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Background: Brain interdependencies can be studied from either a structural/anatomical perspective ("structural connectivity") or by considering statistical interdependencies ("functional connectivity" [FC]). Interestingly, while structural connectivity is by definition pairwise (white-matter fibers project from one region to another), FC is not. However, most FC analyses only focus on pairwise statistics and they neglect higher order interactions. A promising tool to study high-order interdependencies is the recently proposed O-Information, which can quantify the intrinsic statistical synergy and the redundancy in groups of three or more interacting variables. Methods: We analyzed functional magnetic resonance imaging (fMRI) data obtained at rest from 164 healthy subjects with ages ranging in 10 to 80 years and used O-Information to investigate how high-order statistical interdependencies are affected by age. Results: Older participants (from 60 to 80 years old) exhibited a higher predominance of redundant dependencies compared with younger participants, an effect that seems to be pervasive as it is evident for all orders of interaction. In addition, while there is strong heterogeneity across brain regions, we found a "redundancy core" constituted by the prefrontal and motor cortices in which redundancy was evident at all the interaction orders studied. Discussion: High-order interdependencies in fMRI data reveal a dominant redundancy in functions such as working memory, executive, and motor functions. Our methodology can be used for a broad range of applications, and the corresponding code is freely available. Impact statement Past research has showcased multiple changes to the brain's structural and functional properties caused by aging. Here we expand prior work through recent advancements in multivariate information theory, which provide richer and more theoretically principled analyses than existing alternatives. We show that the brains of older participants contain more redundant information at multiple spatial scales-that is, activation in different brain regions is less diverse, compared with younger participants-and identify a "redundancy core" constituted by prefrontal and motor cortices, which might explained impaired performance in the old population in functions such as working memory and executive control. ispartof: BRAIN CONNECTIVITY vol:11 issue:9 pages:734-744 ispartof: location:United States status: published

The human brain generates a rich repertoire of spatio-temporal activity patterns, which support a wide variety of motor and cognitive functions. These patterns of activity change with age in a multi-factorial manner. One of these factors is the variations in the brain’s connectomics that occurs along the lifespan. However, the precise relationship between high-order functional interactions and connnectomics, as well as their variations with age are largely unknown, in part due to the absence of mechanistic models that can efficiently map brain connnectomics to functional connectivity in aging. To investigate this issue, we have built a neurobiologically-realistic whole-brain computational model using both anatomical and functional MRI data from 161 participants ranging from 10 to 80 years old. We show that the age differences in high-order functional interactions can be largely explained by variations in the connectome. Based on this finding, we propose a simple neurodegeneration model that is representative of normal physiological aging. As such, when applied to connectomes of young participant it reproduces the age-variations that occur in the high-order structure of the functional data. Overall, these results begin to disentangle the mechanisms by which structural changes in the connectome lead to functional differences in the ageing brain. Our model can also serve as a starting point for modelling more complex forms of pathological ageing or cognitive deficits.Author summaryModern neuroimaging techniques allow us to study how the human brain’s anatomical architecture (a.k.a. structural connectome) changes under different conditions or interventions. Recently, using functional neuroimaging data, we have shown that complex patterns of interactions between brain areas change along the lifespan, exhibiting increased redundant interactions in the older population. However, the mechanisms that underlie these functional differences are still unclear. Here, we extended this work and hypothesized that the variations of functional patterns can be explained by the dynamics of the brain’s anatomical networks, which are known to degenerate as we age. To test this hypothesis, we implemented a whole-brain model of neuronal activity, where different brain regions are anatomically wired using real connectomes from 161 participants with ages ranging from 10 to 80 years old. Analyzing different functional aspects of brain activity when varying the empirical connectomes, we show that the increased redundancy found in the older group can indeed be explained by precise rules affecting anatomical connectivity, thus emphasizing the critical role that the brain connectome plays for shaping complex functional interactions and the efficiency in the global communication of the human brain.

