{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T14:15:53Z","timestamp":1768572953750,"version":"3.49.0"},"posted":{"date-parts":[[2025,10,27]]},"group-title":"Neurology","reference-count":65,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:00:00Z","timestamp":1761523200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Two-thirds of the world\u2019s languages, including Mandarin and Cantonese, employ pitch variation to convey meaning (lexical tone). Existing diagnostic frameworks for primary progressive aphasia (PPA) have been developed for English speakers, and have not considered the impact of salient language-specific variations, such as tone. This study investigates lexical tone processing in Mandarin- and Cantonese-speaking individuals with PPA and examines their neural signatures using structural neuroimaging.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Seventy-eight native Chinese speakers (54 with PPA; 24 healthy controls) were assessed using the CLAP (Chinese Language Assessment for PPA) battery, a series of neuropsychological and linguistic tasks developed to characterize the linguistic features of Mandarin and Cantonese speakers with PPA. Lexical tone production was examined through repetition and reading of \u201ctone-twister\u201d phrases, as well as repetition of multicharacter phrases varying in articulatory features (place, manner, and tone). Tone perception and comprehension was assessed via identification, discrimination, and tone-word\/picture matching tasks. Group differences were analyzed using nonparametric tests and generalized estimating equations, with ROC analyses determining diagnostic accuracy. Structural MRI data were acquired for 55 participants, and voxel-based morphometry (VBM) was used to examine the neural correlates of tone performance.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Participants with nonfluent\/agrammatic variant PPA (nfvPPA) showed marked impairments in lexical tone production (all p&lt;0.001), with a disproportionately high rate of tonal relative to syllabic errors (p&lt;0.001). In contrast, semantic variant PPA (svPPA) exhibited prominent deficits in three tone perception tasks (all p&lt;0.001). Patients with logopenic variant PPA (lvPPA) showed relatively preserved tone production but a predominance of syllabic errors (p&lt;0.001), suggesting underlying phonological deficits. Lexical tone production tasks demonstrated strong discrimination of nfvPPA (AUC= 0.702-0.907). In contrast, three tone perception tasks exhibited high sensitivity for detecting svPPA (90.9-100%), though specificity was modest (37-63%). Neural correlate analyses revealed that tone production deficits were associated with reduced grey matter volume in the left inferior frontal gyrus, insula, and temporal cortex, whereas tone perception performance correlated with atrophy in the left superior and middle temporal gyri, temporal pole, and orbitofrontal regions.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Discussion<\/jats:title>\n                  <jats:p>Lexical tone processing is differentially impaired across PPA subtypes, with tone production and perception deficits mapping onto distinct neural substrates. These findings underscore the necessity of developing language-specific diagnostic approaches for tonal language speakers and call into question the cross-cultural applicability of current PPA diagnostic strategies, which have been largely shaped by Indo-European language frameworks.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.10.24.25338751","type":"posted-content","created":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T15:25:11Z","timestamp":1761578711000},"source":"Crossref","is-referenced-by-count":0,"title":["Speaking in Tones: The role of lexical tones in Chinese-speaking Primary Progressive Aphasia"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4412-8688","authenticated-orcid":false,"given":"Boon Lead","family":"Tee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ta-Fu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorinda Kwan-Chen","family":"Li-Ying","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raymond Y.","family":"Lo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua","family":"Tsoh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew Lung-Tat","family":"Chan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrian","family":"Wong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chien Jung","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei-Ning","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"YiChen","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel Elaine","family":"Allen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Chen","family":"Chuang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Wen","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"FangDa","family":"Leng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2518-2520","authenticated-orcid":false,"given":"Maria-Luisa","family":"Mandelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"de Leon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1808-8843","authenticated-orcid":false,"given":"Jet","family":"Vonk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Luisa","family":"Gorno-Tempini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025102921200714000_2025.10.24.25338751v1.1","doi-asserted-by":"crossref","unstructured":"Best CT . 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