Dopamine signals and physiological origin of cognitive dysfunction in Parkinson's disease.

The pathological hallmark of Parkinson's disease (PD) is the degeneration of midbrain dopamine neurons. Cognitive dysfunction is a feature of PD patients even at the early stages of the disease. Electrophysiological studies on dopamine neurons in awake animals provide contradictory accounts of the role of dopamine. These studies have established that dopamine neurons convey a unique signal associated with rewards rather than cognitive functions. Emphasizing their role in reward processing leads to difficulty in developing hypothesis as to how cognitive impairments in PD are associated with the degeneration of dopamine circuitry. A hint to resolve this contradiction came from recent electrophysiological studies reporting that dopamine neurons transmit more diverse signals than previously thought. These studies suggest that dopamine neurons are divided into at least two functional subgroups, one signaling "motivational value" and the other signaling "salience." The former subgroup fits well with the conventional reward theory, whereas the latter subgroup has been shown to transmit signals related to salient but non-rewarding experiences such as aversive stimulations and cognitively demanding situations. This article reviews recent advances in understanding the non-reward functions of dopamine, and then discusses the possibility that cognitive dysfunction in PD is at least partially caused by the degeneration of the dopamine neuron subgroup signaling the salience of events in the environment.