Structural equation models to estimate dynamic effective connectivity networks in resting fMRI. A comparison between individuals with Down syndrome and controls.

Emerging evidence suggests that an effective or functional connectivity network does not use a static process over time but incorporates dynamic connectivity that shows changes in neuronal activity patterns. Using structural equation models (SEMs), we estimated a dynamic component of the effective network through the effects (recursive and nonrecursive) between regions of interest (ROIs), taking into account the lag 1 effect. The aim of the paper was to find the best structural equation model (SEM) to represent dynamic effective connectivity in people with Down syndrome (DS) in comparison with healthy controls. Twenty-two people with DS were registered in a functional magnetic resonance imaging (fMRI) resting-state paradigm for a period of six minutes. In addition, 22 controls, matched by age and sex, were analyzed with the same statistical approach. In both groups, we found the best global model, which included 6 ROIs within the default mode network (DMN). Connectivity patterns appeared to be different in both groups, and networks in people with DS showed more complexity and had more significant effects than networks in control participants. However, both groups had synchronous and dynamic effects associated with ROIs 3 and 4 related to the upper parietal areas in both brain hemispheres as axes of association and functional integration. It is evident that the correct classification of these groups, especially in cognitive competence, is a good initial step to propose a biomarker in network complexity studies.

Complexity Analysis of the Default Mode Network Using Resting-State fMRI in Down Syndrome: Relationships Highlighted by a Neuropsychological Assessment.

BACKGROUND: Studies on complexity indicators in the field of functional connectivity derived from resting-state fMRI (rs-fMRI) in Down syndrome (DS) samples and their possible relationship with cognitive functioning variables are rare. We analyze how some complexity indicators estimated in the subareas that constitute the default mode network (DMN) might be predictors of the neuropsychological outcomes evaluating Intelligence Quotient (IQ) and cognitive performance in persons with DS. METHODS: Twenty-two DS people were assessed with the Kaufman Brief Test of Intelligence (KBIT) and Frontal Assessment Battery (FAB) tests, and fMRI signals were recorded in a resting state over a six-minute period. In addition, 22 controls, matched by age and sex, were evaluated with the same rs-fMRI procedure. RESULTS: There was a significant difference in complexity indicators between groups: the control group showed less complexity than the DS group. Moreover, the DS group showed more variance in the complexity indicator distributions than the control group. In the DS group, significant and negative relationships were found between some of the complexity indicators in some of the DMN networks and the cognitive performance scores. CONCLUSIONS: The DS group is characterized by more complex DMN networks and exhibits an inverse relationship between complexity and cognitive performance based on the negative parameter estimates.

Resting-state default mode network connectivity in young individuals with Down syndrome.

BACKGROUND: Down syndrome (DS) is a chromosomal disorder that causes intellectual disability. Few studies have been conducted on functional connectivity using resting-state fMRI (functional magnetic resonance imaging) signals or more specifically, on the relevant structure and density of the default mode network (DMN). Although data on this issue have been reported in adult DS individuals (age: >45 years), the DMN properties in young DS individuals have not been studied. The aim of this study was to describe the density and structure of the DMN network from fMRI signals in young DS (age: <36 years). METHOD: A sample of 22 young people with DS between the ages of 16 and 35 (M = 25.5 and SD = 5.1) was recruited in various centers for people with intellectual disability (ID). In addition to sociodemographic data, a six-minute fMRI session was recorded with a 3. T Philips Ingenia scanner. A control group of 22 young people, matched by age and gender, was obtained from the Human Connectome Project (to compare the networks properties between groups). RESULTS: The values of the 48 ROIs that configured the DMN were obtained, and the connectivity graphs for each subject, the average connectivity graph for each group, the clustering and degree values for each ROI, and the average functional connectivity network were estimated. CONCLUSIONS: A higher density of overactivation was identified in DS group in the ventral, sensorimotor, and visual DMN networks, although within a framework of a wide variability of connectivity patterns in comparison with the control group network. These results extend our understanding of the functional connectivity networks pattern and intrasubject variability in DS.

Network change point detection in resting-state functional connectivity dynamics of mild cognitive impairment patients.

Background/Objective: This study aims to characterize the differences on the short-term temporal network dynamics of the undirected and weighted whole-brain functional connectivity between healthy aging individuals and people with mild cognitive impairment (MCI). The Network Change Point Detection algorithm was applied to identify the significant change points in the resting-state fMRI register, and we analyzed the fluctuations in the topological properties of the sub-networks between significant change points. Method: Ten MCI patients matched by gender and age in 1:1 ratio to healthy controls screened during patient recruitment. A neuropsychological evaluation was done to both groups as well as functional magnetic images were obtained with a Philips 3.0T. All the images were preprocessed and statistically analyzed through dynamic point estimation tools. Results: No statistically significant differences were found between groups in the number of significant change points in the functional connectivity networks. However, an interaction effect of age and state was detected on the intra-participant variability of the network strength. Conclusions: The progression of states was associated to higher variability in the patient's group. Additionally, higher performance in the prospective and retrospective memory scale was associated with higher median network strength.

