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The pathophysiology underlying the response of FoG to dopaminergic treatment is poorly understood. Prior vesicular acetylcholine transporter positron emission tomography (VAChT PET) imaging studies implicate the degeneration of cholinergic pathways, including bilateral striatal and limbic archicortex deficits, as significant contributors to FoG.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We aim to investigate whether specific cholinergic system changes are associated with FoG responsiveness to levodopa treatment in PD patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Thirty six PD subjects (31M\/5F) completed [\n                      <jats:sup>18<\/jats:sup>\n                      F]\u2010fluoroethoxybenzovesamicol ([\n                      <jats:sup>18<\/jats:sup>\n                      F]FEOBV) vesicular acetylcholine transporter positron emission tomography (VAChT PET) and underwent videotaped clinical assessments for FoG on and off levodopa.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Sixteen subjects had\n                      <jats:sc>l<\/jats:sc>\n                      \u2010dopa\u2010unresponsive FoG. Whole brain voxel\u2010based analyses of [\n                      <jats:sup>18<\/jats:sup>\n                      F]FEOBV PET (false discovery rate\u2010corrected at\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05 and adjusted for levodopa\u2010equivalent dose) showed that those with\n                      <jats:sc>l<\/jats:sc>\n                      \u2010dopa\u2010unresponsive FoG had more severe cholinergic terminal deficits in the bilateral insula, hippocampi, fimbria, and lateral geniculate nuclei; left mid\u2010temporal, putamen, and posterior cingulate regions; and the right mid\u2010frontal region and anterior ventral nucleus of the thalamus compared to those with\n                      <jats:sc>l<\/jats:sc>\n                      \u2010dopa\u2010responsive FoG.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      FoG unresponsive to levodopa is associated with bilateral cholinergic terminal reductions, mostly in extra\u2010striatal regions involved in multisensory and cognitive integration of gait and postural control as well as spatial navigation. The lack of specific striatal involvement points to the disruption of widespread cerebral network functions underlying\n                      <jats:sc>l<\/jats:sc>\n                      \u2010dopa\u2010unresponsive FoG in PD and may explain the treatment\u2010resistant nature of FoG to levodopa. \u00a9 2025 The Author(s).\n                      <jats:italic>Movement Disorders<\/jats:italic>\n                      published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.30196","type":"journal-article","created":{"date-parts":[[2025,4,12]],"date-time":"2025-04-12T02:32:01Z","timestamp":1744425121000},"page":"1584-1594","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Cholinergic System Changes in Dopa\u2010Unresponsive Freezing of Gait in Parkinson's Disease"],"prefix":"10.1002","volume":"40","author":[{"given":"Kelvin L.","family":"Chou","sequence":"first","affiliation":[{"name":"Department of Neurology University of Michigan  Ann Arbor Michigan USA"},{"name":"Functional Neuroimaging, Cognitive, and Mobility Laboratory, Department of Radiology University of Michigan  Ann Arbor Michigan USA"},{"name":"Morris K. 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