En la actualidad la obesidad es considerada como una pandemia, ademas de los cambios metabolicos ya sabidos, se producen alteraciones estructurales como las generadas en el sistema ventilatorio. Sin embargo, se ha observado que dependiendo de la forma de categorizacion de esta condicion, puede o no existir alteracion sobre este sistema generando asi una complicacion al momento de la eleccion de esta herramienta. Por lo tanto el objetivo de esta investigacion fue comparar parametros de la funcion pulmonar en individuos obesos (O) y normo-peso (Np) segun indice de masa corporal (IMC) y porcentaje de grasa corporal (PGC). Se midio la funcion ventilatoria en 57 participantes, posteriormente estas variables se contrastaron entre los sujetos normo-peso (Np) y obesos (O) segun IMC y PGC. Se observo un aumento significativo en el valor de la capacidad inspiratoria (CI) de O versus Np y del volumen de reserva espiratoria (VRE) y capacidad residual funcional (CRF) de Np en relacion a O, tanto para la division por IMC como por PGC, en el grupo dividido por IMC las variables de resistencia especifica de las vias aereas (sRaw) y presion inspiratoria maxima (PImax) fueron significativamente mayor en los participantes O, asimismo, la conductancia especifica de las vias aereas (sGaw) fue significativamente mayor en sujetos Np. En conclusion, el IMC mostro mayor versatilidad como predictor de la funcion ventilatoria, sin embargo, se necesitan mayores estudios de los efectos mecanicos de este indicador y del PGC sobre las vias aereas.

The structural connectivity of human brain allows the coexistence of segregated and integrated states of activity. Neuromodulatory systems facilitate the transition between these functional states and recent computational studies have shown how an interplay between the noradrenergic and cholinergic systems define these transitions. However, there is still much to be known about the interaction between the structural connectivity and the effect of neuromodulation, and to what extent the connectome facilitates dynamic transitions. In this work, we use a whole brain model, based on the Jasen and Rit equations plus a human structural connectivity matrix, to find out which structural features of the human connectome network define the optimal neuromodulatory effects. We simulated the effect of the noradrenergic system as changes in filter gain, and studied its effects related to the global-, local-, and meso-scale features of the connectome. At the global-scale, we found that the ability of the network of transiting through a variety of dynamical states is disrupted by randomization of the connection weights. By simulating neuromodulation of partial subsets of nodes, we found that transitions between integrated and segregated states are more easily achieved when targeting nodes with greater connection strengths—local feature—or belonging to the rich club—meso-scale feature. Overall, our findings clarify how the network spatial features, at different levels, interact with neuromodulation to facilitate the switching between segregated and integrated brain states and to sustain a richer brain dynamics.

Psychedelic drugs, including lysergic acid diethylamide and other agonists of the serotonin 2A receptor (5HT2A-R), induce drastic changes in subjective experience, and provide a unique opportunity to study the neurobiological basis of consciousness. One of the most notable neurophysiological signatures of psychedelics, increased entropy in spontaneous neural activity, is thought to be of relevance to the psychedelic experience, mediating both acute alterations in consciousness and long-term effects. However, no clear mechanistic explanation for this entropy increase has been put forward so far. We sought to do this here by building upon a recent whole-brain model of serotonergic neuromodulation, to study the entropic effects of 5HT2A-R activation. Our results reproduce the overall entropy increase observed in previous experiments in vivo, providing the first model-based explanation for this phenomenon. We also found that entropy changes were not uniform across the brain: entropy increased in some regions and decreased in others, suggesting a topographical reconfiguration mediated by 5HT2A-R activation. Interestingly, at the whole-brain level, this reconfiguration was not well explained by 5HT2A-R density, but related closely to the topological properties of the brain’s anatomical connectivity. These results help us understand the mechanisms underlying the psychedelic state and, more generally, the pharmacological modulation of whole-brain activity.

Psychedelic drugs, including lysergic acid diethylamide (LSD) and other agonists of the serotonin 2A receptor (5HT2A-R), induce drastic changes in subjective experience, and provide a unique opportunity to study the neurobiological basis of consciousness. One of the most notable neurophysiological signatures of psychedelics, increased entropy in spontaneous neural activity, is thought to be of relevance to the psychedelic experience, encoding both acute alterations in consciousness and mediating long-term effects. However, no clear mechanistic explanation for this ‘entropic’ phenomenon has been put forward so far. We sought to do this here by building upon a recent whole-brain model of serotonergic neuromodulation, to study the entropic effects of 5HT2A-R activation. Our results reproduce the overall entropy increase observed in previous experiments in vivo, providing the first model-based explanation for this phenomenon. We also found that entropy changes were not uniform across the brain: entropy increased in some regions and decreased in others, suggesting a topographical reconfiguration mediated by 5HT2A-R activation. Interestingly, at the whole-brain level, this reconfiguration was not well explained by 5HT2A-R density, but related closely to the topological properties of the brain’s anatomical connectivity. These results help us understand the mechanisms underlying the psychedelic state and, more generally, the pharmacological modulation of whole-brain activity.

