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PPN\u2010deep brain stimulation inconsistently alleviates PGD, due to stereotactic targeting inaccuracies resulting from insufficiently detailed human PPN anatomical descriptions. Relatedly, rodent studies show rostro\u2010caudal clustering of PPN\u2010cholinergic neurons, reflecting functional sub\u2010territories. We applied unbiased cerebro\u2010bilateral 3\u2010dimensional (3\u2010D) stereology to post\u2010mortem PPNs from PD versus neurological\u2010control cases, to estimate total numbers of cholinergic neurons and describe their rostro\u2010caudal distribution. Given ambiguous descriptions of the PPN's confines, we utilized two complimentary definitions of the PPN's anatomical boundaries. The first was based on the structure's gross anatomy, by considering the nucleus as a recognizable \u201cchannel\u201d enclosed by distinct white matter fiber tracts (WMFT) encompassing the medial lemniscus, central tegmental tract and decussation of the superior cerebellar peduncle. Second, the PPN was recognized by its histological architecture, as a dense collection of cholinergic neurons (the \u201cCh5\u201d group) that were immunoreactive for choline acetyltransferase (ChAT), the enzyme responsible for biosynthesis of the neurotransmitter acetylcholine. Many such ChAT\u2010immunoreactive neurons were dispersed within the traversing tracks and hence the PPN's Ch5\u2010based outlining method permitted their stereological capture while also allowing distinction between the PPN's two subnuclei, namely the pars compacta (PPNc) and pars dissipata (PPNd), based on subnuclei\u2010specific cholinergic cytoarchitectural organization. We further reconstructed template data as 3\u2010D renders, revealing gross morphological differences between control and PD\u2010affected PPNs. PD brains revealed significant PPN cholinergic neuronal loss, particularly affecting the PPNd. Control cases showed bimodal clustering of cholinergic neurons, prominently affecting left\u2010sided PPNs. Most PD cases revealed more severe cholinergic neuronal loss in right\u2010sided PPNs, potentially driving symptom lateralization. Our study provides a comprehensive cholinergic cytoarchitectural atlas of the human PPN in health versus during PD.<\/jats:p>","DOI":"10.1111\/bpa.70011","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T09:13:30Z","timestamp":1748337210000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Stereological analysis of cholinergic neurons within bilateral pedunculopontine nuclei in health and when affected by Parkinson's disease"],"prefix":"10.1111","volume":"35","author":[{"given":"Puneet Kumar","family":"Sharma","sequence":"first","affiliation":[{"name":"Department of Brain Sciences Imperial College London  London UK"},{"name":"Department of Neurosurgery Imperial College Healthcare Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Gentleman","sequence":"additional","affiliation":[{"name":"Department of Brain Sciences Imperial College 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