Antecedentes/Objetivo: Este estudio tiene como objetivo caracterizar las diferencias en la red dinámica de conectividad funcional no dirigida entre un grupo de personas sanas y otro con deterioro cognitivo leve. Se aplicó un algoritmo de detección de puntos de cambio en redes complejas para identificarlos en registros fMRI en estado de reposo y se analizaron las fluctuaciones en las propiedades topológicas de las subredes entre puntos de cambio significativos. Método: Diez pacientes emparejados por sexo y edad en proporción 1:1 a controles sanos. Se realizó una evaluación neuropsicológica a ambos grupos y se obtuvieron imágenes funcionales con un Philips Ingenia 3.0T. Todas las imágenes fueron preprocesadas y analizadas estadísticamente a través de herramientas de estimación dinámica de puntos. Resultados: No se encontraron diferencias estadísticamente significativas entre ambos grupos en el número de puntos de cambio en las redes de conectividad funcional. Se detectó un efecto de interacción entre edad y la variabilidad intra-sujeto en algunos indicadores de complejidad (strength) de la red dinámica. Conclusiones: La progresión de la conectividad se asoció a una mayor variabilidad en el grupo de pacientes. Además, se puede asociar un mayor rendimiento en la escala de memoria prospectiva y retrospectiva con un mayor valor de la mediana de strength de la red.

Estimation of Brain Functional Connectivity in Patients with Mild Cognitive Impairment.

Mild cognitive impairment is defined as greater cognitive decline than expected for a person at a particular age and is sometimes considered a stage between healthy aging and Alzheimer's disease or other dementia syndromes. It is known that functional connectivity patterns change in people with this diagnosis. We studied functional connectivity patterns and functional segregation in a resting-state fMRI paradigm comparing 10 MCI patients and 10 healthy controls matched by education level, age and sex. Ninety ROIs from the automated anatomical labeling (AAL) atlas were selected for functional connectivity analysis. A correlation matrix was created for each group, and a third matrix with the correlation coefficient differences between the two matrices was created. Functional segregation was analyzed with the 3-cycle method, which is novel in studies of this topic. Finally, cluster analyses were also performed. Our results showed that the two correlation matrices were visually similar but had many differences related to different cognitive functions. Differences were especially apparent in the anterior default mode network (DMN), while the visual resting-state network (RSN) showed no differences between groups. Differences in connectivity patterns in the anterior DMN should be studied more extensively to fully understand its role in the differentiation of healthy aging and an MCI diagnosis.

The supramarginal and angular gyri underlie orthographic competence in Spanish language.

Orthographic competence allows automatic word recognition and reading fluency. To elucidate how the orthographic competence in Spanish-speaking adults might affect the neurofunctional mechanisms of visual word recognition, 32 young adults equally divided in two groups (HSS: High Spelling Skills, and LSS: Low Spelling Skills) were evaluated using fMRI methods, while they performed an orthographic recognition task involving pseudohomophones. HSS achieved significantly more correct responses and lower reaction times than LSS. Interestingly, LSS showed greater activation in the left angular and supramarginal regions with increased bilateral activation pattern in the inferior frontal gyrus, and the anterior temporal and posterior parietal regions. In contrast, HSS showed a more left-lateralized pattern over these regions along with higher activation of the anterior cingulated gyrus for misspelled words. Results suggest that the differences found in cortical activation patterns might be explained by the higher degree of specialization for word recognition in HSS, a group of participants that due to their greater orthographic skills require less engagement of processing resources to succeed in the task.

Analysis of Pseudohomophone Orthographic Errors through Functional Magnetic Resonance Imaging (fMRI).

The study of orthographic errors in a transparent language such as Spanish is an important topic in relation to writing acquisition because in Spanish it is common to write pseudohomophones as valid words. The main objective of the present study was to explore the possible differences in activation patterns in brain areas while processing pseudohomophone orthographic errors between participants with high (High Spelling Skills (HSS)) and low (Low Spelling Skills (LSS)) spelling orthographic abilities. We hypothesize that (a) the detection of orthographic errors will activate bilateral inferior frontal gyri, and that (b) this effect will be greater in the HSS group. Two groups of 12 Mexican participants, each matched by age, were formed based on their results in a group of spelling-related ad hoc tests: HSS and LSS groups. During the fMRI session, two experimental tasks were applied involving correct and pseudohomophone substitution of Spanish words. First, a spelling recognition task and second a letter searching task. The LSS group showed, as expected, a lower number of correct responses (F(1, 21) = 52.72, p <.001, η2 = .715) and higher reaction times compared to the HSS group for the spelling task (F(1, 21) = 60.03, p <.001, η2 = .741). However, this pattern was reversed when the participants were asked to decide on the presence of a vowel in the words, regardless of spelling. The fMRI data showed an engagement of the right inferior frontal gyrus in HSS group during the spelling task. However, temporal, frontal, and subcortical brain regions of the LSS group were activated during the same task.

Effective connectivity of visual word recognition and homophone orthographic errors.

The study of orthographic errors in a transparent language like Spanish is an important topic in relation to writing acquisition. The development of neuroimaging techniques, particularly functional magnetic resonance imaging (fMRI), has enabled the study of such relationships between brain areas. The main objective of the present study was to explore the patterns of effective connectivity by processing pseudohomophone orthographic errors among subjects with high and low spelling skills. Two groups of 12 Mexican subjects each, matched by age, were formed based on their results in a series of ad hoc spelling-related out-scanner tests: a high spelling skills (HSSs) group and a low spelling skills (LSSs) group. During the f MRI session, two experimental tasks were applied (spelling recognition task and visuoperceptual recognition task). Regions of Interest and their signal values were obtained for both tasks. Based on these values, structural equation models (SEMs) were obtained for each group of spelling competence (HSS and LSS) and task through maximum likelihood estimation, and the model with the best fit was chosen in each case. Likewise, dynamic causal models (DCMs) were estimated for all the conditions across tasks and groups. The HSS group's SEM results suggest that, in the spelling recognition task, the right middle temporal gyrus, and, to a lesser extent, the left parahippocampal gyrus receive most of the significant effects, whereas the DCM results in the visuoperceptual recognition task show less complex effects, but still congruent with the previous results, with an important role in several areas. In general, these results are consistent with the major findings in partial studies about linguistic activities but they are the first analyses of statistical effective brain connectivity in transparent languages.