Relación entre las alteraciones estructurales y el deterioro cognitivo en pacientes con Esclerosis Múltiple

Setzenes Jornades de Foment de la Investigació (Any 2011)Las causas del deterioro cognitivo en los pacientes de Esclerosis Múltiple (EM) son todavía desconocidas, así como la relación entre dicho deterioro y el daño cerebral observado con distintas técnicas de adquisición y análisis de neuroimagen. Objetivos Observar la distribución de la atrofia en sustancia gris y blanca en pacientes de EM con Deterioro Cognitivo (DC) y Sin Deterioro Cognitivo (SDC), así como su relación con variables clínicas y cognitivas Pacientes y métodos Se reclutaron para el estudio a 22 participantes control (edad= 32,22 +6,24) y a 75 pacientes diagnosticados de EM (edad= 40,06 +10,01). Todos los participantes fueron valorados con la Batería Neuropsicológica Breve (BNB) especifica para valorar deterioro cognitivo en EM. Los pacientes fueron seleccionados en dos grupos: 1) DC: los que presentaban al menos 1 test de la batería por debajo de 2 DT (n=41); 2) SDC: rendimiento normal en pruebas neuropsicológicas (n=34). Posteriormente se adquirieron los datos morfométricos de todos los participantes en una Resonancia Magnética Siemens Avanto 1.5 T. Se obtuvieron parámetros de volumen en sustancia blanca y gris utilizando el programa de análisis Diffeomorphic Anatomical Registrations Through Exponentiated Lie Algebra (DARTEL). Resultados Los pacientes con DC muestran un menor rendimiento cognitivo en todas las pruebas neuropsicológicas. Estos pacientes también muestran más atrofia en distintas zonas corticales y subcorticales tanto en sustancia blanca como en sustancia gris respecto al grupo control y respecto al grupo de pacientes SDC. Finalmente, se observa una relación entre el rendimiento neuropsicológico en distintas pruebas cognitivas y la atrofia en sustancia gris en el grupo de pacientes con DC. Conclusiones: Se observa en pacientes de EM con DC un mayor grado de atrofia así como una consistente relación entre la atrofia en sustancia gris y rendimiento en pruebas neuropsicológicas

Effects of different intracranial volume correction methods on univariate sex differences in grey matter volume and multivariate sex prediction

Sex differences in 116 local gray matter volumes (GMVOL) were assessed in 444 males and 444 females without correcting for total intracranial volume (TIV) or after adjusting the data with the scaling, proportions, power‑corrected proportions (PCP), and residuals methods. The results confirmed that only the residuals and PCP methods completely eliminate TIV‑variation and result in sex‑differences that are “small” (∣d∣ 80%) when using raw local GMVOL, but also when using scaling or proportions adjusted‑data or TIV as a single predictor. Conversely, after properly controlling TIV variation with the PCP and residuals’ methods, prediction accuracy dropped to ≈ 60%. It is concluded that gross morphological differences account for most of the univariate and multivariate sex differences in GMVO

Cambios estructurales y funcionales del hipocampo en pacientes con esclerosis múltiple y su relación con procesos de memoria

