Transfer entropy between cortical and basal ganglia electrophysiology

Linear measures such as cross-correlation, coherence, and directed transfer functions have previously been applied to investigate the functional connectivity between brain regions. However, such methods do not account for nonlinear interactions between the signals. Separately, dopaminergic cell transplants have been shown to provide symptomatic amelioration and partial electrophysiological normalization of aberrant basal ganglia firing patterns in Parkinson's Disease. However, the precise extent and mechanisms of basal ganglia electrophysiological normalization have remained unclear. In this experiment we computed the transfer entropy between electroencephalograms (EEGs) and basal ganglia local field potentials (LFPs) from urethane-anesthetized rats, in order to investigate both linear and nonlinear interactions. We used the 6-hydroxy-dopamine lesioned medial forebrain bundle hemiparkinsonian (HP) rat model, and recorded from the substantia nigra and subthalamic nucleus of normal rats, HP rats, and HP rats with murine fetal ventral mesencephalic cell transplants, looking separately at slow wave EEG epochs versus global activation epochs. We found that both the crosscorrelation and the transfer entropy between the motor cortical EEG and basal ganglia LFPs was increased in the HP group (p<0.05) and returned to normal levels in the grafted group, in most nuclei and conditions. However, the transfer entropy more robustly showed the difference between the groups. Our findings indicate that transfer entropy is a sensitive tool for nonlinear inter-nucleic functional connectivity analyses, and demonstrate the novel restorative ability of dopaminergic grafts for the parkinsonian basal ganglia electrophysiology.