The dynamic of basal ganglia activity with a multiple covariance method: influences of Parkinson's disease

The closed-loop cortico-subcortical pathways of basal ganglia have been extensively used to describe the physiology of these centres and to justify the functional disorders of basal ganglia diseases. This approach justifies some experimental and clinical data but not others, and furthermore, it does not include a number of subcortical circuits that may produce a more complex basal ganglia dynamic than that expected for closed-loop linear networks. This work studied the functional connectivity of the main regions of the basal ganglia motor circuit with magnetic resonance imaging and a new method (functional profile method), which can analyse the multiple covariant activity of human basal ganglia. The functional profile method identified the most frequent covariant functional status (profiles) of the basal ganglia motor circuit, ordering them according to their relative frequency and identifying the most frequent successions between profiles (profile transitions). The functional profile method classified profiles as input profiles that accept the information coming from other networks, output profiles involved in the output of processed information to other networks and highly interconnected internal profiles that accept transitions from input profiles and send transitions to output profiles. Profile transitions showed a previously unobserved functional dynamic of human basal ganglia, suggesting that the basal ganglia motor circuit may work as a dynamic multiple covariance network. The number of internal profiles and internal transitions showed a striking decrease in patients with Parkinson's disease, a fact not observed for input and output profiles. This suggests that basal ganglia of patients with Parkinson's disease respond to requirements coming from other neuronal networks, but because the internal processing of information is drastically weakened, its response will be insufficient and perhaps also self-defeating. These marked effects were found in patients with few motor disorders, suggesting that the functional profile method may be an early procedure to detect the first stages of the Parkinson's disease when the motor disorders are not very evident. The multiple covariance activity found presents a complementary point of view to the cortico-subcortical closed-loop model of basal ganglia. The functional profile method may be easily applied to other brain networks, and it may provide additional explanations for the clinical manifestations of other basal ganglia disorders.