Introducción. Una de las alteraciones cognitivas más prevalentes en los pacientes con esclerosis múltiple son los proble- mas de codificación de la información (tanto verbal como visual), proceso relacionado con el hipocampo. Objetivo. Estudiar la relación entre los procesos de aprendizaje y retención de la información a largo plazo con el volumen hipocampal y la conectividad funcional (CF) en pacientes con esclerosis múltiple comparados con un grupo control. Sujetos y métodos. Ambos grupos fueron evaluados con la batería neuropsicológica breve, que incluye pruebas de me- moria verbal y visual. Se realizó el estudio de volumetría de la sustancia gris mediante la técnica de morfometría basada en el vóxel y un estudio de CF de vóxel de semilla centrado en la zona de interés (hipocampo). Se realizaron análisis de asociación entre rendimiento en memoria y cambios volumétricos y de CF. Resultados. Los resultados mostraron atrofia en la sustancia gris en el hipocampo izquierdo y una menor CF entre el hipo- campo izquierdo y el troncoencéfalo, el cerebelo, el giro fusiforme y el giro temporal superior en los pacientes respecto al grupo control. En el grupo de pacientes se observa una correlación positiva entre la sustancia gris en ambos hipocampos y el rendimiento en memoria verbal, así como una correlación positiva entre el rendimiento en memoria visual y la CF entre el hipocampo izquierdo y diversas regiones temporales. Conclusiones. Los resultados muestran una relación entre el rendimiento de memoria verbal y visual, y cambios estructu- rales y funcionales en el hipocampo en pacientes con esclerosis múltiple.Introduction. One of the most prevalent cognitive deficits in multiple sclerosis (MS) patients relates to (both verbal and visual) information encoding, a process related the hippocampus. Aim. To assess the relationship between information learning and long-term retention processes and hippocampal volume and functional connectivity (FC) in MS patients. Subjects and methods. MS patients and a control group of healthy volunteers were assessed using the brief neuro- psychological battery, which includes tests of verbal and visual memory. Gray matter volume was assessed through the voxel based morphometry technique, and a study of seed-based FC focused on the region of interest (hippocampus) was also conducted. Results. Results revealed that, as compared to the control group, MS patients display gray matter atrophy at the left hippocampus gray matter and smaller FC between left hippocampus and brainstem, cerebellum, fusiform gyrus and superior temporal gyrus. Association analyses were performed between memory tests performance and both volumetric and FC changes. Results showed a positive correlation between gray matter hippocampal (bilateral) volume and verbal memory performance of the MS group. Further, in MS patients, a positive correlation between visual memory performance and FC between the left hippocampus and several temporal regions was also found. Conclusions. The results of the present study reveal a relationship between structural and functional changes in the hippocampus of MS patients and their performance on verbal and visual memory tests.Subvención concedida por la Universitat Jaume I (P1.1B2014-05)

Increased regional gray matter atrophy and enhanced functional connectivy in male multiple sclerosis patients

Evidence suggests that sex/gender is an important factor for understanding multiple sclerosis (MS) and that some of its neuropathological consequences might manifest earlier in males. In the present study, we assessed gray matter (GM) volume and functional connectivity (FC) in a sample of female and male MS patients (MSp) and female and male healthy controls (HCs). As compared to female MSp, male MSp showed decreased GM volume in the bilateral frontal areas and increased FC between different brain regions. Because both sets of changes correlated significantly and no differences in cognitive performance were observed, we suggest that the FC increase observed in male MSp acts as a compensatory mechanism for their more extensive GM loss and that it promotes a functional convergence between male- and female-MSp.This research has been supported by grant P1-1B2014-15 provided to Cristina Forn by the Universitat Jaume I

Hippocampal dysfunction is associated with memory impairment in multiple sclerosis: A volumetric and functional connectivity study

BACKGROUND: Previous studies have suggested a relationship between neuroanatomical and neurofunctional hippocampal alterations and episodic memory impairments in multiple sclerosis (MS) patients OBJECTIVE: We examined hippocampus volume and functional connectivity (FC) changes in MS patients with different episodic memory capabilities. METHODS: hippocampal subfield volume and FC changes were compared in two subgroups of MS patients with and without episodic memory impairment (MSi and MSp, respectively) and healthy controls. A discriminant function (DF) analysis was used to identify which of these neuroanatomical and neurofunctional parameters were the most relevant components of the mnemonic profiles of HC, MSp and MSi. RESULTS: MSi showed reduced volume in several hippocampal subfields compared to MSp and HC. Ordinal gradation (MSi>MSp>HC) was also observed for FC between the posterior hippocampus and several cortical areas. DF-based analyses revealed that reduced right fimbria volume and enhanced FC at the right posterior hippocampus were the main neural signatures of the episodic memory impairments observed in the MSi group. CONCLUSIONS: Before any sign of episodic memory alterations (MSp), FC increased on several pathways that connect the hippocampus with cortical areas. These changes further increased when the several hippocampal volumes reduced and memory deficits appeared (MSi).This study was sponsored by grants P1-1B2014-15 awarded by Universitat Jaume I and PSI2015-67285-R awarded by MINECO to Dr. Cristina For

