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FIGURE 5. Proposed functional model of basal ganglia in patients with parkinsonism (A) and hypothetic schematic diagram of mechanisms by which STN-DBS produces its clinical benefit in the long term (B). For clarity, the neuroanatomy and interconnections shown are incomplete. Excitatory connections are indicated by solid arrowheads and inhibitory connections are indicated by open arrowheads. Relative increases and decreases in tonic discharge rates associated with parkinsonism and DBS are denoted by wider and thinner lines and outlining of each box, respectively. Dashed line indicates the inhibitory effect of long-term DBS on overactive STN. Cortical and subcortical regions resulting in activation in our study are displayed on a glass brain. (A) Parkinsonism arises from loss of dopaminergic neurons in the pars compacta segments of the substantia nigra (SNc). Reduced inhibition via the direct pathway (striatum to the globus pallidus pars interna [Gpi] and the pars reticulata of the substantia nigra [SNr]) combined with increased excitation from the STN via the indirect pathway (striatum to the globus pallidus pars externa [Gpe]) leads to overactivity of GPi and SNr. This abnormal activity may determine motor impairment by suppressing thalamocortical and cerebellocortical facilitation and by altering brainstem locomotor areas. (B) Reduction of excessive excitatory activity of the STN would partially reverse this state by eliminating excessive inhibition of both components of the output of basal ganglia. This may lead to enhanced activation responses in motor/associative areas of frontal lobes, possibly involving elements within the basal ganglia–thalamocortical motor circuits during the first months of stimulation as well as within the cerebellothalamocortical motor loop, the nigral dopaminergic system, and the brainstem during subsequent years of therapy.
