Our understanding of the physiology of the basal ganglia and deep brain stimulation (DBS) has evolved and has been shaped by decades of studies of the basal ganglia in experimental animal models and human patients.
The classical models of the basal ganglia describe direct, indirect, and hyper-direct pathways connecting the cortex with the striatum and the basal ganglia output structures. The basal ganglia output nuclei modulate the excitability of the motor cortex. In Parkinson’s disease, dopamine depletion leads to reduced excitability of the motor cortex and akinesia. This model predicted increased activity in the subthalamic nucleus (STN) following dopamine depletion and suggested that the therapeutic effects of DBS are achieved through the restoration of normal STN discharge rate.
More recent computational models of the basal ganglia depict these as an actor/critic reinforcement learning network. The actor is the main axis of the basal ganglia connecting between all cortical areas encoding current state and the brain motor centers. The critic, or the teacher, is composed of midbrain dopaminergic neurons encoding the mismatch between predictions and reality. In this model, the main effect of dopamine is to modulate the efficacy of the cortico-striatal synapse. The efficacy of the cortico-striatal synapse dedicates the behavioral policy that is the coupling between state and action.
Finally, the recently formulated computational model of the basal ganglia combines the main features of the classical direct/indirect pathways and modern reinforcement learning models. The basal ganglia critics (neuromodulators, including the dopaminergic, cholinergic, serotonergic, and histaminergic projections to the striatum) modulate both the excitability of striatal neurons and the efficacy of the cortico-striatal synapses. The model further suggests that the basal ganglia networks are the default connection between the brain structures encoding state and actions.
Degeneration or abnormal activity of basal ganglia neuromodulators leads to abnormal activity of neurons in the main axis of the basal ganglia. Since the basal ganglia networks are the default connection between state and actions, the other neural networks (e.g., cortico-cortical networks) cannot compensate for the abnormal basal ganglia activity. Therapy of basal ganglia-related neurological and psychiatric disorders can be therefore achieved by inactivation of the basal ganglia main axis. Functional inactivation (information lesion) of the basal ganglia networks is achieved by lesion or DBS paradigms and enables compensation by other neuronal networks and restoration of normal behavioral policy.
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