An evaluation of the role of internal cues in the pathogenesis of parkinsonian hypokinesia.

Our animal studies suggest that the basal ganglia provide an internal non-specific cue to trigger movement and imply that Parkinson's disease involves a deficiency in this cueing mechanism. Indeed parkinsonian patients typically rely upon external visual cues. To assess the effects of such non-specific cueing mechanisms on movement, we examined patients' utilization of a variety of auditory cues. Ten patients suffering from Parkinson's disease, and their matched controls, pressed buttons at a series of two-way choice points sequentially down a pathway, both when the latter remained illuminated throughout its length, and when it had to be followed from memory alone. In other experimental conditions, auditory cues were also provided, either contingent upon the previous response, at its initiation (a medium level of advance information) or at its completion (a low level of advance information), or as a series of regularly paced (non-contingent) auditory cues (from a metronome). In addition to error data, we recorded down time (DT, time to initiate each next response) and movement time (MT, time to execute each next response). However, both DT and MT measurements showed that parkinsonian patients were enormously disadvantaged by the absence of external cues. While contingent auditory cues were of some help, the performance of patients with Parkinson's disease was dramatically improved by the provision of non-contingent auditory information. Moreover, parkinsonian patients, unlike controls, were greatly affected by the length of individual sub-movements, especially in the absence of external cues. When the pathway to be followed remained illuminated, sub-movement length had little effect. We conclude that for well-learnt, predictable sequences the basal ganglia provide a non-specific internal cue that is necessary for switching between one movement and the next in a movement sequence, and also for development of preparatory activity for each sub-movement in the sequence.