Computational physiology of the basal ganglia in Parkinson's disease

The normal activity of basal ganglia neurons is characterized by Poisson-like (random) firing patterns. Correlations between neurons of the same structure are weak or non-existent. By contrast, synchronous oscillations are commonly found in the basal ganglia of human patients and animal models of Parkinson's disease. The frequency of these oscillations is often similar to that of the parkinsonian tremor, but their role in generating the tremor or other parkinsonian symptoms is still under debate. The tremor is intermittent and does not appear in all human patients. Similarly, primate models tend to develop tremor as a function of species of monkey. African green (vervet) monkeys usually demonstrate a high-amplitude, low-frequency (4-7. Hz) tremor beyond their akinesia and bradykinesia, whereas macaques tend to be akinetic rigid and rarely demonstrate a low-amplitude high-frequency (10-12. Hz) action-postural tremor. We took advantage of this fact and studied the appearance of the synchronicity and oscillations in six monkeys, three vervets and three macaques, before and after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) systemic treatment and induction of parkinsonism. Multiple extracellular recordings were conducted in the primary motor cortex of two monkeys and in the globus pallidus (GP) of all six monkeys. All the monkeys became akinetic and bradykinetic as a result of the MPTP treatment, but only vervets demonstrated prolonged episodes of low-frequency (4-6. Hz) tremor, whereas macaques were non-tremulous. The GP population exhibited ~5. Hz oscillatory activity in all six monkeys, whereas ~10. Hz neural oscillations were only detected in the tremulous monkeys. The activity of the cortical neurons became strongly oscillatory at ~10. Hz in one of these monkeys, but not the other, although both were tremulous and exhibited comparable pallidal oscillatory activity. Finally, synchronous oscillations, when present, were centred around the higher frequencies of oscillations. These findings suggest that there is a correlation between high-frequency GP neural oscillations and tremor. Furthermore, these pallidal 10. Hz oscillations are probably transferred to the periphery through cortical and brainstem pathways.