Interdisciplinar Neurociencias Clin, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychiat, São Paulo, BrazilHosp Clin Porto Alegre, Child & Adolescent Psychiat Div, ADHD Outpatient Program, Porto Alegre, RS, BrazilNYU, Ctr Child Study, Phyllis Green & Randolph Cowen Inst Pediat Neuros, New York, NY USAInst Nacl Psiquiatria Desenvolvimento, Porto Alegre, RS, BrazilUniversidade Federal de São Paulo, Lab Interdisciplinar Neurociencias Clin, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychiat, São Paulo, BrazilNational Institute of Mental Health: R01MH083246Web of Scienc

Abnormal brain connectivity patterns in adults with ADHD : a coherence study

Studies based on functional magnetic resonance imaging (fMRI) during the resting state have shown decreased functional connectivity between the dorsal anterior cingulate cortex (dACC) and regions of the Default Mode Network (DMN) in adult patients with Attention-Deficit/Hyperactivity Disorder (ADHD) relative to subjects with typical development (TD). Most studies used Pearson correlation coefficients among the BOLD signals from different brain regions to quantify functional connectivity. Since the Pearson correlation analysis only provides a limited description of functional connectivity, we investigated functional connectivity between the dACC and the posterior cingulate cortex (PCC) in three groups (adult patients with ADHD, n = 21; TD age-matched subjects, n = 21; young TD subjects, n = 21) using a more comprehensive analytical approach – unsupervised machine learning using a one-class support vector machine (OC-SVM) that quantifies an abnormality index for each individual. The median abnormality index for patients with ADHD was greater than for TD agematched subjects (p = 0.014); the ADHD and young TD indices did not differ significantly (p = 0.480); the median abnormality index of young TD was greater than that of TD age-matched subjects (p = 0.016). Low frequencies below 0.05 Hz and around 0.20 Hz were the most relevant for discriminating between ADHD patients and TD age-matched controls and between the older and younger TD subjects. In addition, we validated our approach using the fMRI data of children publicly released by the ADHD-200 Competition, obtaining similar results. Our findings suggest that the abnormal coherence patterns observed in patients with ADHD in this study resemble the patterns observed in young typically developing subjects, which reinforces the hypothesis that ADHD is associated with brain maturation deficits

Podem as técnicas de imagem molecular identificar biomarcadores nos distúrbios neuropsiquiátricos?

Universidade Federal de São Paulo (UNIFESP) Laboratório Interdisciplinar de Neurociências ClínicasInstituto Israelita de Ensino e Pesquisa Albert EinsteinSINAPSE InstituteUNIFESP, Laboratório Interdisciplinar de Neurociências ClínicasSciEL

Measuring network's entropy in ADHD: A new approach to investigate neuropsychiatric disorders

The application of graph analysis methods to the topological organization of brain connectivity has been a useful tool in the characterization of brain related disorders. However, the availability of tools, which enable researchers to investigate functional brain networks, is still a major challenge. Most of the studies evaluating brain images are based on centrality and segregation measurements of complex networks. in this study, we applied the concept of graph spectral entropy (GSE) to quantify the complexity in the organization of brain networks. in addition, to enhance interpretability, we also combined graph spectral clustering to investigate the topological organization of sub-network's modules. We illustrate the usefulness of the proposed approach by comparing brain networks between attention deficit hyperactivity disorder (ADHD) patients and the brain networks of typical developing (TD) controls. the main findings highlighted that GSE involving sub-networks comprising the areas mostly bilateral pre and post central cortex, superior temporal gyrus, and inferior frontal gyri were statistically different (p-value = 0.002) between ADHD patients and TO controls. in the same conditions, the other conventional graph descriptors (betweenness centrality, clustering coefficient, and shortest path length) commonly used to identify connectivity abnormalities did not show statistical significant difference. We conclude that analysis of topological organization of brain sub-networks based on GSE can identify networks between brain regions previously unobserved to be in association with ADHD. (C) 2013 Elsevier Inc. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Pew Latin American FellowshipFed Univ ABC, Ctr Math Computat & Cognit, BR-09210170 Santo Andre, SP, BrazilPrinceton Univ, Dept Psychol, Princeton, NJ 08540 USAPrinceton Univ, Neurosci Inst, Princeton, NJ 08540 USAUniversidade Federal de São Paulo, Dept Psychiat, Lab Interdisciplinar Neurociencias Clin, São Paulo, BrazilUniv Estadual Campinas, Ctr Mol Biol & Genet Engn, BR-13083875 Campinas, SP, BrazilUniv São Paulo, Dept Comp Sci, Inst Math & Stat, BR-05508090 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychiat, Lab Interdisciplinar Neurociencias Clin, São Paulo, BrazilWeb of Scienc

Frontal-subcortical behaviors during Alzheimer's disease in individuals with Down syndrome.