Univariate and multivariate sex differences and similarities in gray matter volume within essential language-processing areas

Background: Sex differences in language-related abilities have been reported. It is generally assumed that these differences stem from a different organization of language in the brains of females and males. However, research in this area has been relatively scarce, methodologically heterogeneous and has yielded conflicting results. Methods: Univariate and multivariate sex differences and similarities in gray matter volume (GMVOL) within 18 essential language-processing brain areas were assessed in a sex-balanced sample (N = 588) of right-handed young adults. Univariate analyses involved location, spread, and shape comparisons of the females’ and males’ distributions and were conducted with several robust statistical methods able to quantify the size of sex differences and similarities in a complementary way. Multivariate sex differences and similarities were estimated by the same methods in the continuous scores provided by two distinct multivariate procedures (logistic regression and a multivariate analog of the Wilcoxon–Mann–Whitney test). Additional analyses were addressed to compare the outcomes of these two multivariate analytical strategies and described their structure (that is, the relative contribution of each brain area to the multivariate effects). Results: When not adjusted for total intracranial volume (TIV) variation, “large” univariate sex differences (males > females) were found in all 18 brain areas considered. In contrast, “small” differences (females > males) in just two of these brain areas were found when controlling for TIV. The two multivariate methods tested provided very similar results. Multivariate sex differences surpassed univariate differences, yielding "large" differences indicative of larger volumes in males when calculated from raw GMVOL estimates. Conversely, when calculated from TIV-adjusted GMVOL, multivariate differences were "medium" and indicative of larger volumes in females. Despite their distinct size and direction, multivariate sex differences in raw and TIV-adjusted GMVOL shared a similar structure and allowed us to identify the components of the SENT_CORE network which more likely contribute to the observed effects. Conclusions: Our results confirm and extend previous findings about univariate sex differences in language-processing areas, offering unprecedented evidence at the multivariate level. We also observed that the size and direction of these differences vary quite substantially depending on whether they are estimated from raw or TIV-adjusted GMVOL measurements

Multiple Sclerosis and Depression: Translation and Adaptation of the Spanish Version of the Chicago Multiscale Depression Inventory and the Study of Factors Associated with Depressive Symptoms

Objective: Depressive disorder occurs in up to 50% of persons with Multiple Sclerosis (PwMS). Accurate assessment of depression in MS is essential in clinical settings because depressive symptomatology can affect the clinical course of the disease. Methods: We translated, adapted, and tested the Spanish version of the Chicago Multiscale Depression Inventory (CMDI), a specific test to assess depression in neurological disorders. We compare our results with those obtained with previous versions of the questionnaire (English and Italian). Finally, we also analyze the relationship between the results obtained on the CMDI and demographic, clinical, and cognitive variables. Results: The results obtained with the Spanish version of the CMDI were similar to those observed in previous published versions. We also observed higher depression scores in PwMS (especially in progressive forms) compared with healthy controls. Moreover, depression symptomatology was related to higher disability and fatigue and worse cognitive performance in PwMS. Conclusions: The results support the validity of the CDMI in the Spanish population, as well as the association between depression and other characteristic symptoms of MS. These findings also emphasize the importance of good assessment and multidisciplinary treatment of depression in PwMS.We appreciate the collaboration of the Associació Esclerosis Múltiple de Castelló (AEMC).MCI/AEI (UJI B2020-02 to CF and CS-S); UJI (PREDOC/2020/22 to SFA). These funding sources did not play any role in designing the study or in the collection, analysis, and interpretation of the data

MAPPING THE EVOLUTION OF MENTAL HEALTH RESEARCH IN RELATION TO PHYSICAL ACTIVITY: PRE AND POST GLOBAL PANDEMIC PERSPECTIVES

