title: Physiology of freezing of gait.
abstract: Freezing of gait (FOG) is a common and debilitating, but largely mysterious, symptom of Parkinson disease. In this review, we will discuss the cerebral substrate of FOG focusing on brain physiology and animal models. Walking is a combination of automatic movement processes, afferent information processing, and intentional adjustments. Thus, normal gait requires a delicate balance between various interacting neuronal systems. To further understand gait control and specifically FOG, we will discuss the basic physiology of gait, animal models of gait disturbance including FOG, alternative etiologies of FOG, and functional magnetic resonance studies investigating FOG. The outcomes of these studies point to a dynamic network of cortical areas such as the supplementary motor area, as well as subcortical areas such as the striatum and the mesencephalic locomotor region including the pedunculopontine nucleus (PPN). Additionally, we will review PPN (area) stimulation as a possible treatment for FOG, and ponder whether PPN stimulation truly is the right step forward. Ann Neurol 2016;80:644-659.
authors.affiliation: Department of Neurology, Donders Institute for Brain, Cognition, and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands.|Maasziekenhuis Pantein, Boxmeer, the Netherlands.
authors.forename: Anke H
authors.initials: AH
authors.lastname: Snijders
authors.affiliation: Research Center for Brain Function and Medical Engineering, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Takakusaki
authors.affiliation: Joseph Fourier University, Grenoble Universities, Grenoble, France.
authors.forename: Bettina
authors.initials: B
authors.lastname: Debu
authors.affiliation: Division of Neurosurgery, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Andres M
authors.initials: AM
authors.lastname: Lozano
authors.affiliation: Division of Neurosurgery, University of Toronto, Toronto, Ontario, Canada.|Department of Neurosurgery, Ohio State University, Columbus, OH.
authors.forename: Vibhor
authors.initials: V
authors.lastname: Krishna
authors.affiliation: Morton and Gloria Shulman Movement Disorders Centre and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Fasano
authors.affiliation: John Radcliffe Hospital, Headington, Oxford, United Kingdom.
authors.forename: Tipu Z
authors.initials: TZ
authors.lastname: Aziz
authors.affiliation: Department of Neurology, Jean and Paul Amos Parkinson's Disease and Movement Disorders Center, Emory University School of Medicine, Atlanta, GA.
authors.forename: Stella M
authors.initials: SM
authors.lastname: Papa
authors.affiliation: Department of Neurology, Jean and Paul Amos Parkinson's Disease and Movement Disorders Center, Emory University School of Medicine, Atlanta, GA.
authors.forename: Stewart A
authors.initials: SA
authors.lastname: Factor
authors.affiliation: Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.
authors.forename: Mark
authors.initials: M
authors.lastname: Hallett
mesh_terms: D000818:Animals; D046690:Deep Brain Stimulation; D059907:Functional Neuroimaging; D020233:Gait Disorders, Neurologic / Q000209:etiology / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D045042:Pedunculopontine Tegmental Nucleus