CONECTIVIDAD CORTICAL EN EL TEA

A menudo hablamos de la prevalencia de los trastornos del espectro del autismo (TEA) y damos cifras como 1 de cada 160 niños presentada por la Organización Mundial de la Salud (OMS, 2017) o las cifras más preocupantes presentadas por los Centros de Control de Enfermedades de Estados Unidos que llegan a hablar de 1 de cada 59.

Sin embargo, estos números generales ocultan una realidad que es muy importante, el impacto del TEA en la vida de cada individuo es enormemente diverso y hay personas que tienen una discapacidad grave y generalizada mientras que otras preservan habilidades en muchos ámbitos y consiguen un nivel de autonomía muy satisfactorio.

Una vez establecido el diagnóstico nada hay tan importante como conseguir disminuir el número de personas que se engloban en el primer grupo y desplazar la curva hacia el segundo grupo, los que tienen mayor autonomía personal y un futuro mucho más favorable.

No sabemos mucho sobre el porqué de estas diferencias pero hay evidencias de que los déficits sociales que se observan en la vida adulta tienen mucho que ver con cómo eran los síntomas durante la infancia, algo en lo que la genética probablemente tiene mucho que ver y con qué terapias se pusieron en marcha, algo que depende mucho del país, la localidad de residencia, no es lo mismo las zonas urbanas que las rurales, y el nivel socioeconómico de la familia, porque el apoyo, que es imprescindible, cuesta dinero.

Es siempre importante recordar que los mejores resultados van ligados al trabajo con terapeutas especializados y que se haya llevado a cabo con la mayor intensidad posible.

Además, sería importante entender el sustrato neurobiológico de estas diferencias individuales y el cerebro es el lugar lógico para encontrar diferencias que expliquen la distinta gravedad de los síntomas y que la evolución a medio y largo plazo sea mejor o peor.

Técnicas de neuroimagen

La gran ventaja es que en los últimos años disponemos de técnicas de neuroimagen, no invasivas y cada vez con mayor poder de resolución, que nos permiten saber más sobre el cerebro vivo y en funcionamiento de personas con TEA y de controles, por supuesto sin causar ningún daño.

De esta manera, estamos comenzando a entender más sobre la miríada de conexiones entre regiones cerebrales y de qué forma el cerebro coordina toda esa actividad neuronal para producir comportamientos.

Hasta el momento los trabajos sobre conectividad en los TEA son poco sólidos, los resultados son heterogéneos, se centran en unas pocas rutas neuronales, las metodologías van quedando anticuadas y las muestras son con frecuencia pequeñas y heterogéneas.

Por tanto, un trabajo reciente de Marc-Antoine d’albis y su grupo, que soluciona parte de estos problemas, es un avance bienvenido. Este trabajo ejemplifica la potencia de las técnicas recientes de neuroimagen para entender la relación entre diferencias en la conectividad cerebral y las habilidades sociales en personas con TEA.

Para ello este equipo de investigadores se ha centrado en personas con autismo de alto funcionamiento y con una nueva metodología especialmente enfocada a los tractos de corta distancia, en forma de U, que asocian entre sí distintas regiones de la corteza cerebral y que son clave en muchos de los comportamientos sociales.

También aprovechan el desarrollo reciente de un atlas del cerebro más detallado y ajustado que permite localizar con mucha mayor fiabilidad esos fascículos superficiales de sustancia blanca (Guevara et al., 2017).

Los estudios más modernos se han hecho con resonancia magnética funcional o con imagen de tensores de difusión (DTI). Los estudios de resonancia magnética funcional se basan en la sincronización de los niveles de oxigenación sanguínea mientras al cerebro se le presenta una tarea social, emocional o cognitiva, frente a un nivel de activación basal, cuando no está sometido a una actividad particular.

Una zona cerebral que se activa necesita más oxígeno y la resonancia magnética funcional permite detectar esta diferencia en el consumo de oxígeno e identificar por tanto a las regiones cerebrales implicadas en una tarea determinada.

La DTI, por su parte, mide la difusión de agua lo que permite valorar las propiedades microestructurales de la sustancia blanca, los gruesos fascículos de axones mielinizados que se utilizan para conectar diferentes partes del encéfalo. La DTI usa un valor llamado anisotropía fraccional. Suena complicado pero es fácil de entender. Tenemos una molécula de agua, si está en un vaso con agua puede difundir con la misma probabilidad en todas direcciones, es un proceso isotrópico.

Por tanto, el valor de su anisotropía, lo contrario, es cero. Si la molécula está dentro de un tubo de plástico diminuto, difunde sin problema en el eje del tubo, pero no lo puede hacer en las otras direcciones, porque la pared del tubo se lo impide. El valor de su anisotropía es uno, el máximo.

En un sistema biológico como un fascículo nervioso, un grupo de axones rodeados por una envuelta lipídica de mielina, la anisotropía fraccional nos da un valor que va a variar en función de la densidad de fibras, del diámetro de esos axones y del grado de mielinización que presentan. Es decir, nos da una información indirecta sobre los fascículos nerviosos y permite saber más sobre un cerebro vivo y funcionando.

