Basal ganglia neurodynamics in Parkinson's disease

It is well known that Parkinson's disease (PD) is caused by the loss of midbrain dopaminergic neurons that project to the striatum but there is little understanding of how this loss affects the organization of motor systems in the brain to give rise to the symptoms. A model of basal ganglia (BG) function has been proposed, according to which two anatomically segregated pathways from the striatum have opposing effects on the BG output. Despite its successes, this model does not explain some symptoms of PD, such as rigidity, tremor, and drug-induced dyskinesias, nor the effects of some lesions like pallidotomy and thalamotomy. I argue in this thesis that an important reason for this is that the dynamics of neural interactions in the BG have been neglected in the current model. In order to study this problem, I used spectral methods to analyze neural and electromyographic (EMG) data from the BG and thalamus of 18 patients undergoing stereotaxic surgery. The analysis revealed distinct dynamical modes of activity in the BG and thalamus: tremor-related activity, high frequency (15–30Hz) activity, and dyskinesia-related activity. Coherence analysis of tremor-related neural and neural-EMG pairs showed that they could be phase locked in some cases but not always. In a second study I analyzed EMGs in several muscles of four PD patients with tremor. Muscles in the same limb were shown to oscillate in a phase-locked fashion but muscles in different limbs were independent. These results suggest that tremor arises from the activity of a topographically organized network, where largely segregated oscillators span the different limb representations. The structures comprising this network must, therefore, have a topographic organization and show tremor related activity. Accordingly, I propose that this network includes the motor cortex, subthalamic nucleus, the internal segment of the globus pallidus and the motor thalamus, and forms a closed loop. This loop is proposed to interact with the cortico-spino-thalamocortical loop and the cortico-cerebello-thalamocortical loops in the motor cortex to give rise to tremor. The possible involvement of the proposed tremor-generating network in PD symptoms other than tremor is also discussed.