Cholinergic mesencephalic neurons are involved in gait and postural disorders in Parkinson disease
Carine Karachi, … , Etienne C. Hirsch, Chantal François
Carine Karachi, … , Etienne C. Hirsch, Chantal François
Published July 12, 2010
Citation Information: J Clin Invest. 2010;120(8):2745-2754. https://doi.org/10.1172/JCI42642.
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Research Article Neuroscience

Cholinergic mesencephalic neurons are involved in gait and postural disorders in Parkinson disease

Abstract

Gait disorders and postural instability, which are commonly observed in elderly patients with Parkinson disease (PD), respond poorly to dopaminergic agents used to treat other parkinsonian symptoms. The brain structures underlying gait disorders and falls in PD and aging remain to be characterized. Using functional MRI in healthy human subjects, we have shown here that activity of the mesencephalic locomotor region (MLR), which is composed of the pedunculopontine nucleus (PPN) and the adjacent cuneiform nucleus, was modulated by the speed of imagined gait, with faster imagined gait activating a discrete cluster within the MLR. Furthermore, the presence of gait disorders in patients with PD and in aged monkeys rendered parkinsonian by MPTP intoxication correlated with loss of PPN cholinergic neurons. Bilateral lesioning of the cholinergic part of the PPN induced gait and postural deficits in nondopaminergic lesioned monkeys. Our data therefore reveal that the cholinergic neurons of the PPN play a central role in controlling gait and posture and represent a possible target for pharmacological treatment of gait disorders in PD.

Authors

Carine Karachi, David Grabli, Frédéric A. Bernard, Dominique Tandé, Nicolas Wattiez, Hayat Belaid, Eric Bardinet, Annick Prigent, Hans-Peter Nothacker, Stéphane Hunot, Andreas Hartmann, Stéphane Lehéricy, Etienne C. Hirsch, Chantal François

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Figure 1

Cerebral activity during IG and IOM in 15 healthy volunteers.

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Cerebral activity during IG and IOM in 15 healthy volunteers. (A) Region...
(A) Regions of significant activation superimposed on a rendered brain viewed from above, showing increased activity in the superior frontal gyrus bilaterally (yellow circles) and the right precentral gyrus (blue circle) for the comparison of IG versus IOM (P < 0.001, uncorrected for multiple comparisons; cluster size, >30 voxels). (B) Regions of significant activation superimposed on T1-weighted images (top, sagittal; middle, transverse; bottom, coronal), showing increased activity in the left PPN and cuneiform nucleus for the comparison of faster versus normal IG (P < 0.001, uncorrected for multiple comparisons; cluster size, >30 voxels). Activity in this region survived a small volume correction (10-mm radius) for multiple comparisons (family-wise error, P < 0.05). (C) Regions of significant activation, superimposed on the tracing of cerebral contours in the PPN region, in a coronal MRI section. (D) Posterior view of the PPN and cuneiform nucleus. (E) Plots of activity in left PPN and cuneiform nucleus (x, –3; y, –22; z, –13) for normal and faster IG conditions. For t values of each contrast, see Table 1. CuN, cuneiform nucleus; DSCP, decussation of superior cerebellar peduncle; L, left; ML, medial lemniscus. Scale bars: 10 mm.