There is evidence that frontal-subcortical circuits play an important role in the initial presentation of dementia in Down syndrome (DS), including changes in behavior, a decline in working memory and executive dysfunction. We evaluated 92 individuals with DS (≥30 years of age), divided into 3 groups by diagnosis-stable cognition, prodromal dementia, and Alzheimer's disease. Each individual was evaluated with an executive protocol developed for people with intellectual disabilities and was rated for behaviors related to frontal lobe dysfunction (disinhibition, executive dysfunction, and apathy) by an informant using the Frontal Systems Behavior Scale. Informant-reported behaviors related to frontal lobe dysfunction were found to correlate negatively with executive function performance. Disinhibition and executive dysfunction were associated with the clinical stage of dementia. The odds of having Alzheimer's disease increased in parallel with increases in the domain and total Frontal Systems Behavior Scale scores (p ≤ 0.5). Disinhibition, executive dysfunction and apathy should be taken into consideration during the clinical evaluation of adults with DS, and future studies should consider the intersection of neuropathology, brain connectivity, and behavior

Gray Matter Volumes in Obsessive-Compulsive Disorder Before and After Fluoxetine or Cognitive-Behavior Therapy: A Randomized Clinical Trial

Serotonin reuptake inhibitors and cognitive-behavior therapy (CBT) are considered first-line treatments for obsessive-compulsive disorder (OCD). However, little is known about their modulatory effects on regional brain morphology in OCD patients. We sought to document structural brain abnormalities in treatment-naive OCD patients and to determine the effects of pharmacological and cognitive-behavioral treatments on regional brain volumes. Treatment-naive patients with OCD (n = 38) underwent structural magnetic resonance imaging scan before and after a 12-week randomized clinical trial with either fluoxetine or group CBT. Matched-healthy controls (n = 36) were also scanned at baseline. Voxel-based morphometry was used to compare regional gray matter (GM) volumes of regions of interest (ROIs) placed in the orbitofrontal, anterior cingulate and temporolimbic cortices, striatum, and thalamus. Treatment-naive OCD patients presented smaller GM volume in the left putamen, bilateral medial orbitofrontal, and left anterior cingulate cortices than did controls (p<0.05, corrected for multiple comparisons). After treatment with either fluoxetine or CBT (n = 26), GM volume abnormalities in the left putamen were no longer detectable relative to controls. ROI-based within-group comparisons revealed that GM volume in the left putamen significantly increased (p<0.012) in fluoxetine-treated patients (n = 13), whereas no significant GM volume changes were observed in CBT-treated patients (n = 13). This study supports the involvement of orbitofronto/cingulo-striatal loops in the pathophysiology of OCD and suggests that fluoxetine and CBT may have distinct neurobiological mechanisms of action. Neuropsychopharmacology (2012) 37, 734-745; doi: 10.1038/npp.2011.250; published online 26 October 2011Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)MedtronicEli LillyMcNeilCyberonicsNIMHNARSADTSAOCFTufts UniversityMGH Psychiatry AcademyBrainCellsSystems Research and Applications CorporationBoston UniversityCatalan Agency for Health Technology Assessment and ResearchNational Association of Social Workers MassachusettsMassachusetts Medical SocietyNIDAGerman Research Foundation/Federal Ministry for Education and ResearchOxford University PressNIHNIAAHRQJanssen PharmaceuticalsForest Research InstituteShire DevelopmentNorthstarJanssenAstraZenecaLundbeckSolvayUniv São Paulo, Sch Med, Dept Psychiat, São Paulo, BrazilUniv São Paulo, Sch Med, Inst Psychiat, São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Psychiat, Interdisciplinary Lab Clin Neurosci LiNC, São Paulo, BrazilHarvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USAUniversidade Federal de São Paulo UNIFESP, Dept Psychiat, Interdisciplinary Lab Clin Neurosci LiNC, São Paulo, BrazilFAPESP: 2005/55628-8FAPESP: 06/61459-7FAPESP: 06/50273-0FAPESP: 2008/10257-0FAPESP: 06/58286-3FAPESP: 2005/04206-6CAPES: 4375/08-4Web of Scienc

Características clínicas e de neuroimagem molecular de pacientes brasileiros com doença de Parkinson e mutações nos genes PARK2 ou PARK8

