Check for updates RESEARCH ARTICLE Anatomo-Functional Mapping of the Primate Mesencephalic Locomotor Region Using Stereotactic Lesions Marion Gay, MSc,1 Hayat Belaid, MD, PHD,1,2 Alister Rogers, MD,1,2 Fernando Pérez-GarcÃa, MSc, 1,3 Maxime Roustan,1 Eric Bardinet, PhD,1,3 Chantal François, PhD,1 and Carine Karachi, MD, PhD 1,4* 1 Sorbonne University, Univ. Pierre & Marie Curie Paris 06, CNRS, INSERM, APHP GH Pitié-Salpêtrière, Institut du cerveau et de la moelle épinière, Paris, France 2 Department of Neurosurgery, Rothschild Foundation, Paris, France 3Center of Neurolmaging Research-CENIR, Paris, France 4AP-HP, Department of Neurosurgery, La Pitié-Salpêtrière University Hospital, Paris, France ABSTRACT: Background: Dysfunction of the mesen- cephalic locomotor region has been implicated in gait disorders. However, the role of its 2 components, the pedunculopontine and the cuneiform nuclei, in locomo- tion is poorly understood in primates. Objectives: To analyze the effect of cuneiform lesions on gait and balance in 2 monkeys and to compare them with those obtained after cholinergic pedunculopontine lesions in 4 monkeys and after lesions in both the cunei- form and pedunculopontine nuclei in 1 monkey. Methods: After each stereotactic lesion, we performed a neurological examination and gait and balance assess- ments with kinematic measures during a locomotor task. The 3-dimensional location of each lesion was analyzed on a common brainstem space. Results: After each cuneiform lesion, we observed a contra- lateral cervical dystonia including an increased tone in the proximal forelimb and an increase in knee angle, back curva- ture and walking speed. Conversely, cholinergic - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - *Correspondence to: Dr. Carine Karachi, Institut du cerveau et de la moelle épinière (ICM), 75013 Paris, France; E-mail: carine. karachi@gmail.com - - - - - - - - - - - - - - - - from gait and balance disorders that are resistant to dopaminergic medication and deep brain stimulation (DBS) of the subthalamic nucleus, leading to freezing of gait and falls with increased morbidity and mortality. Experimental and clinical data have highlighted the cen- tral role of the mesencephalic locomotor region (MLR) that could play a role in the appearance of these gait and balance disorders. The MLR is part of the mesencephalic reticular formation comprising the pedunculopontine (PPN) and the cuneiform nucleus (CuN). In PD patients, the number of cholinergic neurons within the PPN is +Marion Gay and Hayat Belaid contributed equally to this work. Funding agency: This work was funded by Investissements d'avenir (Investing in the Future program) ANR-10-IAIHU-O6 Relevant conflicts of interests/financial disclosures: Nothing to report. Received: 23 October 2019; Revised: 24 December 2019; Accepted: 27 December 2019 Published online 00 Month 2020 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/mds.27983 pedunculopontine lesions increased tail rigidity and back cur- vature and an imbalance of the muscle tone between the ipsi- and contralateral hindlimb with decreased knee angles. The walking speed was decreased. Moreover,