Obesity is associated with a rapid decrease in ventilatory function. The most common way of assessing nutritional status and measuring abdominal fat and hips are the body mass index (BMI) and the waist-hip ratio (WHR). There is scarce evidence suggesting their relation to functional residual capacity (FRC). Our objective was to determine the relation among BMI, WHR, and FRC in obese children in the city of Talca, Chile.Male and female children were recruited (6-12 years). Weight, height, BMI, WHR, and pulmonary function were assessed; the latter with body plethysmography. Depending on data distribution, Student's t test or the Mann-Whitney U test were used for independent samples, while Pearson's or Spearman's r test was used to establish the correlation between WHR and FRC.Children were divided into normal weight (n = 18) and obese (n = 18). A significant reduction in FRC (p = 0.025) was reported in obese children, while a reverse association was observed between WHR and FRC, which was moderate in normal weight children (s = -0.489; p = 0.03) and high in obese children (r = -0.681; p = 0.001).Obese children showed a lower FRC compared to normal weight children, which, in turn, was associated with WHR. These results are indicative of the systemic effects caused by obesity on children's ventilatory function and the need to use body fat distribution indicators at an early age.Introducción. La obesidad está asociada a un descenso acelerado de la función ventilatoria. Las formas más frecuentes de evaluar el estado nutricional y medir la grasa abdominal y las caderas son el índice de masa corporal (IMC) y el índice cintura-cadera (ICC). Existe escasa evidencia que sugiera su relación con la capacidad residual funcional (CRF). Nuestro objetivo fue determinar la relación entre el IMC, el ICC y la CRF en niños obesos de la ciudad de Talca, Chile. Población y métodos. Se reclutaron niños de ambos sexos (6-12 años). Se evaluaron peso, talla, IMC, ICC y función pulmonar a través de pletismografía corporal. Dependiendo de la distribución de los datos, se utilizó la prueba t de Student o U de Mann-Whitney para muestras independientes y, la prueba r de Pearson o Spearman para establecer la correlación entre ICC y CRF. Resultados. Los niños se dividieron en normopeso (n= 18) y obesos (n= 18). Se reportó una disminución significativa de la CRF (p= 0,025) en niños obesos y una relación inversa entre ICC y CRF, la cual fue moderada en niños normopeso (s= -0,489; p= 0,03) y alta en obesos (r= -0,681; p= 0,001). Conclusiones. Los niños obesos mostraron una menor CRF respecto de los normopeso, que, a su vez, se relacionó con el ICC. Estos resultados indican efectos sistémicos que produce la obesidad en la función ventilatoria en niños y la necesidad de incorporar indicadores de distribución de grasa corporal a temprana edad.

We propose a novel, scalable, and accurate method for detecting neuronal ensembles from a population of spiking neurons. Our approach offers a simple yet powerful tool to study ensemble activity. It relies on clustering synchronous population activity (population vectors), allows the participation of neurons in different ensembles, has few parameters to tune and is computationally efficient. To validate the performance and generality of our method, we generated synthetic data, where we found that our method accurately detects neuronal ensembles for a wide range of simulation parameters. We found that our method outperforms current alternative methodologies. We used spike trains of retinal ganglion cells obtained from multi-electrode array recordings under a simple ON-OFF light stimulus to test our method. We found a consistent stimuli-evoked ensemble activity intermingled with spontaneously active ensembles and irregular activity. Our results suggest that the early visual system activity could be organized in distinguishable functional ensembles. We provide a Graphic User Interface, which facilitates the use of our method by the scientific community.

