Causality methods to study the functional connectivity in brain networks: the basal ganglia - thalamus causal interactions.

This study uses methods recently developed to study the complex evolution of atmospheric phenomena which have some similarities with the dynamics of the human brain. In both cases, it is possible to record the activity of particular centers (geographic regions or brain nuclei) but not to make an experimental modification of their state. The study of "causality", which is necessary to understand the dynamics of these complex systems and to develop robust models that can predict their evolution, is hampered by the experimental restrictions imposed by the nature of both systems. The study was performed with data obtained in the thalamus and basal ganglia of awake humans executing different tasks. This work studies the linear, non-linear and more complex relationships of these thalamic centers with the cortex and main BG nuclei, using three complementary techniques: the partial correlation regression method, the Gaussian process regression/distance correlation and a model-free method based on nearest-neighbor that computes the conditional mutual information. These causality methods indicated that the basal ganglia present a different functional relationship with the anterior-ventral (motor), intralaminar and medio-dorsal thalamic centers, and that more than 60% of these thalamus-basal ganglia relationships present a non-linear dynamic (35 of the 57 relationships found). These functional interactions were observed for basal ganglia nuclei with direct structural connections with the thalamus (primary somatosensory and motor cortex, striatum, internal globus pallidum and substantia nigra pars reticulata), but also for basal ganglia without structural connections with the thalamus (external globus pallidum and subthalamic nucleus). The motor tasks induced rapid modifications of the thalamus-basal ganglia interactions. These findings provide new perspectives of the thalamus - BG interactions, many of which may be supported by indirect functional relationships and not by direct excitatory/inhibitory interactions.

The causal interaction in human basal ganglia.

The experimental study of the human brain has important restrictions, particularly in the case of basal ganglia, subcortical centers whose activity can be recorded with fMRI methods but cannot be directly modified. Similar restrictions occur in other complex systems such as those studied by Earth system science. The present work studied the cause/effect relationships between human basal ganglia with recently introduced methods to study climate dynamics. Data showed an exhaustive (identifying basal ganglia interactions regardless of their linear, non-linear or complex nature) and selective (avoiding spurious relationships) view of basal ganglia activity, showing a fast functional reconfiguration of their main centers during the execution of voluntary motor tasks. The methodology used here offers a novel view of the human basal ganglia which expands the perspective provided by the classical basal ganglia model and may help to understand BG activity under normal and pathological conditions.