Regional brain atrophy is related to social cognition impairment in multiple sclerosis / La atrofia cerebral regional se relaciona con el deterioro de la cognición social en sclerosis múltiple

ABSTRACT Background: Multiple sclerosis exhibits specific neuropathological phenomena driving to both global and regional brain atrophy. At the clinical level, the disease is related to functional decline in cognitive domains as the working memory, processing speed, and verbal fluency. However, the compromise of social-cognitive abilities has concentrated some interest in recent years despite the available evidence suggesting the risk of disorganization in social life. Recent studies have used the MiniSEA test to assess the compromise of social cognition and have found relevant relationships with memory and executive functions, as well as with the level of global and regional brain atrophy. Objective: The present article aimed to identify structural changes related to socio-cognitive performance in a sample of patients with relapsing-remitting multiple sclerosis. Methods: 68 relapsing-remitting multiple sclerosis Chilean patients and 50 healthy control subjects underwent MRI scans and neuropsychological evaluation including social-cognition tasks. Total brain, white matter, and gray matter volumes were estimated. Also, voxel-based morphometry was applied to evaluate regional structural changes. Results: Patients exhibited lower scores in all neuropsychological tests. Social cognition exhibited a significant decrease in this group mostly related to the declining social perception. Normalized brain volume and white matter volume were significantly decreased when compared to healthy subjects. The regional brain atrophy analysis showed that changes in the insular cortex and medial frontal cortices are significantly related to the variability of social-cognitive performance among patients. Conclusions: In the present study, social cognition was only correlated with the deterioration of verbal fluency, despite the fact that previous studies have reported its link with memory and executive functions. The identification of specific structural correlates supports the comprehension of this phenomenon as an independent source of cognitive disability in these patients.

RESUMEN Antecedentes: La esclerosis múltiple presenta fenómenos neuropatológicos específicos que conducen a la atrofia cerebral global y regional. A nivel clínico, la enfermedad está relacionada con el deterioro funcional de los dominios cognitivos como la memoria de trabajo, la velocidad de procesamiento y la fluidez verbal. Sin embargo, el compromiso de las habilidades socio-cognitivas ha concentrado cierto interés en los últimos años debido a la evidencia disponible que sugiere el riesgo de desorganización en la vida social. Estudios recientes han utilizado la prueba MiniSEA para evaluar el compromiso de la cognición social y han encontrado relaciones relevantes con la memoria y funciones ejecutiva, así como con el nivel de atrofia cerebral global y regional. Objetivo: El presente artículo tiene como objetivo identificar cambios estructurales relacionados con el rendimiento sociocognitivo en una muestra de pacientes con esclerosis múltiple recurrente-remitente. Métodos: 68 pacientes Chilenos con esclerosis múltiple recurrente-remitente y 50 sujetos de control sanos se sometieron a resonancias magnéticas y evaluación neuropsicológica, incluidas las tareas de cognición social. Se estimaron los volúmenes cerebrales totales, de materia blanca y materia gris. Además, se aplicó la morfometría basada en vóxel para evaluar los cambios estructurales regionales. Resultados: Los pacientes muestran puntuaciones más bajas en todas las pruebas neuropsicológicas. La cognición social exhibe una disminución significativa en este grupo principalmente relacionada con la disminución de la percepción social. El volumen normalizado del cerebro y el volumen de la materia blanca disminuyeron significativamente en comparación con los sujetos sanos. El análisis regional de atrofia cerebral mostró que los cambios en la corteza insular y la corteza frontal medial están significativamente relacionados con la variabilidad del rendimiento sociocognitivo entre los pacientes. Conclusiones: En el presente estudio, la cognición social sólo se correlacionó con el deterioro de la fluencia verbal, a pesar de que estudios previos han reportado su vinculación con la memoria y funciones ejecutivas. La identificación de correlatos estructurales específicos apoya la comprensión de este fenómeno como una fuente independiente de discapacidad cognitiva en estos pacientes.

Differences in total brain volume between sexes in a cognitively unimpaired elderly population

OBJECTIVES: Although a large number of studies have shown brain volumetric differences between men and women, only a few investigations have analyzed brain tissue volumes in representative samples of the general elderly population. We investigated differences in gray matter (GM) volumes, white matter (WM) volumes, and intracranial volumes (ICVs) between the sexes in individuals older than 66 years using structural magnetic resonance imaging (MRI). METHODS: Using FreeSurfer version 5.3, we obtained the ICVs and GM and WM volumes from the MRI datasets of 84 men and 92 women. To correct for interindividual variations in ICV, GM and WM volumes were adjusted with a method using the residuals of a least-square-derived linear regression between raw volumes and ICVs. We then performed an analysis of covariance comparing men and women, including age and years of schooling as confounding factors. RESULTS: Women had a lower socioeconomic status overall and fewer years of schooling than men. The comparison of unadjusted brain volumes showed larger GM and WM volumes in men. After the ICV correction, the adjusted volumes of GM and WM were larger in women. CONCLUSION: After the ICV correction and taking into account differences in socioeconomic status and years of schooling, our results confirm previous findings of proportionally larger GM in women, as well as larger WM volumes. These results in an elderly population indicate that brain volumetric differences between sexes persist throughout the aging process. Additional studies combining MRI and other biomarkers to identify the hormonal and molecular bases influencing such differences are warranted.