Segregation and integration are two fundamental principles of brain structural and functional organization. Neuroimaging studies have shown that the brain transits between different functionally segregated and integrated states, and neuromodulatory systems have been proposed as key to facilitate these transitions. Although whole-brain computational models have reproduced this neuromodulatory effect, the role of local inhibitory circuits and their cholinergic modulation has not been studied. In this article, we consider a Jansen & Rit whole-brain model in a network interconnected using a human connectome, and study the influence of the cholinergic and noradrenergic neuromodulatory systems on the segregation/integration balance. In our model, we introduce a local inhibitory feedback as a plausible biophysical mechanism that enables the integration of whole-brain activity, and that interacts with the other neuromodulatory influences to facilitate the transition between different functional segregation/integration regimes in the brain., Author summary Segregation of brain activity refers to the fact that some brain regions are specialized to handle particular features of external and internal stimuli. However, to produce a coherent behavioral outcome, the brain must coordinate the activity of these specialized brain areas, and this is called integration of brain activity. Based on a fixed connectome (the brain anatomical structure), the neuromodulatory systems are one of the plausible candidates to manage the transitions of brain states in short timescales. Understanding the role of neuromodulators in brain dynamics and the segregation/integration balance is relevant, in particular, as it is known that in several neuropsychiatric disorders the segregation/integration balance its impaired. Here, we used a computational model of the whole brain to study the dual effect of the cholinergic and noradrenergic neuromodulatory systems in the switching from segregated to integrated brain states. The novelty of our work is the inclusion of a homeostatic local inhibitory loop. This specific inhibition, modulated by the cholinergic system, maintains the excitation/inhibition balance while promoting integration. Our work links the local effects of cholinergic neuromodulation, with the more global influences of the structural connectivity and neuromodulatory systems. This constitutes a step forward in the understanding of the neural mechanisms behind the segregation/integration balance of brain activity.

Child and adolescent obesity is an epidemiological problem in developing countries. Its prevalence among preschoolers and schoolchildren is over 30%. It has been associated with a wide range of health complications, including rapid loss of lung function leading to changes in physiology and ventilatory mechanics. The objective of this study was to analyze the association between obesity and the increase in specific airway resistance (sRaw) in a sample of obese children and adolescents from the district of Talca.In a sample of 36 subjects with an average age of 9.38 ± 1.99 years, divided into 2 groups (normal weight and obese), the tricipital, subscapular, and abdominal skinfolds and lung volumes were measured. For the statistical analysis, data normality was determined and then the Student's t test or the Mann-Whitney U test and Pearson's or Spearman's correlations were used, as applicable. A value of p0.05 was considered statistically significant.When comparing normal weight and obese subjects, a significant increase in sRaw and a significant reduction in specific airway conductance (sGaw) were observed in obese subjects. In addition, an adequate and significant correlation was observed between sRaw and fat percentage.Obese subjects showed an increased sRaw and a reduced sGaw.La obesidad infantojuvenil es un problema epidemiológico en los países en vías de desarrollo. Su prevalencia entre los niños en edad preescolar y escolar supera el 30%. Esta se asocia a una amplia variedad de complicaciones de salud, entre ellas, una acelerada pérdida de la función pulmonar, que provoca cambios en la fisiología y mecánica ventilatoria. El objetivo de este estudio fue estudiar la asociación entre obesidad y aumento de la resistencia específica de las vías aéreas (specific resistance airway; sRaw, por sus siglas en inglés) en una muestra infantojuvenil obesa de la comuna de Talca.En una muestra de 36 sujetos con un promedio de edad de 9,38 ± 1,99 años, dividida en dos grupos, peso normal y obesos, se midieron los pliegues tricipital, subescapular, abdominal y volúmenes pulmonares. Para el análisis estadístico, se determinó la normalidad de los datos y, posteriormente, se utilizaron los test t de Student o U de Mann-Whitney y Pearson o Spearman según correspondiera. Se consideró un nivel de significancia estadística de p0,05.Al comparar sujetos de peso normal con obesos, se observó un aumento significativo de la sRaw y una disminución significativa de la conductancia específica de la vía aérea en sujetos obesos. Además, se observó una correlación buena y significativa entre sRaw y porcentaje de grasa.Los sujetos obesos mostraron un aumento de la sRaw y disminución de la conductancia específica de la vía aérea.