Two patients, apparently successfully treated with pedunculopontine nucleus stimulation, had persistent remission of freezing despite having ceased stimulation for >12 h.
Interestingly, the nature of the defensive behaviors evoked in this study depended on the intensity of the optogenetic stimulation: avoidance was evoked by low intensity stimulation, while freezing and the interruption of ongoing appetitive behavior required a higher intensity, and activity bursts yet more intense stimulation.
Patient 22 suffered from worsening of pre-existing gait freezing under high amplitude stimulation of more caudal electrode contacts.
(C ) Average number of vesicles per profile docked in the active zone is plotted relative to the intervals between stimulation and freezing.
Under low temperature conditions, CCA1β production is reduced, and thus CCA1α activity is elevated, leading to the stimulation of freezing tolerance [ 27], linking the clock with temperature response.
This approach made it possible to control stimulation and freezing on a millisecond time scale, enabling the team to obtain snapshots of exocytosis and endocytosis.
However, in an experimental setting, we found that bilateral pedunculopontine nucleus stimulation improved OFF medication gait freezing approximately twice as much as unilateral stimulation (in terms of percentage improvements).
Under experimental conditions, while OFF medication, Parkinsonian patients with severe gait freezing implanted with pedunculopontine nucleus stimulators below the pontomesencephalic junction were assessed during three conditions; off stimulation, unilateral stimulation and bilateral stimulation.
However, we found that pedunculopontine nucleus stimulation did not improve step length or its variability, supporting the proposition that pedunculopontine nucleus stimulation may improve gait freezing through alternative, potentially complementary, pathways (Jenkinson et al., 2006; Thevathasan et al., 2011 b ).
In the Giladi Freezing of Gait Questionnaire, freezing of gait improved with combined STN+SNr stimulation compared with standard STN stimulation, although not significantly (14.50 ± 4.89 versus 16.17 ± 3.83; P = 0.1).