OBJECTIVE: To describe clinical and neuroimaging (SPECT) characteristics of Brazilian patients with Parkinson's disease (PD) and mutations in PARK2 or PARK8 genes. METHOD: A total of 119 patients meeting clinical criteria for PD were evaluated. RESULTS: Of all patients studied, 13 had mutations in either PARK2 (n=9) or PARK8 genes (n=4). No statistically significant differences in clinical characteristics in both groups were seen. SPECT with [99mTc] TRODAT-1 showed significant differences between patient and control and the most remarkable difference was between PARK2 and control. CONCLUSION: The study found a frequency of mutation of 10.1% and it was most commonly seen in women. These patients had long disease course and high rates of dyskinesia after L-DOPA use. PARK8 patients did not have a relevant family history of PD.OBJETIVO: Descrever as características clínicas e de neuroimagem (SPECT) de pacientes brasileiros com doença de Parkinson e mutações PARK2 e PARK8. MÉTODO: Foram avaliados 119 pacientes com critérios clínicos para a doença de Parkinson. RESULTADO: Entre os pacientes avaliados foram encontrados 13 pacientes com mutação nos genes PARK2 (n=9) ou PARK8 (n=4). Não houve diferença significativa na avaliação das características clínicas entre os dois grupos. Os resultados de SPECT mostraram diferenças significativas quanto ao potencial de ligação do [99mTc] TRODAT-1 SPECT entre pacientes vs. controle, sendo a diferença mais pronunciada entre PARK2 e controle. CONCLUSÃO: A freqüência de mutação encontrada foi 10,1%, sendo mais comum em mulheres. Estes pacientes apresentavam longo tempo de doença e alta prevalência de discinesias associadas ao uso da levodopa. Nossos pacientes com PARK8 não apresentaram uma história familiar relevante de doença de Parkinson.Hospital Israelita Albert Einstein Instituto Israelita de Ensino e PesquisaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Division of Movement DisordersUNIFESP-EPM Laboratório Interdisciplinar de Neurociências ClínicasUNIFESP, EPM, Division of Movement DisordersUNIFESP, EPM Laboratório Interdisciplinar de Neurociências ClínicasSciEL

Neuroimaging of the dopamine transporter in Parkinson s disease: first study using [99mTc]-TRODAT-1 and SPECT in Brazil

BACKGROUND: Dopamine transporter (DAT) neuroimaging radiotracers were developed to estimate dopamine neuronal loss in vivo in Parkinson s disease (PD). OBJECTIVE: To evaluate DAT density in vivo using [99mTc]-TRODAT-1 and single photon computerized tomography (SPECT) in a population of Brazilian PD. METHOD: Fifteen PD patients and 15 matched healthy controls scanned with [99mTc]-TRODAT-1 (INER-Taiwan) and SPECT. Estimates of striatum DAT density were calculated using binding potential (BP). Patients were assessed with PD scales. RESULTS: PD patients had significantly lower striatal DAT-BP (mean±SD) (0.38±0.12) compared to controls (BP=0.84±0.16; p<0.01). A 100% sensitivity and 100% specificity was obtained to discriminate PD cases from controls. Negative correlations between striatal DAT-BP and PD severity (rho= -0.7, p<0.001) and motor scales (rho= -0.80, p<0.001) were found. CONCLUSION: [99mTc]TRODAT-1 SPECTs scanning was able to discriminate PD patients from controls. The technique is a powerful instrument to measure DAT density that can be used in clinical and research settings in Brazil.INTRODUÇÃO: Radiotraçadores para neuroimagem de transportador de dopamina (TDA) foram desenvolvidos para estimar a perda de neurônios dopaminérgicos in vivo na doença de Parkinson (DP). OBJETIVO: Avaliar a densidade de TDA in vivo utilizando [99mTc]-TRODAT-1 (INER-Taiwan) e SPECT em uma população de pacientes brasileiros com DP. MÉTODO: Quinze pacientes com DP e 15 controles saudáveis pareados realizaram exames de SPECT com [99mTc]-TRODAT-1 (INER-Taiwan). Estimativas da densidade de TDA estriatal foram calculadas usando potencial de ligação (PL). Pacientes foram avaliados com escalas para PD. RESULTADOS: Pacientes com DP apresentaram redução significativa do PL-TDA (0,38±0,12) comparado aos controles (0,84±0,16, p<0,01). Foi possível discriminar casos de DP de controles com uma sensibilidade de 100% e especificidade de 100%. Foram obtidas correlações negativas entre PL-TDA e escalas de severidade da DP (rho= -0,7, p<0,001) e disfunção motora (rho= -0,8, p<0,001). CONCLUSÃO: Exames de SPECT com [99mTc]-TRODAT-1 foram capazes de discriminar pacientes com DP de controles. Esta técnica é um instrumento útil para medir a densidade de TDA e pode ser utilizado para clínica e pesquisa no Brasil.Universidade Federal de São Paulo (UNIFESP) Laboratório Interdiciplinar de Neuroimagem e CogniçãoHIAE Instituto Israelita de Ensino e Pesquisa Albert EinsteinHospital Israelita Albert Einstein Departamento de ImagemInstitute of Nuclear Energy Research TaiwanUNIFESP Departamento de NeurologiaUNIFESP Departamento de PsicobiologiaUNIFESP Departamento de PsiquiatriaUNIFESP, Laboratório Interdiciplinar de Neuroimagem e CogniçãoUNIFESP, Depto. de NeurologiaUNIFESP, Depto. de PsicobiologiaUNIFESP, Depto. de PsiquiatriaSciEL