The research highlights the significant impact of the COVID-19 pandemic on mental health, leading to stress, anxiety, and depression. Physical activity is recognized as a preventive strategy for overall well-being and a beneficial factor for mental health, reducing symptoms of depression and anxiety. The study uses a quantitative-bibliometric method based on keywords related to mental health, exercise, sport, social health, cognitive health, wellbeing, human development, and sports fan. The goal is to locate possible future directionalities and fields of study yet to be discovered and to study the evolution of scientific research on mental health in the social sciences in recent years. The results show that the key concepts have been evolving towards a worsening of mental health, and research linking mental health with physical activity has multiplied, particularly due to the negative effect of the readaptation to the new normality caused by the pandemic. The discussion also emphasizes the importance of social support and engagement in physical activity for mental health outcomes. The research states that group-based exercise programs and social connections are crucial for reducing symptoms of depression and anxiety. The future direction of research is also highlighted to identify effective strategies for promoting physical activity and social support during times of stress and uncertainty. Overall, understanding the relationship between physical activity and mental health can lead to improved coping skills and overall well-being

Sex differences in gray matter volume: how many and how large are they really?

Background: Studies assessing volumetric sex differences have provided contradictory results. Total intracranial volume (TIV) is a major confounding factor when estimating local volumes of interest (VOIs). We investigated how the number, size, and direction of sex differences in gray matter volume (GMv) vary depending on how TIV variation is statistically handled. Methods: Sex differences in the GMv of 116 VOIs were assessed in 356 participants (171 females) without correcting for TIV variation or after adjusting the data with 5 different methods (VBM8 non-linear-only modulation, proportions, power-corrected-proportions, covariation, and the residuals method). The outcomes obtained with these procedures were compared to each other and to those obtained in three criterial subsamples, one comparing female-male pairs matched on their TIV and two others comparing groups of either females or males with large/small TIVs. Linear regression was used to quantify TIV effects on raw GMv and the efficacy of each method in controlling for them. Results: Males had larger raw GMv than females in all brain areas, but these differences were driven by direct TIV-VOIs relationships and more closely resembled the differences observed between individuals with large/small TIVs of sex-specific subsamples than the sex differences observed in the TIV-matched subsample. All TIV-adjustment methods reduced the number of sex differences but their results were very different. The VBM8- and the proportions-adjustment methods inverted TIV-VOIs relationships and resulted in larger adjusted volumes in females, promoting sex differences largely attributable to TIV variation and very distinct from those observed in the TIV-matched subsample. The other three methods provided results unrelated to TIV and very similar to those of the TIV-matched subsample. In these datasets, sex differences were bidirectional and achieved satisfactory replication rates in 19 VOIs, but they were “small” (d < ∣0.38∣) and most of them faded away after correcting for multiple comparisons. Conclusions: There is not just one answer to the question of how many and how large the sex differences in GMv are, but not all the possible answers are equally valid. When TIV effects are ruled out using appropriate adjustment methods, few sex differences (if any) remain statistically significant, and their size is quite reduced

Repeated Working Memory Training Improves Task Performance and Neural Efficiency in Multiple Sclerosis Patients and Healthy Controls

Background/Objective. To explore the efectiveness of a specifc working memory (WM) training program in MS patients and healthy controls (HC). Method. 29 MS patients and 29 matched HC were enrolled in the study. MS and HC were randomly split into two groups: nontraining groups (15HC/14 MS) and training groups (14 HC/15 MS). Training groups underwent adaptive n-back training (60 min/day; 4 days). Functional magnetic resonance imaging (fMRI) was used to monitor brain activity during n-back performance (conditions: 0-back, 2-back, and 3-back) at 3 time points: (1) baseline, (2) post-training (+7days), and (3) followup (+35days). Results. In post-training and follow-up fMRI sessions, trained groups (HC and MS patients) exhibited signifcant reaction time (RT) reductions and increases in Correct Responses (CRs) during 2-back and 3-back performance.Tis improvement of task performance was accompanied by a decrease in brain activation in the WM frontoparietal network. Te two efects were signifcantly correlated. Conclusions. Afer WM training, both cognitively preserved MS patients and HC participants showed task performance improvement made possible by neuroplastic processes that enhanced neural efciency