Gray matter atrophy in parkinsons disease and the parkinsonian variant of multiple system atrophy: a combined roi- and voxel-based morphometric study

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.

Voxel-wise meta-analysis of structural changes in gray matter of Parkinsons disease patients with mild cognitive impairment

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.

White matter volume is decreased in bipolar disorder at early and late stages / O volume da substância branca está reduzido tanto nos estágios iniciais quanto nos estágios avançados do transtorno bipolar

Abstract Introduction: Bipolar disorder (BD) is a debilitating mood condition that affects approximately 1.3% of people worldwide, although some studies report up to 3.9% lifetime prevalence and 4-6% in adults when broad diagnostic criteria are applied. Objective: To compare differences in total white matter (WM), corpus callosum (CC) and total gray matter (GM) volumes in patients with type I BD at early and late stages compared with controls. Methods: Fifty-five subjects were enrolled in this study protocol. The double case-control design included 14 patients with BD at early stage; 15 patients at late stage; and their respective matched controls (14 and 12 subjects). Results: CC and total WM volumes were significantly smaller in patients with BD at early and late stages vs. controls. There was no difference for total GM volume in the early stage group, but in patients at late stage total GM volume was significantly smaller than in controls. The total GM volume reduction in patients at late stage is in agreement with the neuroprogression theory of BD. The reduction of WM volumes in total WM and in the CC at early and late stages supports the possibility that an early demyelination process could occur underlying the clinical manifestation of BD. Conclusion: Our findings may direct to the investigation of WM abnormalities in populations at high risk to develop BD, perhaps as early biomarkers before the overt syndrome.

Resumo Introdução: O transtorno do humor bipolar (THB) é uma condição debilitante que afeta aproximadamente 1,3% das pessoas em todo o mundo, embora alguns estudos relatem uma prevalência acumulada de até 3,9% e de 4-6% em adultos quando os critérios diagnósticos mais abrangentes são aplicados. Objetivo: Comparar as diferenças nos volumes totais de substância branca (SB), corpo caloso (CC) e volume total de substância cinzenta (SC) em pacientes com THB tipo I em estágios iniciais e tardios em comparação com controles. Métodos: Cinquenta e cinco sujeitos foram incluídos neste protocolo de estudo. O desenho de caso com duplo controle incluiu 14 pacientes com THB em estágio inicial; 15 pacientes com THB em fase tardia; e seus respectivos controles correspondentes (14 e 12 sujeitos). Resultados: Os volumes do CC e total de SB foram significativamente menores nos pacientes com THB nos estágios iniciais e tardios vs. controles. Não houve diferença para o volume total de SC no grupo em estágio inicial, mas em pacientes em fase tardia o volume total de SC foi significativamente menor do que nos controles. A redução do volume total de SC em pacientes em fase tardia está de acordo com a teoria da neuroprogressão do THB. A redução dos volumes de SB em SB total e no CC em fases precoces e tardias suporta a possibilidade de que um processo de desmielinização precoce poderia ocorrer subjacente à manifestação clínica de THB. Conclusão: Nossos achados podem direcionar a investigação de anormalidades da SB em populações de alto risco para o desenvolvimento de THB, talvez como biomarcadores precoces antes da síndrome aberta.

Neural correlates of hallucinations in bipolar disorder

Objective: Approximately one-half of all patients affected by bipolar disorder present with psychotic features on at least one occasion. Several studies have found that alterations in the activity of mesolimbic and prefrontal regions are related to aberrant salience in psychotic patients. The aim of the present study was to investigate the structural correlates of a history of hallucinations in a sample of euthymic patients with bipolar I disorder (BD-I). Methods: The sample consisted of 21 euthymic patients with BD-I and no comorbid axis I DSM-IV-TR disorders. Voxel based morphometry (VBM) was used to compare patients with and without a lifetime history of hallucinations. Preprocessing was performed using the Diffeomorphic Anatomical Registration through Exponentiated Lie Algebra (DARTEL) algorithm for VBM in SPM8. Images were processed using optimized VBM. Results: The main finding of the present study was a reduction in gray matter volume in the right posterior insular cortex of patients with BD-I and a lifetime history of hallucinations, as compared to subjects with the same diagnosis but no history of hallucinations. Conclusions: This finding supports the presence of abnormalities in the salience network in BD patients with a lifetime history of hallucinations. These alterations may be associated with an aberrant assignment of salience to the elements of one’s own experience, which could result in psychotic symptoms.