Tenemos cada vez más evidencias de que las conexiones entre diferentes regiones cerebrales están alteradas en los TEA. La idea más o menos aceptada es que las personas con TEA tienen hipoconectividad en las conexiones de larga distancia; es decir la conectividad estructural y funcional a larga distancia está reducida en las personas con TEA frente a otras personas sin esta condición.

Con respecto a los fascículos de corta distancia la idea hasta ahora es que había una hiperconectividad en los tractos de corta distancia, es decir, un exceso, pero eran datos poco fiables. D’Albis ha usado DTI para ver cambios en la conectividad a corta distancia (fascículos que tienen una longitud entre 20 y 80 milímetros) en hombres con TEA entre 18 y 55 años, con un cociente de inteligencia igual o superior a 70, por tanto sin discapacidad intelectual. La muestra final incluía 27 hombres con TEA y 31 controles y en ellos se estudiaron 63 fascículos nerviosos de corta distancia.

Los investigadores analizaron las diferencias en la anisotropía fraccional de esos fascículos entre el grupo con TEA y el grupo sin TEA y la relación con las características clínicas de las personas afectadas, en palabras sencillas, con su nivel de TEA. La anisotropía fraccional de componentes de los lóbulos frontal, temporal y parietal era menor entre los hombres con TEA frente a los controles.

Las puntuaciones de ese componente en los hombres con TEA presentaban los menores valores en aquellos que presentaban el mayor índice de discapacidad en varias subescalas de la Escala de Respuesta Social y que demostraban la menor empatía.

Los análisis más finos mostraron que en particular la anisotropía de las conexiones entre la ínsula y la corteza temporal y dentro del lóbulo temporal estaban especialmente asociadas a los déficits cognitivos y sociales más significativos. En otras palabras, los hombres con TEA que tenían conexiones cerebrales a corta distancia de peor calidad tenían también una habilidad menor para establecer y mantener relaciones sociales.

Por tanto, este estudio proporciona información sobre las diferencias neurobiológicas, en concreto en los sistemas de conexión local, que subyacen en el funcionamiento social de personas con TEA y pone de relieve cómo las nuevas técnicas de neuroimagen nos pueden ayudar a entender los síntomas de esta condición y su nivel de gravedad.

HACE FALTA MAS INVESTIGACIÓN

Hace falta más investigación para determinar cómo se desarrollan estas anomalías en la conectividad neuronal y las alteraciones en los procesos cognitivos sociales a lo largo del tiempo. De momento, tenemos evidencias de que se observan cambios prenatales en los niños que posteriormente serán diagnosticados con TEA.

Muchas investigaciones muestran un incremento temprano del volumen cerebral y el estudio postmorten de niños pequeños muestra un exceso de neuronas corticales lo que puede sugerir una hiperconectividad temprana en los TEA. Solso y cols. (2016) mostraron que las conexiones frontales de larga distancia medidas con DTI tenían una anisotropía fraccional más alta y un volumen mayor en niños pequeños posteriormente diagnosticados con TEA y que los cambios asociadas a la edad variaban más lentamente que en controles de las mismas edades.

También hay datos que muestran mayor anisotropía fraccional entre niños muy pequeños con TEA lo que pone de manifestó que la hiperconectividad está presenta en las fases clínicas más tempranas del trastorno y que influye en la forma en que los niños aprenden y desarrollan sus habilidades sociales.

El trabajo de d’Albis y su grupo se centra en las de corta distancia que eran mucho menos conocidas. El seguimiento del desarrollo personal junto con medidas sobre el cerebro y los comportamientos nos puede ayudar a entender la diversidad de trayectorias que tienen las personas con TEA y nos permitirá diseñar estrategias individuales para permitir a cada persona alcanzar su máximo potencial, algo que todavía no conseguimos.

Referencias d’Albis MA, Guevara P, Guevara M, Laidi C, Boisgontier J, Sarrazin S, Duclap D, Delorme R, Bolognani F, Czech C, Bouquet C, Ly-Le Moal M, Holiga S, Amestoy A, Scheid I, Gaman A, Leboyer M, Poupon C, Mangin JF, Houenou J (2018) Local structural connectivity is associated with social cognition in autism spectrum disorder. Brain 141(12): 3472-3481. Eyler LT (2018) Brain connections and social connections in autism spectrum disorders. Brain 141(12): 3287-3289. Guevara M, Roman C, Houenou J, Duclap D, Duclap D, Poupon C, Mangin JF, Guevara P (2017) Reproducibility of superficial white matter tracts using diffusion-weighted imaging tractography. Neuroimage 147: 703–725. Solso S, Xu R, Proudfoot J, Hagler DJ Jr, Campbell K, Venkatraman V, Carter Barnes C, Ahrens-Barbeau C, Pierce K, Dale A, Eyler L, Courchesne E (2016) Diffusion tensor imaging provides evidence of posible axonal overconnectivity in frontal lobes in autism spectrum disorder toddlers. Biol Psychiatry 79: 676–684.

Artículo de José R. Alonso Neurobiólogo (ver su blog)

https://www.monkeyselection.com

Esta entrada fue publicada en AUTISMO, INVESTIGACION. Guarda el enlace permanente.

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