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)

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

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

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

Deciduous and evergreen oaks: unravelling the co-occurrence of different functional strategies in Quercus L. species under Mediterranean type climates

El clima mediterráneo presenta inviernos suaves o fríos y húmedos, mientras que el verano está afectado por las altas presiones que traen aire seco y caluroso (aridez estival), siendo esta última, la característica genuina que lo diferencia de otros tipos de clima. De este modo, el periodo vegetativo se ve afectado por la sequía en verano, que, junto con las bajas temperaturas en invierno, pueden limitar el crecimiento vegetativo esencialmente a dos estaciones: primavera y otoño. Aún con estas restricciones, los ecosistemas mediterráneos tienen una alta riqueza de especies que representan la sexta parte de la flora del planeta. Este es el caso del género Quercus, que, con más de 400 especies distribuidas por todo el hemisferio norte, es el elemento dominante de una amplia variedad de hábitats y en especial, del clima mediterráneo.En la actualidad es posible hablar de dos tipos de robles bien diferenciados que coexisten en las regiones mediterráneas: el roble perennifolio esclerófilo con un origen en la Flora Paleotropical y el malacófilo caducifolio de origen Arctoterciario. Estos dos modelos, que influyen en la adecuación de la planta al ambiente, pueden ser muy diferentes a nivel morfológico, fenológico y fisiológico. De este modo, los dos tipos de robles deben constituir dos modelos de funcionamiento muy distintos frente al clima mediterráneo. Es por eso por lo que el principal objetivo de esta tesis es el estudio comparado del funcionamiento de los dos tipos de especies de robles con diferentes hábitos foliares y grado de esclerofilia que coexisten en el clima mediterráneo. Por consiguiente, esta tesis consta de cinco capítulos que corresponden a cinco artículos ya publicados o en fase de revisión que pretenden arrojar luz al tema planteado anteriormente.Así, se realizó una revisión bibliográfica sobre la esclerofilia en el género Quercus para definir los mecanismos que hay detrás y sus consecuencias económicas para la hoja. Pese a al amplio rango de variación en los rasgos funcionales de las hojas y sus estrategias adaptativas contrastantes, no puede explicarse por sí sola por ninguno de los factores ecológicos considerados (sequía, escasez de nutrientes, bajas temperaturas y daño físico). El estudio sugiere que estas restricciones pueden tener un efecto sinérgico, y desde un punto de vista funcional, podemos concluir que, en los robles, el hábito foliar modula en gran medida las implicaciones fisiológicas de la esclerofilia.Usando un enfoque filogenético, se cuantificaron las variables anatómicas, composicionales y climáticas en 85 especies de Quercus caducifolios y perennifolios que mostraron diferencias morfológicas foliares fundamentales revelando una respuesta adaptativa diversa. Mientras que la LMA en los caducifolios parece haberse diversificado en coordinación con el grosor modulado principalmente por la aridez, la diversificación de la LMA en los perennifolios parece depender del grupo infragenérico. Así, en estos últimos, la diversificación en el grosor de la hoja fue modulada tanto por la aridez como por el frío, mientras que la diversificación en la densidad de la hoja es sólo modulada por la aridez.Asimismo, se estudió la importancia relativa de cada característica de la hoja sobre las propiedades mecánicas en 25 especies de Quercus. Se sugiere que las hojas de Quercus esclerófilos son más duras y fuertes debido a la pared externa de su epidermis más gruesa y/o a una mayor concentración de celulosa. Además, las especies de la sección Ilex comparten rasgos comunes independientemente de que ocupen climas bastante diferentes. De modo similar, las especies de hoja perenne que viven en climas de tipo mediterráneo comparten rasgos foliares comunes independientemente de su diferente origen filogenético.Además, se evaluaron los cambios dependientes de la edad foliar en los rasgos morfológicos, anatómicos, químicos y fotosintéticos en Quercus ilex subsp. rotundifolia Lam., un roble perennifolio con hojas de alta longevidad. Se observan disminuciones de todos los rasgos fotosintéticos con el aumento de la edad de la hoja. Los cambios en la anatomía y bioquímica de la hoja fueron responsables de las modificaciones dependientes de la edad en la asimilación neta de CO2 y la conductancia del CO2 a través del mesófilo. Estos hallazgos revelaron un deterioro fisiológico gradual relacionado con el desmantelamiento del aparato fotosintético en hojas más viejas de Q. ilex subsp. rotundifolia.Por último, se analizaron las características fotosintéticas, fotoquímicas e hidráulicas de diferentes órganos de Q. faginea y Q. ilex subsp. rotundifolia bajo condiciones de sequía severa. La fuerte disminución de los rasgos fotosintéticos de Q. faginea estuvo acompañada de una fuerte disminución de la conductancia hidráulica de las hojas en respuesta a la sequía. Este hecho probablemente evitó una embolia xilemática en los tallos (¿segmentación de la vulnerabilidad¿). Por el contrario, las hojas de Q. ilex subsp. rotundifolia mostraron mecanismos fotoprotectores efectivos y alta resistencia a la cavitación inducida por la sequía, lo que estaría relacionado con la mayor longevidad de las hojas de las encinas mediterráneas.<br /

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

Living in Drylands: Functional Adaptations of Trees and Shrubs to Cope with High Temperatures and Water Scarcity

Plant functioning and survival in drylands are affected by the combination of high solar radiation, high temperatures, low relative humidity, and the scarcity of available water. Many ecophysiological studies have dealt with the adaptation of plants to cope with these stresses in hot deserts, which are the territories that have better evoked the idea of a dryland. Nevertheless, drylands can also be found in some other areas of the Earth that are under the Mediterranean-type climates, which imposes a strong aridity during summer. In this review, plant species from hot deserts and Mediterranean-type climates serve as examples for describing and analyzing the different responses of trees and shrubs to aridity in drylands, with special emphasis on the structural and functional adaptations of plants to avoid the negative effects of high temperatures under drought conditions. First, we analyze the adaptations of plants to reduce the input of energy by diminishing the absorbed solar radiation through (i) modifications of leaf angle and (ii) changes in leaf optical properties. Afterwards, we analyze several strategies that enhance the ability for heat dissipation through (i) leaf size reduction and changes in leaf shape (e.g., through lobed leaves), and (ii) increased transpiration rates (i.e., water-spender strategy), with negative consequences in terms of photosynthetic capacity and water consumption, respectively. Finally, we also discuss the alternative strategy showed by water-saver plants, a common drought resistance strategy in hot and dry environments that reduces water consumption at the expense of diminishing the ability for leaf cooling. In conclusion, trees and shrubs living in drylands have developed effective functional adaptations to cope with the combination of high temperature and water scarcity, all of them with clear benefits for plant functioning and survival, but also with different costs concerning water use, carbon gain, and/or leaf cooling.This research was funded by Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA) grant number RTA2015-00054-C02-01, by Ministerio de Ciencia e Innovación grant number PID2019-106701RR-I00/AEI/10.13039/501100011033 and INERTIA project (PID-2019-111332-C22), project IMAGINA (Prometeu program/2019/110, GVA) and from Gobierno de Aragón H09_20R research group. Work of D.A.F. is supported by a FPI-INIA contract BES-2017-081208. CEAM is funded by Generalitat Valenciana

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